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Sample records for cells precocious improvement

  1. True precocious puberty following treatment of a Leydig cell tumour: two case reports and literature review

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    Alberto eVerrotti

    2015-11-01

    Full Text Available Leydig cell testicular tumours are a rare cause of precocious pseudopuberty in boys. Surgery is the main therapy and shows good overall prognosis. The physical signs of precocious puberty are expected to disappear shortly after surgical removal of the mass. We report two children, 7.5 and 7.7 year-old boys, who underwent testis-sparing surgery for a Leydig cell testicular tumour causing precocious pseudopuberty. During follow-up, after an immediate clinical and laboratory regression, both boys presented signs of precocious puberty and ultimately developed central precocious puberty. They were successfully treated with gonadotropin releasing hormone analogues. Only 6 other cases have been described regarding the development of central precocious puberty after successful treatment of a Leydig cell tumour causing precocious pseudo puberty. Gonadotropin-dependent precocious puberty should be considered in children treated for a Leydig cell tumour presenting persistent or recurrent physical signs of puberty activation. In such cases, therapy with gonadotropin releasing hormone analogues appears to be the most effective medical treatment.

  2. Precocious pseudopuberty due to juvenile granulosa cell tumor

    International Nuclear Information System (INIS)

    Saeed, G.A.; Farooq, N.

    2003-01-01

    A case of precocious puberty occurring in a young girl is presented. Vaginal bleeding and secondary sexual characteristics had occurred at 7 years of age associated with an abdominal mass. These findings were due to a functional juvenile granulosa cell tumor in the right ovary. Right adenectomy was performed. Histopathology was confirmatory. (author)

  3. Precocious Puberty in Children

    International Nuclear Information System (INIS)

    Atta, I.; Laghari, T. M.; Khan, N. Y.; Lone, W. S.; Ibrahim, M.; Raza, J.

    2015-01-01

    Objective: To determine the etiology of precocious puberty in children and to compare the clinical and laboratory parameters of central and peripheral precocious puberty. Study Design: Cross-sectional study. Place and Duration of Study: Endocrine Clinic at National Institute of Child Health, Karachi, from January 2009 to December 2011. Methodology: Children presenting with precocious puberty were included. The age of onset of puberty was documented. Clinical evaluation, Tanner staging, height, height SDS, weight, weight SDS, body mass index, bone age, pelvic USG, plasma estradiol level and GnRH stimulation were done. Ultrasound of adrenal glands, serum level of 17 hydroxyprogesterone, ACTH, Renin, aldosterone and testosterone were performed in children with peripheral precocious puberty. MRI of adrenal glands and gonads was done in patients with suspected tumor of that organ and MRI of brain was done in patients with central precocious puberty. Skeletal survey was done in patients with Mc Cune-Albright syndrome. Results: CAH (81.8%) indentified as a main cause in peripheral percocious puberty and idiopathic (67.74%) in central precocious puberty. Eighty five patients were registered during this period. The conditions causing precocious puberty were central precocious puberty (36.47%), peripheral precocious puberty (38.82%), premature pubarche (10.58%) and premature thelarche (14.11%). There was a difference in the age of onset of puberty in case of central precocious puberty (mean=3, 2-6 years) versus peripheral precocious puberty (mean=5.25; 3.62 - 7.0 years). Children with central precocious puberty showed higher height SDS, weight SDS, FSH, LH than those with peripheral precocious puberty. Conclusion: Etiology in majority of cases with peripheral precocious puberty was congenital adrenal hyperplasia and idiopathic in central precocious puberty. Central precocious puberty children showed higher height SDS, weight SDS, FSH, LH than peripheral precocious puberty

  4. Altricial-precocial spectra in animal kingdom

    NARCIS (Netherlands)

    Augustine, Starrlight; Lika, Konstadia; Kooijman, Sebastiaan A.L.M.

    2018-01-01

    Traditionally, the terms altricial and precocial are used to described the state at birth of birds and mammals. We suggest an explanation for why birds evolved from precocial to altricial and mammals from altricial to precocial. However, the concept is not confined to these groups alone and is an

  5. Genetics Home Reference: familial male-limited precocious puberty

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    ... male-limited precocious puberty Familial male-limited precocious puberty Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Familial male-limited precocious puberty is a condition that causes early sexual development ...

  6. [Precocious puberty and von Recklinghausen's disease].

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    Barg, Ewa; Wikiera, Beata; Basiak, Aleksander; Głab, Ewa

    2006-01-01

    Von Recklinghausen's disease belongs to a group of neurocutaneous syndromes and is characterised by skin, nerve and bone abnormalities. We present a case of von Recklinghausen's disease and precocious puberty in 7-year-old boy. At the age of three café au lait spots on the skin and an incranial tumour situated near the optic chiasm--qualified as inoperable--were discovered. At the age of 7 first signs of precocious puberty appeared (pubic hair P3 and enlargement of the testes (15 ml) and penis). Laboratory measurements included: LH 7.5 mIU/ml, FSH 1.1 mIU/ml, testosterone 183 ng/ml, assessment of bone age: 9 years. The response to LHRH stimulation was characteristic for true precocious puberty (LH 15.9 mIU/ml and FSH 1.5 mIU/ml after 30 minutes). The MRI of the brain showed a tumour of the suprasellar region with compression of pituitary stalk. True precocious puberty was diagnosed. Treatment with Diphereline was introduced. At present the boy is 9 years old and has been treated with Diphereline for 16 months. The volume of the testicles has decreased to 7 ml and loss of pubic hair was noted. The MRI does not show any progression in tumour growth. The authors would like to underline the need of close observation of children with von Reclinghausen disease with regard to possibility of uncovering true precocious puberty which is critical for rapid diagnosis and introduction of correct treatment.

  7. Ussefulnes of imaging techniques in the diagnostics of precocious puberty in boys

    International Nuclear Information System (INIS)

    Jakubowska, Anna; Grajewska-Ferens, Magdalena; Brzewski, Michał; Sopyło, Barbara

    2011-01-01

    Precocious puberty (PP) is defined as the appearance of symptoms of puberty in girls before 8 years of age and in boys under 9. Statistically, it occurs much more frequently in girls, while it is a rare pathology in boys. Over the period of 10 years, between 1999 and 2009, 39 girls and 17 boys aged 18 months – 9 years were diagnosed with precocious puberty,, and treated at the Endocrinology Clinic. The following tests were performed in all children: physical and anthropometric examinations, abdominal ultrasound scan (US) with evaluation of adrenal glands, examination of testes in boys or breasts and pelvic organs in girls, evaluation of skeletal age and, in selected cases, CT scans of the abdomen, MRI of the CNS, and hormonal laboratory tests. In the group of 17 boys the findings included: gonadotropin –dependent central puberty in 6 boys: idiopathic in 5 cases, and 1 case of a brain tumor – astrocytoma. Gonadotropin-independent precocious pseudopuberty was diagnosed in 11 boys: congenital adrenal hyperplasia in 5; in 1case – hyperandrogenism caused by overactivity of 5-α reductase; in 2 subjects – adrenal adenoma; in 2 boys adrenocortical carcinoma was diagnosed and Leydig cell tumor of testis in 1. 1. Precocious puberty occurs less often in boys, but in our population it was found in 17 boys of 56 treated children, which constituted as much as 30%. 2. Precocious pseudopuberty was found in 64% of the boys with PP. 3. Adrenal and testicular tumors were the causes of precocious puberty in the youngest group of boys aged 18 months – 6 years

  8. Granulosa cell tumor in a six-year-old girl presented as precocious puberty

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    Mahin Hashemipour

    2010-01-01

    Microscopic features of the resected mass were characteristic of juvenile GCT. Although in most of girls with precocious puberty, the etiology is idiopathic, important causes, such as ovarian tumors must be considered.

  9. Precocious Puberty (For Parents)

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    ... spurt" start of menstruation (her period) acne "mature" body odor In boys, the signs of precocious puberty before ... growth — a growth "spurt" voice deepening acne "mature" body odor Many kids who show some of the early ...

  10. MRI study of pituitary in girls with central precocious puberty

    International Nuclear Information System (INIS)

    Ye Zhiqiu; Guo Qinglu; Feng Changzheng; Wei Beiyang; Liu Yongxi; Zhang Yan

    2008-01-01

    Objective: To study the shape, size and signal intensity of pituitary gland in girls aged 3-10 year old with central precocious puberty. Methods: MRI data of pituitary glands in 40 girls aged 3-10 years old with central precocious puberty were selected. The shape, height and the appearances of pituitary glands were measured and observed on sagittal T 1 WI. Results: Quantitative data about size, shape and single intensity changes of pituitary glands in central precocious puberty were obtained in two groups, including girls aged from 3-5 and 5-10. The convex pituitary gland were 85.0% in former group. The height of pituitary gland were 6.1±0.2mm (former group) and 6.4± 0.4mm (latter one) respectively. The width of pituitary stalk was 1.93±0.50mm. The posterior pituitary gland demonstrated high signal intensity in all cases. Conclusion: Obvious changes of the size and shape of pituitary glands were found in central precocious puberty of girls aged from 3-10. The pituitary glands manifested physiologic hypertrophy with more convex in central precocious puberty girls than in normal ones. The changes on MRI could reflect the function of hypothalamus-pituitary-gonadal axis. It is of important value and significance in the diagnosis of central precocious puberty. (authors)

  11. Molecular mechanism underlying juvenile hormone-mediated repression of precocious larval-adult metamorphosis.

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    Kayukawa, Takumi; Jouraku, Akiya; Ito, Yuka; Shinoda, Tetsuro

    2017-01-31

    Juvenile hormone (JH) represses precocious metamorphosis of larval to pupal and adult transitions in holometabolous insects. The early JH-inducible gene Krüppel homolog 1 (Kr-h1) plays a key role in the repression of metamorphosis as a mediator of JH action. Previous studies demonstrated that Kr-h1 inhibits precocious larval-pupal transition in immature larva via direct transcriptional repression of the pupal specifier Broad-Complex (BR-C). JH was recently reported to repress the adult specifier gene Ecdysone-induced protein 93F (E93); however, its mechanism of action remains unclear. Here, we found that JH suppressed ecdysone-inducible E93 expression in the epidermis of the silkworm Bombyx mori and in a B. mori cell line. Reporter assays in the cell line revealed that the JH-dependent suppression was mediated by Kr-h1. Genome-wide ChIP-seq analysis identified a consensus Kr-h1 binding site (KBS, 14 bp) located in the E93 promoter region, and EMSA confirmed that Kr-h1 directly binds to the KBS. Moreover, we identified a C-terminal conserved domain in Kr-h1 essential for the transcriptional repression of E93 Based on these results, we propose a mechanism in which JH-inducible Kr-h1 directly binds to the KBS site upstream of the E93 locus to repress its transcription in a cell-autonomous manner, thereby preventing larva from bypassing the pupal stage and progressing to precocious adult development. These findings help to elucidate the molecular mechanisms regulating the metamorphic genetic network, including the functional significance of Kr-h1, BR-C, and E93 in holometabolous insect metamorphosis.

  12. Etiology of precocious puberty, 10 years study in Endocrine Reserch Centre (Firouzgar, Tehran

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    Fatemeh Safari

    2012-01-01

    Full Text Available Background: Precocious puberty, as early physical development and low final height might lead to psychosocial problems.Objective: To evaluate etiology and clinical feature of precocious puberty in a cohort of Iranian children.Materials and Methods: In this case-series study, 44 girls and 8 boys with precocious puberty referred to Endocrine Reserch Centre (Firouzgar, Institute of Endocrinology and Metabolism (Hemmat Campus, were examined in a 10 years period of time. Results: Mean age of girls and boys was 7.43±1.4 years and 5.8±2.1 years respectively. Most of the patients fell within the age category of 7-7.9 years old (40.9% for girls and 50% for boys. Patients, concerning etiology of precocious puberty were classified in three categories: 42.6% of patients had central precocious puberty (CPP, including idiopathic CPP (87.5% and neurogenic CPP (12.5%. 23.3% of patients had peripheral precocious puberty (PPP, including congenital adrenal hyperplasia (CAH (42.8%, ovarian cysts (28.4%, McCune-Albright syndrome (14.2% and adrenal carcinoma (14.2%. 34.1% of girls and 25% of boys had normal variant puberty including premature thelarche (57%, premature adrenarche (38% as well as premature menarche (4.7%l. Conclusion: The most common etiology of precocious puberty in girls was idiopathic central precocious puberty and premature thelarche, while in boys they were neurogenic central precocious puberty and CAH. Therefore precocious puberty in girls is usually benign. In boys, CNS anomalies should first be considered in the differential diagnosis of CPP. Therefore brain Magnetic Resonance Imaging (MRI is mandatory in all cases.

  13. Prostate specific antigen in boys with precocious puberty before and during gonadal suppression by GnRH agonist treatment

    DEFF Research Database (Denmark)

    Juul, A; Müller, J; Skakkebaek, N E

    1997-01-01

    antigen (PSA) is a marker of the androgen-dependent prostatic epithelial cell activity and it is used in the diagnosis and surveillance of adult patients with prostatic cancer. We have measured PSA concentrations in serum from boys with precocious puberty before and during gonadal suppression with Gn......RH agonists to evaluate the effect of normal and precocious puberty on PSA levels and to study the correlation between testosterone and PSA in boys....

  14. PRECOCIOUS PUBERTY DUE TO OVARIAN CYST – CASE REPORT

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    Teresa M Guimarães

    2017-01-01

    Discussion/Conclusion: Most autonomous ovarian cysts regress spontaneously with regression of pubertal signs, as in the present case. Therapy with a GnRH agonist may become necessary in the case of transformation from precocious pseudopuberty to central precocious puberty after recurrences of the ovarian cysts or when there is significant loss of height potential.

  15. Central precocious puberty: evaluation by neuroimaging

    International Nuclear Information System (INIS)

    Kornreich, L.; Horev, G.; Blaser, S.; Daneman, D.; Kauli, R.; Grunebaum, M.

    1995-01-01

    To evaluate the incidence of abnormal intracranial findings in children with central precocious puberty, 62 children (51 girls, 11 boys) were examined by computerized tomography and/or magnetic resonance imaging (MRI) of the brain. Forty-four had normal examinations; 18 (11 girls, 7 boys) showed intracranial pathologies, including hamartoma of the tuber cinereum (8 cases), parenchymal loss (3 cases), hypothalamicchiasmatic lesions (2 cases), lesions of the corpus callosum (2 cases), suprasellar cyst (1 case), and pineal cyst and mesiotemporal sclerosis (1 case each). Based on the correlation between the clinical and the imaging results of this series, the authors recommend MRI as the imaging method of choice in the investigation of precocious puberty. (orig.)

  16. Central precocious puberty: evaluation by neuroimaging

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    Kornreich, L. [Dept. of Pediatric Imaging, Children`s Medical Center of Israel, Petah Tiqva (Israel)]|[Sackler Faculty of Medicine, Tel Aviv Univ. (Israel); Horev, G. [Dept. of Pediatric Imaging, Children`s Medical Center of Israel, Petah Tiqva (Israel)]|[Sackler Faculty of Medicine, Tel Aviv Univ. (Israel); Blaser, S. [Dept. of Radiology, Hospital for Sick Children, Toronto, ON (Canada); Daneman, D. [Div. of Endocrinology, Dept. of Pediatrics, Hospital for Sick Children, Toronto, ON (Canada); Kauli, R. [Sackler Faculty of Medicine, Tel Aviv Univ. (Israel)]|[Inst. of Pediatric and Adolescent Endocrinology, Children`s Medical Center of Israel, Petah Tiqva (Israel); Grunebaum, M. [Dept. of Pediatric Imaging, Children`s Medical Center of Israel, Petah Tiqva (Israel)]|[Sackler Faculty of Medicine, Tel Aviv Univ. (Israel)

    1995-02-01

    To evaluate the incidence of abnormal intracranial findings in children with central precocious puberty, 62 children (51 girls, 11 boys) were examined by computerized tomography and/or magnetic resonance imaging (MRI) of the brain. Forty-four had normal examinations; 18 (11 girls, 7 boys) showed intracranial pathologies, including hamartoma of the tuber cinereum (8 cases), parenchymal loss (3 cases), hypothalamicchiasmatic lesions (2 cases), lesions of the corpus callosum (2 cases), suprasellar cyst (1 case), and pineal cyst and mesiotemporal sclerosis (1 case each). Based on the correlation between the clinical and the imaging results of this series, the authors recommend MRI as the imaging method of choice in the investigation of precocious puberty. (orig.)

  17. Safety Extension Study Of Leuprolide Acetate (Lupron Depot) In The Treatment Of Central Precocious Puberty

    Science.gov (United States)

    2014-01-08

    Precocious; Leuprolide Acetate; Luteinizing Hormone (LH); Gonadotrophin-releasing Hormone Agonist (GnRHa); Tanner Staging; Depot Formulation; Suppression of LH; Central Precocious Puberty (CPP); Gonadotrophin-releasing Hormone (GnRH); Lupron; GnRH Analog; Pediatrics Central Precocious Puberty

  18. Papular, profuse, and precocious keratosis pilaris.

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    Castela, Emeline; Chiaverini, Christine; Boralevi, Franck; Hugues, Rosalind; Lacour, Jean Philippe

    2012-01-01

    Keratosis pilaris (KP) is a frequent and benign condition in children characterized by the presence of rough, follicular papules and varying degrees of erythema. Different variants have been described, including simple KP and red KP. Between September 2007 and October 2010, 11 children with profuse and precocious KP seen at the department of pediatric dermatology were included. They defined an underemphasized clinical variant of childhood KP: the papular, profuse, and precocious KP characterized by early age of onset (<18 mos), extensive involvement of the limbs and cheeks, and papular nature of lesions. No clinical association has been found. The main complication was episodes of folliculitis. Diagnosis was delayed for all patients. Treatment is difficult, but association between emollient and keratolytic agents can provide some help. © 2011 Wiley Periodicals, Inc.

  19. An FSH and TSH pituitary adenoma, presenting with precocious puberty and central hyperthyroidism

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    Guadalupe Vargas

    2017-07-01

    Full Text Available A 19-year-old woman with a history of isosexual precocious puberty and bilateral oophorectomy at age 10 years because of giant ovarian cysts, presents with headaches and mild symptoms and signs of hyperthyroidism. Hormonal evaluation revealed elevated FSH and LH levels in the postmenopausal range and free hyperthyroxinemia with an inappropriately normal TSH. Pituitary MRI showed a 2-cm macroadenoma with suprasellar extension. She underwent successful surgical resection of the pituitary tumor, which proved to be composed of two distinct populations of cells, each of them strongly immunoreactive for FSH and TSH, respectively. This mixed adenoma resulted in two different hormonal hypersecretion syndromes: the first one during childhood and consisting of central precocious puberty and ovarian hyperstimulation due to the excessive secretion of biologically active FSH and which was not investigated in detail and 10 years later, central hyperthyroidism due to inappropriate secretion of biologically active TSH. Although infrequent, two cases of isosexual central precocious puberty in girls due to biologically active FSH secreted by a pituitary adenoma have been previously reported in the literature. However, this is the first reported case of a mixed adenoma capable of secreting both, biologically active FSH and TSH.

  20. Hypothalamic hamartoma associated with precocious puberty: Case report

    International Nuclear Information System (INIS)

    Bae, Won Kyong; Kim, Pyo Nuyn; Kim, Il Young; Lee, Byoung Ho; Lee, Kyeong Seok; Bae, Hack Gun; Yun, Il Gyu

    1989-01-01

    Hamartoma of the hypothalamic area is a well recognized cause of central precocious puberty. We report a case of histologically proven hypothalamic hamartoma in a 8 year old girl with precocious puberty. The CT showed an isodense, nonenhancing mass in suprasellar area, measuring 4.2 X 3.1 cm, which, to our knowledge, seems to be the largest one of the published cases. On MR imaging, the signal intensity of the mass was homogeneous and isointense relative to gray matter on T1-, and hyperintense on T2-weighted images. The clinical and radiologic findings of the published cases of hypothalamic hamartoma are reviewed

  1. Hypothalamic hamartoma associated with precocious puberty: Case report

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Won Kyong; Kim, Pyo Nuyn; Kim, Il Young; Lee, Byoung Ho; Lee, Kyeong Seok; Bae, Hack Gun; Yun, Il Gyu [Soonchunhyang University, Chonan Hospital, Chonan (Korea, Republic of)

    1989-12-15

    Hamartoma of the hypothalamic area is a well recognized cause of central precocious puberty. We report a case of histologically proven hypothalamic hamartoma in a 8 year old girl with precocious puberty. The CT showed an isodense, nonenhancing mass in suprasellar area, measuring 4.2 X 3.1 cm, which, to our knowledge, seems to be the largest one of the published cases. On MR imaging, the signal intensity of the mass was homogeneous and isointense relative to gray matter on T1-, and hyperintense on T2-weighted images. The clinical and radiologic findings of the published cases of hypothalamic hamartoma are reviewed.

  2. Serum levels of growth hormone binding protein in children with normal and precocious puberty

    DEFF Research Database (Denmark)

    Juul, A; Fisker, Sidse; Scheike, Thomas Harder

    2000-01-01

    To study the regulation of GHBP serum levels by gonadal steroids in normal and precocious puberty.......To study the regulation of GHBP serum levels by gonadal steroids in normal and precocious puberty....

  3. Increased risk of precocious puberty in internationally adopted children in Denmark

    DEFF Research Database (Denmark)

    Teilmann, G.; Pedersen, Carsten Bøcker; Skakkebæk, N.E.

    2006-01-01

    settings from birth to adoption, whereas most other countries are reported to take care of the children in orphanages before adoption. It can only be speculated whether a relation between preadoption living conditions and later risk of precocious puberty exists. Genetic factors play a key role...... identified through the unique Danish Civil Registration System and subsequently categorized as being Danish (N = 1,062,333), adopted (N = 10,997), immigrating with their family (N = 72,181), or being descendants of immigrants (N = 128,152). The incidence rate ratio of precocious puberty was estimated by log......-linear Poisson regression. All rate ratios were adjusted for age and its interaction with gender and calendar year. P values were based on likelihood ratio tests, and 95% confidence intervals were calculated by Wald's test. RESULTS: In the study period, 655 children developed precocious puberty during 5...

  4. Central precocious puberty: from physiopathological mechanisms to treatment.

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    Chirico, V; Lacquaniti, A; Salpietro, V; Buemi, M; Salpietro, C; Arrigo, T

    2014-01-01

    Puberty is a complex, coordinated biological process with multiple levels of regulations. The timing of puberty varies greatly in children and it is influenced by environmental, endocrine and genetic factors. Precocious puberty (PP) is an important issue, affecting between 1 in 5.000-10.000 children. The physiopathological mechanism is still unknown. From an etiological point of view, PP may be subdivided into gonadotropin-releasing hormone (GnRH) -dependent and independent causes. GnRH-dependent PP, often called central precocious puberty (CPP), is based on hypothalamic-pituitary-gonadal axis activation associated with progressive pubertal development, accelerated growth rate and advancement of skeletal age. Conversely, peripheral precocious puberty (PPP) is related to sex steroid exposure, independently of hypothalamic-–pituitary-–gonadal (HPG) axis activation. Kisspeptins play a central role in the modulation of GnRH secretion with peripheral factors that influence the timing of puberty, such as adipokines and endocrine disrupting chemicals. Moreover, PP could be related to genetic disorders, involving pivotal genes of the HPG axis. The standard test used to verify HPG activity is the gonadotropin response to administered GnRH analogs. We describe the physiopathological mechanisms of PP and its clinical implications, analysing diagnostic flow-chart and new potential biomarkers that could reveal PP. An update of the current literature was also carried out regarding the recent novelty for treatment.

  5. Origins of knowledge: Insights from precocial species

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    Elisabetta eVersace

    2015-12-01

    Full Text Available Behavioural responses are influenced by knowledge acquired during the lifetime of an individual and by predispositions transmitted across generations. Establishing the origin of knowledge and the role of the unlearned component is a challenging task, given that both learned and unlearned knowledge can orient perception, learning, and the encoding of environmental features since the first stages of life. Ethical and practical issues constrain the investigation of unlearned knowledge in altricial species, including human beings. On the contrary, precocial animals can be tested on a wide range of tasks and capabilities immediately after birth and in controlled rearing conditions. Insects and precocial avian species are very convenient models to dissect the knowledge systems that enable young individuals to cope with their environment in the absence of specific previous experience. We present the state of the art of research on the origins of knowledge that come from different models and disciplines. Insects have been mainly used to investigate unlearned sensory preferences and prepared learning mechanisms. The relative simplicity of the neural system and fast life cycle of insects make them ideal models to investigate the neural circuitry and evolutionary dynamics of unlearned traits. Among avian species, chicks of the domestic fowl have been the focus of many studies, and showed to possess unlearned knowledge in the sensory, physical, spatial, numerical and social domains. Solid evidence shows the existence of unlearned knowledge in different domains in several species, from sensory and social preferences to the left-right representation of the mental number line. We show how non-mammalian models of cognition, and in particular precocial species, can shed light into the adaptive value and evolutionary history of unlearned knowledge.

  6. Origins of Knowledge: Insights from Precocial Species.

    Science.gov (United States)

    Versace, Elisabetta; Vallortigara, Giorgio

    2015-01-01

    Behavioral responses are influenced by knowledge acquired during the lifetime of an individual and by predispositions transmitted across generations. Establishing the origin of knowledge and the role of the unlearned component is a challenging task, given that both learned and unlearned knowledge can orient perception, learning, and the encoding of environmental features since the first stages of life. Ethical and practical issues constrain the investigation of unlearned knowledge in altricial species, including human beings. On the contrary, precocial animals can be tested on a wide range of tasks and capabilities immediately after birth and in controlled rearing conditions. Insects and precocial avian species are very convenient models to dissect the knowledge systems that enable young individuals to cope with their environment in the absence of specific previous experience. We present the state of the art of research on the origins of knowledge that comes from different models and disciplines. Insects have been mainly used to investigate unlearned sensory preferences and prepared learning mechanisms. The relative simplicity of the neural system and fast life cycle of insects make them ideal models to investigate the neural circuitry and evolutionary dynamics of unlearned traits. Among avian species, chicks of the domestic fowl have been the focus of many studies, and showed to possess unlearned knowledge in the sensory, physical, spatial, numerical and social domains. Solid evidence shows the existence of unlearned knowledge in different domains in several species, from sensory and social preferences to the left-right representation of the mental number line. We show how non-mammalian models of cognition, and in particular precocial species, can shed light into the adaptive value and evolutionary history of unlearned knowledge.

  7. Precocious puberty secondary to a mixed germ cell-sex cord-stromal tumor associated with an ovarian yolk sac tumor: a case report

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    Metwalley Kotb

    2012-06-01

    Full Text Available Abstract Introduction Ovarian tumors are the least common cause of sexual precocity in girls. Mixed germ cell-sex cord-stromal tumors associated with a yolk sac tumor of the ovary are rare neoplasms, of which only a small number of well-documented cases have been described so far. Here, we report precocious puberty in a four-year-old Egyptian girl caused by a mixed germ cell-sex cord-stromal tumor associated with a yolk sac tumor of the ovary. Case presentation A four-year-old Egyptian girl was referred to our pediatric endocrinology unit for evaluation of bilateral breast budding, pubic hair and vaginal bleeding. On examination, we found that her breast enlargement and pubic hair were compatible with Tanner III. A thorough workup revealed a large mass in her right ovary. Magnetic resonance imaging ofher brain showed that her pituitary gland was normal. A hormonal assay revealed high levels of estradiol, 280 to 375pmol/L; progesterone, 5.3 nmol/L; testosterone 38.9 pg/mL; and androstenedione, 4.1 ng/mL. Her basal and stimulated levels of luteinizing hormone and follicle-stimulating hormone were low. Tumor markers levels were high, with a total inhibin of 1,069U/L and an alpha-fetoprotein of 987 μg/L. Her chromosomes were normal (46XX. Our patient underwent an explorative laparotomy and a solid tumor localized to her right ovary was identified. A right salpingo-oophorectomy was performed and the histopathological diagnosis was a mixed germ cell-sex cord-stromal tumorwith a yolk sac tumor of the ovary. Postoperatively, she was started on treatment with chemotherapy. Our patient is doing well without evidence of tumor recurrence or metastasis during eight months of postoperative follow-up. Conclusion Although a mixed germ cell-sex cord-stromal tumor associated with a yolk sac tumor of the ovary is a rare occurrence, it should be considered in the differential diagnosis for a prepubescent girl with an abdominal mass and precocious puberty.

  8. Central precocious puberty in girls

    International Nuclear Information System (INIS)

    Argyropoulou, M.; Malandry, F.; Perignon, F.; Brunelle, F.; Brauner, R.; Rappaport, R.

    1990-01-01

    The treatment of central precocious puberty (CPP) in girls depends on its etiology and evolution, the latter based on the degree of accelerated bone maturation. The goal of this paper is to assess the diagnostic value of MR imaging in studying CPP in girls. Thirty-four girls with CPP were studied with MR imaging. Pituitary gland height (PGH) was measured on a sagittal midline image and compared with normal measurements. Correlations among clinical presentation, PGH, estradiol levels, and LH/FSH ratio were evaluated

  9. A case of late presentation of precocious puberty due to pituitary astrocytoma

    OpenAIRE

    Fahimeh Soheilipour; Hossein Ghalaenov; Seyyed-Hossein Samedanifard; Fatemeh Jesmi

    2015-01-01

    The importance of assessing precocious puberty, especially in boys, is not only due to the great complications it has for the affected patients, but also to the fatal underlying diseases. Therefore, children with central precocious puberty should first undergo neuroimaging. In this case study, we present a 9.5-year-old boy who was referred to Rasoul-e-Akram Medical Center with increased intracranial pressure, nausea/vomiting, and severe headache having begun three months earlier. ...

  10. Factors related to the occurrence of precocious menarche in female primary school students in Makassar

    Science.gov (United States)

    Renjani, Rizky Swastika; Mappaware, Nasrudin A.; Nontji, Werna; Marniati

    2017-09-01

    Precocious menarche currently affects 1 in 5000 girls and likely to occur as many as 10 times and possess greater risk to the emergence of cancer in women. The aim of this research is to determine the relationship of nutrition status and lipid profile with precocious menarche occurrence onstudents of primary school in Makassar city. The design of this research was cross sectional design. The samples werethe students of grades IV, V and VI who have already menarche occurrence as many as 20 studentscollected with purposive sampling. The data were analyzed with Mann Whitney U test. The results indicate that there are 17 students (85%) do not undergoprecocious menarche, normal nutrition status is 11 persons (55%), normal cholesterol levelis 12 persons (60%), and level of normal LDL = 19 persons (95%). While the respondents who undergo precocious menarche is 3 persons (15%), fat nutrition status is 9 persons (45%), cautious cholesterol level is 8 persons (40%) and cautious LDL level is 1 person (5%). Based on Mann Whitney U test, there is relationship between nutrition status and precocious menarche occurrence (p = 0.043) and there is correlation of total cholesterol and LDLcholesterollevelswith precocious menarche (p = 0.025) and (p = 0.017). The decrease of knowledge about health of reproduction can be promoted in school by making cooperation with nutritionist to give information to parents and students of primary schools about good and healthy food.

  11. Salt tolerance of precocious-dwarf cashew rootstocks: physiological and growth indexes

    Directory of Open Access Journals (Sweden)

    Carneiro Paulo Torres

    2004-01-01

    Full Text Available The cashew crop (Anacardium occiedentale L. is of great economic and social importance for Northeast Brazil, a region usually affected by water and soil salinity. The present study was conducted in a greenhouse to evaluate the effects of four salinity levels established through electrical conductivity of irrigation water (ECw: 0.7, 1.4, 2.1 and 2.8 dS m-1, at 25ºC, on growth and physiological indexes of five rootstocks of dwarf-precocious cashew varieties CCP06, CCP09, CCP1001, EMBRAPA50, and EMBRAPA51. Plant height, leaf area, dry weight of root, shoot and total; water content of leaves, root/shoot ratio, leaf area ratio, absolute and relative growth rates and rate of net assimilation were evaluated. The majority of the evaluated variables were found to be affected by ECw and the effects varied among clones; however, no significant interactive effects were observed for factors. The value of ECw = 1.39 dS m-1 was considered as a threshold tolerance for the precocious cashew rootstocks used in this study. The dwarf-precocious cashew is moderately sensible to soil salinity during the formation phase of rootstock. Clones EMBRAPA51 and EMBRAPA50 presented, respectively, the least and the best development indexes.

  12. Hormonal changes during GnRH analogue therapy in children with central precocious puberty

    DEFF Research Database (Denmark)

    Müller, J; Juul, A; Andersson, A M

    2000-01-01

    Gonadotropin releasing hormone analogues (GnRHa) have been used for treatment of central precocious puberty (CPP) for more than 15 years. They are generally considered safe although data on potential long-term side effects are scarce. However, GnRHa therapy has profound effects on both the hypoth......Gonadotropin releasing hormone analogues (GnRHa) have been used for treatment of central precocious puberty (CPP) for more than 15 years. They are generally considered safe although data on potential long-term side effects are scarce. However, GnRHa therapy has profound effects on both...

  13. Qualitative assessment of precocious puberty-related user-created contents on YouTube

    Directory of Open Access Journals (Sweden)

    Hyo-Kyoung Nam

    2015-09-01

    Full Text Available PurposeUser-created content (UCC has provided a considerable amount of medical information and become an important source. We aimed to evaluate the quality and scientific accuracy of precocious puberty-related UCC on YouTube.MethodsThe keywords "precocious puberty", "early puberty", "sexual precocity", and "precocity" were searched for on YouTube during June and July 2014. More than 1,500 UCC matched the keywords. According to the information provider, UCC was classified as medical, oriental, or commercial & others. We evaluated the quality and scientific accuracy of the information provided in UCC using the DISCERN instrument and information scores, respectively.ResultsWe selected 51 UCC, which were categorized into three types: medical (n=17, oriental (n=17, or commercial & others (n=17. The overall quality score for medical UCC (3.4 was significantly higher relative to those of oriental and commercial & others UCC (2.8 and 2.3, respectively (P<0.001. In the assessment of scientific accuracy, the mean information score for medical UCC (30.7 was significantly higher than those of oriental and commercial & others UCC (15.9 and 5.1, respectively (P<0.001. The mean duration of oriental UCC was the longest (P<0.001, however, it was viewed less frequently among them (P=0.086.ConclusionThe quality and accuracy of precocious puberty-related health information in UCC were variable and often unreliable. The overall quality of UCC regarding precocious puberty was moderate. Only medical UCC provided scientifically accurate information. As UCC becomes a popular source of health information, it is important to provide reliable, scientifically accurate information.

  14. A case of late presentation of precocious puberty due to pituitary astrocytoma

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    Fahimeh Soheilipour

    2015-08-01

    Full Text Available The importance of assessing precocious puberty, especially in boys, is not only due to the great complications it has for the affected patients, but also to the fatal underlying diseases. Therefore, children with central precocious puberty should first undergo neuroimaging. In this case study, we present a 9.5-year-old boy who was referred to Rasoul-e-Akram Medical Center with increased intracranial pressure, nausea/vomiting, and severe headache having begun three months earlier. The development of secondary sexual changes had started two years earlier, and had been neglected. His testes, penis, and pubic hair were at the fourth Tanner stage. He had elevated luteinizing and follicle stimulating hormones. Microscopic evaluation confirmed low-grade pilocytic astrocytoma WHO grade 1. Emergency brain surgery was conducted in which the brain was decompressed, and chemotherapy was started postoperatively. Two years after the surgery, he remains under chemotherapy, with obvious sexual maturation and a height of 154 cm. Training families and medical staff efficiently can help prevent the late diagnosis and treatment of precocious puberty and, as a result, help patients in their social life.

  15. Evaluating methodological assumptions of a catch-curve survival estimation of unmarked precocial shorebird chickes

    Science.gov (United States)

    McGowan, Conor P.; Gardner, Beth

    2013-01-01

    Estimating productivity for precocial species can be difficult because young birds leave their nest within hours or days of hatching and detectability thereafter can be very low. Recently, a method for using a modified catch-curve to estimate precocial chick daily survival for age based count data was presented using Piping Plover (Charadrius melodus) data from the Missouri River. However, many of the assumptions of the catch-curve approach were not fully evaluated for precocial chicks. We developed a simulation model to mimic Piping Plovers, a fairly representative shorebird, and age-based count-data collection. Using the simulated data, we calculated daily survival estimates and compared them with the known daily survival rates from the simulation model. We conducted these comparisons under different sampling scenarios where the ecological and statistical assumptions had been violated. Overall, the daily survival estimates calculated from the simulated data corresponded well with true survival rates of the simulation. Violating the accurate aging and the independence assumptions did not result in biased daily survival estimates, whereas unequal detection for younger or older birds and violating the birth death equilibrium did result in estimator bias. Assuring that all ages are equally detectable and timing data collection to approximately meet the birth death equilibrium are key to the successful use of this method for precocial shorebirds.

  16. Virilizing adrenocortical carcinoma advancing to central precocious puberty after surgery.

    Science.gov (United States)

    Kim, Min Sun; Yang, Eu Jeen; Cho, Dong Hyu; Hwang, Pyung Han; Lee, Dae-Yeol

    2015-05-01

    Adrenocortical carcinoma (ACC) in pediatric and adolescent patients is rare, and it is associated with various clinical symptoms. We introduce the case of an 8-year-old boy with ACC who presented with peripheral precocious puberty at his first visit. He displayed penis enlargement with pubic hair and facial acne. His serum adrenal androgen levels were elevated, and abdominal computed tomography revealed a right suprarenal mass. After complete surgical resection, the histological diagnosis was ACC. Two months after surgical removal of the mass, he subsequently developed central precocious puberty. He was treated with a gonadotropin-releasing hormone agonist to delay further pubertal progression. In patients with functioning ACC and surgical removal, clinical follow-up and hormonal marker examination for the secondary effects of excessive hormone secretion may be a useful option at least every 2 or 3 months after surgery.

  17. Idiopathic central precocious puberty in a Nigerian boy | Ojukwu ...

    African Journals Online (AJOL)

    A case of idiopathic central precocious puberty, a rare condition is reported in a 21/2 year-old Nigerian boy. He presented with progressive genital growth, a growth spurt, advanced skeletal maturation, and inappropriately high serum concentrations of pituitary and gonadal sex homones for his age. There was no family ...

  18. TAK1 modulates satellite stem cell homeostasis and skeletal muscle repair

    Science.gov (United States)

    Ogura, Yuji; Hindi, Sajedah M.; Sato, Shuichi; Xiong, Guangyan; Akira, Shizuo; Kumar, Ashok

    2015-01-01

    Satellite cells are resident adult stem cells that are required for regeneration of skeletal muscle. However, signalling mechanisms that regulate satellite cell function are less understood. Here we demonstrate that transforming growth factor-β-activated kinase 1 (TAK1) is important in satellite stem cell homeostasis and function. Inactivation of TAK1 in satellite cells inhibits muscle regeneration in adult mice. TAK1 is essential for satellite cell proliferation and its inactivation causes precocious differentiation. Moreover, TAK1-deficient satellite cells exhibit increased oxidative stress and undergo spontaneous cell death, primarily through necroptosis. TAK1 is required for the activation of NF-κB and JNK in satellite cells. Forced activation of NF-κB improves survival and proliferation of TAK1-deficient satellite cells. Furthermore, TAK1-mediated activation of JNK is essential to prevent oxidative stress and precocious differentiation of satellite cells. Collectively, our study suggests that TAK1 is required for maintaining the pool of satellite stem cells and for regenerative myogenesis. PMID:26648529

  19. Adrenocorticotropin-dependent precocious puberty of testicular origin in a boy with X-linked adrenal hypoplasia congenita due to a novel mutation in the DAX1 gene.

    Science.gov (United States)

    Domenice, S; Latronico, A C; Brito, V N; Arnhold, I J; Kok, F; Mendonca, B B

    2001-09-01

    Primary adrenal insufficiency is a rare condition in pediatric age, and its association with precocious sexual development is very uncommon. We report a 2-yr-old Brazilian boy with DAX1 gene mutation whose first clinical manifestation was isosexual gonadotropin-independent precocious puberty. He presented with pubic hair, enlarged penis and testes, and advanced bone age. T levels were elevated, whereas basal and GnRH-stimulated LH levels were compatible with a prepubertal pattern. Chronic GnRH agonist therapy did not reduce T levels, supporting the diagnosis of gonadotropin-independent precocious puberty. Testotoxicosis was ruled out after normal sequencing of exon 11 of the LH receptor gene. At age 3 yr he developed clinical and hormonal features of severe primary adrenal insufficiency. The entire coding region of the DAX1 gene was analyzed through direct sequencing. A nucleotide G insertion between nucleotides 430 and 431 in exon 1, resulting in a novel frameshift mutation and a premature stop codon at position 71 of DAX-1, was identified. Surprisingly, steroid replacement therapy induced a clear decrease in testicular size and T levels to the prepubertal range. These findings suggest that chronic excessive ACTH levels resulting from adrenal insufficiency may stimulate Leydig cells and lead to gonadotropin-independent precocious puberty in some boys with DAX1 gene mutations.

  20. Insulin sensitivity and lipid profiles in girls with central precocious puberty before and during gonadal suppression

    DEFF Research Database (Denmark)

    Sørensen, Kaspar; Mouritsen, Annette; Mogensen, Signe Sloth

    2010-01-01

    Early menarche is associated with increased risk of cardiovascular disease in adulthood. It is unknown whether metabolic risk factors are adversely affected in girls with central precocious puberty (CPP) already at time of diagnosis.......Early menarche is associated with increased risk of cardiovascular disease in adulthood. It is unknown whether metabolic risk factors are adversely affected in girls with central precocious puberty (CPP) already at time of diagnosis....

  1. A novel MKRN3 missense mutation causing familial precocious puberty.

    Science.gov (United States)

    de Vries, L; Gat-Yablonski, G; Dror, N; Singer, A; Phillip, M

    2014-12-01

    Central precocious puberty may be familial in about a quarter of the idiopathic cases. However, little is known about the genetic causes responsible for the disorder. In this report we describe a family with central precocious puberty associated with a mutation in the makorin RING-finger protein 3 (MKRN3) gene. A novel missense mutation (p.H420Q) in the imprinted MKRN3 gene was identified in the four affected siblings, in their unaffected father and in his affected mother. An in silico mutant MKRN3 model predicts that the mutation p.H420Q leads to reduced zinc binding and, subsequently, impaired RNA binding. These findings support the fundamental role of the MKRN3 protein in determining pubertal timing. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Precocious metamorphosis in the juvenile hormone-deficient mutant of the silkworm, Bombyx mori.

    Directory of Open Access Journals (Sweden)

    Takaaki Daimon

    Full Text Available Insect molting and metamorphosis are intricately governed by two hormones, ecdysteroids and juvenile hormones (JHs. JHs prevent precocious metamorphosis and allow the larva to undergo multiple rounds of molting until it attains the proper size for metamorphosis. In the silkworm, Bombyx mori, several "moltinism" mutations have been identified that exhibit variations in the number of larval molts; however, none of them have been characterized molecularly. Here we report the identification and characterization of the gene responsible for the dimolting (mod mutant that undergoes precocious metamorphosis with fewer larval-larval molts. We show that the mod mutation results in complete loss of JHs in the larval hemolymph and that the mutant phenotype can be rescued by topical application of a JH analog. We performed positional cloning of mod and found a null mutation in the cytochrome P450 gene CYP15C1 in the mod allele. We also demonstrated that CYP15C1 is specifically expressed in the corpus allatum, an endocrine organ that synthesizes and secretes JHs. Furthermore, a biochemical experiment showed that CYP15C1 epoxidizes farnesoic acid to JH acid in a highly stereospecific manner. Precocious metamorphosis of mod larvae was rescued when the wild-type allele of CYP15C1 was expressed in transgenic mod larvae using the GAL4/UAS system. Our data therefore reveal that CYP15C1 is the gene responsible for the mod mutation and is essential for JH biosynthesis. Remarkably, precocious larval-pupal transition in mod larvae does not occur in the first or second instar, suggesting that authentic epoxidized JHs are not essential in very young larvae of B. mori. Our identification of a JH-deficient mutant in this model insect will lead to a greater understanding of the molecular basis of the hormonal control of development and metamorphosis.

  3. Diagnosis and constitutional and laboratory features of Korean girls referred for precocious puberty

    Directory of Open Access Journals (Sweden)

    Doosoo Kim

    2012-12-01

    Full Text Available &lt;B&gt;Purpose:&lt;/B&gt; Precocious puberty is defined as breast development before the age of 8 years in girls. The present study aimed to reveal the diagnosis of Korean girls referred for precocious puberty and to compare the constitutional and endocrinological features among diagnosis groups. &lt;B&gt;Methods:&lt;/B&gt; The present study used a retrospective chart review of 988 Korean girls who had visited a pediatric endocrinology clinic from 2006 to 2010 for the evaluation of precocious puberty. Study groups comprised fast puberty, true precocious puberty (PP, pseudo PP, premature thelarche, and control. We determined the height standard deviation score (HSDS, weight standard deviation score (WSDS, and body mass index standard deviation score (BMISDS of each group using the published 2007 Korean growth charts. Hormone tests were performed at our outpatient clinic. &lt;B&gt;Results:&lt;/B&gt; The PP groups comprised fast puberty (67%, premature thelarche (17%, true PP (15%, and pseudo PP (1%. Advanced bone age and levels of estradiol, basal luteinizing hormone (LH, and peak LH after gonadotropin-releasing hormone stimulation testing were significantly high in the fast puberty and true PP groups compared with the control group. HSDS, WSDS, and BMISDS were significantly higher in the true PP group than in the control group (P&lt;0.05. &lt;B&gt;Conclusion:&lt;/B&gt; The frequent causes of PP were found to be fast puberty, true PP, and premature thelarche. Furthermore, BMISDS were significantly elevated in the true PP group. Therefore, we emphasize the need for regular follow-up of girls who are heavier or taller than others in the same age group.

  4. Prospective assessment of pituitary size and shape on MR imaging after suppressive hormonal therapy in central precocious puberty

    Energy Technology Data Exchange (ETDEWEB)

    Beek, J.T. van; Sharafuddin, M.J.A.; Kao, S.C.S. [Department of Radiology-JPP 3889, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52246 (United States); Luisiri, A. [Cardinal Glennon Children' s Hospital, St. Louis, Missouri (United States); Garibaldi, L.R. [Children' s Hospital of New Jersey, Newark Beth Israel Medical Center, Newark, New Jersey (United States); St. Barnabas Medical Center, Livingston, New Jersey (United States)

    2000-07-01

    Objective. The diagnostic significance of an enlarged pituitary gland regarding both shape and size parameters on MR imaging has previously been demonstrated in children with central precocious puberty. This study was designed to assess changes in these parameters following successful suppressive therapy of central precocious puberty with the gonadotropin-releasing hormone (GnRH) analogue. Materials and methods. Twelve girls (mean age 7.3 years) with central precocious puberty were prospectively enrolled in our study protocol. Sagittal and coronal MR images of the pituitary region were obtained in all patients before treatment and after at least 6 months of GnRH analogue therapy (mean 18.0 months). Parameters measured included pituitary gland height, length, width, sagittal cross-sectional area, and volume. Results. All patients had excellent clinical response to treatment with arrest of secondary sexual development, normalization of serum estradiol levels, and complete obliteration of the LH response to diagnostic GnRH stimulation. No significant change occurred in any pituitary size or shape parameter following GnRH analogue therapy. Conclusion. Favorable clinical response to GnRH analogue therapy in central precocious puberty is not accompanied by significant a change in pituitary gland size and shape. (orig.)

  5. Prospective assessment of pituitary size and shape on MR imaging after suppressive hormonal therapy in central precocious puberty

    International Nuclear Information System (INIS)

    Beek, J.T. van; Sharafuddin, M.J.A.; Kao, S.C.S.; Luisiri, A.; Garibaldi, L.R.

    2000-01-01

    Objective. The diagnostic significance of an enlarged pituitary gland regarding both shape and size parameters on MR imaging has previously been demonstrated in children with central precocious puberty. This study was designed to assess changes in these parameters following successful suppressive therapy of central precocious puberty with the gonadotropin-releasing hormone (GnRH) analogue. Materials and methods. Twelve girls (mean age 7.3 years) with central precocious puberty were prospectively enrolled in our study protocol. Sagittal and coronal MR images of the pituitary region were obtained in all patients before treatment and after at least 6 months of GnRH analogue therapy (mean 18.0 months). Parameters measured included pituitary gland height, length, width, sagittal cross-sectional area, and volume. Results. All patients had excellent clinical response to treatment with arrest of secondary sexual development, normalization of serum estradiol levels, and complete obliteration of the LH response to diagnostic GnRH stimulation. No significant change occurred in any pituitary size or shape parameter following GnRH analogue therapy. Conclusion. Favorable clinical response to GnRH analogue therapy in central precocious puberty is not accompanied by significant a change in pituitary gland size and shape. (orig.)

  6. Testes and brain gene expression in precocious male and adult maturing Atlantic salmon (Salmo salar

    Directory of Open Access Journals (Sweden)

    Houeix Benoit

    2010-03-01

    Full Text Available Abstract Background The male Atlantic salmon generally matures in fresh water upon returning after one or several years at sea. Some fast-growing male parr develop an alternative life strategy where they sexually mature before migrating to the oceans. These so called 'precocious' parr or 'sneakers' can successfully fertilise adult female eggs and so perpetuate their line. We have used a custom-built cDNA microarray to investigate gene expression changes occurring in the salmon gonad and brain associated with precocious maturation. The microarray has been populated with genes selected specifically for involvement in sexual maturation (precocious and adult and in the parr-smolt transformation. Results Immature and mature parr collected from a hatchery-reared stock in January were significantly different in weight, length and condition factor. Changes in brain expression were small - never more than 2-fold on the microarray, and down-regulation of genes was much more pronounced than up-regulation. Significantly changing genes included isotocin, vasotocin, cathepsin D, anamorsin and apolipoprotein E. Much greater changes in expression were seen in the testes. Among those genes in the testis with the most significant changes in expression were anti-Mullerian hormone, collagen 1A, and zinc finger protein (Zic1, which were down-regulated in precocity and apolipoproteins E and C-1, lipoprotein lipase and anti-leukoproteinase precursor which were up-regulated in precocity. Expression changes of several genes were confirmed in individual fish by quantitative PCR and several genes (anti-Mullerian hormone, collagen 1A, beta-globin and guanine nucleotide binding protein (G protein beta polypeptide 2-like 1 (GNB2L1 were also examined in adult maturing testes. Down-regulation of anti-Mullerian hormone was judged to be greater than 160-fold for precocious males and greater than 230-fold for November adult testes in comparison to July testes by this method. For

  7. Precocious puberty and large multicystic ovaries in young girls with primary hypothyroidism.

    Science.gov (United States)

    Sanjeevaiah, Aravind Raj; Sanjay, Subbarayappa; Deepak, Tejesweni; Sharada, Ardanareshwaran; Srikanta, Sri S

    2007-10-01

    To describe 2 cases of primary hypothyroidism, precocious puberty, large multicystic ovaries, possible diagnostic dilemma, unilateral oophorectomies, and subsequent response to levothyroxine replacement therapy. We present the clinical, biochemical, radiologic, and histopathologic findings in 2 patients with rare cases of Van Wyk-Grumbach syndrome and megaovaries, who underwent unilateral oophorectomy. Two patients, an 8-year-old girl and a 3-year-old girl (cases 1 and 2, respectively), were referred to our center. Both patients presented with precocious puberty and vaginal bleeding and had undergone unilateral oophorectomy before referral. In the first patient (case 1), the surgical intervention was a consequence of torsion of the left megaovary, necessitating emergency oophorectomy. Oophorectomy in the second patient (case 2) was a result of initial diagnostic confusion, inasmuch as a sexcord stromal tumor was suspected. A detailed history, physical examination, and laboratory results pointed toward primary hypothyroidism due to Hashimoto's thyroiditis and thyroid dysgenesis, respectively. Serial ultrasound studies of the abdomen and pelvis revealed large multicystic ovaries, with progressive enlargement (including regrowth from an apparent ovarian "postsurgical remnant"). Both patients responded dramatically after initiation of levothyroxine replacement therapy, with no further vaginal bleeding and reversal of megaovary to normal size (in case 1). In a highly selected minority of children with untreated primary hypothyroidism, there is development of precocious puberty and progressively enlarging multicystic ovaries. The precise endocrine, neuroanatomic, and neurophysiologic bases for this phenomenon are unclear. Nevertheless, the entire clinicopathologic picture, including giant ovaries, dramatically reverts to normal status with the restoration of a euthyroid state by means of simple levothyroxine replacement therapy.

  8. Acquired versus innate prey capturing skills in super-precocial live-bearing fish

    NARCIS (Netherlands)

    Lankheet, Martin J.; Stoffers, Twan; Leeuwen, van Johan L.; Pollux, Bart J.A.

    2016-01-01

    Live-bearing fish start hunting for mobile prey within hours after birth, an example of extreme precociality. Because prenatal, in utero, development of this behaviour is constrained by the lack of free-swimming sensory-motor interactions, immediate success after birth depends on innate,

  9. Prostate specific antigen in boys with precocious puberty before and during gonadal suppression by GnRH agonist treatment

    DEFF Research Database (Denmark)

    Juul, A; Müller, J; Skakkebaek, N E

    1997-01-01

    antigen (PSA) is a marker of the androgen-dependent prostatic epithelial cell activity and it is used in the diagnosis and surveillance of adult patients with prostatic cancer. We have measured PSA concentrations in serum from boys with precocious puberty before and during gonadal suppression with Gn......In healthy boys, the pituitary-gonadal axis exhibits diurnal variation in early puberty. Serum testosterone levels are higher during the night and low or immeasurable during the day. These fluctuating levels of circulating androgens in early pubertal boys are difficult to monitor. Prostate specific...

  10. Cup Blocks the Precocious Activation of the Orb Autoregulatory Loop

    Science.gov (United States)

    Wong, Li Chin; Schedl, Paul

    2011-01-01

    Translational regulation of localized mRNAs is essential for patterning and axes determination in many organisms. In the Drosophila ovary, the germline-specific Orb protein mediates the translational activation of a variety of mRNAs localized in the oocyte. One of the Orb target mRNAs is orb itself, and this autoregulatory activity ensures that Orb proteins specifically accumulate in the developing oocyte. Orb is an RNA-binding protein and is a member of the cytoplasmic polyadenylation element binding (CPEB) protein family. We report here that Cup forms a complex in vivo with Orb. We also show that cup negatively regulates orb and is required to block the precocious activation of the orb positive autoregulatory loop. In cup mutant ovaries, high levels of Orb accumulate in the nurse cells, leading to what appears to be a failure in oocyte specification as a number of oocyte markers inappropriately accumulate in nurse cells. In addition, while orb mRNA is mislocalized and destabilized, a longer poly(A) tail is maintained than in wild type ovaries. Analysis of Orb phosphoisoforms reveals that loss of cup leads to the accumulation of hyperphosphorylated Orb, suggesting that an important function of cup in orb-dependent mRNA localization pathways is to impede Orb activation. PMID:22164257

  11. [Evolutionary perspective in precocious puberty].

    Science.gov (United States)

    Hochberg, Ze'ev

    2014-10-01

    Pubertal development is subject to substantial heritability, but much variation remains to be explained, including fast changes over the last 150 years, that cannot be explained by changes of gene frequency in the population. This article discusses the influence of environmental factors to adjust maturational tempo in the service of fitness goals. Utilizing evolutionary development thinking (evo-devo), the author examines adolescence as an evolutionary life-history stage in its developmental context. The transition from the preceding stage of juvenility entails adaptive plasticity in response to energy resources, social needs of adolescence and maturation toward youth and adulthood. Using Belsky's evolutionary theory of socialization, I show that familial psychosocial environment during the infancy-childhood and childhood-juvenility transitions foster a fast life-history and reproductive strategy rather than early maturation being just a risk factor for aggression and delinquency. The implications of the evo-devo framework for theory building, illuminates new directions in the understanding of precocious puberty other than a diagnosis of a disease.

  12. Experience with the once-yearly histrelin (GnRHa subcutaneous implant in the treatment of central precocious puberty

    Directory of Open Access Journals (Sweden)

    Katherine A Lewis

    2008-12-01

    Full Text Available Katherine A Lewis, Erica A EugsterDepartment of Pediatrics, Indiana University School of Medicine, Riley Hospital for Children, Indianapolis, USAAbstract: In 2007, a hydrogel histrelin implant was approved for the treatment of children with central precocious puberty (CPP. Children with CPP commonly have reduced height potential due to premature closure of the epiphyseal growth plates from exposure to sex steroids. Gonadotropin-releasing hormone analog (GnRHa treatment halts puberty and allows for improvement of adult height. A hydrogel implant delivery system utilizing the potent GnRHa, histrelin, was first developed for use in men with prostate cancer. A once yearly histrelin subcutaneous implant was subsequently developed for the treatment of children with CPP. Studies to date have demonstrated safety, tolerability, and effectiveness of this treatment option in patients treated up to 2 years. The most common adverse effects of the implant relate to implant site pain or bruising. Cost of this treatment seems comparable to somewhat higher than the commonly used GnRHa treatment option, depot leuprolide. While long term studies are needed to establish continued efficacy and safety beyond 2 years of treatment, the histrelin implant appears to be an attractive option for GnRHa treatment in patients with CPP.Keywords: central precocious puberty, histrelin, implant, gonadotropin-releasing-hormone analogs

  13. The significance of measuring serum IGF1, IGFBP3 and OST for the judgement of abnormal skeletal development and therapeutic monitoring in precocious children

    International Nuclear Information System (INIS)

    Ji Zhiying; Zhao Ruifang; Lv Xiaomei; Gu Fanlei; Cai Depei

    2004-01-01

    Objective: To study the value of measuring serum insulin-like growth factor I (IGF 1 ), insulin-like growth factor binding protein III (IGFBP 3 ) and osteocalcin (OST) for evaluating acceleration of skeletal growth and skeletal maturity, and its value for therapeutic monitoring in precocious children. Methods: Serum IGF 1 and IGFBP 3 were measured with immunoradiometric assay, serum OST was measured with radioimmunoassay in 117 girls with idiopathic precocious puberty. The girls were grouped according to age, and various parameters collected from them were compared with normal values of matched girls. Furthermore, the girls were grouped according to Tanner's staging (the extent of precocious puberty), the analysis of correlativity between various parameters to the extent of precocious puberty was performed, and the analysis of correlativity between the level of serum IGF 1 and advancing of bone age was performed. Various parameters were measured once more in 38 of the study girls after six months of the treatment, and the parameters were compared with that before treatment. Results: 1) The levels of serum IGF 1 and OST in the girls with precocious puberty were elevated obviously than that in matched normal girls, but the level of serum IGFBP 3 was reduced obviously than that in matched normal girls. It was demonstrated that typical elevation of serum IGF 1 and OST occurred in normal adolescence appeared ahead of time in the girls with precocious puberty. 2) The extent of precocious puberty correlated closely with the level of serum IGF 1 (r=0.489, P 1 (r=0.411, P 1 was. 3) After the treatment, the concentration of serum IGF 1 reduced from (455.52 ± 119.45) μg/L to (284.55 ± 99.52) μg/L (P 1 and OST reduced obviously. Conclusions: Serum IGF 1 and OST could act as quantitative parameters for evaluating acceleration of skeletal growth and advancing of skeletal maturity in girls with idiopathic true precocious puberty. It could act as a parameter for therapeutic

  14. A single sample GnRHa stimulation test in the diagnosis of precocious puberty

    Science.gov (United States)

    Gonadotropin-releasing hormone (GnRH) has been the standard test for diagnosing central precocious puberty. Because GnRH is no longer available, GnRH analogues (GnRHa) are now used. Random LH concentration, measured by the third-generation immunochemiluminometric assay, is a useful screening tool ...

  15. Virilizing Adrenocortical Carcinoma Advancing to Central Precocious Puberty after Surgery

    OpenAIRE

    Kim, Min Sun; Yang, Eu Jeen; Cho, Dong Hyu; Hwang, Pyung Han; Lee, Dae-Yeol

    2015-01-01

    Adrenocortical carcinoma (ACC) in pediatric and adolescent patients is rare, and it is associated with various clinical symptoms. We introduce the case of an 8-year-old boy with ACC who presented with peripheral precocious puberty at his first visit. He displayed penis enlargement with pubic hair and facial acne. His serum adrenal androgen levels were elevated, and abdominal computed tomography revealed a right suprarenal mass. After complete surgical resection, the histological diagnosis was...

  16. Community effect triggers terminal differentiation of myogenic cells derived from muscle satellite cells by quenching Smad signaling

    Energy Technology Data Exchange (ETDEWEB)

    Yanagisawa, Michiko [Department of Regenerative Medicine, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 35 Gengo, Morioka, Oobu, Aichi 474-8522 (Japan); Aging Research, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550 (Japan); Mukai, Atsushi; Shiomi, Kosuke [Department of Regenerative Medicine, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 35 Gengo, Morioka, Oobu, Aichi 474-8522 (Japan); Song, Si-Yong [Institute of Neuroscience, Faculty of Pharmaceutical Sciences at Kagawa, Tokushima Bunri University, 1314-1 Shido, Sanuki-shi, Kagawa 769-2193 (Japan); Hashimoto, Naohiro, E-mail: nao@ncgg.go.jp [Department of Regenerative Medicine, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 35 Gengo, Morioka, Oobu, Aichi 474-8522 (Japan)

    2011-01-15

    A high concentration of bone morphogenetic proteins (BMPs) stimulates myogenic progenitor cells to undergo heterotopic osteogenic differentiation. However, the physiological role of the Smad signaling pathway during terminal muscle differentiation has not been resolved. We report here that Smad1/5/8 was phosphorylated and activated in undifferentiated growing mouse myogenic progenitor Ric10 cells without exposure to any exogenous BMPs. The amount of phosphorylated Smad1/5/8 was severely reduced during precocious myogenic differentiation under the high cell density culture condition even in growth medium supplemented with a high concentration of serum. Inhibition of the Smad signaling pathway by dorsomorphin, an inhibitor of Smad activation, or noggin, a specific antagonist of BMP, induced precocious terminal differentiation of myogenic progenitor cells in a cell density-dependent fashion even in growth medium. In addition, Smad1/5/8 was transiently activated in proliferating myogenic progenitor cells during muscle regeneration in rats. The present results indicate that the Smad signaling pathway is involved in a critical switch between growth and differentiation of myogenic progenitor cells both in vitro and in vivo. Furthermore, precocious cell density-dependent myogenic differentiation suggests that a community effect triggers the terminal muscle differentiation of myogenic cells by quenching the Smad signaling.

  17. Community effect triggers terminal differentiation of myogenic cells derived from muscle satellite cells by quenching Smad signaling

    International Nuclear Information System (INIS)

    Yanagisawa, Michiko; Mukai, Atsushi; Shiomi, Kosuke; Song, Si-Yong; Hashimoto, Naohiro

    2011-01-01

    A high concentration of bone morphogenetic proteins (BMPs) stimulates myogenic progenitor cells to undergo heterotopic osteogenic differentiation. However, the physiological role of the Smad signaling pathway during terminal muscle differentiation has not been resolved. We report here that Smad1/5/8 was phosphorylated and activated in undifferentiated growing mouse myogenic progenitor Ric10 cells without exposure to any exogenous BMPs. The amount of phosphorylated Smad1/5/8 was severely reduced during precocious myogenic differentiation under the high cell density culture condition even in growth medium supplemented with a high concentration of serum. Inhibition of the Smad signaling pathway by dorsomorphin, an inhibitor of Smad activation, or noggin, a specific antagonist of BMP, induced precocious terminal differentiation of myogenic progenitor cells in a cell density-dependent fashion even in growth medium. In addition, Smad1/5/8 was transiently activated in proliferating myogenic progenitor cells during muscle regeneration in rats. The present results indicate that the Smad signaling pathway is involved in a critical switch between growth and differentiation of myogenic progenitor cells both in vitro and in vivo. Furthermore, precocious cell density-dependent myogenic differentiation suggests that a community effect triggers the terminal muscle differentiation of myogenic cells by quenching the Smad signaling.

  18. Serum IGF1 and insulin levels in girls with normal and precocious puberty

    DEFF Research Database (Denmark)

    Sørensen, Kaspar; Aksglaede, Lise; Petersen, Jørgen Holm

    2012-01-01

    IGF1 plays an important role in growth and metabolism during puberty. IGF1 levels are increased in girls with central precocious puberty (CPP). However, the relationship with insulin before and during gonadal suppression is unknown. In addition, the influence of the exon 3-deleted GH receptor gene...

  19. Data from: Acquired versus innate prey capturing skills in super-precocial live-bearing fish

    NARCIS (Netherlands)

    Lankheet, M.J.M.; Stoffers, Twan; Leeuwen, van J.L.; Pollux, B.J.A.

    2016-01-01

    Live-bearing fish start hunting for mobile prey within hours after birth, an example of extreme precociality. Because prenatal, in utero, development of this behaviour is constrained by the lack of free-swimming sensory-motor interactions, immediate success after birth depends on innate,

  20. Spring Chinook Salmon Interactions Indices and Residual/Precocial Monitoring in the Upper Yakima Basin, Annual Report 1998

    International Nuclear Information System (INIS)

    James, Brenda B.; Pearsons, Todd N.; McMichael, Geoffrey A.

    1999-01-01

    Select ecological interactions and spring chinook salmon residual/precocial abundance were monitored in 1998 as part of the Yakima/Klickitat Fisheries Project's supplementation monitoring program. Monitoring these variables is part of an effort to help evaluate the factors that contribute to, or limit supplementation success. The ecological interactions that were monitored were prey consumption, competition for food, and competition for space. The abundance of spring chinook salmon life-history forms that have the potential to be influenced by supplementation and that have important ecological and genetic roles were monitored (residuals and precocials). Residual spring chinook salmon do not migrate to the ocean during the normal emigration period and continue to rear in freshwater. Precocials are those salmon that precocially mature in freshwater. The purpose of sampling during 1998 was to collect baseline data one year prior to the release of hatchery spring chinook salmon which occurred during the spring of 1999. All sampling that the authors report on here was conducted in upper Yakima River during summer and fall 1998. The stomach fullness of juvenile spring chinook salmon during the summer and fall averaged 12%. The food competition index suggested that mountain whitefish (0.59), rainbow trout (0.55), and redside shiner (0.55) were competing for food with spring chinook salmon. The space competition index suggested that rainbow trout (0.31) and redside shiner (0.39) were competing for space with spring chinook salmon but mountain whitefish (0.05) were not. Age-0 spring chinook salmon selected a fairly narrow range of microhabitat parameters in the summer and fall relative to what was available. Mean focal depths and velocities for age 0 spring chinook salmon during the summer were 0.5 m ± 0.2 m and 0.26 m/s ± 0.19 m/s, and during the fall 0.5 m ± 0.2 m and 0.24 m/s ± 0.18 m/s. Among potential competitors, age 1+ rainbow trout exhibited the greatest degree

  1. Intervention levels in a precocious detection program for breast cancer and evaluation of four participant units

    International Nuclear Information System (INIS)

    Carrera M, F.; Velazquez M, S.; Manzano M, F.J.; Sanchez S, J.

    1998-01-01

    It is presented the basis to make a cost benefit analysis for a breast cancer precocious detection program and consequently the keys for its optimization from the radiological point of view. Taking this as a reference it is made an exhaustive quality control to four mammographic unities which were participating or they were candidates to participate in a breast cancer precocious detection program. Also it is presented its results. It is followed the protocol for quality control in mammography in Spain obtaining values for the measurement of twelve interesting parameters. It should be maintained the standard breast dose about 1 mGy/ image. It should be available a 24 x 30 cm portacassete and considering the utilization of a single projection by breast. (Author)

  2. DEHP exposure in utero disturbs sex determination and is potentially linked with precocious puberty in female mice

    International Nuclear Information System (INIS)

    Wang, Yongan; Yang, Qing; Liu, Wei; Yu, Mingxi; Zhang, Zhou; Cui, Xiaoyu

    2016-01-01

    Human's ubiquitous exposure to di (2-ethylhexyl) phthalate (DEHP) is thought to be associated with female reproductive toxicity. Previous studies found that DEHP inhibited follicle growth and decreased estradiol levels in adult female mice. However, limited information is available on the link between in utero DEHP exposure and ovarian development in female mouse offspring. The present study evaluates the disturbances in regulatory genes involved in female sex determination and the ovarian outcomes in fetal and postnatal female mice treated with in utero DEHP exposure. Pregnant mice were exposed to DEHP by gavage, with the dosage regime beginning at human relevant exposure levels. After in utero DEHP exposure, increased follicular atresia was observed in the female pups at postnatal days (PND) 21. Foxl2 expression was significantly upregulated, and Fst was significantly downregulated by DEHP above 2 mg/kg/d at PND 1 and 21. This suggests that lesion of granulosa cell differentiation and disturbance of follicle development in postnatal female mice. The expression of Cyp11a1 and Star were significantly downregulated by in utero DEHP exposure, indicating effects on estradiol biosynthesis. The female sex determination pathway was disturbed in fetus by DEHP at 2 mg/kg/d and above during the critical time window of sex determination causing significant upregulation of Foxl2, Wnt4, β-catenin and Fst. Furthermore, the increased expression of Wnt4 was supported by whole-mount in situ hybridization (WISH). These results suggest a possible association between in utero DEHP exposure and precocious puberty in the postnatal life of mice offspring, where disturbance of the sex determination regulating pathway acted as an important mechanism. - Highlights: • Maternal exposure to di (2-ethylhexyl) phthalate disturbs fetus sex determination. • DEHP upregulated Foxl2 expression potentially disturbs postnatal granulosa cell differentiation. • DEHP accelerated medulla

  3. DEHP exposure in utero disturbs sex determination and is potentially linked with precocious puberty in female mice

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yongan [Key Laboratory of Industrial Ecology and Environmental Engineering (MOE), School of Environmental Science and Technology, Dalian University of Technology, Dalian, Liaoning 116024 (China); Yang, Qing [School of Life Science and Biotechnology, Dalian University of Technology, Dalian, Liaoning 116024 (China); Liu, Wei, E-mail: liu_wei@dlut.edu.cn [Key Laboratory of Industrial Ecology and Environmental Engineering (MOE), School of Environmental Science and Technology, Dalian University of Technology, Dalian, Liaoning 116024 (China); Yu, Mingxi; Zhang, Zhou; Cui, Xiaoyu [Key Laboratory of Industrial Ecology and Environmental Engineering (MOE), School of Environmental Science and Technology, Dalian University of Technology, Dalian, Liaoning 116024 (China)

    2016-09-15

    Human's ubiquitous exposure to di (2-ethylhexyl) phthalate (DEHP) is thought to be associated with female reproductive toxicity. Previous studies found that DEHP inhibited follicle growth and decreased estradiol levels in adult female mice. However, limited information is available on the link between in utero DEHP exposure and ovarian development in female mouse offspring. The present study evaluates the disturbances in regulatory genes involved in female sex determination and the ovarian outcomes in fetal and postnatal female mice treated with in utero DEHP exposure. Pregnant mice were exposed to DEHP by gavage, with the dosage regime beginning at human relevant exposure levels. After in utero DEHP exposure, increased follicular atresia was observed in the female pups at postnatal days (PND) 21. Foxl2 expression was significantly upregulated, and Fst was significantly downregulated by DEHP above 2 mg/kg/d at PND 1 and 21. This suggests that lesion of granulosa cell differentiation and disturbance of follicle development in postnatal female mice. The expression of Cyp11a1 and Star were significantly downregulated by in utero DEHP exposure, indicating effects on estradiol biosynthesis. The female sex determination pathway was disturbed in fetus by DEHP at 2 mg/kg/d and above during the critical time window of sex determination causing significant upregulation of Foxl2, Wnt4, β-catenin and Fst. Furthermore, the increased expression of Wnt4 was supported by whole-mount in situ hybridization (WISH). These results suggest a possible association between in utero DEHP exposure and precocious puberty in the postnatal life of mice offspring, where disturbance of the sex determination regulating pathway acted as an important mechanism. - Highlights: • Maternal exposure to di (2-ethylhexyl) phthalate disturbs fetus sex determination. • DEHP upregulated Foxl2 expression potentially disturbs postnatal granulosa cell differentiation. • DEHP accelerated medulla

  4. Sex hormone binding globulin, free estradiol index, and lipid profiles in girls with precocious puberty

    Directory of Open Access Journals (Sweden)

    Hyun-Wook Chae

    2013-06-01

    Full Text Available PurposeSex hormone-binding globulin (SHBG modulates the availability of biologically active free sex hormones. The regulatory role of SHBG might be important in the relationship between hormone levels and the modification of lipid profiles in girls with precocious puberty. However, few studies have evaluated the relationship of SHBG, free estradiol index (FEI, and lipid levels in these girls.MethodsOne hundred and nine girls less than 8 years of age with pubertal development were enrolled. FEI was calculated with SHBG and estradiol (E2. We analyzed SHBG between peak luteinizing hormone (LH≥5 (IU/L (group 1 and LH<5 (IU/L (group 2 through a gonadotropin releasing hormone stimulation test.ResultsBody mass index (BMI standard deviation score (SDS was higher in group 2 than in group 1 (P=0.004. Serum SHBG levels did not differ and FEI was not higher in group 1 (P=0.122. Serum cholesterol, HDL, and LDL did not differ; however, triglyceride levels were higher in group 2 (P=0.023. SHBG was negatively correlated with bone age advancement, BMI, BMI SDS, and FEI, and was positively correlated with HDL. However, SHBG was not correlated with E2 or peak LH.ConclusionSerum SHBG itself might not be associated with precocious puberty in girls, but it might be related to BMI and lipid profiles. Further studies are needed to reveal the relationship between sex hormone and obesity in girls with precocious puberty.

  5. Activity cycles and foraging behaviors of free-ranging sidewinder rattlesnakes (Crotalus cerastes): the ontogeny of hunting in a precocial vertebrate.

    Science.gov (United States)

    Clark, Rulon W; Dorr, Scott W; Whitford, Malachi D; Freymiller, Grace A; Putman, Breanna J

    2016-06-01

    Predators often employ a complex series of behaviors to overcome antipredator defenses and effectively capture prey. Although hunting behaviors can improve with age and experience, many precocial species are necessarily effective predators from birth. Additionally, many predators experience innate ontogenetic shifts in predatory strategies as they grow, allowing them to adapt to prey more appropriate for their increased size and energetic needs. Understanding how the relative roles of innate age-specific adaptation and learning have evolved requires information on how predation behavior develops in situ, in free-ranging predators. However, most of the research on the ontogeny of predation behavior is based on laboratory studies of captive animals, largely due to the difficulty of following newborn individuals in nature. Here, we take advantage of the unique tracks left by juveniles of a precocial viperid, the sidewinder rattlesnake (Crotalus cerastes), which we used to follow free-ranging snakes in the field. We recorded details of their ambush hunting behavior, and compared the behaviors of these juveniles to adult snakes that we monitored in the field via radio telemetry. Although juvenile and adult behaviors were similar in most respects, we did find that adults chose more effective ambush sites, which may be due to their increased experience. We also found that juveniles (but typically not adults) perform periodic tail undulations while in ambush, and that juveniles displayed slightly different activity cycles. Both of these latter differences are likely the result of age-specific adaptations for juveniles' greater reliance on lizards versus small mammals as prey. We also compared the general predatory behavior of sidewinders to that of other species in the genus Crotalus. These findings will provide important baseline field information for more detailed empirical research on the ontogeny of predation behavior in precocial vertebrates. Copyright © 2016

  6. Association of aromatase (TTTA)n repeat polymorphisms with central precocious puberty in girls.

    Science.gov (United States)

    Lee, Hae Sang; Kim, Kyung Hee; Hwang, Jin Soon

    2014-09-01

    Precocious puberty is characterized by early activation of the pituitary-gonadal axis. Oestrogen is the final key factor to start the onset of puberty. The cytochrome P450 19A1 (CYP19A1) gene encodes an aromatase that is responsible for the conversion of androgens to oestrogen, which is a key step in oestrogen biosynthesis. The aim of this study was to identify CYP19A1 gene mutations or polymorphisms in girls with central precocious puberty (CPP). We evaluated the frequency of allelic variants of the CYP19A1 exons and the tetranucleotide tandem repeat (TTTA)n in intron 4 in 203 idiopathic central precocious puberty (CPP) girls and 101 normal healthy women. The genotype analysis of the CYP19A1 (TTTA)n polymorphism revealed six different alleles ranging from seven to 13 repeats. Among the six different repeat alleles detected in this study, the (TTTA)₁₃ repeat allele was only detected in the patient group and carriers of the (TTTA)₁₃ allele were significantly associated with an increased risk of CPP (OR = 1·509, 95% CI = 1·425-1·598, P = 0·033). Carriers of the (TTTA)₁₃ repeat allele were significantly younger at pubertal onset and had higher levels of oestrogen than noncarriers of the (TTTA)₁₃ repeat allele. Although nine polymorphisms were detected in exons of the CYP19A1 gene, no clinical significance was observed. In this study, carriers of a higher repeat (TTTA)₁₃ polymorphism in intron 4 of the CYP19A1 gene had higher levels of oestrogen. Those carrying the (TTTA)₁₃ repeat allele may have a higher risk of developing CPP. © 2014 John Wiley & Sons Ltd.

  7. Luteinizing hormone-releasing hormone analogue (Buserelin) treatment for central precocious puberty: a multi-centre trial.

    Science.gov (United States)

    Werther, G A; Warne, G L; Ennis, G; Gold, H; Silink, M; Cowell, C T; Quigley, C; Howard, N; Antony, G; Byrne, G C

    1990-02-01

    A multi-centre open trial of Buserelin, a luteinizing hormone-releasing hormone (LHRH) analogue, was conducted in 13 children with central precocious puberty. Eleven children (eight girls and three boys), aged 3.4-10.2 years at commencement, completed the required 12 month period of treatment. Initially all patients received the drug by intranasal spray in a dose of 1200 micrograms/day, but by the end of the 12 month period two were having daily subcutaneous injections and three were receiving an increased dose intranasally. The first month of treatment was associated in one boy with increased aggression and masturbation, and in the girls with an increase in the prevalence of vaginal bleeding. Thereafter, however, both behavioural abnormalities and menstruation were suppressed. Median bone age increased significantly during the study, but without any significant change in the ratio of height age to bone age. The median predicted adult height for the group therefore did not alter significantly over the twelve months of the study. Buserelin treatment caused a reduction in the peak luteinizing hormone and follicle-stimulating hormone (FSH) responses to LHRH, mostly to prepubertal levels, and also suppressed basal FSH. In the first weeks of treatment, the girls' serum oestradiol levels rose significantly and then fell to prepubertal or early pubertal levels. A similar pattern was seen for serum testosterone levels. Serum somatomedin-C levels, however, showed little fluctuation over the course of the study. Buserelin treatment was safe and well accepted, and offers the promise of improved linear growth potential in precocious puberty.

  8. Insulin sensitivity and lipid profiles in girls with central precocious puberty before and during gonadal suppression

    DEFF Research Database (Denmark)

    Sørensen, Kaspar; Mouritsen, Annette; Mogensen, Signe Sloth

    2010-01-01

    Early menarche is associated with increased risk of cardiovascular disease in adulthood. It is unknown whether metabolic risk factors are adversely affected in girls with central precocious puberty (CPP) already at time of diagnosis....

  9. The lack of autophagy triggers precocious activation of Notch signaling during Drosophila oogenesis

    Directory of Open Access Journals (Sweden)

    Barth Julia MI

    2012-12-01

    Full Text Available Abstract Background The proper balance of autophagy, a lysosome-mediated degradation process, is indispensable for oogenesis in Drosophila. We recently demonstrated that egg development depends on autophagy in the somatic follicle cells (FC, but not in the germline cells (GCs. However, the lack of autophagy only affects oogenesis when FCs are autophagy-deficient but GCs are wild type, indicating that a dysfunctional signaling between soma and germline may be responsible for the oogenesis defects. Thus, autophagy could play an essential role in modulating signal transduction pathways during egg development. Results Here, we provide further evidence for the necessity of autophagy during oogenesis and demonstrate that autophagy is especially required in subsets of FCs. Generation of autophagy-deficient FCs leads to a wide range of phenotypes that are similar to mutants with defects in the classical cell-cell signaling pathways in the ovary. Interestingly, we observe that loss of autophagy leads to a precocious activation of the Notch pathway in the FCs as monitored by the expression of Cut and Hindsight, two downstream effectors of Notch signaling. Conclusion Our findings point to an unexpected function for autophagy in the modulation of the Notch signaling pathway during Drosophila oogenesis and suggest a function for autophagy in proper receptor activation. Egg development is affected by an imbalance of autophagy between signal sending (germline and signal receiving cell (FC, thus the lack of autophagy in the germline is likely to decrease the amount of active ligand and accordingly compensates for increased signaling in autophagy-defective follicle cells.

  10. Serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 levels are increased in central precocious puberty

    DEFF Research Database (Denmark)

    Juul, A; Scheike, Thomas Harder; Nielsen, C T

    1995-01-01

    Central precocious puberty (CPP) is characterized by early activation of the pituitary-gonadal axis, which leads to increased growth velocity and development of secondary sexual characteristics. It is generally believed that gonadal sex steroids stimulate pulsatile GH secretion, which, in turn......, stimulates insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3) production. However, little is known about GH, IGF-I, and IGFBP-3 serum levels in children with precocious puberty. Treatment of CPP by GnRH agonists has become the treatment of choice. However, the effect of long term...

  11. Four generations in a family with neurofibromatosis 1: precocious puberty and optic nerve tumor (OPT).

    Science.gov (United States)

    Gucev, Z; Krstevska-Konstantinova, M; Tasic, V; Jancevska, A; Kirovski, I; Pop-Jordanova, N

    2010-01-01

    Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with varied clinical manifestations. The proband is a 6-year-old boy with signs of precocious puberty. His penis was 10 cm, testicles 8 ml, pubic hair P2-3, and the genital skin was hyperpigmented. Multiple cafe au lait spots well above 5 mm were noticeable on his skin, as well as hard subcutaneous nodules, mostly on his trunk. His intelligence and hearing are normal. He has no history of seizures. Laboratory analysis showed: LH LH 1.4 mIU/ml, FSH 6.2 mIU/ml, testosterone 183 ng/ml. Bone age was 9 years. LHRH stimulation was characteristic of true precocious puberty (LH 9.8 mIU/ml and FSH 8.9 mIU/ml after 30 minutes). The MRI of the brain showed a tumor of the suprasellar region with compression of the pituitary stalk. At present the boy is 6 years old and has been treated with triptoreline acetate for 3 months. The volume of the testicles has decreased to 7 ml and a slight loss of pubic hair was noted. In addition, his mother and his grandfather exhibited dermal masses, and focal cutaneous and subcutaneous growths. The great-grand father had had the same cutaneous changes and died at the age of 75 from unrelated causes. It has already been well documented that NF is associated with an increased risk of malignancy and precocious puberty. Hence, we emphasize the need for a close and regular clinical follow-up of the OPT, puberty and patterns of growth.

  12. Assessment of High Rates of Precocious Male Maturation in a Spring Chinook Salmon Supplementation Hatchery Program, Annual Report 2002-2003.

    Energy Technology Data Exchange (ETDEWEB)

    Larsen, Donald; Beckman, Brian; Cooper, Kathleen

    2003-08-01

    The Yakima River Spring Chinook Salmon Supplementation Project in Washington State is currently one of the most ambitious efforts to enhance a natural salmon population in the United States. Over the past five years we have conducted research to characterize the developmental physiology of naturally- and hatchery-reared wild progeny spring chinook salmon (Oncorhynchus tshawytscha) in the Yakima River basin. Fish were sampled at the main hatchery in Cle Elum, at remote acclimation sites and, during smolt migration, at downstream dams. Throughout these studies the maturational state of all fish was characterized using combinations of visual and histological analysis of testes, gonadosomatic index (GSI), and measurement of plasma 11-ketotestosterone (11-KT). We established that a plasma 11-KT threshold of 0.8 ng/ml could be used to designate male fish as either immature or precociously maturing approximately 8 months prior to final maturation (1-2 months prior to release as 'smolts'). Our analyses revealed that 37-49% of the hatchery-reared males from this program undergo precocious maturation at 2 years of age and a proportion of these fish appear to residualize in the upper Yakima River basin throughout the summer. An unnaturally high incidence of precocious male maturation may result in loss of potential returning anadromous adults, skewing of female: male sex ratios, ecological, and genetic impacts on wild populations and other native species. Precocious male maturation is significantly influenced by growth rate at specific times of year and future studies will be conducted to alter maturation rates through seasonal growth rate manipulations.

  13. Hypothalamic hamartoma with precocious puberty: a case report.

    Science.gov (United States)

    Amin, M S; Kader, M A; Huq, F I; Khan, N A

    2012-07-01

    Hypothalamic hamartoma (HH) is one of the most important causes of central precocious puberty in male children. Hamartomas are malformations composed of ectopic gonadotropic hormone (GnRH) neurons which secrete pulsatile gonadotropin releasing hormone. They are generally observed in children under 3 years. A case of 11/3 year-old male child presented with premature development of secondary sexual characters i.e., growth of pubic and axillary hair, enlargement of penis and acne over the face for the last 5 months. On physical examination, his height was 1.02 m and his weight 18kg, enlarged penile length of which 58mm; testicles were enlarged in size right one measuring 32X25mm and the left 30X23mm. His hematological and other biochemical investigations revealed no abnormality. Plain radiographic examination revealed radiological bone age of about 8-9 years. Endocrinological findings were as follows: Follicle stimulating hormone (FSH): 1.5mIU/ml, Luteinizing hormone (LH): 9.1mIU/ml, Testosterone: 701ng/dl (Testosterone level less than 30ng/dl in prepubertal age). Thyroid function tests were normal. Patient showed no adrenal pathology on ultrasound and his testicular parenchyma was homogeneous echotexture with the size of 30X22X16mm on the right (volume 5.4ml) and 30X20X15mm on the left (volume 4.6ml). With above physical & endocrinological findings and age of the child, it was suspected as a case of central precocious puberty. Subsequently MR imaging of the brain done & showed an oval non-enhancing pedunculated hypothalamic mass arising from the tubercinereum that was iso to hypointense to brain parenchyma on T1 - and intermediate signal on T2-weighted images, 20X10X10mm in diameter, extending into suprasellar cistern. During follow up after 06 months of starting conservative medication with gonadotropin-releasing hormone (GnRH) analog (Leuprolide acetate), his progression of puberty has been arrested and the testosterone level 18ng/dl, which is normal for his age.

  14. Treatment of central precocious puberty by subcutaneous injections of leuprorelin 3-month depot (11.25 mg).

    Science.gov (United States)

    Carel, Jean-Claude; Lahlou, Najiba; Jaramillo, Orlando; Montauban, Vincent; Teinturier, Cécile; Colle, Michel; Lucas, Christel; Chaussain, Jean Louis

    2002-09-01

    Depot GnRH agonists are widely used for the treatment of precocious puberty. Leuprorelin 3-month depot is currently used in adults but has not been evaluated in children. We evaluated the efficacy of this new formulation (11.25 mg every 3 months), for the suppression of gonadotropic activation and pubertal signs in children with central precocious puberty. We included 44 children (40 girls) with early-onset pubertal development in a 6-month open trial. The inclusion criteria were clinical pubertal development before the age of 8 (girls) or 10 (boys), advanced bone age, enlarged uterus (>36 mm), testosterone more than 1.7 nmol/liter (boys), and pubertal response of LH to GnRH (peak >5 IU/liter). The principal criterion for efficacy assessment, GnRH-stimulated LH peak less than 3 IU/liter, was met in 81 of 85 (95%) of the tests performed at months 3 and 6. The remaining four values were slightly above the threshold. The levels of sex steroids were also significantly reduced and clinical pubertal development was arrested. Plasma leuprorelin levels, measured every 30 d, were essentially stable after d 60. Local intolerance was noted after 10 of 86 injections (12%), and was mild in four cases, moderate in five cases, and severe in one. Among these 10 events, 4 consisted in local pain at injection's site. In conclusion, leuprorelin 3-month depot efficiently inhibits the gonadotropic axis in 95% of children with central precocious puberty studied for a 6-month period. This regimen allows the reduction of the number of yearly injections from 12 to 4.

  15. Precocious scaling in antiproton-proton scattering at low energies

    International Nuclear Information System (INIS)

    Ion, D.B.; Petrascu, C.; Topor Pop, V.; Popa, V.

    1993-08-01

    The scaling of the diffraction peak in antiproton-proton scattering has been investigated from nera threshold up to 3 GeV/c laboratory momenta. It was shown that the scaling of the differential cross sections are evidentiated with a surprising accuracy not only at high energies, but also at very low ones (e.g. p LAB = 0.1 - 0.5 GeV/c), beyond the resonance and exotic resonance regions. This precocious scaling strongly suggests that the s-channel helicity conservation (SCHC) can be a peculiar property that should be tested in antiproton-proton interaction not only at high energies but also at low energy even below p LAB = 1 GeV/c. (author). 36 refs, 9 figs

  16. GnRH-dependent precocious puberty manifested at the age of 14 months in a girl with 47,XXX karyotype.

    Science.gov (United States)

    Skordis, Nicos; Ferrari, Eleana; Antoniadou, Aria; Phylactou, Leonidas A; Fanis, Pavlos; Neocleous, Vassos

    2017-07-01

    This case report describes a 47,XXX girl who presented very early, at the age of 14 months, with signs of sexual precocity (breast and pubic hair development, menarche) and was finally diagnosed with GnRH dependent precocious puberty with no evidence of underlying central nervous system pathology. Molecular testing did not identify any genetic defect in any of the genes tested (KISS1, KISS1R, DLK1 and the intronless MKRN3). Though previous studies have shown a link between karyotype 47,XXX and precocious puberty, this is the youngest patient reported so far. Treatment with GnRH analog was commenced and proved to be effective, indicating a successful suppression of the hypothalamic-pituitary-ovarian axis.

  17. Precocious Degenerative Arthropathy And Bluish Patches On Ears : Ochronosis And Alkaptonuria

    Directory of Open Access Journals (Sweden)

    Mahajan Vikram K

    2004-01-01

    Full Text Available Alkaptonuria is a rare, autosomal recessive disorder of phenylalanin/tyrosine metabolism due to congenital deficiency of the enzyme homogentisic acid oxidase. The diagnosis is clinical and the triad of homogentisic aciduria, ochronosis and precocious degenerative arthritis is characteristic. Its diagnosis in infancy and early therapeutic intervention help delaying its complications. These patients may remain undiagnosed until the darkening of urine soaked diapers is noticed or the early degenerative arthropathy develops. This paper describes two cases of alkaptonuria presenting late in life; one of them had associated hyperthyroidism.

  18. Final height after gonadotrophin releasing hormone agonist treatment for central precocious puberty : The Dutch experience

    NARCIS (Netherlands)

    Mul, D; Oostdijk, W; Otten, BJ; Rouwe, C; Jansen, M; Delemarre-van de Waal, HA; Waelkens, JJJ; Drop, SLS

    Final height (FH) data of 96 children (87 girls) treated with GnRH agonist for central precocious puberty were studied. In girls mean FH exceeded initial height prediction by 7.4 (5.7) cm (p <0.001); FH was significantly lower than target height, but still in the genetic target range. When treatment

  19. Idiopathic precocious puberty in girls: Psychosexual development.

    Science.gov (United States)

    Meyer-Bahlburg, H F; Ehrhardt, A A; Bell, J J; Cohen, S F; Healey, J M; Feldman, J F; Morishima, A; Baker, S W; New, M I

    1985-08-01

    A promising model syndrome for the examination of the role of physical maturation in the development of female sexuality is idiopathic precocious puberty (IPP). In this first controlled study of psychosexual development in IPP females, 16 females between 13 and 20 years of age with a history of IPP were compared to 16 control subjects with a history of normal puberty pair-matched to the index subjects on the basis of sex, race, age, socioeconomic level, and menarcheal status. The psychosexual history and the current psychosexual status were assessed by a systematic half-structured interview. The IPP females on average passed the psychosexual milestones at an earlier age than their normal maturing peers, with a particularly early onset of masturbation. Those who were sociosexually active tended to report a higher total orgasmic outlet and a higher sex drive. There was no increase in homosexuality among IPP girls. The timing of puberty has a (modest) influence on psychosexual development in females.

  20. Precocious germination and its regulation in embryos of triticale caryopses

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    Stanisław Weidner

    2014-01-01

    Full Text Available Triticale var. Lasko embryos, isolated from grain gathered at milk ripeness, the beginning of wax ripeness and at full ripeness, were allowed to germinate for 48 h on agar with glucose. The highest incorporation of tritiated adenosine into polyribosomal RNA during germination was found in the ribosome fractions from embryos of grain gathered at full ripeness, lower incorporation was in preparations from embryos of milk ripe grain and the lowest in preparations from embryos of wax ripe grain. Different tendencies were observed in respect to the synthesis of ribosomal proteins. The highest incorporation of 14C-amino acids into ribosomal proteins was found in preparations of ribosome fractions from embryos of milk ripe grain, lower in preparations of embryos from fully ripe grain, the lowest in preparations of embryos from wax ripe grain. ABA (10-4 M completely inhibited the external symptoms of germination of immature embryos, while its inhibition of the synthesis of polyribosomal RNA and ribosomal proteins was greater the more mature the embryos that were germinated. The greatest stimulation of precocious germination by exogenous BA and GA3 was demonstrated in the least mature embryos isolated from milk ripe grain. Under the influence of both stimulators, an increase of the proportion of polyribosomes in the total ribosome fraction occurred in this sample, as did a rise in the intensity of ribosomal protein synthesis. The incorporation of 3H-adenosine into polyribosomal RNA, however, was lower than in the control sample. The results obtained suggest that the regulation of precocious germination of triticale embryos by phyto-hormones is not directly related to transcription.

  1. Trabalho precoce: realidade social e desafio de política pública Precocious labor: a social reality and a challenge to public policy

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    Sonia Rocha

    2003-01-01

    Full Text Available This article presents the basic characteristics of precocious labor in Brazil in the nineties. Since the age individuals start working does not seem to be an important determinant of future income, we examined its related aspects, such as school attendance and hard work incidence of. As precocious labor still involves large contingents of children in Brazil under quite different working conditions, it is essential to distinguish the most critical situations so as to support a social policy design targeted at a specific clientele.

  2. Precocious development of lectin (Ulex europaeus agglutinin I) receptors in dome epithelium of gut-associated lymphoid tissues.

    Science.gov (United States)

    Roy, M J

    1987-06-01

    Dome epithelium (DE), the tissue covering lymphoid domes of gut-associated lymphoid tissues, was examined in both adult and neonatal rabbit appendix or sacculus rotundus to determine if dome epithelial cells matured earlier than epithelial cells covering adjacent villi. The localization of well-differentiated epithelial cells in rabbit gut-associated lymphoid tissues (GALT) was accomplished histochemically by use of molecular probes: fluorescein isothiocyanate or horseradish peroxidase conjugates of Ulex europaeus agglutinin I (UEA), a lectin specific for terminal L-fucose molecules on certain glycoconjugates. The villus epithelial cells of newborn and 2-, 5-, or 10-day-old rabbits did not bind UEA, but between the twelfth and fifteenth days of postnatal life, UEA receptors were expressed by well-differentiated villus epithelial cells. In contrast to villus epithelium, DE in appendix and sacculus rotundus of neonatal rabbits expressed UEA receptors two days after birth, a feature that distinguished the DE of neonatal GALT for the next two weeks. In adult rabbits, UEA receptors were associated with dome epithelial cells extending from the mouths of glandular crypts to the upper domes; in contrast to the domes, UEA receptors were only present on well-differentiated epithelial cells at the villus tips. Results suggested that in neonatal rabbits most dome epithelial cells developed UEA receptors shortly after birth, reflecting precocious development of DE as compared to villus epithelium. In adult rabbit dome epithelium UEA receptors appeared on dome epithelial cells as they left the glandular crypts, representing accelerated epithelial maturation.

  3. Maternal-fetal communication of circadian phase in a precocious rodent, the spiny mouse

    International Nuclear Information System (INIS)

    Weaver, D.R.; Reppert, S.M.

    1987-01-01

    The development of circadian rhythms was examined in a precocious rodent species, the spiny mouse. Spiny mouse pups born and reared in constant darkness expressed robust circadian rhythms in locomotor activity as early as day 5 of live. Free-running activity rhythms of pups born and reared in constant darkness were coordinated with the dam on the day of birth. Postnatal maternal influences on pup rhythmicity are minimal in this species, as pups fostered on the day of birth to dams whose circadian phases were opposite to the pups' original dams were coordinated with their original dams on the day of birth. Studies using 2-deoxy-D-[1- 14 C]-glucose authoradiography showed that there were synchronous (coordinated) rhythms in metabolic activity in the maternal and fetal suprachiasmatic nuclei, directly demonstrating prenatal coordination of maternal and fetal rhythmicity. Maternal-fetal coordination of circadian phase was not the result of direct entrainment of the fetuses to the environmental light-dark cycle. These results demonstrate that there is prenatal communication of circadian phase in this precocious species, without demonstrable postnatal maternal influences on pup circadian rhythmicity. Spiny mice therefore represent an important animal model in which circadian rhythms in the postnatal period can be used to precisely assess prenatal influences on circadian phase

  4. Temporal dynamics of milk composition of the precocial caviomorph Octodon degus (Rodentia: Octodontidae Dinámica temporal de la composición de la leche del caviomorfo precocial Octodon degus (Rodentia: Octodentidae

    Directory of Open Access Journals (Sweden)

    CLAUDIO VELOSO

    2005-06-01

    Full Text Available During lactation, both the nutritional and energetic requirements of suckling change gradually. These changes normally are accompanied by modifications in chemical composition of the milk. We investigated the temporal course of milk composition during lactation in a precocial caviomorph rodent, the "degu" (Octodon degus under laboratory condition. Female degus were kept in laboratory during gestation and lactation and fed with commercial food pellets. Milk was collected at three stages of lactation: early (days 5-8, n = 12, middle (days 15-21, n = 7 and late (days 26-40, n = 6, and analyzed for protein, carbohydrates, lipids, ash, total solids and energy. On average, carbohydrates decreased from 3.1 ± 0.3 % (early to 1.1 ± 0.3 % (late during lactation; lipids, protein, ash, total solids and energy remained about the same. Lipids, the main component of the milk, were 17.3 % and protein remained near 4.4 %. Over lactation, total energy concentration of milk remained near 4.0 kJ mL-1. The maintenance of milk composition during lactation may be related to the initially high energetic and nutritional requirements associated with a precocial reproductive modeDurante la lactancia, tanto los requerimientos energéticos como nutricionales de las crías cambian gradualmente. Estos cambios normalmente van acompañados por modificaciones en la composición química de la leche. Se investigaron los cambios temporales de la composición de la leche durante la lactancia en el roedor caviomorfo precocial "degu" (Octodon degus bajo condiciones de laboratorio. Las hembras de degu fueron mantenidas en el laboratorio durante preñez y lactancia, y fueron alimentadas con alimento comercial de conejo. La leche fue colectada en tres estados de lactancia: temprana (días 5-8, n = 12, media (días 15-21, n = 7 y tardía (días 26-40, n = 6, y analizadas para proteínas, hidratos de carbono, lípidos, ceniza, sólidos totales y energía. En promedio, los hidratos de

  5. Stephen C. Woods: a precocious scientist.

    Science.gov (United States)

    Smith, Gerard P

    2011-04-18

    To investigate the early scientific development of Steve Woods, I reviewed his research during the first decade after he received his doctoral degree in 1970. The main parts of his research program were conditioned insulin secretion and hypoglycemia, Pavlovian conditioning of insulin secretion before a scheduled access to food, and basal insulin as a negative-feedback signal from fat mass to the brain. These topics were pursued with experimental ingenuity; the resulting publications were interesting, clear, and rhetorically effective. Although the theoretical framework for his experiments with insulin was homeostatic, by the end of the decade he suggested that classic negative-feedback homeostasis needed to be revised to include learning acquired by lifestyle. Thus, Woods functioned as a mature scientist from the beginning of his research-he was very precocious. This precocity also characterized his teaching and mentoring as recalled by two of his students during that time, Joseph Vasselli and Paul Kulkosky. The most unusual and exemplary aspect of his precocity is that the outstanding performance of his first decade was maintained during the subsequent 30years. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. The CXC chemokine cCAF stimulates precocious deposition of ECM molecules by wound fibroblasts, accelerating development of granulation tissue

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    Li Qi-Jing

    2002-06-01

    Full Text Available Abstract Background During wound repair, fibroblasts orchestrate replacement of the provisional matrix formed during clotting with tenascin, cellular fibronectin and collagen III. These, in turn, are critical for migration of endothelial cells, keratinocytes and additional fibroblasts into the wound site. Fibroblasts are also important in the deposition of collagen I during scar formation. The CXC chemokine chicken Chemotactic and Angiogenic Factor (cCAF, is highly expressed by fibroblasts after wounding and during development of the granulation tissue, especially in areas where extracellular matrix (ECM is abundant. We hypothesized that cCAF stimulates fibroblasts to produce these matrix molecules. Results Here we show that this chemokine can stimulate precocious deposition of tenascin, fibronectin and collagen I, but not collagen III. Studies in culture and in vivo show that tenascin stimulation can also be achieved by the N-terminal 15 aas of the protein and occurs at the level of gene expression. In contrast, stimulation of fibronectin and collagen I both require the entire molecule and do not involve changes in gene expression. Fibronectin accumulation appears to be linked to tenascin production, and collagen I to decreased MMP-1 levels. In addition, cCAF is chemotactic for fibroblasts and accelerates their migration. Conclusions These previously unknown functions for chemokines suggest that cCAF, the chicken orthologue of human IL-8, enhances healing by rapidly chemoattracting fibroblasts into the wound site and stimulating them to produce ECM molecules, leading to precocious development of granulation tissue. This acceleration of the repair process may have important application to healing of impaired wounds.

  7. Laterization of epileptiform discharges in patients with epilepsy and precocious destructive brain insults

    Directory of Open Access Journals (Sweden)

    Teixeira Ricardo A.

    2004-01-01

    Full Text Available Unilateral destructive brain lesions of early development can result in compensatory thickening of the ipsilateral cranial vault. The aim of this study was to determine the frequency of these bone changes among patients with epilepsy and precocious destructive lesions, and whether a relationship exists between these changes and epileptiform discharges lateralization. Fifty-one patients had their ictal / interictal scalp EEG and skull thickness symmetry on MRI analyzed. Patients were divided into three main groups according to the topographic distribution of the lesion on the MRI: hemispheric (H (n=9; main arterial territory (AT (n=25; arterial borderzone (Bdz (n=17. The EEG background activity was abnormal in 26 patients and were more frequent among patients of group H (p= 0.044. Thickening of the skull was more frequent among patients of group H (p= 0.004. Five patients (9.8% showed discordant lateralization between epileptiform discharges and structural lesion (four of them with an abnormal background, and only two of them with skull changes. In one of these patients, ictal SPECT provided strong evidence for scalp EEG false lateralization. The findings suggest that compensatory skull thickening in patients with precocious destructive brain insults are more frequent among patients with unilateral and large lesions. However, EEG lateralization discordance among these patients seems to be more related to EEG background abnormalities and extent of cerebral damage than to skull changes.

  8. Final height in central precocious puberty after long term treatment with a slow release GnRH agonist

    NARCIS (Netherlands)

    Oostdijk, W; Rikken, B; Schreuder, S; Otten, Barto; Odink, R; Rouwe, C; Jansen, M; Gerver, WJ; Waelkens, J; Drop, S

    1996-01-01

    Objective-To study the resumption of puberty and the final height achieved in children with central precocious puberty (CPP) treated with the GnRH agonist triptorelin. Patients-31 girls and five boys with CPP who were treated with triptorelin 3.75 mg intramuscularly every four weeks. Girls were

  9. Influence of GnRH analogue on body mass index in girls with precocious puberty: a prospective study

    Directory of Open Access Journals (Sweden)

    Heshmat Moaieri

    2014-06-01

    Conclusion: Gonadotropin-releasing hormone analog (GnRHa therapy in central precocious puberty (CPP is safe for BMI and increasing of BMI is not significant, long- term follow-up study is required to elucidate whether GnRHa treatment affects adult obesity. Using growth hormone concomitantly, the effect on increasing height is significant.

  10. Energetics of growth in semi-precocial shorebird chicks in a warm environment : The African black oystercatcher, Haematopus moquini

    NARCIS (Netherlands)

    Tjorve, Kathleen M. C.; Underhill, Les G.; Visser, G. Henk

    2007-01-01

    We studied prefledging growth, energy expenditure and time budgets of African Black Oystercatcher, Haematopus moquini, chicks on Robben Island, Western Cape, South Africa. The aim of the study was to investigate the effect of parental feeding on the growth and energetics of semi-precocial shorebird

  11. Advanced bone age as an indicator facilitates the diagnosis of precocious puberty

    Directory of Open Access Journals (Sweden)

    Yue-Qin Xu

    Full Text Available Abstract Objective: Diagnosis of central precocious puberty has always been challenging in clinical practice. As an important method in the diagnosis of central precocious puberty, luteinizing hormone-releasing hormone stimulation test is complex and time-consuming. In many cases, clinical traits are inconsistent with luteinizing hormone-releasing hormone stimulation test results, therefore not reliable for diagnosis. In this study, the authors intended to find an indicator that predicts the results of the luteinizing hormone-releasing hormone stimulation test among subjects with early pubertal signs. Methods: Cases of 382 girls with early breast development before 8 years old and luteinizing hormone-releasing hormone stimulation test before 9 years old were included and underwent follow-up tests. Patients with peak luteinizing hormone level ≥5 IU/L were considered positive in the luteinizing hormone-releasing hormone stimulation test. Anthropometric data, body mass index, bone age evaluation, blood hormones levels of luteinizing hormone, estradiol, follicle-stimulating hormone, and uterine and ovarian volumes were analyzed. Results: Subjects with positive results in the initial test demonstrated early bone maturation, accelerated growth, and elevated basal blood luteinizing hormone, estradiol, and follicle-stimulating hormone levels, when compared with subjects with negative results in the initial test. Subjects with positive results in the follow-up test presented a more advanced bone age and more accelerated linear growth, when compared with subjects with negative results in the follow-up test. Conclusions: According to the statistical analysis, advanced bone age is the most effective predictor of the result of luteinizing hormone-releasing hormone stimulation test.

  12. The Diagnostic Value of Pelvic Ultrasound in Girls with Central Precocious Puberty.

    Science.gov (United States)

    Lee, Sang Heon; Joo, Eun Young; Lee, Ji-Eun; Jun, Yong-Hoon; Kim, Mi-Young

    2016-01-01

    The gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard for differentiating central precocious puberty (CPP) from exaggerated thelarche (ET). Because of this test's limitations, previous studies have clarified the clinical and laboratory factors that predict CPP. The present study investigated the early diagnostic significance of pelvic ultrasound in girls with CPP. The GnRH stimulation test and pelvic ultrasound were performed between March 2007 and February 2015 in 192 girls (aged values in pelvic ultrasound for differentiating between CPP and ET. Pelvic ultrasound should be combined with clinical and laboratory tests to maximize its diagnostic value for CPP.

  13. Chancre of the eyelid as manifestation of primary syphilis, and precocious chorioretinitis and uveitis in an HIV-infected patient: a case report

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    Cillino Salvatore

    2012-09-01

    Full Text Available Abstract Background Ocular syphilis is often difficult to diagnose because of the wide variation in clinical features. HIV co-infection may further complicate the picture. Case presentation Herein the authors report an unusual primary syphilitic ocular lesion in a 45-year-old Italian HIV-infected bisexual man who presented with a unilateral eyelid lesion. Associated precocious signs and symptoms in the posterior segment of both eyes, bilateral chorioretinitis and uveitis, are described. Intravenous penicillin and steroid treatment produced a rapid improvement in clinical status and complete resolution. Conclusions Careful questioning about sexual behavior is crucial for unmasking unusual features of ocular syphilis in HIV-infected subjects.

  14. RNAi-mediated knockdown of SPOOK reduces ecdysteroid titers and causes precocious metamorphosis in the desert locust Schistocerca gregaria.

    Science.gov (United States)

    Sugahara, Ryohei; Tanaka, Seiji; Shiotsuki, Takahiro

    2017-09-01

    The Halloween gene SPOOK (SPO) is involved in the production of the active metabolite of ecdysteroid, 20-hydroxyecdysone (20E), in insects. A previous study showed that RNAi-mediated knockdown of SPO in Schistocerca gregaria last instar nymphs markedly reduced the hemolymph 20E titer, but did not affect metamorphosis. In the present study, the effects of SPO interference on development were re-examined in this locust. Injections of SPO double-stranded RNA (dsSPO) into nymphs at mid and late instars significantly delayed nymphal development and interfered with molting. The 20E levels of dsSPO-treated nymphs were generally low, with a delayed, small peak, suggesting that disturbance of the 20E levels caused the above developmental abnormalities. A small proportion of the dsSPO-injected nymphs metamorphosed precociously, producing adults and adultoids. Precocious adults were characterized by small body size, short wings with abbreviated venation, and normal reproductive activity. Fourth instar nymphs that precociously metamorphosed at the following instar exhibited temporal expression patterns of ecdysone-induced protein 93F and the juvenile hormone (JH) early-inducible gene Krüppel homolog 1 similar to those observed at the last instar in normal nymphs. Adultoids displayed mating behavior and adultoid females developed eggs, but never laid eggs. JH injection around the expected time of the 20E peak in the dsSPO-injected nymphs completely inhibited the appearance of adultoids, suggesting that appearance of adultoids might be due to a reduced titer of JH rather than of 20E. These results suggest that SPO plays an important role in controlling morphogenesis, metamorphosis, and reproduction in S. gregaria. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. A boy with Prader-Willi syndrome: unmasking precocious puberty during growth hormone replacement therapy.

    Science.gov (United States)

    Ludwig, Natasha G; Radaeli, Rafael F; Silva, Mariana M X; Romero, Camila M; Carrilho, Alexandre J F; Bessa, Danielle; Macedo, Delanie B; Oliveira, Maria L; Latronico, Ana Claudia; Mazzuco, Tânia L

    2016-01-01

    Prader-Willi syndrome (PWS) is a genetic disorder frequently characterized by obesity, growth hormone deficiency, genital abnormalities, and hypogonadotropic hypogonadism. Incomplete or delayed pubertal development as well as premature adrenarche are usually found in PWS, whereas central precocious puberty (CPP) is very rare. This study aimed to report the clinical and biochemical follow-up of a PWS boy with CPP and to discuss the management of pubertal growth. By the age of 6, he had obesity, short stature, and many clinical criteria of PWS diagnosis, which was confirmed by DNA methylation test. Therapy with recombinant human growth hormone (rhGH) replacement (0.15 IU/kg/day) was started. Later, he presented psychomotor agitation, aggressive behavior, and increased testicular volume. Laboratory analyses were consistent with the diagnosis of CPP (gonadorelin-stimulated LH peak 15.8 IU/L, testosterone 54.7 ng/dL). The patient was then treated with gonadotropin-releasing hormone analog (GnRHa). Hypothalamic dysfunctions have been implicated in hormonal disturbances related to pubertal development, but no morphologic abnormalities were detected in the present case. Additional methylation analysis (MS-MLPA) of the chromosome 15q11 locus confirmed PWS diagnosis. We presented the fifth case of CPP in a genetically-confirmed PWS male. Combined therapy with GnRHa and rhGH may be beneficial in this rare condition of precocious pubertal development in PWS.

  16. Central precocious puberty in a 3 year-old girl with Phenylketonuria: a rare association?

    Science.gov (United States)

    2014-01-01

    Background Central precocious puberty (CPP) and phenylketonuria (PKU) are two rare conditions, the latter being the rarer. To date, only one case featuring both these conditions has been reported, and hyperphenylalaninemia was assumed triggering CPP. Case presentation We present a 3.2 years old girl referred with a 12 months history of breast and pubic hair development, and vaginal discharge. Hyperphenylalaninemia had been identified by newborn screening and PKU subsequently confirmed by plasma amino acid and genetic analysis. Early dietary control of plasma phenylalanine had been excellent afterwards, resulting in phenylalanine concentrations consistently within the recommended range. Clinical scenario, hormonal assessment and imaging were in keeping with true idiopathic central precocious puberty. Treatment with long lasting gonadotropin-releasing hormone analogue led to regression of secondary sexual characteristics. Conclusion We describe for the first time CPP in a girl affected with PKU but with persistently well controlled blood phenylalanine concentrations. This finding is in contrast to a previous report which suggested persistently high phenylalaninemia levels as potential trigger for CPP in PKU patients. Our report, together with the lack of evidence in published cohort studies of children with PKU, strongly suggests this rare association is coincidental and independent of the presence of severe hyperphenylalaninemia. PMID:24773629

  17. Adolescent Violent Victimization and Precocious Union Formation.

    Science.gov (United States)

    C Kuhl, Danielle; Warner, David F; Wilczak, Andrew

    2012-11-01

    This article bridges scholarship in criminology and family sociology by extending arguments about "precocious exits" from adolescence to consider early union formation as a salient outcome of violent victimization for youths. Research indicates that early union formation is associated with several negative outcomes; yet the absence of attention to union formation as a consequence of violent victimization is noteworthy. We address this gap by drawing on life course theory and data from the National Longitudinal Study of Adolescent Health (Add Health) to examine the effect of violent victimization ("street" violence) on the timing of first co-residential union formation-differentiating between marriage and cohabitation-in young adulthood. Estimates from Cox proportional hazard models show that adolescent victims of street violence experience higher rates of first union formation, especially marriage, early in the transition to adulthood; however, this effect declines with age, as such unions become more normative. Importantly, the effect of violent victimization on first union timing is robust to controls for nonviolent delinquency, substance abuse, and violent perpetration. We conclude by discussing directions for future research on the association between violent victimization and coresidential unions with an eye toward the implications of such early union formation for desistance.

  18. Repair of the myocardium infarct, with intracoronary implant of mother cells (stem cells) precocious improvement of the ventricular function and the ischemy (first reports of the TECELCOR report)

    International Nuclear Information System (INIS)

    Fernandez Vina, Roberto; Vrsalovic, Francisco; Andrin, Oberdan and others

    2004-01-01

    Twenty patients who suffered extensive anterior myocardial infarction with an evolution of 5 to 72 hours were submitted to a primary PTCA with Stent. The ventricular ejection fraction oscillated between 21 to 30% in correlation to the bidimensional echocardiography. Between the 7th and 12th day, mononuclear CD 34(+) and CD 38(-) cells extracted from the patient's bone marrow were implanted through the anterior descendent coronary artery, with occlusion of the anterior coronary vein, in an average amount of 22 x 10 P6. echocardiographic controls were performed each 7 days until 60 days, noticing a progressive increment in the ejection fraction (EF) from 25 to 45% in the first 60 days, and an improvement of the EF up to 80% after 90 days. Between 90 and 120 days after, a coronary ventriculography was performed, and the permeability of all the implanted stents and an improvement of the EF up to 80% with respect to the basal EF, were observed. The Spect studies were negative with negative ergonometry at 700 kgm. This group of patients was comparing red with 16 patients who were submitted only to primary PTCA with Stent. They had an increase of only 45% of the EF respect to the basal one in the next 90 days and 12 % presented restenosis. Stems cells implant improves the left ventricular performance after a myocardial infarction and it seems to avoid the coronary post-restenosis

  19. Serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 levels are increased in central precocious puberty

    DEFF Research Database (Denmark)

    Juul, A; Scheike, Thomas Harder; Nielsen, C T

    1995-01-01

    between IGF-I and IGFBP-3 (i.e. free biologically active IGF-I) declined concomitantly with a decrease in growth velocity. Serum levels of IGF-I and IGFBP-3 (expressed as the SD score for bone age), but not those of estradiol, correlated with height velocity before and during treatment (r = 0.34; P ...Central precocious puberty (CPP) is characterized by early activation of the pituitary-gonadal axis, which leads to increased growth velocity and development of secondary sexual characteristics. It is generally believed that gonadal sex steroids stimulate pulsatile GH secretion, which, in turn......, stimulates insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3) production. However, little is known about GH, IGF-I, and IGFBP-3 serum levels in children with precocious puberty. Treatment of CPP by GnRH agonists has become the treatment of choice. However, the effect of long term...

  20. Adolescent Violent Victimization and Precocious Union Formation*

    Science.gov (United States)

    C. Kuhl, Danielle; Warner, David F.; Wilczak, Andrew

    2013-01-01

    This article bridges scholarship in criminology and family sociology by extending arguments about “precocious exits” from adolescence to consider early union formation as a salient outcome of violent victimization for youths. Research indicates that early union formation is associated with several negative outcomes; yet the absence of attention to union formation as a consequence of violent victimization is noteworthy. We address this gap by drawing on life course theory and data from the National Longitudinal Study of Adolescent Health (Add Health) to examine the effect of violent victimization (“street” violence) on the timing of first co-residential union formation—differentiating between marriage and cohabitation—in young adulthood. Estimates from Cox proportional hazard models show that adolescent victims of street violence experience higher rates of first union formation, especially marriage, early in the transition to adulthood; however, this effect declines with age, as such unions become more normative. Importantly, the effect of violent victimization on first union timing is robust to controls for nonviolent delinquency, substance abuse, and violent perpetration. We conclude by discussing directions for future research on the association between violent victimization and coresidential unions with an eye toward the implications of such early union formation for desistance. PMID:24431471

  1. Boy with central precocious puberty probably due to a peripheral cause.

    Science.gov (United States)

    Sahana, Pranab Kumar; Gopal Sankar, Krishna Shankar; Sengupta, Nilanjan; Chattopadhyay, Kaustubh

    2016-06-02

    A 6½ years Indian boy was brought by his parents, who were anxious about the excessive increase in the size of the boy's phallus, from the age of 2 years. On physical examination, the child had a penis length greater than the 97th centile for age, a sexual maturity rating of gonads at stage 2 and pubic hair at stage 3, with height in the high normal range (90-97th centile). The bone age was 12 years. Laboratory evaluation showed pubertal levels of testosterone and pubertal gonadotropin response to stimulation, confirming central precocious puberty (CPP). Incidentally, the hormonal profile also suggested congenital adrenal hyperplasia (CAH). This case report depicts a case of CPP probably caused by CAH in boys, which is rare. 2016 BMJ Publishing Group Ltd.

  2. Study on the relationship between serum E2, FSH, LH levels and morphologic changes of uterus and ovary in girls with idiopathic central precocious puberty

    International Nuclear Information System (INIS)

    Li Jingsong; Du Xueliang; Fu Hongliang; Wu Zhen; Gu Rong; Feng Guoqiang; Wu Jingchuan

    2003-01-01

    Objective: To explore the characteristics of the girls with idiopathic central precocious puberty (ICPP) through study on the relationship between serum E 2 , FSH, LH levels and morphologic changes of uterus and ovary. Methods: Serum E 2 , FSH and LH levels were measured with ECLIA and morphologic changes of uterus and ovary were studied with B-US in 67 girls with idiopathic central precocious puberty. Results: 1) Among the three types of ovaries (type 1, homogeneous type; type 2, small follicular type; type 3, large follicular type), differences of the serum LH and E 2 values were significant (p 2 levels (p 2 levels were correlated to the maximal follicular diameter but not to the total volume of ovary. It proved that there was close relationship between LH levels and follicular development. It also proved that serum E 2 levels was mainly decided by the development status of the follicles irrespective the total ovary volume. 2) Volume of uterus was correlated to both LH and E 2 levels. Development of uterus was significantly estrogen-dependent. 3) Judgement based upon observations on measurement of serum E 2 , LH, FSH levels and morphologic changes of uterus and ovary would be crucial for establishing the diagnosis of idiopathic central precocious puberty

  3. Pathological and incidental findings on brain MRI in a single-center study of 229 consecutive girls with early or precocious puberty

    DEFF Research Database (Denmark)

    Mogensen, Signe Sloth; Aksglaede, Lise; Mouritsen, Annette

    2012-01-01

    Central precocious puberty may result from organic brain lesions, but is most frequently of idiopathic origin. Clinical or biochemical factors which could predict a pathological brain MRI in girls with CPP have been searched for. With the recent decline in age at pubertal onset among US and Europ...

  4. MR imaging of the pituitary gland in central precocious puberty

    International Nuclear Information System (INIS)

    Kao, S.C.S.; Cook, J.S.; Hansen, J.R.; Simonson, T.M.

    1992-01-01

    Cranial magnetic resonance imaging was performed in 17 children with central precocious puberty (CPP) and 19 aged-matched controls to compare the appearance of the pituitary gland. Gland size was measured on T1-weighted sagittal and coronal images. The gland was graded according to the concavity or convexity of the upper surface, and the signal intensity of the gland was assessed visually. The mean pituitary volume in 13 CPP children without hypothalamic tumor (292.6 mm 3 ) was significantly greater than that in normal controls (181.35 mm 3 ). The mean volume for the four CPP children with hypothalamic tumor was smaller (145.0 mm 3 ). Compared to controls, the upper pituitary surface in CPP patients appeared convex in a higher proportion. The anterior pituitary was isointense to pons in all patients and controls. Although the posterior pituitary bright spot was present in 14 controls and 11 CPP patients, none with hypothalamic tumor showed it. (orig.)

  5. MR imaging of the pituitary gland in central precocious puberty

    Energy Technology Data Exchange (ETDEWEB)

    Kao, S.C.S. (Dept. of Radiology, Univ. of Iowa Coll. of Medicine, Iowa City, IA (United States)); Cook, J.S. (Dept. of Pediatrics, Univ. of Iowa Coll. of Medicine, Iowa City, IA (United States)); Hansen, J.R. (Dept. of Pediatrics, Univ. of Iowa Coll. of Medicine, Iowa City, IA (United States)); Simonson, T.M. (Dept. of Radiology, Univ. of Iowa Coll. of Medicine, Iowa City, IA (United States))

    1992-11-01

    Cranial magnetic resonance imaging was performed in 17 children with central precocious puberty (CPP) and 19 aged-matched controls to compare the appearance of the pituitary gland. Gland size was measured on T1-weighted sagittal and coronal images. The gland was graded according to the concavity or convexity of the upper surface, and the signal intensity of the gland was assessed visually. The mean pituitary volume in 13 CPP children without hypothalamic tumor (292.6 mm[sup 3]) was significantly greater than that in normal controls (181.35 mm[sup 3]). The mean volume for the four CPP children with hypothalamic tumor was smaller (145.0 mm[sup 3]). Compared to controls, the upper pituitary surface in CPP patients appeared convex in a higher proportion. The anterior pituitary was isointense to pons in all patients and controls. Although the posterior pituitary bright spot was present in 14 controls and 11 CPP patients, none with hypothalamic tumor showed it. (orig.)

  6. Precocious development of self-awareness in dolphins.

    Directory of Open Access Journals (Sweden)

    Rachel Morrison

    Full Text Available Mirror-self recognition (MSR is a behavioral indicator of self-awareness in young children and only a few other species, including the great apes, dolphins, elephants and magpies. The emergence of self-awareness in children typically occurs during the second year and has been correlated with sensorimotor development and growing social and self-awareness. Comparative studies of MSR in chimpanzees report that the onset of this ability occurs between 2 years 4 months and 3 years 9 months of age. Studies of wild and captive bottlenose dolphins (Tursiops truncatus have reported precocious sensorimotor and social awareness during the first weeks of life, but no comparative MSR research has been conducted with this species. We exposed two young bottlenose dolphins to an underwater mirror and analyzed video recordings of their behavioral responses over a 3-year period. Here we report that both dolphins exhibited MSR, indicated by self-directed behavior at the mirror, at ages earlier than generally reported for children and at ages much earlier than reported for chimpanzees. The early onset of MSR in young dolphins occurs in parallel with their advanced sensorimotor development, complex and reciprocal social interactions, and growing social awareness. Both dolphins passed subsequent mark tests at ages comparable with children. Thus, our findings indicate that dolphins exhibit self-awareness at a mirror at a younger age than previously reported for children or other species tested.

  7. Leuprolide Acetate 1-Month Depot for Central Precocious Puberty: Hormonal Suppression and Recovery

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    Neely EKirk

    2011-01-01

    Full Text Available Methods. This prospective US multicenter trial of leuprolide acetate 1-month depot (7.5–15 mg for central precocious puberty utilized an open-label treatment period, long-term follow-up, and adult callback. Forty-nine females Results. Subjects were treated for years. Mean peak GnRH-stimulated LH and FSH were prepubertal after the first dose and remained suppressed throughout treatment. During treatment, mean estradiol decreased to the limit of detection and mean testosterone decreased but remained above prepubertal norms. During posttreatment follow-up ( years, all patients achieved a pubertal hormonal response within 1 year and menses were reported in all females ≥12 years old. No impairment of reproductive function was observed at adulthood (mean age: 24.8 years.

  8. Psychological assessment of mothers and their daughters at the time of diagnosis of precocious puberty.

    Science.gov (United States)

    Schoelwer, Melissa J; Donahue, Kelly L; Bryk, Kristina; Didrick, Paula; Berenbaum, Sheri A; Eugster, Erica A

    2015-01-01

    Concerns about psychological distress are often used to justify treatment of girls with precocious puberty, but there is little evidence to support these concerns. The extent to which psychological problems are associated with central precocious puberty (CPP) compared with other forms of early puberty in girls has likewise not been established. Girls presenting with untreated CPP, premature adrenarche (PA) or early normal puberty (ENP) were recruited from our pediatric endocrine clinic along with their mothers. Child psychological adjustment was assessed by child self-report and parent report. Parent self-reported personality, anxiety, and depression were also assessed. Differences between groups were explored using one-way ANOVA and Dunnett's T3 test. Sixty-two subjects (aged 7.5 ± 1.4 years, range 4.8-10.5) were enrolled, of whom 19 had CPP, 22 had PA, and 21 had ENP. Girls with ENP were significantly older (8.9 ± .9 years) than girls with CPP (6.9 ± 1.1 years, p psychological adjustment. However, mothers of girls with PA scored significantly higher than mothers of girls with ENP on one measure of depression (p = .04) and stress (p = .01). While mothers of girls with PA report increased psychological distress on some measures, no differences in psychological adjustment were found at baseline amongst the girls themselves. Whether these results will change as puberty progresses in the PA and ENP groups or with treatment of CPP is unknown. Long-term prospective studies are needed in order to further investigate psychological correlates of early puberty in girls.

  9. Multicenter clinical trial of leuprolide acetate depot (Luphere depot 3.75 mg for efficacy and safety in girls with central precocious puberty

    Directory of Open Access Journals (Sweden)

    You Jin Kim

    2013-12-01

    Full Text Available PurposeWe evaluated the efficacy, safety and psychological aspect of monthly administrations of the gonadotropin-releasing hormone agonists (GnRHa, leuprolide acetate depot (Luphere depot 3.75 mg, in patients with precocious puberty.MethodsA total of 54 girls with central precocious puberty were administered with leuprolide acetate (Luphere depot 3.75 mg every four weeks over 24 weeks. We evaluated the percentage of children exhibiting a suppressed luteinizing hormone (LH response to GnRH (LH peak≤3 IU/L, peak LH/follicle stimulating hormone (FSH ratio of GnRH stimulation test less than 1, change in bone age/chronologic age ratio, change in the Tanner stage and change in eating habit and psychological aspect.Results(1 The percentage of children exhibiting a suppressed LH response to GnRH, defined as an LH peak≤3 IU/L at 24 weeks was 96.3 % (52/54. (2 The percentage of children exhibiting peak LH/FSH ratio<1 at 24 weeks of the study was 94.4 % (51/54. (3 The ratio of bone age and chronological age significantly declined from 1.27±0.07 to 1.24±0.01 after the 6 months of the study. (4 The mean Tanner stage manifested a significant change 2.3±0.48 at baseline, down to 1.70±0.61 at 24 weeks. (5 Based on the questionnaires, the score for eating habits showed a significant change from the baseline 34.0±6.8 to 31.3±6.8. (6 The psychological assessment did not exhibit a significant difference except with scores for sociability, problem behavior total score and other problems.ConclusionThe leuprolide 3.75 mg (Luphere depot is useful and safety for treating children with central precocious puberty.

  10. RNAi-mediated silencing of vitellogenin gene function turns honeybee ( Apis mellifera) workers into extremely precocious foragers

    Science.gov (United States)

    Marco Antonio, David Santos; Guidugli-Lazzarini, Karina Rosa; Do Nascimento, Adriana Mendes; Simões, Zilá Luz Paulino; Hartfelder, Klaus

    2008-10-01

    The switch from within-hive activities to foraging behavior is a major transition in the life cycle of a honeybee ( Apis mellifera) worker. A prominent regulatory role in this switch has long been attributed to juvenile hormone (JH), but recent evidence also points to the yolk precursor protein vitellogenin as a major player in behavioral development. In the present study, we injected vitellogenin double-stranded RNA (dsVg) into newly emerged worker bees of Africanized genetic origin and introduced them together with controls into observation hives to record flight behavior. RNA interference-mediated silencing of vitellogenin gene function shifted the onset of long-duration flights (>10 min) to earlier in life (by 3 4 days) when compared with sham and untreated control bees. In fact, dsVg bees were observed conducting such flights extremely precociously, when only 3 days old. Short-duration flights (<10 min), which bees usually perform for orientation and cleaning, were not affected. Additionally, we found that the JH titer in dsVg bees collected after 7 days was not significantly different from the controls. The finding that depletion of the vitellogenin titer can drive young bees to become extremely precocious foragers could imply that vitellogenin is the primary switch signal. At this young age, downregulation of vitellogenin gene activity apparently had little effect on the JH titer. As this unexpected finding stands in contrast with previous results on the vitellogenin/JH interaction at a later age, when bees normally become foragers, we propose a three-step sequence in the constellation of physiological parameters underlying behavioral development.

  11. α-fetoprotein involvement during glucocorticoid-induced precocious maturation in rat colon.

    Science.gov (United States)

    Chen, Min; Sun, Peng; Liu, Xiao-Yan; Dong, Dan; Du, Jun; Gu, Luo; Ge, Ying-Bin

    2011-06-28

    To investigate the role of α-fetoprotein (AFP), a cancer-associated fetal glycoprotein, in glucocorticoid-induced precocious maturation in rat colon. Colons from suckling Sprague-Dawley rats were used in this study. Corticosterone acetate at a dose of 100 μg/g body weight was given to normal pups on days 7, 9 and 11 after birth to induce hypercorticoidism. Control animals were injected with identical volumes of normal saline. Some rats receiving corticosterone 7 d after birth were also treated with mifepristone (RU38486), a glucocorticoid cytoplasm receptor antagonist to investigate the effects of glucocorticoids (GCs). The morphological changes of the crypt depth and villous height of the villous zone in colon were observed as indices of colon maturation. Expression levels of AFP in colons were detected by reverse transcriptase polymerase chain reaction and Western blotting. To identify the cellular localization of AFP in developing rat colons, double-immunofluorescent staining was performed using antibodies to specific mesenchymal cell marker and AFP. Corticosterone increased the crypt depth and villous height in the colon of 8- and 10-d-old rats with hypercorticoidism compared with that in the control animals (120% in 8-d-old rats and 118% in 10-d-old rats in villous height, P = 0.021; 145% in 8-d-old rats and 124% in 10-d-old rats in crypt depth, P = 0.017). These increases were accompanied by an increase of AFP expression in both mRNA and protein (2.5-folds in 8-d-old and 2.5-folds in 10-d-old rats higher than in control animals, P = 0.035; 1.8-folds in 8-d-old and 1.3-folds in 10-d-old rats higher than in control animals, P = 0.023). Increased crypt depth and villous height and increased expression of AFP in the colon of rats with hypercorticoidism were blocked by mifepristone. Both had positive staining for AFP or vimentin, and overlapped in mesenchymal cells at each tested colon. GCs promote the development of rat colon. AFP appears to be involved, in

  12. Loss of Igfbp7 causes precocious involution in lactating mouse mammary gland.

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    Sumanta Chatterjee

    Full Text Available BACKGROUND: Insulin like growth factors (IGFs and their binding proteins (IGFBPs are secreted peptides that play major roles in regulating the normal development and maturation of mammary gland. While Igfbp7 has been shown to decrease breast tumor growth, its role in regulating the normal mammary gland development has not been studied. To this end, we generated Igfbp7-null mice and examined the development and maturation of mammary glands in the virgin, pregnant and lactating animals. RESULTS: We report here that loss of Igfbp7 significantly retards mammary gland development in the virgin animals. More significantly, the pregnant Igfpb7-null glands contained fewer alveolar structures and that during lactation these glands exhibit the morphological changes that are associated with involution. The transcriptome profile of the Igfbp7-null glands on the lactation day 3 revealed a distinct involution-related gene signature compared to the lactating WT glands. Interestingly, we found that the lactating Igfbp7-null glands exhibit increased expression of Stat3 and enhanced activation of (phosphorylated Stat3, combined with decreased expression of Stat5 suggesting that the absence of Igfbp7 accelerates the onset of involution. We also found that in absence of Igfpb7, the lactating glands contain increased Igfbp5 protein along with decreased expression of IGF-1 Receptor and Akt activation. Finally, we show that during the normal course of involution, Igfbp7 expression is significantly decreased in the mammary gland. CONCLUSION: Our data suggest that loss of Igfbp7 induces precocious involution possibly through diminished cell survival signals. Our findings identify Igfbp7 as major regulator of involution in the mammary gland.

  13. Concise Review: Quiescence in Adult Stem Cells

    DEFF Research Database (Denmark)

    Rumman, M; Dhawan, J; Kassem, Moustapha

    2015-01-01

    Adult stem cells (ASCs) are tissue resident stem cells responsible for tissue homeostasis and regeneration following injury. In uninjured tissues, ASCs exist in a nonproliferating, reversibly cell cycle-arrested state known as quiescence or G0. A key function of the quiescent state is to preserve...... stemness in ASCs by preventing precocious differentiation, and thus maintaining a pool of undifferentiated ASCs. Recent evidences suggest that quiescence is an actively maintained state and that excessive or defective quiescence may lead to compromised tissue regeneration or tumorigenesis. The aim...

  14. The effects of swimming exercise and dissolved oxygen on growth performance, fin condition and precocious maturation of early-rearing Atlantic salmon Salmo salar

    Science.gov (United States)

    Waldrop, Thomas; Summerfelt, Steven T.; Mazik, Patricia M.; Good, Christopher

    2018-01-01

    Swimming exercise, typically measured in body-lengths per second (BL/s), and dissolved oxygen (DO), are important environmental variables in fish culture. While there is an obvious physiological association between these two parameters, their interaction has not been adequately studied in Atlantic salmon Salmo salar. Because exercise and DO are variables that can be easily manipulated in modern aquaculture systems, we sought to assess the impact of these parameters, alone and in combination, on the performance, health and welfare of juvenile Atlantic salmon. In our study, Atlantic salmon fry were stocked into 12 circular 0.5 m3 tanks in a flow-through system and exposed to either high (1.5–2 BL/s) or low (salmon early rearing can result in improved growth performance and a lower incidence of precocious parr.

  15. [Diagnostic value of baseline serum luteinizing hormone level for central precocious puberty in girls].

    Science.gov (United States)

    Ou-Yang, Li-Xue; Yang, Fan

    2017-07-01

    To evaluate the diagnostic value of baseline serum luteinizing hormone (LH) level for central precocious puberty (CPP) in girls. A total of 279 girls with precocious puberty were subjected to assessment of growth and development, bone age determination, baseline LH test, and follicle-stimulating hormone (FSH) test, gonadotropin-releasing hormone stimulation test, and other related examinations. Of the 279 patients, 175 were diagnosed with CPP and 104 with premature thelarche (PT). The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of baseline LH and FSH levels and their peak levels for CPP, and the correlation between the baseline LH level and the peak LH level was analyzed. The CPP group had significantly higher bone age, baseline LH and FSH levels, peak LH and FSH levels, and ratio of peak LH level to peak FSH level than the PT group (Pbaseline LH level and peak LH level had good diagnostic values for CPP. Among the three bone age subgroups in the CPP group (7.0-9.0 years, 9.0-11.0 years, and >11.0 years), baseline LH level showed the best diagnostic value in the >11.0 years subgroup, with the largest area under the ROC curve. At a baseline LH level of 0.45 IU/L, the Youden index reached the peak value, and the sensitivity and specificity were 66.7% and 80% respectively, for the diagnosis of CPP. At a peak LH level of 9.935 IU/L, the Youden index reached the peak value, and the sensitivity and specificity were 74.8% and 100% respectively, for the diagnosis of CPP. The baseline LH level was positively correlated with the peak LH level (r=0.440, PBaseline LH level can be used as an primary screening index for the diagnosis of CPP. It has a certain diagnostic value for CPP at different bone ages, and may be used as a monitoring index during the treatment and follow-uP.

  16. Longitudinal follow-up of bone density and body composition in children with precocious or early puberty before, during and after cessation of GnRH agonist therapy

    NARCIS (Netherlands)

    I.M. van der Sluis (Inge); A.M. Boot (Annemieke); E.P. Krenning (Eric); S.L.S. Drop (Stenvert); S.M.P.F. de Muinck Keizer-Schrama (Sabine)

    2002-01-01

    textabstractWe studied bone mineral density (BMD), bone metabolism, and body composition in 47 children with central precocious puberty (n = 36) or early puberty (n = 11) before, during, and after cessation of GnRH agonist. Bone density and body composition were measured with dual

  17. [Primary glucocorticoid resistance syndrome presenting as pseudo-precocious puberty and galactorrhea].

    Science.gov (United States)

    Xiang, Shu-lin; He, Li-ping; Ran, Xing-wu; Tian, Hao-ming; Li, Xiu-jun; Liang, Jin-zhong

    2008-09-01

    Primary glucocorticoid resistance syndrome (PGRS) is a rare condition characterized by hypercortisolism without Cushing's syndrome. This report describes a 7-year-old boy of PGRS with pseudo-precocious puberty and galactorrhea as the main manifestation. His height was 135 cm and body weight was 31 kg. Pigmentation could be seen in the skin, mammary areola and penis. He had hirsutism, low hair line, coarse voice, Tanner stage 3 pubic hair, penis in adult form, accelerated linear growth, and advanced bone age (13 yr.), but normal (for age) testes. Furthermore, he had mammoplasia and galactorrhea. There were no features of glucocorticoid (GC) excess. Hepatic function was impaired (ALT 1426 IU/L, AST 611 IU/L) with no definite causes. Serum cortisol concentration was 1294 nmol/L, 777 nmol/L, 199.3 nmol/L at 8:00, 16:00 and 24:00 respectively. Plasma adrenocorticotropic hormone (ACTH) was normal or a little higher (43.9-80 ng/L). Urinary-free cortisol (UFC) was normal (55.5-62.4 microg/24 h). Serum estradiol (E2), progesterone (P), testosterone (T), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were normal. Serum dehydroepiandrosterone sulfate (DHEAS, 60 microg/dL) and serum prolactin (PRL, 58.7-183.9 ng/mL) level were high, urinary dehydroepiandrosterone (DHEA) level was also elevated (0.96-3.2 mg/mL). Gonadotrophin hormone-releasing hormone (GnRH) stimulation test was negative. Serum cortisol responded normally to insulin-induced hypoglycemia. However, serum cortisol and plasma ACTH concentration was suppressed to more than 50% by 0.5 mg dexamethasone (DEX). The diagnosis of PGRS was made. TREATMENT AND FOLLOW-UP: The patient received a treatment of 0.75-1.0 mg/d DEX. Because of galactorrhea, bromocriptine was given by 1.25-3.75 mg/d. After 24 months follow-up, the pigmentation was relieved and galactorrhea disappeared. No advanced development of the external genitalia and breast was found. The acceleration of the bone age was also slowed down. But

  18. Paraneoplastic precocious puberty and excessively rapid somatic growth associated with pediatric malignant hepatic tumor: 1 report of 2 cases

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ok Hwa; Bahk, Yong Whee [Cathalic University College of Medicine, Seoul (Korea, Republic of)

    1990-04-15

    Sexual precocity in a 28-months-old boy and markedly accelerated skeletal growth with large body in a 5 years and 5 months-old-girl are reported. The former resulted from human chorionic gonadotropin-producing hepatoblastoma and the latter from cerebral gigantism associated with hepatoma. These two different disorders are discussed on the common basis of rare association of malignant hepatic tumors with precocious sexual and / or somatic growth. The clinical manifestations, chemical abnormalities, and the radiologic findings are presented with a brief review of the literature.

  19. Paraneoplastic precocious puberty and excessively rapid somatic growth associated with pediatric malignant hepatic tumor: 1 report of 2 cases

    International Nuclear Information System (INIS)

    Kim, Ok Hwa; Bahk, Yong Whee

    1990-01-01

    Sexual precocity in a 28-months-old boy and markedly accelerated skeletal growth with large body in a 5 years and 5 months-old-girl are reported. The former resulted from human chorionic gonadotropin-producing hepatoblastoma and the latter from cerebral gigantism associated with hepatoma. These two different disorders are discussed on the common basis of rare association of malignant hepatic tumors with precocious sexual and / or somatic growth. The clinical manifestations, chemical abnormalities, and the radiologic findings are presented with a brief review of the literature

  20. Increasing abscisic acid levels by immunomodulation in barley grains induces precocious maturation without changing grain composition.

    Science.gov (United States)

    Staroske, Nicole; Conrad, Udo; Kumlehn, Jochen; Hensel, Götz; Radchuk, Ruslana; Erban, Alexander; Kopka, Joachim; Weschke, Winfriede; Weber, Hans

    2016-04-01

    Abscisic acid (ABA) accumulates in seeds during the transition to the seed filling phase. ABA triggers seed maturation, storage activity, and stress signalling and tolerance. Immunomodulation was used to alter the ABA status in barley grains, with the resulting transgenic caryopses responding to the anti-ABA antibody gene expression with increased accumulation of ABA. Calculation of free versus antibody-bound ABA reveals large excess of free ABA, increasing signficantly in caryopses from 10 days after fertilization. Metabolite and transcript profiling in anti-ABA grains expose triggered and enhanced ABA-functions such as transcriptional up-regulation of sucrose-to-starch metabolism, storage protein synthesis and ABA-related signal transduction. Thus, enhanced ABA during transition phases induces precocious maturation but negatively interferes with growth and development. Anti-ABA grains display broad constitutive gene induction related to biotic and abiotic stresses. Most of these genes are ABA- and/or stress-inducible, including alcohol and aldehyde dehydrogenases, peroxidases, chaperones, glutathione-S-transferase, drought- and salt-inducible proteins. Conclusively, ABA immunomodulation results in precocious ABA accumulation that generates an integrated response of stress and maturation. Repression of ABA signalling, occurring in anti-ABA grains, potentially antagonizes effects caused by overshooting production. Finally, mature grain weight and composition are unchanged in anti-ABA plants, although germination is somewhat delayed. This indicates that anti-ABA caryopses induce specific mechanisms to desensitize ABA signalling efficiently, which finally yields mature grains with nearly unchanged dry weight and composition. Such compensation implicates the enormous physiological and metabolic flexibilities of barley grains to adjust effects of unnaturally high ABA amounts in order to ensure and maintain proper grain development. © The Author 2016. Published by

  1. Spring Chinook Salmon Interactions Indices and Residual/Precocious Male Monitoring in the Upper Yakima Basin; Yakima/Klickitat Fisheries Project Monitoring and Evaluation, 2004-2005 Annual Report.

    Energy Technology Data Exchange (ETDEWEB)

    Pearsons, Todd N.; Johnson, Christopher L. (Washington Department of Fish and Wildlife, Olympia, WA); James, Brenda B. (Cascade Aquatics, Ellensburg, WA)

    2005-05-01

    This report examines some of the factors that can influence the success of supplementation, which is currently being tested in the Yakima Basin using upper Yakima stock of spring chinook salmon. Supplementation success in the Yakima Basin is defined relative to four topic areas: natural production, genetics, ecological interactions, and harvest (Busack et al. 1997). The success of spring chinook salmon supplementation in the Yakima Basin is dependent, in part, upon fish culture practices and favorable physical and biological conditions in the natural environment (Busack et al. 1997; James et al. 1999; Pearsons et al., 2003; Pearsons et al. 2004). Shortfalls in either of these two topics (i.e., failure in culturing many fish that have high long-term fitness or environmental conditions that constrain spring chinook salmon production) will cause supplementation success to be limited. For example, inadvertent selection or propagation of spring chinook that residualize or precocially mature may hinder supplementation success. Spring chinook salmon that residualize (do not migrate during the normal migration period) may have lower survival rates than migrants and, additionally, may interact with wild fish and cause unacceptable impacts to non-target taxa. Large numbers of precocials (nonanadromous spawners) may increase competition for females and significantly skew ratios of offspring sired by nonanadromous males, which could result in more nonanadromous spring chinook in future generations. Conditions in the natural environment may also limit the success of spring chinook supplementation. For example, intra or interspecific competition may constrain spring chinook salmon production. Spring chinook salmon juveniles may compete with each other for food or space or compete with other species that have similar ecological requirements. Monitoring of spring chinook salmon residuals, precocials, prey abundance, carrying capacity, and competition will help researchers

  2. Radiation induced mutation to develop dwarf and precocious lines of papaya

    International Nuclear Information System (INIS)

    Singh, K.; Prakash, Jai; Goswami, A.K.

    2014-01-01

    Papaya (Carica papaya L.) is one of the most important fruit cultivated throughout the tropical and subtropical regions of the country. Almost all the varieties of papaya developed either through selection or hybridization. As regards mutation breeding, very little work has been done in India. Only one variety PusaNanha has been developed through mutation breeding by treating the seed of papaya strain Pusa 1-15 with 15 Kr gamma rays. Mutation breeding is the most appropriate for improving one or two easily identifiable traits in an otherwise well accepted breeding lines or commercial variety. Dwarfness and earliness in flowering are important traits in high density planting as breeding objective for improving papaya varieties for high yield with medium size fruits and good fruit quality. With these objectives, seeds of the papaya P 7-2 were treated with gamma rays 0.1, 0.15, 0.2, 0.25 and 0.3 kGy. The control recorded maximum germination (68%). Among the other treatments maximum germination (64.25%) was recorded at 0.1 kGy. The germination percentage was observed to be least (45%) at 0.3 kGy. Minimum length of seedlings (8.5 cm) and diameter (3.92 mm) was recorded in treatment 0.1 kGy while maximum length (19.2 cm) and diameter (6.26 mm) was recorded in treatment 0.3 kGy after 30 days of sowing. Minimum height of the plant (79.24 cm) was recorded in treatment 0.1 kGy while maximum (112.20) in control. Minimum plant girth (33.40 cm) was measured in 0.3 kGy while maximum (44.34 cm) in 0.15 kGy treatment. Minimum height at first flower initiation (55.28 cm), days to flower initiation (78.28) and length of petiole (60.45 cm) was noted in treatment 0.1 kGy while maximum height at first flower initiation (78.2 cm), days to flower initiation (87.46) and length of petiole (68.24 cm) was found in control. Among treatments, maximum number (18) of fruit was counted in 0.3 kGy treatment while maximum weight of fruit (750 g) was recorded in control. Maximum TSS (10.6 °Brix) in

  3. Comparison of learning ability and memory retention in altricial (Bengalese finch, Lonchura striata var. domestica) and precocial (blue-breasted quail, Coturnix chinensis) birds using a color discrimination task.

    Science.gov (United States)

    Ueno, Aki; Suzuki, Kaoru

    2014-02-01

    The present study sought to assess the potential application of avian models with different developmental modes to studies on cognition and neuroscience. Six altricial Bengalese finches (Lonchura striata var. domestica), and eight precocial blue-breasted quails (Coturnix chinensis) were presented with color discrimination tasks to compare their respective faculties for learning and memory retention within the context of the two developmental modes. Tasks consisted of presenting birds with discriminative cues in the form of colored feeder lids, and birds were considered to have learned a task when 80% of their attempts at selecting the correctly colored lid in two consecutive blocks of 10 trials were successful. All of the finches successfully performed the required experimental tasks, whereas only half of the quails were able to execute the same tasks. In the learning test, finches required significantly fewer trials than quails to learn the task (finches: 13.5 ± 9.14 trials, quails: 45.8 ± 4.35 trials, P memory retention tests, which were conducted 45 days after the learning test, finches retained the ability to discriminate between colors correctly (95.0 ± 4.47%), whereas quails did not retain any memory of the experimental procedure and so could not be tested. These results suggested that altricial and precocial birds both possess the faculty for learning and retaining discrimination-type tasks, but that altricial birds perform better than precocial birds in both faculties. The present findings imply that developmental mode is an important consideration for assessing the suitability of bird species for particular experiments. © 2013 Japanese Society of Animal Science.

  4. Characterization of patients diagnosed with central precocious puberty starting treatment with leuprolide acetate, at the Hospital Nacional de Ninos in the period January 2004 to December 2009

    International Nuclear Information System (INIS)

    Viquez Viquez, Natalia

    2013-01-01

    Clinical characteristics and laboratory and cabinet findings (hormone levels, bone age, pelvic ultrasound) were determined in a sample of 39 patients diagnosed with central precocious puberty (CPP) who started treatment with leuprolide acetate (LPA). The cross-sectional observational study was developed at the Hospital Nacional de Ninos 'Dr. Carlos Saenz Herrera' during the period 2004 and 2009. The chronological age of patients with CPP was specified at the time of diagnosis and to start treatment with LPA. Epidemiological characteristics (sex, origin) were described in patients with CPP. Bone age with respect to chronological age was identified in patients with CPP. Sexual maturity of patients with CPP was established by the Tanner scale. The hormone levels of estrogen, testosterone, luteinizing hormone and follicle stimulating hormone were specified in patients with CPP. The etiology was determined in patients with CPP treated with LPA. The adverse effects of treatment with LPA were described. Anthropometric measurements were detailed. The heredo-familial antecedents of precocious puberty were established in patients with diagnosis of CPP. The size of the pelvic organs was evaluated by pelvic ultrasound [es

  5. An 11-month-old girl with central precocious puberty caused by hypothalamic hamartoma

    Directory of Open Access Journals (Sweden)

    Da Young Yoon

    2016-12-01

    Full Text Available Central precocious puberty (CPP is caused by premature activation of the hypothalamic-gonadal axis, and must be treated adequately. In particular, CPP that occurs at a relatively young age or in boys is likely to be caused by an organic lesion. Hypothalamic hamartoma (HH is the most common organic cause of CPP. The present case report describes an 11-month-old female infant who presented with vaginal bleeding and rapidly progressive secondary sex characteristics from the age of 6 months. She was diagnosed with CPP following the detection of HH via magnetic resonance imaging. The infant girl was successfully treated with gonadotropin-releasing hormone agonist. After 6 months, her breast had regressed and clinical and radiological follow-up demonstrated stable findings with no evidence of tumor growth or secondary sexual characteristics until the fourth year after the initiation of treatment. This patient is the one of the youngest infants presenting with CPP and HH in Korea; treatment was successful over a relatively long follow-up period.

  6. Factors that predict a positive response on gonadotropin-releasing hormone stimulation test for diagnosing central precocious puberty in girls

    Directory of Open Access Journals (Sweden)

    Junghwan Suh

    2013-12-01

    Full Text Available PurposeThe rapid increase in the incidence of precocious puberty in Korea has clinical and social significance. Gonadotropin-releasing hormone (GnRH stimulation test is required to diagnose central precocious puberty (CPP, however this test is expensive and time-consuming. This study aimed to identify factors that can predict a positive response to the GnRH stimulation test.MethodsClinical and laboratory parameters, including basal serum luteinizing hormone (LH, follicle-stimulating hormone (FSH, and estradiol (E2, were measured in 540 girls with clinical signs of CPP.ResultsTwo hundred twenty-nine of 540 girls with suspected CPP had a peak serum LH level higher than 5 IU/L (the CPP group. The CPP group had advanced bone age (P<0.001, accelerated yearly growth rate (P<0.001, increased basal levels of LH (P=0.02, FSH (P<0.001, E2 (P=0.001, and insulin-like growth factor-I levels (P<0.001 compared to the non-CPP group. In contrast, body weight (P<0.001 and body mass index (P<0.001 were lower in the CPP group. Although basal LH was significantly elevated in the CPP group compared to the non-CPP group, there was considerable overlap between the 2 groups. Cutoff values of basal LH (0.22 IU/L detected CPP with 87.8% sensitivity and 20.9% specificity.ConclusionNo single parameter can predict a positive response on the GnRH stimulation test with both high sensitivity and specificity. Therefore, multiple factors should be considered in evaluation of sexual precocity when deciding the timing of the GnRH stimulation test.

  7. Intervention levels in a precocious detection program for breast cancer and evaluation of four participant units; Niveles de intervencion en un programa de deteccion precoz del cancer de mama y evaluacion de cuatro unidades participantes

    Energy Technology Data Exchange (ETDEWEB)

    Carrera M, F.; Velazquez M, S.; Manzano M, F.J.; Sanchez S, J. [Hospital `Juan Ramon Jimenez` Ronda Norte s/n 21005. Huelva, Espana (Spain)

    1998-12-31

    It is presented the basis to make a cost benefit analysis for a breast cancer precocious detection program and consequently the keys for its optimization from the radiological point of view. Taking this as a reference it is made an exhaustive quality control to four mammographic unities which were participating or they were candidates to participate in a breast cancer precocious detection program. Also it is presented its results. It is followed the protocol for quality control in mammography in Spain obtaining values for the measurement of twelve interesting parameters. It should be maintained the standard breast dose about 1 mGy/ image. It should be available a 24 x 30 cm portacassete and considering the utilization of a single projection by breast. (Author)

  8. Spring Chinook Salmon Interactions Indices and Residual/Precocial Monitoring in the Upper Yakima Basin; Yakima/Klickitat Fisheries Project Monitoring and Evaluation, 2001-2002 Annual Report.

    Energy Technology Data Exchange (ETDEWEB)

    Pearsons, Todd N.; James, Brenda B.; Johnson, Christopher L. (Washington Department of Fish and Wildlife, Olympia, WA)

    2003-05-01

    This report examines some of the factors that can influence the success of supplementation, which is currently being tested in the Yakima Basin using upper Yakima stock of spring chinook salmon. Supplementation success in the Yakima Basin is defined relative to four topic areas: natural production, genetics, ecological interactions, and harvest (Busack et al. 1997). The success of spring chinook salmon supplementation in the Yakima Basin is dependent, in part, upon fish culture practices and favorable physical and biological conditions in the natural environment (Busack et al. 1997). Shortfalls in either of these two topics (i.e., failure in culturing many fish that have high long-term fitness or environmental conditions that constrain spring chinook salmon production) will cause supplementation success to be limited. For example, inadvertent selection or propagation of spring chinook that residualize or precocially mature may hinder supplementation success. Spring chinook salmon that residualize (do not migrate during the normal migration period) may have lower survival rates than migrants and, additionally, may interact with wild fish and cause unacceptable impacts to non-target taxa. Large numbers of precocials (nonanadromous spawners) may increase competition for females and significantly skew ratios of offspring sired by nonanadromous males, which could result in more nonanadromous spring chinook in future generations. Conditions in the natural environment may also limit the success of spring chinook supplementation. For example, intra or interspecific competition may constrain spring chinook salmon production. Spring chinook salmon juveniles may compete with each other for food or space or compete with other species that have similar ecological requirements. Monitoring of spring chinook salmon residuals, precocials, prey abundance, carrying capacity, and competition will help researchers interpret why supplementation is working or not working (Busack et al

  9. The effects of swimming exercise and dissolved oxygen on growth performance, fin condition and precocious maturation of early-rearing Atlantic salmon Salmo salar

    Science.gov (United States)

    Waldrop, Thomas; Summerfelt, Steven T.; Mazik, Patricia M.; Good, Christopher

    2018-01-01

    Swimming exercise, typically measured in body-lengths per second (BL/s), and dissolved oxygen (DO), are important environmental variables in fish culture. While there is an obvious physiological association between these two parameters, their interaction has not been adequately studied in Atlantic salmon Salmo salar. Because exercise and DO are variables that can be easily manipulated in modern aquaculture systems, we sought to assess the impact of these parameters, alone and in combination, on the performance, health and welfare of juvenile Atlantic salmon. In our study, Atlantic salmon fry were stocked into 12 circular 0.5 m3 tanks in a flow-through system and exposed to either high (1.5–2 BL/s) or low (exercise and DO concentration on growth, feed conversion, survival and fin condition. By study's end, both increased swimming speed and higher DO were independently associated with a statistically significant increase in growth performance (p exercise and dissolved oxygen at saturation during Atlantic salmon early rearing can result in improved growth performance and a lower incidence of precocious parr.

  10. Hes1-deficient mice show precocious differentiation of Paneth cells in the small intestine

    International Nuclear Information System (INIS)

    Suzuki, Katsumasa; Fukui, Hirokazu; Kayahara, Takahisa; Sawada, Mitsutaka; Seno, Hiroshi; Hiai, Hiroshi; Kageyama, Ryoichiro; Okano, Hideyuki; Chiba, Tsutomu

    2005-01-01

    We have previously shown that Hes1 is expressed both in putative epithelial stem cells just above Paneth cells and in the crypt base columnar cells between Paneth cells, while Hes1 is completely absent in Paneth cells. This study was undertaken to clarify the role of Hes1 in Paneth cell differentiation, using Hes1-knockout (KO) newborn (P0) mice. Electron microscopy revealed premature appearance of distinct cells containing cytoplasmic granules in the intervillous region in Hes1-KO P0 mice, whereas those cells were absent in wild-type (WT) P0 mice. In Hes1-KO P0 mice, the gene expressions of cryptdins, exclusively present in Paneth cells, were all enhanced compared with WT P0 mice. Immunohistochemistry demonstrated increased number of both lysozyme-positive and cryptdin-4-positive cells in the small intestinal epithelium of Hes1-KO P0 mice as compared to WT P0 mice. Thus, Hes1 appears to have an inhibitory role in Paneth cell differentiation in the small intestine

  11. Herbal medicine for idiopathic central precocious puberty: A protocol for a systematic review of controlled trials.

    Science.gov (United States)

    Lee, Hye Lim; Lee, Yoo Been; Choi, Jun-Yong; Lee, Ju Ah

    2018-03-01

    Herbal medicine is widely used in East Asia to treat idiopathic central precocious puberty (ICPP). Most of the available clinical trials that investigated herbal medicine for ICPP have been included in this review. This systematic review will assess the efficacy and safety of herbal medicine for ICPP. Eleven databases, including Asian databases, will be searched for studies conducted through 2018. We will include randomized controlled trials assessing herbal medicine for ICPP. The risk of bias will be evaluated using the Cochrane risk of bias assessment tool, and confidence in the cumulative evidence will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation instrument. This systematic review will be published in a peer-reviewed journal and disseminated both electronically and in print. The review will be updated to inform and guide health care practices. PROSPER 2018 CRD42018087988.

  12. Significance of determination of female sex hormones (E2, LH, FSH), insulin-like growth factor I (IGF-I) and leptin in girls with precocious puberty

    International Nuclear Information System (INIS)

    Huang Jianrong

    2004-01-01

    Objective: To investigate the diagnostic value of determination of serum levels of estradiol (E 2 ), luteinizing hormone (LH) and follicle stimulating hormone (FSH), insulin-like growth factor (IGF-I) and leptin in girls with idiopathic central precocious puberty (ICPP). Methods: Serum E 2 , LH, FSH, IGF-I (with chemiluminescence immunoassay) and leptin (with RIA) levels were determined in 35 girls with early development of breast as the sign of precocious puberty, of which, 15 was considered to be of the ICPP group and 20 of simple premature thelarche group (SPT). Criteria of diagnosis for ICPP were: peak LH value>12IU/L and LH/FSH>1 after GnRH stimulating test. Results: Serum E 2 , LH, FSH, IGF-I leptin levels in girls with ICPP were significantly higher than those in the girls with SPT (P 0.2 as the cut-off value for diagnosis of ICPP there would still be a positive rate of 86.6% suggesting that the diagnostic criteria might be set lower. Serum IGF-I levels were positively correlated to those of E 2 (r=0.47, P 2 and IGF-I. Conclusion: Determinations of serum E 2 , LH, FHS, IGF-I and leptin levels were helpful for the early diagnosis of ICPP. (author)

  13. Serum inhibin A and inhibin B in central precocious puberty before and during treatment with GnRH agonists

    DEFF Research Database (Denmark)

    Sehested, A; Andersson, A M; Müller, J

    2000-01-01

    both gonadotropins and estradiol levels become suppressed. We therefore investigated serum levels of inhibin A and inhibin B in girls with CPP at diagnosis and during treatment in order to test the hypothesis that inhibin secretion would increase and decrease in parallel with the activation......Serum levels of the gonadal hormones inhibin A and inhibin B are undetectable or low in prepubertal girls, and rise during puberty. In girls with central precocious puberty (CPP) the hypothalamic-pituitary-gonadal axis is prematurely activated, if the girl is thereafter treated with GnRH agonists...... and suppression of the hypothalamic-pituitary-gonadal axis. Serum levels of inhibin A and inhibin B were significantly (p 0.0005) elevated in 42 girls at diagnosis of CPP (inhibin A: 7 pg/ml (...

  14. Bacterial cells with improved tolerance to polyamines

    DEFF Research Database (Denmark)

    2017-01-01

    Provided are bacterial cells genetically modified to improve their tolerance to certain commodity chemicals, such as polyamines, and methods of preparing and using such bacterial cells for production of polyamines and other compounds.......Provided are bacterial cells genetically modified to improve their tolerance to certain commodity chemicals, such as polyamines, and methods of preparing and using such bacterial cells for production of polyamines and other compounds....

  15. Improved biolistic transfection of hair cells.

    Directory of Open Access Journals (Sweden)

    Hongyu Zhao

    Full Text Available Transient transfection of hair cells has proven challenging. Here we describe modifications to the Bio-Rad Helios Gene Gun that, along with an optimized protocol, improve transfection of bullfrog, chick, and mouse hair cells. The increased penetrating power afforded by our method allowed us to transfect mouse hair cells from the basal side, through the basilar membrane; this configuration protects hair bundles from damage during the procedure. We characterized the efficiency of transfection of mouse hair cells with fluorescently-tagged actin fusion protein using both the optimized procedure and a published procedure; while the efficiency of the two methods was similar, the morphology of transfected hair cells was improved with the new procedure. In addition, using the improved method, we were able to transfect hair cells in the bullfrog sacculus and chick cochlea for the first time. We used fluorescent-protein fusions of harmonin b (USH1C and PMCA2 (ATP2B2; plasma-membrane Ca(2+-ATPase isoform 2 to examine protein distribution in hair cells. While PMCA2-EGFP localization was similar to endogenous PMCA2 detected with antibodies, high levels of harmonin-EGFP were found at stereocilia tapers in bullfrog and chick, but not mouse; by contrast, harmonin-EGFP was concentrated in stereocilia tips in mouse hair cells.

  16. A novel splice mutation in the TP53 gene associated with Leydig cell tumor and primitive neuroectodermal tumor

    DEFF Research Database (Denmark)

    Stecher, Chalotte Willemann; Grønbaek, Kirsten; Hasle, Henrik

    2008-01-01

    A 20-month-old boy presented with precocious puberty due to a Leydig cell tumor, and at the age of 6 years with a primitive neuroectodermal brain-tumor (PNET). A novel splice site mutation of the TP53-gene, likely to be associated with a nonfunctional protein, was found in the proband, his father...

  17. Nuclear receptor TLX regulates cell cycle progression in neural stem cells of the developing brain.

    Science.gov (United States)

    Li, Wenwu; Sun, Guoqiang; Yang, Su; Qu, Qiuhao; Nakashima, Kinichi; Shi, Yanhong

    2008-01-01

    TLX is an orphan nuclear receptor that is expressed exclusively in vertebrate forebrains. Although TLX is known to be expressed in embryonic brains, the mechanism by which it influences neural development remains largely unknown. We show here that TLX is expressed specifically in periventricular neural stem cells in embryonic brains. Significant thinning of neocortex was observed in embryonic d 14.5 TLX-null brains with reduced nestin labeling and decreased cell proliferation in the germinal zone. Cell cycle analysis revealed both prolonged cell cycles and increased cell cycle exit in TLX-null embryonic brains. Increased expression of a cyclin-dependent kinase inhibitor p21 and decreased expression of cyclin D1 provide a molecular basis for the deficiency of cell cycle progression in embryonic brains of TLX-null mice. Furthermore, transient knockdown of TLX by in utero electroporation led to precocious cell cycle exit and differentiation of neural stem cells followed by outward migration. Together these results indicate that TLX plays an important role in neural development by regulating cell cycle progression and exit of neural stem cells in the developing brain.

  18. Bacterial cells with improved tolerance to polyols

    DEFF Research Database (Denmark)

    2017-01-01

    The present invention relates to bacterial cells genetically modified to improve their tolerance to certain commodity chemicals, such as diols and other polyols, and to methods of preparing and using such bacterial cells for production of polyols and other compounds.......The present invention relates to bacterial cells genetically modified to improve their tolerance to certain commodity chemicals, such as diols and other polyols, and to methods of preparing and using such bacterial cells for production of polyols and other compounds....

  19. Direct fuel cell product design improvement

    Energy Technology Data Exchange (ETDEWEB)

    Maru, H.C.; Farooque, M. [Energy Research Corp., Danbury, CT (United States)

    1996-12-31

    Significant milestones have been attained towards the technology development field testing and commercialization of direct fuel cell power plant since the 1994 Fuel Cell Seminar. Under a 5-year cooperative agreement with the Department of Energy signed in December 1994, Energy Research Corporation (ERC) has been developing the design for a MW-scale direct fuel cell power plant with input from previous technology efforts and the Santa Clara Demonstration Project. The effort encompasses product definition in consultation with the Fuel Cell Commercialization Group, potential customers, as well as extensive system design and packaging. Manufacturing process improvements, test facility construction, cell component scale up, performance and endurance improvements, stack engineering, and critical balance-of-plant development are also addressed. Major emphasis of this product design improvement project is on increased efficiency, compactness and cost reduction to establish a competitive place in the market. A 2.85 MW power plant with an efficiency of 58% and a footprint of 420 m{sup 2} has been designed. Component and subsystem testing is being conducted at various levels. Planning and preparation for verification of a full size prototype unit are in progress. This paper presents the results obtained since the last fuel cell seminar.

  20. Orbiter fuel cell improvement assessment

    International Nuclear Information System (INIS)

    Johnson, R.E.

    1981-08-01

    The history of fuel cells and the theory of fuel cells is given. Expressions for thermodynamic and electrical efficiencies are developed. The voltage losses due to electrode activation, ohmic resistance and ionic diffusion are discussed. Present limitations of the Orbiter Fuel Cell, as well as proposed enhancements, are given. These enhancements are then evaluated and recommendations are given for fuel cell enhancement both for short-range as well as long-range performance improvement. Estimates of reliability and cost savings are given for enhancements where possible

  1. Formação do enfermeiro para detecção precoce de desvios psicomotores em lactentes - Fortaleza, estado do Ceará, Brasil - DOI: 10.4025/actascihealthsci.v25i2.2230 Nurse formation for precocious detection of psychomotor deviations in suckling - Fortaleza, state of Ceará, Brazil - DOI: 10.4025/actascihealthsci.v25i2.2230

    Directory of Open Access Journals (Sweden)

    Maria Teresa Moreno Valdés

    2003-04-01

    Full Text Available Objetivou-se identificar a formação dos enfermeiros para detecção precoce dos desvios psicomotores em lactentes, os fatores que interferem na atuação profissional e elaborar um roteiro para subsidiá-lo. Trata-se de estudo exploratório-descritivo realizado em cinco Unidades do Programa de Saúde da Família (Fortaleza - CE. Foram entrevistados 17 enfermeiros que realizam consulta em puericultura. A coleta dos dados ocorreu de julho a outubro de 2001, por meio de observação e entrevista semi - estruturada. Os dados foram analisados, discutidos e apresentados por meio de Tabelas. Onze enfermeiros consideram-se despreparados para a detecção precoce de tais desvios. Os obstáculos apontados foram: falta de treinamento, tempo reduzido para aperfeiçoamento e carga horária excessiva de trabalho. Os enfermeiros sugerem aperfeiçoamento profissional, associado à melhoria das condições de trabalho e aquisição de material didático e audiovisual para implementação de programas preventivos. Conclui-se ser necessária a implementação de um plano com ações que capacitem o enfermeiro para a detecção precoce desses desvios.This paper aimed to identify nurses formation for precocious detection of psychomotor deviations in suckling, the factors that interfere in their performance and to make a proposal of a schedule to subsidize them. Exploratory-descriptive study was carried out in five Units of Family Health Program, in the city of Fortaleza, state of Ceará, Brazil. Seventeen nurses who had accomplished consultation in puericulture were interviewed. Data were collected from July to October 2001, through observation and semi-structured interview. The data were analyzed, debated, and presented through tables. Eleven nurses considered themselves unprepared for precocious identification of such deviations. The obstacles pointed were: insufficient training, reduced time to improvement and excessive work routine. The nurses suggest the

  2. New protocetid whale from the middle eocene of pakistan: birth on land, precocial development, and sexual dimorphism.

    Directory of Open Access Journals (Sweden)

    Philip D Gingerich

    Full Text Available BACKGROUND: Protocetidae are middle Eocene (49-37 Ma archaeocete predators ancestral to later whales. They are found in marine sedimentary rocks, but retain four legs and were not yet fully aquatic. Protocetids have been interpreted as amphibious, feeding in the sea but returning to land to rest. METHODOLOGY/PRINCIPAL FINDINGS: Two adult skeletons of a new 2.6 meter long protocetid, Maiacetus inuus, are described from the early middle Eocene Habib Rahi Formation of Pakistan. M. inuus differs from contemporary archaic whales in having a fused mandibular symphysis, distinctive astragalus bones in the ankle, and a less hind-limb dominated postcranial skeleton. One adult skeleton is female and bears the skull and partial skeleton of a single large near-term fetus. The fetal skeleton is positioned for head-first delivery, which typifies land mammals but not extant whales, evidence that birth took place on land. The fetal skeleton has permanent first molars well mineralized, which indicates precocial development at birth. Precocial development, with attendant size and mobility, were as critical for survival of a neonate at the land-sea interface in the Eocene as they are today. The second adult skeleton is the most complete known for a protocetid. The vertebral column, preserved in articulation, has 7 cervicals, 13 thoracics, 6 lumbars, 4 sacrals, and 21 caudals. All four limbs are preserved with hands and feet. This adult is 12% larger in linear dimensions than the female skeleton, on average, has canine teeth that are 20% larger, and is interpreted as male. Moderate sexual dimorphism indicates limited male-male competition during breeding, which in turn suggests little aggregation of food or shelter in the environment inhabited by protocetids. CONCLUSIONS/SIGNIFICANCE: Discovery of a near-term fetus positioned for head-first delivery provides important evidence that early protocetid whales gave birth on land. This is consistent with skeletal

  3. How innate is locomotion in precocial animals? A study on the early development of spatio-temporal gait variables and gait symmetry in piglets.

    Science.gov (United States)

    Vanden Hole, Charlotte; Goyens, Jana; Prims, Sara; Fransen, Erik; Ayuso Hernando, Miriam; Van Cruchten, Steven; Aerts, Peter; Van Ginneken, Chris

    2017-08-01

    Locomotion is one of the most important ecological functions in animals. Precocial animals, such as pigs, are capable of independent locomotion shortly after birth. This raises the question whether coordinated movement patterns and the underlying muscular control in these animals is fully innate or whether there still exists a rapid maturation. We addressed this question by studying gait development in neonatal pigs through the analysis of spatio-temporal gait characteristics during locomotion at self-selected speed. To this end, we made video recordings of piglets walking along a corridor at several time points (from 0 h to 96 h). After digitization of the footfalls, we analysed self-selected speed and spatio-temporal characteristics (e.g. stride and step lengths, stride frequency and duty factor) to study dynamic similarity, intralimb coordination and interlimb coordination. To assess the variability of the gait pattern, left-right asymmetry was studied. To distinguish neuromotor maturation from effects caused by growth, both absolute and normalized data (according to the dynamic similarity concept) were included in the analysis. All normalized spatio-temporal variables reached stable values within 4 h of birth, with most of them showing little change after the age of 2 h. Most asymmetry indices showed stable values, hovering around 10%, within 8 h of birth. These results indicate that coordinated movement patterns are not entirely innate, but that a rapid neuromotor maturation, potentially also the result of the rearrangement or recombination of existing motor modules, takes place in these precocial animals. © 2017. Published by The Company of Biologists Ltd.

  4. Bacterial cells with improved tolerance to isobutyric acid

    DEFF Research Database (Denmark)

    2017-01-01

    Bacterial cells genetically modified to improve their tolerance to certain commodity chemicals, such as isobutyric acid and related compounds, and methods of preparing and using such bacterial cells for production of isobutyric acid and related compounds.......Bacterial cells genetically modified to improve their tolerance to certain commodity chemicals, such as isobutyric acid and related compounds, and methods of preparing and using such bacterial cells for production of isobutyric acid and related compounds....

  5. Exploring viral reservoir: The combining approach of cell sorting and droplet digital PCR.

    Science.gov (United States)

    Gibellini, Lara; Pecorini, Simone; De Biasi, Sara; Pinti, Marcello; Bianchini, Elena; De Gaetano, Anna; Digaetano, Margherita; Pullano, Rosalberta; Lo Tartaro, Domenico; Iannone, Anna; Mussini, Cristina; Cossarizza, Andrea; Nasi, Milena

    2018-02-01

    Combined antiretroviral therapy (cART) blocks different steps of HIV replication and maintains plasma viral RNA at undetectable levels. The virus can remain in long-living cells and create a reservoir where HIV can restart replicating after cART discontinuation. A persistent viral production triggers and maintains a persistent immune activation, which is a well-known feature of chronic HIV infection, and contributes either to precocious aging, or to the increased incidence of morbidity and mortality of HIV positive patients. The new frontier of the treatment of HIV infection is nowadays eradication of the virus from all host cells and tissues. For this reason, it is crucial to have a clear and precise idea of where the virus hides, and which are the cells that keep it silent. Important efforts have been made to improve the detection of viral reservoirs, and new techniques are now giving the opportunity to characterize viral reservoirs. Among these techniques, a strategic approach based upon cell sorting and droplet digital PCR (ddPCR) is opening new horizons and opportunities of research. This review provides an overview of the methods that combine cell sorting and ddPCR for the quantification of HIV DNA in different cell types, and for the detection of its maintenance. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Spring Chinook Salmon Interactions Indices and Residual/Precocial Monitoring in the Upper Yakima Basin; Yakima/Klickitat Fisheries Project Monitoring and Evaluation Report 5 of 7, 2003-2004 Annual Report.

    Energy Technology Data Exchange (ETDEWEB)

    Pearsons, Todd N.; Johnson, Christopher L.; James, Brenda B. (Washington Department of Fish and Wildlife, Olympia, WA)

    2004-05-01

    This report examines some of the factors that can influence the success of supplementation, which is currently being tested in the Yakima Basin using upper Yakima stock of spring chinook salmon. Supplementation success in the Yakima Basin is defined relative to four topic areas: natural production, genetics, ecological interactions, and harvest (Busack et al. 1997). The success of spring chinook salmon supplementation in the Yakima Basin is dependent, in part, upon fish culture practices and favorable physical and biological conditions in the natural environment (Busack et al. 1997; James et al. 1999; Pearsons et al., 2003). Shortfalls in either of these two topics (i.e., failure in culturing many fish that have high long-term fitness or environmental conditions that constrain spring chinook salmon production) will cause supplementation success to be limited. For example, inadvertent selection or propagation of spring chinook that residualize or precocially mature may hinder supplementation success. Spring chinook salmon that residualize (do not migrate during the normal migration period) may have lower survival rates than migrants and, additionally, may interact with wild fish and cause unacceptable impacts to non-target taxa. Large numbers of precocials (nonanadromous spawners) may increase competition for females and significantly skew ratios of offspring sired by nonanadromous males, which could result in more nonanadromous spring chinook in future generations. Conditions in the natural environment may also limit the success of spring chinook supplementation. For example, intra or interspecific competition may constrain spring chinook salmon production. Spring chinook salmon juveniles may compete with each other for food or space or compete with other species that have similar ecological requirements. Monitoring of spring chinook salmon residuals, precocials, prey abundance, carrying capacity, and competition will help researchers interpret why supplementation

  7. Strategies to improve homing of mesenchymal stem cells for greater efficacy in stem cell therapy.

    Science.gov (United States)

    Naderi-Meshkin, Hojjat; Bahrami, Ahmad Reza; Bidkhori, Hamid Reza; Mirahmadi, Mahdi; Ahmadiankia, Naghmeh

    2015-01-01

    Stem/progenitor cell-based therapeutic approach in clinical practice has been an elusive dream in medical sciences, and improvement of stem cell homing is one of major challenges in cell therapy programs. Stem/progenitor cells have a homing response to injured tissues/organs, mediated by interactions of chemokine receptors expressed on the cells and chemokines secreted by the injured tissue. For improvement of directed homing of the cells, many techniques have been developed either to engineer stem/progenitor cells with higher amount of chemokine receptors (stem cell-based strategies) or to modulate the target tissues to release higher level of the corresponding chemokines (target tissue-based strategies). This review discusses both of these strategies involved in the improvement of stem cell homing focusing on mesenchymal stem cells as most frequent studied model in cellular therapies. © 2014 International Federation for Cell Biology.

  8. Stem Cell Therapy to Improve Burn Wound Healing

    Science.gov (United States)

    2017-03-01

    Award Number: W81XWH-13-2-0024 TITLE: Stem Cell Therapy to Improve Burn Wound Healing PRINCIPAL INVESTIGATOR: Carl Schulman, MD, PhD, MSPH...NUMBER Stem Cell Therapy to Improve Burn Wound Healing 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Carl Schulman, MD, PhD, MSPH...treatments, steroid injections, and compression garments. Mesenchymal stem cells (MSC’s) have been used in a variety of clinical applications to repair

  9. The Stimulatory Effect of Cerebral Intraventricular Injection of cNPY on Precocial Feeding Behavior in Neonatal Chicks (Gallus domesticus.

    Directory of Open Access Journals (Sweden)

    Guiqian Chen

    Full Text Available Neuropeptide Y (NPY is one of the most potent stimulants of food intake in many animals. Most of the supporting evidence for the effects of NPY has been gathered in mammalian species using porcine NPY. To investigate the effects of NPY on precocial feeding initiation in chicks, we firstly used chicken NPY (cNPY to study its role in food intake and spontaneous activities in 3-day-old male chicks. Food intake was monitored at different times after intracerebroventricular (ICV injection of cNPY (2.5, 5.0 or 10.0 μg/10 μL and anti-cNPY antibody (anti-cNPY (1:9000, 1:3000 or 1:1000 in dilution. cNPY given at different doses significantly increased food intake at 30 min, 60 min, 90 min and 120 min after injection. Chicks treated with 5.0 μg/10 μL of cNPY showed a maximal 4.48 fold increase in food intake comparing to the control at 30 min. There is still more than 2 fold increase in food intake at 120 min after injection of cNPY. Food intake was significantly inhibited by a single ICV injection of anti-cNPY diluted to 1:9000 (60% inhibition, 1:3000 (92% inhibition, and 1:1000 (95% inhibition at 30 min with 1:1000 being the maximally effective concentration. The inhibitory effects of anti-cNPY (diluted to1:9000, 1:3000, 1:1000 at 120 min post ICV injection were 22%, 42% and 46%, respectively. But ICV of anti-cNPY (1:3000 in dilution did not block the orexigenic effect of 2.5 μg/10 μL of cNPY. ICV injection of different concentrations of cNPY increases locomotor activity in a dose-dependent manner while ICV anti-cNPY greatly decreased the distance moved by each chick compared to control groups. Taken together, our results demonstrated that cNPY has a promoting effect on chick food intake and locomotor activity, and that endogenous cNPY might play a positive role in regulating precocial feeding behavior in newly hatched chicks.

  10. Improved endothelial cell seeding with cultured cells and fibronectin-coated grafts

    International Nuclear Information System (INIS)

    Seeger, J.M.; Klingman, N.

    1985-01-01

    A possible approach to the low seeding efficiency of endothelial cells into prosthetic grafts is to increase the number of cells to be seeded in cell culture and improve seeding efficiency by graft precoating with fibronectin. The effect of cell culture on cell adhesion is unknown, however, and fibronectin also binds fibrin, which may increase the thrombogenicity of the graft luminal surface. To investigate these questions, freshly harvested canine jugular vein endothelial cells from six animals and similar cells harvested from six primary and eight secondary cell cultures were labeled with 111 Indium and seeded into 5 cm, 4 mm PTFE grafts coated with fibronectin, using similar uncoated PTFE grafts as controls. Platelet accumulation and distribution on six similar coated and uncoated grafts placed in canine carotid, external jugular arterial venous shunts for 2 hr were also determined using autogenous 111 Indium-labeled platelets. Significant differences between group means were determined using the paired Student's t test. Results reveal that seeding efficiency is significantly better in all groups of coated grafts compared to uncoated grafts (P less than 0.01). Cells derived from cell culture also had significantly higher seeding efficiencies than freshly harvested cells when seeded into coated grafts (P less than 0.05) and tended to have higher seeding efficiencies than harvested cells when seeded into uncoated grafts (P = 0.53). Fibronectin coating increased mean platelet accumulation on the entire graft luminal surface, but not to a statistically significant degree (P greater than 0.1). Whether this increased seeding efficiency will improve graft endothelialization remains to be investigated

  11. Improved photovoltaic cells and electrodes

    Science.gov (United States)

    Skotheim, T.A.

    1983-06-29

    Improved photovoltaic cells and electrodes for use therein, particularly electrodes employing amorphous silicon or polyacetylene coating are produced by a process which includes filling pinholes or porous openings in the coatings by electrochemical oxidation of selected monomers to deposit insulating polymer in the openings.

  12. VEGF improves survival of mesenchymal stem cells in infarcted hearts

    International Nuclear Information System (INIS)

    Pons, Jennifer; Huang Yu; Arakawa-Hoyt, Janice; Washko, Daniel; Takagawa, Junya; Ye, Jianqin; Grossman, William; Su Hua

    2008-01-01

    Bone marrow-derived mesenchymal stem cells (MSC) are a promising source for cell-based treatment of myocardial infarction (MI), but existing strategies are restricted by low cell survival and engraftment. We examined whether vascular endothelial growth factor (VEGF) improve MSC viability in infracted hearts. We found long-term culture increased MSC-cellular stress: expressing more cell cycle inhibitors, p16 INK , p21 and p19 ARF . VEGF treatment reduced cellular stress, increased pro-survival factors, phosphorylated-Akt and Bcl-xL expression and cell proliferation. Co-injection of MSCs with VEGF to MI hearts increased cell engraftment and resulted in better improvement of cardiac function than that injected with MSCs or VEGF alone. In conclusion, VEGF protects MSCs from culture-induce cellular stress and improves their viability in ischemic myocardium, which results in improvements of their therapeutic effect for the treatment of MI

  13. Olfactory granule cell development in normal and hyperthyroid rats.

    Science.gov (United States)

    Brunjes, P C; Schwark, H D; Greenough, W T

    1982-10-01

    Dendritic development was examined in olfactory bulbs of both normal 7-, 14-, 21- and 60-day-old rats and littermates treated on postnatal days 1-4 with 1 microgram/g body weight of L-thyroxine sodium. Tissue was processed via the Golgi-Cox technique and subjected to quantitative analyses of mitral and internal layer granule cell development. These populations of granule cells were selected because their pattern of late proliferation suggested potentially greater susceptibility to postnatal hormonal alterations. Although neonatal hyperthyroidism induces widespread acceleration of maturation, including precocious chemosensitivity, granule cell development was unaffected relative to littermate controls. Both normal and hyperthyroid groups exhibited an inverted U-shaped pattern of cellular development, with rapid dendritic dendritic growth and expansion occurring during the earliest ages tested, but with loss of processes and dendritic field size occurring after day 21.

  14. Improvement on LiFePO4 Cell Balancing Algorithm

    OpenAIRE

    Vencislav C. Valchev; Plamen V. Yankov; Dimo D. Stefanov

    2018-01-01

    The paper presents improvement on operation time of cell balancing algorithm compared to conventional multiple cell LiFePO4 charge methodology. A flowchart is synthesised to explain the main steps of the software design, which afterwards is implemented in a microcontroller. Experimental results are provided to clarify the transition between charge and balance process. Graphical data for a voltage equalization of eight cells is presented to verify the proposed improvement.

  15. Trehalose improves cell proliferation and dehydration tolerance of human HaCaT cells

    Directory of Open Access Journals (Sweden)

    Lee Kyung Eun

    2015-01-01

    Full Text Available Trehalose is a disaccharide molecule that serves as a natural osmotic regulator in halophilic microorganisms and plants but not in mammals. We observed that human HaCaT cells supplied with trehalose improved cell proliferation and extended viability under dehydration. In HaCaT cells, in response to increasing concentrations of exogenous trehalose, the levels of heat shock protein (HSP 70 increased and matrix metalloproteinase (MMP 1 decreased. Proteome analysis of trehalose-treated HaCaT cells revealed remarkable increases in the levels of proteins involved in cell signaling and the cell cycle, including p21 activated kinase I, Sec I family domain protein and elongation factor G. Moreover, the proteins for cell stress resistance, tryptophan hydroxylase, serine/cysteine proteinase inhibitors and vitamin D receptors were also increased. In addition, the proteins responsible for the maintenance of the cytoskeleton and cellular structures including procollagen-lysine dioxygenase, vinculin and ezrin were increased. Proteomic data revealed that trehalose affected HaCaT cells by inducing the proteins involved in cell proliferation. These results suggest that trehalose improves the proliferation and dehydration tolerance of HaCaT cells by inducing proteins involved in cell growth and dehydration protection.

  16. Recurrent ovarian Sertoli?Leydig cell tumor in a child with Peutz?Jeghers syndrome

    OpenAIRE

    Bellfield, Edward J.; Alemzadeh, Ramin

    2016-01-01

    We present a female child with Peutz?Jeghers syndrome (PJS) with a recurrent ovarian Sertoli?Leydig cell tumor (SLCT). SLCTs are relatively rare sex cord neoplasms that can occur in PJS. The patient was an African-American female who first presented at the age of 3 years with precocious puberty, and then at the age of 17 years with abdominal pain and irregular menses. In each case, she had resection of the mass, which included oophorectomy. To our knowledge, this is the first reported case in...

  17. Improvement on LiFePO4 Cell Balancing Algorithm

    Directory of Open Access Journals (Sweden)

    Vencislav C. Valchev

    2018-02-01

    Full Text Available The paper presents improvement on operation time of cell balancing algorithm compared to conventional multiple cell LiFePO4 charge methodology. A flowchart is synthesised to explain the main steps of the software design, which afterwards is implemented in a microcontroller. Experimental results are provided to clarify the transition between charge and balance process. Graphical data for a voltage equalization of eight cells is presented to verify the proposed improvement.

  18. A missense mutation in MKRN3 in a Danish girl with central precocious puberty and her brother with early puberty

    DEFF Research Database (Denmark)

    Känsäkoski, Johanna; Raivio, Taneli; Juul, Anders

    2015-01-01

    BACKGROUND: Idiopathic central precocious puberty (ICPP) results from the premature reactivation of the hypothalamic-pituitary-gonadal axis leading to development of secondary sexual characteristics prior to 8 y in girls or 9 y in boys. Since the initial discovery of mutations in the maternally...... hypothalamic complementary DNA (cDNA) was investigated by PCR. RESULTS: One paternally inherited rare variant, c.1034G>A (p.Arg345His), was identified in one girl with ICPP and in her brother with early puberty. The variant is predicted to be deleterious by three different in silico prediction programs....... Expression of MKRN3 was confirmed in adult human hypothalamus. CONCLUSION: Our results are in line with previous studies in which paternally inherited MKRN3 mutations have been found both in males and in females with ICPP or early puberty. Our report further expands the set of MKRN3 mutations identified...

  19. Performance improvement of silicon solar cells by nanoporous silicon coating

    Directory of Open Access Journals (Sweden)

    Dzhafarov T. D.

    2012-04-01

    Full Text Available In the present paper the method is shown to improve the photovoltaic parameters of screen-printed silicon solar cells by nanoporous silicon film formation on the frontal surface of the cell using the electrochemical etching. The possible mechanisms responsible for observed improvement of silicon solar cell performance are discussed.

  20. Improved Activation toward Primary Colorectal Cancer Cells by Antigen-Specific Targeting Autologous Cytokine-Induced Killer Cells

    Directory of Open Access Journals (Sweden)

    Claudia Schlimper

    2012-01-01

    Full Text Available Adoptive therapy of malignant diseases with cytokine-induced killer (CIK cells showed promise in a number of trials; the activation of CIK cells from cancer patients towards their autologous cancer cells still needs to be improved. Here, we generated CIK cells ex vivo from blood lymphocytes of colorectal cancer patients and engineered those cells with a chimeric antigen receptor (CAR with an antibody-defined specificity for carcinoembryonic antigen (CEA. CIK cells thereby gained a new specificity as defined by the CAR and showed increase in activation towards CEA+ colon carcinoma cells, but less in presence of CEA− cells, indicated by increased secretion of proinflammatory cytokines. Redirected CIK activation was superior by CAR-mediated CD28-CD3ζ than CD3ζ signaling only. CAR-engineered CIK cells from colon carcinoma patients showed improved activation against their autologous, primary carcinoma cells from biopsies resulting in more efficient tumour cell lysis. We assume that adoptive therapy with CAR-modified CIK cells shows improved selectivity in targeting autologous tumour lesions.

  1. Cloning higher plants from aseptically cultured tissues and cells

    Science.gov (United States)

    Krikorian, A. D.

    1982-01-01

    A review of aseptic culture methods for higher plants is presented, which focuses on the existing problems that limit or prevent the full realization of cloning plants from free cells. It is shown that substantial progress in clonal multiplication has been made with explanted stem tips or lateral buds which can be stimulated to produce numerous precocious axillary branches. These branches can then be separated or subdivided and induced to root in order to yield populations of genetically and phenotypically uniorm plantlets. Similarly, undifferentiated calluses can sometimes be induced to form shoots and/or roots adventitiously. Although the cell culture techniques required to produce somatic embryos are presently rudimentary, steady advances are being made in learning how to stimulate formation of somatic or adventive embryos from totipotent cells grown in suspension cultures. It is concluded that many problems exist in the producing and growing of totipotent or morphogenetically competent cell suspensions, but the potential benefits are great.

  2. Telomere Length Reprogramming in Embryos and Stem Cells

    Directory of Open Access Journals (Sweden)

    Keri Kalmbach

    2014-01-01

    Full Text Available Telomeres protect and cap linear chromosome ends, yet these genomic buffers erode over an organism’s lifespan. Short telomeres have been associated with many age-related conditions in humans, and genetic mutations resulting in short telomeres in humans manifest as syndromes of precocious aging. In women, telomere length limits a fertilized egg’s capacity to develop into a healthy embryo. Thus, telomere length must be reset with each subsequent generation. Although telomerase is purportedly responsible for restoring telomere DNA, recent studies have elucidated the role of alternative telomeres lengthening mechanisms in the reprogramming of early embryos and stem cells, which we review here.

  3. Boys with precocious or early puberty: incidence of pathological brain magnetic resonance imaging findings and factors related to newly developed brain lesions

    Directory of Open Access Journals (Sweden)

    Keun Hee Choi

    2013-12-01

    Full Text Available PurposeBrain magnetic resonance imaging (MRI findings and factors predictive of pathological brain lesions in boys with precocious puberty (PP or early puberty (EP were investigated.MethodsSixty-one boys with PP or EP who had brain MRI performed were included. PP was classified into the central or peripheral type. Brain MRI findings were categorized into group I (pathological brain lesion known to cause puberty; newly diagnosed [group Ia] or previously diagnosed [group Ib]; group II (brain lesion possibly related to puberty; and group III (incidental or normal findings. Medical history, height, weight, hormone test results, and bone age were reviewed.ResultsBrain lesions in groups I and II were detected in 17 of 23 boys (74% with central PP, 9 of 30 boys (30% with EP, and 7 of 8 boys (88% with peripheral PP. All brain lesions in boys with peripheral PP were germ cell tumors (GCT, and 3 lesions developed later during follow-up. Group I showed earlier pubertal onset (P<0.01 and greater bone age advancement (P<0.05 than group III. Group III had lower birth weight and fewer neurological symptoms than "Ia and II" (all P<0.05.ConclusionEarlier onset of puberty, greater bone age advancement, and/or neurological symptoms suggested a greater chance of pathological brain lesions in boys with central PP or EP. All boys with peripheral PP, even those with normal initial MRI findings, should be evaluated for the emergence of GCT during follow-up.

  4. PRMT5 is essential for the maintenance of chondrogenic progenitor cells in the limb bud.

    Science.gov (United States)

    Norrie, Jacqueline L; Li, Qiang; Co, Swanie; Huang, Bau-Lin; Ding, Ding; Uy, Jann C; Ji, Zhicheng; Mackem, Susan; Bedford, Mark T; Galli, Antonella; Ji, Hongkai; Vokes, Steven A

    2016-12-15

    During embryonic development, undifferentiated progenitor cells balance the generation of additional progenitor cells with differentiation. Within the developing limb, cartilage cells differentiate from mesodermal progenitors in an ordered process that results in the specification of the correct number of appropriately sized skeletal elements. The internal pathways by which these cells maintain an undifferentiated state while preserving their capacity to differentiate is unknown. Here, we report that the arginine methyltransferase PRMT5 has a crucial role in maintaining progenitor cells. Mouse embryonic buds lacking PRMT5 have severely truncated bones with wispy digits lacking joints. This novel phenotype is caused by widespread cell death that includes mesodermal progenitor cells that have begun to precociously differentiate into cartilage cells. We propose that PRMT5 maintains progenitor cells through its regulation of Bmp4 Intriguingly, adult and embryonic stem cells also require PRMT5 for maintaining pluripotency, suggesting that similar mechanisms might regulate lineage-restricted progenitor cells during organogenesis. © 2016. Published by The Company of Biologists Ltd.

  5. Squamous cell carcinoma complicating an hereditary epidermo-lysis bullosa

    International Nuclear Information System (INIS)

    Mseddi, M.; Turki, H.; Marrekchi, S.; Abdelmaksoud, W.; Masmoudi, A.; Bouassida, S.; Zahaf, A.

    2004-01-01

    The dystrophic form of hereditary epidermo-lysis bullosa is associated with an increased frequency of squamous cell carcinoma. We report a new case. An 18-year-old patient, carrying a Hallopeau Siemens hereditary epidermo-lysis bullosa, presented a subcutaneous nodular lesion, for 1 year that ulcerated and budded with inguinal lymphadenopathy. The histological study ted to the conclusion of a well differentiated squamous cell carcinoma. The patient was treated surgically. Tumor and metastatic lymph nodes were excised. A radiotherapy was decided but the postoperative course was fatal due to an infection and to a deterioration of her general condition. Squamous cell carcinoma frequently occurs on the cicatricial lesion of hereditary epidermo-lysis bullosa and usually affects males with recessive hereditary epidermo-lysis bullosa. Metastases are frequent, precocious and multiple. The treatment may be surgical. The particularities of our observation are the young age of patient and the localization. (author)

  6. IMHEX fuel cell repeat component manufacturing continuous improvement accomplishments

    Energy Technology Data Exchange (ETDEWEB)

    Jakaitis, L.A.; Petraglia, V.J.; Bryson, E.S. [M-C Power Corp., Burr Ridge, IL (United States)] [and others

    1996-12-31

    M-C Power is taking a power generation technology that has been proven in the laboratory and is making it a commercially competitive product. There are many areas in which this technology required scale up and refinement to reach the market entry goals for the IMHEX{reg_sign} molten carbonate fuel cell power plant. One of the primary areas that needed to be addressed was the manufacturing of the fuel cell stack. Up to this point, the fuel cell stack and associated components were virtually hand made for each system to be tested. M-C Power has now continuously manufactured the repeat components for three 250 kW stacks. M-C Power`s manufacturing strategy integrated both evolutionary and revolutionary improvements into its comprehensive commercialization effort. M-C Power`s objectives were to analyze and continuously improve stack component manufacturing and assembly techniques consistent with established specifications and commercial scale production requirements. Evolutionary improvements are those which naturally occur as the production rates are increased and experience is gained. Examples of evolutionary (learning curve) improvements included reducing scrap rates and decreasing raw material costs by buying in large quantities. Revolutionary improvements result in significant design and process changes to meet cost and performance requirements of the market entry system. Revolutionary changes often involve identifying new methods and developing designs to accommodate the new process. Based upon our accomplishments, M-C Power was able to reduce the cost of continuously manufactured fuel cell repeat components from the first to third 250 kW stack by 63%. This paper documents the continuous improvement accomplishments realized by M-C Power during IMHEX{reg_sign} fuel cell repeat component manufacturing.

  7. Genome-Nuclear Lamina Interactions Regulate Cardiac Stem Cell Lineage Restriction.

    Science.gov (United States)

    Poleshko, Andrey; Shah, Parisha P; Gupta, Mudit; Babu, Apoorva; Morley, Michael P; Manderfield, Lauren J; Ifkovits, Jamie L; Calderon, Damelys; Aghajanian, Haig; Sierra-Pagán, Javier E; Sun, Zheng; Wang, Qiaohong; Li, Li; Dubois, Nicole C; Morrisey, Edward E; Lazar, Mitchell A; Smith, Cheryl L; Epstein, Jonathan A; Jain, Rajan

    2017-10-19

    Progenitor cells differentiate into specialized cell types through coordinated expression of lineage-specific genes and modification of complex chromatin configurations. We demonstrate that a histone deacetylase (Hdac3) organizes heterochromatin at the nuclear lamina during cardiac progenitor lineage restriction. Specification of cardiomyocytes is associated with reorganization of peripheral heterochromatin, and independent of deacetylase activity, Hdac3 tethers peripheral heterochromatin containing lineage-relevant genes to the nuclear lamina. Deletion of Hdac3 in cardiac progenitor cells releases genomic regions from the nuclear periphery, leading to precocious cardiac gene expression and differentiation into cardiomyocytes; in contrast, restricting Hdac3 to the nuclear periphery rescues myogenesis in progenitors otherwise lacking Hdac3. Our results suggest that availability of genomic regions for activation by lineage-specific factors is regulated in part through dynamic chromatin-nuclear lamina interactions and that competence of a progenitor cell to respond to differentiation signals may depend upon coordinated movement of responding gene loci away from the nuclear periphery. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Improved lithium-vanadium pentoxide cell and comparison with a lithium-thionyl chloride cell

    Energy Technology Data Exchange (ETDEWEB)

    Voorn, G.

    1985-01-15

    This paper describes a programme of experiments conducted to assess the effects of: (a) diluting the electrolyte in lithium-vanadium pentoxide cells; (b) optimizing the volume of electrolyte per unit cathode mass. This programme led to the development of an improved cell, the performance of which is compared with that of a lithium-thionyl chloride cell of similar configuration.

  9. An improved ghost-cell immersed boundary method for compressible flow simulations

    KAUST Repository

    Chi, Cheng

    2016-05-20

    This study presents an improved ghost-cell immersed boundary approach to represent a solid body in compressible flow simulations. In contrast to the commonly used approaches, in the present work ghost cells are mirrored through the boundary described using a level-set method to farther image points, incorporating a higher-order extra/interpolation scheme for the ghost cell values. A sensor is introduced to deal with image points near the discontinuities in the flow field. Adaptive mesh refinement (AMR) is used to improve the representation of the geometry efficiently in the Cartesian grid system. The improved ghost-cell method is validated against four test cases: (a) double Mach reflections on a ramp, (b) smooth Prandtl-Meyer expansion flows, (c) supersonic flows in a wind tunnel with a forward-facing step, and (d) supersonic flows over a circular cylinder. It is demonstrated that the improved ghost-cell method can reach the accuracy of second order in L1 norm and higher than first order in L∞ norm. Direct comparisons against the cut-cell method demonstrate that the improved ghost-cell method is almost equally accurate with better efficiency for boundary representation in high-fidelity compressible flow simulations. Copyright © 2016 John Wiley & Sons, Ltd.

  10. Multispectral fingerprinting for improved in vivo cell dynamics analysis

    Directory of Open Access Journals (Sweden)

    Cooper Cameron HJ

    2010-09-01

    Full Text Available Abstract Background Tracing cell dynamics in the embryo becomes tremendously difficult when cell trajectories cross in space and time and tissue density obscure individual cell borders. Here, we used the chick neural crest (NC as a model to test multicolor cell labeling and multispectral confocal imaging strategies to overcome these roadblocks. Results We found that multicolor nuclear cell labeling and multispectral imaging led to improved resolution of in vivo NC cell identification by providing a unique spectral identity for each cell. NC cell spectral identity allowed for more accurate cell tracking and was consistent during short term time-lapse imaging sessions. Computer model simulations predicted significantly better object counting for increasing cell densities in 3-color compared to 1-color nuclear cell labeling. To better resolve cell contacts, we show that a combination of 2-color membrane and 1-color nuclear cell labeling dramatically improved the semi-automated analysis of NC cell interactions, yet preserved the ability to track cell movements. We also found channel versus lambda scanning of multicolor labeled embryos significantly reduced the time and effort of image acquisition and analysis of large 3D volume data sets. Conclusions Our results reveal that multicolor cell labeling and multispectral imaging provide a cellular fingerprint that may uniquely determine a cell's position within the embryo. Together, these methods offer a spectral toolbox to resolve in vivo cell dynamics in unprecedented detail.

  11. Improved Erythrocyte Osmotic Fragility and Packed Cell Volume ...

    African Journals Online (AJOL)

    Improved Erythrocyte Osmotic Fragility and Packed Cell Volume following administration of Aloe barbadensis Juice Extract in Rats. ... Abstract. Aloe barbadensis is a popular house plant that has a long history of a multipurpose folk remedy. ... Keywords: osmotic fragility, packed cell volume, haemoglobin, Aloe vera ...

  12. Nanoscale Light Manipulation for Improved Organic Solar Cells

    Science.gov (United States)

    Fisher, Brett

    Organic Solar Cells can be made to be flexible, semi-transparent, and low-cost making them ideal for novel energy harvesting applications such as in greenhouses. However, the main disadvantage of this technology is its low energy conversion efficiency (technologies, such as thinfilm GaAs (>30% Efficiency), and Si-based (>20% Efficiency), solar cells, where recombination within these technologies is much less than Organic Solar Cells. There are still many challenges to overcome to improve the efficiency of Organic Solar Cells. Some of these challenges include: Maximising the absorption of the solar spectrum; improving the charge dynamics; and increasing the lifetime of the devices. One method to address some of these challenges is to include plasmonic nanoparticles into the devices, which has been shown to increase the absorption through scattering, and improve the charge dynamic through localised surface plasmon resonance effects. However, including nanoparticles into Organic Solar Cells has shown to adversely affect the performance of the devices in other ways, such as increasing the recombination of excitons. To address this, an additional (insulating) coating around the nanoparticles supresses this increase, and has shown to be able to increase the performance of the solar cells. In this work, we demonstrate the use of our all-inclusive optical model in the design and optimisation of bespoke colour-specific windows (i.e. Red, Green, and Blue), where the solar cells can be made to have a specific transparency and colour, whilst maximizing their efficiency. For example, we could specify that we wish the colour to be red, with 50% transmissivity; the model will then maximise the Power Conversion Efficiency. We also demonstrate how our extension to Mie theory can simulate nanoparticle systems and can be used to tune the plasmon resonance utilising different coatings, and configurations thereof.

  13. Microstructured Electrolyte Membranes to Improve Fuel Cell Performance

    Science.gov (United States)

    Wei, Xue

    Fuel cells, with the advantages of high efficiency, low greenhouse gas emission, and long lifetime are a promising technology for both portable power and stationary power sources. The development of efficient electrolyte membranes with high ionic conductivity, good mechanical durability and dense structure at low cost remains a challenge to the commercialization of fuel cells. This thesis focuses on exploring novel composite polymer membranes and ceramic electrolytes with the microstructure engineered to improve performance in direct methanol fuel cells (DMFCs) and solid oxide fuel cells (SOFCs), respectively. Polymer/particle composite membranes hold promise to meet the demands of DMFCs at lower cost. The structure of composite membranes was controlled by aligning proton conducting particles across the membrane thickness under an applied electric field. The field-induced structural changes caused the membranes to display an enhanced water uptake, proton conductivity, and methanol permeability in comparison to membranes prepared without an applied field. Although both methanol permeability and proton conductivity are enhanced by the applied field, the permeability increase is relatively lower than the proton conductivity improvement, which results in enhanced proton/methanol selectivity and improved DMFC performance. Apatite ceramics are a new class of fast ion conductors being studied as alternative SOFC electrolytes in the intermediate temperature range. An electrochemical/hydrothermal deposition method was developed to grow fully dense apatite membranes containing well-developed crystals with c-axis alignment to promote ion conductivity. Hydroxyapatite seed crystals were first deposited onto a metal substrate electrochemically. Subsequent ion substitution during the hydrothermal growth process promoted the formation of dense, fully crystalline films with microstructure optimal for ion transport. The deposition parameters were systematically investigated, such as

  14. NANOS2 acts downstream of glial cell line-derived neurotrophic factor signaling to suppress differentiation of spermatogonial stem cells.

    Science.gov (United States)

    Sada, Aiko; Hasegawa, Kazuteru; Pin, Pui Han; Saga, Yumiko

    2012-02-01

    Stem cells are maintained by both stem cell-extrinsic niche signals and stem cell-intrinsic factors. During murine spermatogenesis, glial cell line-derived neurotrophic factor (GDNF) signal emanated from Sertoli cells and germ cell-intrinsic factor NANOS2 represent key regulators for the maintenance of spermatogonial stem cells. However, it remains unclear how these factors intersect in stem cells to control their cellular state. Here, we show that GDNF signaling is essential to maintain NANOS2 expression, and overexpression of Nanos2 can alleviate the stem cell loss phenotype caused by the depletion of Gfra1, a receptor for GDNF. By using an inducible Cre-loxP system, we show that NANOS2 expression is downregulated upon the conditional knockout (cKO) of Gfra1, while ectopic expression of Nanos2 in GFRA1-negative spermatogonia does not induce de novo GFRA1 expression. Furthermore, overexpression of Nanos2 in the Gfra1-cKO testes prevents precocious differentiation of the Gfra1-knockout stem cells and partially rescues the stem cell loss phenotypes of Gfra1-deficient mice, indicating that the stem cell differentiation can be suppressed by NANOS2 even in the absence of GDNF signaling. Taken together, we suggest that NANOS2 acts downstream of GDNF signaling to maintain undifferentiated state of spermatogonial stem cells. Copyright © 2011 AlphaMed Press.

  15. An Improved Ghost-cell Immersed Boundary Method for Compressible Inviscid Flow Simulations

    KAUST Repository

    Chi, Cheng

    2015-05-01

    This study presents an improved ghost-cell immersed boundary approach to represent a solid body in compressible flow simulations. In contrast to the commonly used approaches, in the present work ghost cells are mirrored through the boundary described using a level-set method to farther image points, incorporating a higher-order extra/interpolation scheme for the ghost cell values. In addition, a shock sensor is in- troduced to deal with image points near the discontinuities in the flow field. Adaptive mesh refinement (AMR) is used to improve the representation of the geometry efficiently. The improved ghost-cell method is validated against five test cases: (a) double Mach reflections on a ramp, (b) supersonic flows in a wind tunnel with a forward- facing step, (c) supersonic flows over a circular cylinder, (d) smooth Prandtl-Meyer expansion flows, and (e) steady shock-induced combustion over a wedge. It is demonstrated that the improved ghost-cell method can reach the accuracy of second order in L1 norm and higher than first order in L∞ norm. Direct comparisons against the cut-cell method demonstrate that the improved ghost-cell method is almost equally accurate with better efficiency for boundary representation in high-fidelity compressible flow simulations. Implementation of the improved ghost-cell method in reacting Euler flows further validates its general applicability for compressible flow simulations.

  16. Attenuation of a drug-sensitive strain of a turkey protozoan parasite Eimeria meleagrimitis by selection for precocious development.

    Science.gov (United States)

    Rathinam, T; Gadde, U; Chapman, H D

    2016-01-30

    An attenuated line of Eimeria meleagrimitis was established by repeated propagation of the parasite in 9-day old turkey poults and subsequent selection for precocious development. Following 20 passages, the prepatent period decreased from 120 to 104h. A series of experiments were conducted to evaluate the pathogenicity, immunogenicity and fecundity of the newly selected line. Judged by body weight gain, feed consumption and feed efficiency following infection, the attenuated line had appreciably reduced pathogenicity. Immunogenicity of the attenuated line was examined by infecting poults successively with incremental doses of 10(2), 10(3) and 10(4) oocysts at 0, 7, and 14 days of age respectively. No oocysts were detected following challenge with 5×10(2) oocysts, indicating that the attenuated line had retained immunogenicity. Fecundity was assessed by infecting two-week old birds with 5×10(2) oocysts of either parent or attenuated line. Oocyst production from 96 to 240h post-infection showed that the patent period of the attenuated line commenced earlier and was of shorter duration than the parent line. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Improved Cell Culture Method for Growing Contracting Skeletal Muscle Models

    Science.gov (United States)

    Marquette, Michele L.; Sognier, Marguerite A.

    2013-01-01

    An improved method for culturing immature muscle cells (myoblasts) into a mature skeletal muscle overcomes some of the notable limitations of prior culture methods. The development of the method is a major advance in tissue engineering in that, for the first time, a cell-based model spontaneously fuses and differentiates into masses of highly aligned, contracting myotubes. This method enables (1) the construction of improved two-dimensional (monolayer) skeletal muscle test beds; (2) development of contracting three-dimensional tissue models; and (3) improved transplantable tissues for biomedical and regenerative medicine applications. With adaptation, this method also offers potential application for production of other tissue types (i.e., bone and cardiac) from corresponding precursor cells.

  18. An improved lithium-vanadium pentoxide cell and comparison with a lithium-thionyl chloride cell

    Science.gov (United States)

    Voorn, G.

    1985-03-01

    This paper describes a programme of experiments conducted to assess the effects of: (a) diluting the electrolyte in lithium-vanadium pentoxide cells; (b) optimizing the volume of electrolyte per unit cathode mass. This programme led to the development of an improved cell, the performance of which is compared with that of a lithium-thionyl chloride cell of similar configuration.

  19. An analysis of radioisotope power systems using improved ATEC cells

    International Nuclear Information System (INIS)

    El-Genk, M.S.; Tournier, J.M.

    1998-01-01

    Recently, a ground demo of eight AMTEC (PX-3G) cells has been tested successfully in vacuum at the Air Force Research laboratory (AFRL). Results showed that the electric power output and voltage of the best performing PX-3G cell are short of meeting the requirements of the Pluto/Express (PX) mission. Using the basic configuration of the PX-3G cell, several design changes are explored, to improve the cell performance. Also, several integration options of the improved PX-3G cells with General-Purpose Heat Source (GPHS) modules are investigated for an electric power level of 130 W e and a 15-year mission. The options explored include varying the number of GPHS modules and AMTEC cells, and using fresh or aged fuel. The effects of changing the generators' output voltage (24 V or 28 V) on the evaporator and BASE metal-ceramic brazes temperatures and temperature margin in the cell are also examined

  20. Solitary infantile choriocarcinoma of the liver: MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Hoef, Marianne van der; Willi, Ulrich V.; Huisman, Thierry A.G.M. [University Children' s Hospital Zurich, Department of Diagnostic Imaging, Zurich (Switzerland); Niggli, Felix K. [University Children' s Hospital Zurich, Department of Paediatrics, Zurich (Switzerland)

    2004-10-01

    Infantile hepatic choriocarcinoma is a rare, highly malignant germ-cell tumour believed to result from a choriocarcinoma of the placenta that spreads to the child. Most infants present with a characteristic clinical picture of anaemia, hepatomegaly and precocious puberty. Imaging findings, including conventional MRI, may be non-specific. To improve the accuracy of diagnosis, we present the imaging findings of contrast-enhanced dynamic MRI in a 4.5-month-old boy with infantile hepatic choriocarcinoma. (orig.)

  1. Continued SOFC cell and stack technology and improved production methods

    Energy Technology Data Exchange (ETDEWEB)

    Wandel, M.; Brodersen, K.; Phair, J. (and others)

    2009-05-15

    Within this project significant results are obtained on a number of very diverse areas ranging from development of cell production, metallic creep in interconnect to assembling and test of stacks with foot print larger than 500 cm2. Out of 38 milestones 28 have been fulfilled and 10 have been partly fulfilled. This project has focused on three main areas: 1) The continued cell development and optimization of manufacturing processes aiming at production of large foot-print cells, improving cell performance and development environmentally more benign production methods. 2) Stack technology - especially stacks with large foot print and improving the stack design with respect to flow geometry and gas leakages. 3) Development of stack components with emphasis on sealing (for 2G as well as 3G), interconnect (coat, architecture and creep) and test development. Production of cells with a foot print larger than 500 cm2 is very difficult due to the brittleness of the cells and great effort has been put into this topic. Eight cells were successfully produced making it possible to assemble and test a real stack thereby giving valuable results on the prospects of stacks with large foot print. However, the yield rate is very low and a significant development to increase this yield lies ahead. Several lessons were learned on the stack level regarding 'large foot print' stacks. Modelling studies showed that the width of the cell primarily is limited by production and handling of the cell whereas the length (in the flow direction) is limited by e.g. pressure drop and necessary manifolding. The optimal cell size in the flow direction was calculated to be between approx20 cm and < 30 cm. From an economical point of view the production yield is crucial and stacks with large foot print cell area are only feasible if the cell production yield is significantly enhanced. Co-casting has been pursued as a production technique due to the possibilities in large scale production

  2. Pulmonary hypertension in sickle cell disease children under 10 years of age.

    Science.gov (United States)

    Colombatti, Raffaella; Maschietto, Nicola; Varotto, Elena; Grison, Alessandra; Grazzina, Nicoletta; Meneghello, Linda; Teso, Simone; Carli, Modesto; Milanesi, Ornella; Sainati, Laura

    2010-09-01

    Despite the finding of elevated Tricuspid Regurgitant Velocity (TRV) in children below 5 years of age, the prevalence and evolution of Pulmonary Hypertension (PH) in young children with sickle cell disease (SCD) are unclear. In order to identify predictive factors of precocious PH development, SCD children > or =3 years old, at steady state, underwent annual echocardiography and Tissue Doppler Imaging (TDI). Patients receiving chronic transfusion were excluded. Thirty-seven of seventy-five patients were > or =3 years, with measurable TRV. In our young population (mean age 6.2 years) of mainly African, HbS/HbS patients, 8/37 (21.6%) had TRV > or =2.5 m/s, 8% being only 3 years old. Significant correlation was found between precocious TRV elevation and high platelet and reticulocyte counts and frequent acute chest syndromes (ACS). In multivariate analysis, ACS was the only variable predicting TRV > or =2.5 m/s. TDI of the 37 patients showed signs of diastolic dysfunction of the left ventricle. At follow-up all eight patients with high TRV displayed further increase and seven more developed TRV > or =2.5 m/s. PH seems to begin in children earlier than expected. Factors involved in its early onset might be different from the ones causing its development in older children or adults. African children might benefit from early screening and re-assessment once a year.

  3. Engineering CHO cells with an oncogenic KIT improves cells growth, resilience to stress, and productivity.

    Science.gov (United States)

    Mahameed, Mohamed; Tirosh, Boaz

    2017-11-01

    An optimized biomanufacturing process in mammalian cells is contingent on the ability of the producing cells to reach high viable cell densities. In addition, at the peak of growth, cells need to continue producing the biological entity at a consistent quality. Thus, engineering cells with robust growth performance and resilience to variable stress conditions is highly desirable. The tyrosine kinase receptor, KIT, plays a key role in cell differentiation and the survival of several immune cell types. Its oncogenic mutant, D816V, endows cells with high proliferation capacity, and resistance to kinase inhibitors. Importantly, this onco-KIT mutant when introduced into various cell types is arrested in the endoplasmic reticulum in a constitutively active form. Here, we investigated the effect of oncogenic D816V KIT on the performance of CHO-K1 cells under conventional tissue culture growth settings and when adapted, to shaking conditions. The onco-KIT promoted global protein synthesis, elevated the expression of a secretable transgene, enhanced proliferation, and improved the overall titers of a model glycoprotein. Moreover, the expression of the onco-KIT endowed the cells with a remarkable resistance to various stress conditions. Our data suggest that the introduction of onco-KIT can serve as a strategy for improving glycoprotein biomanufacturing. Biotechnol. Bioeng. 2017;114: 2560-2570. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  4. Efficiency Improvement of HIT Solar Cells on p-Type Si Wafers.

    Science.gov (United States)

    Wei, Chun-You; Lin, Chu-Hsuan; Hsiao, Hao-Tse; Yang, Po-Chuan; Wang, Chih-Ming; Pan, Yen-Chih

    2013-11-22

    Single crystal silicon solar cells are still predominant in the market due to the abundance of silicon on earth and their acceptable efficiency. Different solar-cell structures of single crystalline Si have been investigated to boost efficiency; the heterojunction with intrinsic thin layer (HIT) structure is currently the leading technology. The record efficiency values of state-of-the art HIT solar cells have always been based on n-type single-crystalline Si wafers. Improving the efficiency of cells based on p-type single-crystalline Si wafers could provide broader options for the development of HIT solar cells. In this study, we varied the thickness of intrinsic hydrogenated amorphous Si layer to improve the efficiency of HIT solar cells on p-type Si wafers.

  5. Improved Cathode Structure for a Direct Methanol Fuel Cell

    Science.gov (United States)

    Valdez, Thomas; Narayanan, Sekharipuram

    2005-01-01

    An improved cathode structure on a membrane/electrode assembly has been developed for a direct methanol fuel cell, in a continuing effort to realize practical power systems containing such fuel cells. This cathode structure is intended particularly to afford better cell performance at a low airflow rate. A membrane/electrode assembly of the type for which the improved cathode structure was developed (see Figure 1) is fabricated in a process that includes brush painting and spray coating of catalyst layers onto a polymer-electrolyte membrane and onto gas-diffusion backings that also act as current collectors. The aforementioned layers are then dried and hot-pressed together. When completed, the membrane/electrode assembly contains (1) an anode containing a fine metal black of Pt/Ru alloy, (2) a membrane made of Nafion 117 or equivalent (a perfluorosulfonic acid-based hydrophilic, proton-conducting ion-exchange polymer), (3) a cathode structure (in the present case, the improved cathode structure described below), and (4) the electrically conductive gas-diffusion backing layers, which are made of Toray 060(TradeMark)(or equivalent) carbon paper containing between 5 and 6 weight percent of poly(tetrafluoroethylene). The need for an improved cathode structure arises for the following reasons: In the design and operation of a fuel-cell power system, the airflow rate is a critical parameter that determines the overall efficiency, cell voltage, and power density. It is desirable to operate at a low airflow rate in order to obtain thermal and water balance and to minimize the size and mass of the system. The performances of membrane/electrode assemblies of prior design are limited at low airflow rates. Methanol crossover increases the required airflow rate. Hence, one way to reduce the required airflow rate is to reduce the effect of methanol crossover. Improvement of the cathode structure - in particular, addition of hydrophobic particles to the cathode - has been

  6. Constitutive luteinizing hormone receptor signaling causes sexual dysfunction and Leydig cell adenomas in male mice.

    Science.gov (United States)

    Hai, Lan; Hiremath, Deepak S; Paquet, Marilène; Narayan, Prema

    2017-05-01

    The luteinizing hormone receptor (LHCGR) is necessary for fertility, and genetic mutations cause defects in reproductive development and function. Activating mutations in LHCGR cause familial male-limited precocious puberty (FMPP). We have previously characterized a mouse model (KiLHRD582G) for FMPP that exhibits the same phenotype of precocious puberty, Leydig cell hyperplasia, and elevated testosterone as boys with the disorder. We observed that KiLHRD582G male mice became infertile by 6 months of age, although sperm count and motility were normal. In this study, we sought to determine the reason for the progressive infertility and the long-term consequences of constant LHCGR signaling. Mating with superovulated females showed that infertile KiLHRD582G mice had functional sperm and normal accessory gland function. Sexual behavior studies revealed that KiLHRD582G mice mounted females, but intromission was brief and ejaculation was not achieved. Histological analysis of the reproductive tract showed unique metaplastic changes resulting in pseudostratified columnar epithelial cells with cilia in the ampulla and chondrocytes in the penile body of the KiLHRD582G mice. The infertile KiLHRD582G exhibited enlarged sinusoids and a decrease in smooth muscle content in the corpora cavernosa of the penile body. However, collagen content was unchanged. Leydig cell adenomas and degenerating seminiferous tubules were seen in 1-year-old KiLHRD582G mice. We conclude that progressive infertility in KiLHRD582G mice is due to sexual dysfunction likely due to functional defects in the penis. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please journals.permissions@oup.com.

  7. Premature pubarche before one year of age: distinguishing between mini-puberty variants and precocious puberty.

    Science.gov (United States)

    Bourayou, Rafik; Giabicani, Eloïse; Pouillot, Monique; Brailly-Tabard, Sylvie; Brauner, Raja

    2015-04-02

    The aim of this study was to facilitate the distinction between the benign "mini-puberty of early infancy" and precocious puberty (PP). We compared 59 patients (21 boys and 38 girls) seen for pubic hair development before one year of age diagnosed as mini-puberty to 13 patients (2 boys) in whom pubertal development before one year revealed a PP. The boys with mini-puberty presented with pubic hair development and prepubertal testicular volume, with low plasma testosterone concentrations. Their gonadotropin responses to gonadotropin releasing hormone (GnRH) test showed predominant luteinising hormone increase in 9/13. The girls presented with pubic hair development that was accompanied by breast development in 47% of cases, with low plasma estradiol concentrations. Their gonadotropin responses showed predominant follicle-stimulating hormone increase in the 17 evaluated. The patients with PP had organic central PP (5 hypothalamic hamartoma) or idiopathic central PP (n=6), or peripheral PP (one ovarian tumor and one congenital adrenal hyperplasia). The diagnosis was challenging only in 3 girls with idiopathic central PP presenting with prepubertal plasma estradiol concentrations and responses to GnRH test. The diagnosis of PP was easily determined based on the clinical presentation and the pubertal concentrations of testosterone in boys or of estradiol in girls, as was the diagnosis of central or peripheral origin of PP based on gonadotropin response to the GnRH test. Once PP is excluded, these patients need careful follow-up and physician consultation is needed if clinical pubertal signs progress.

  8. In silico analysis of a novel MKRN3 missense mutation in familial central precocious puberty.

    Science.gov (United States)

    Neocleous, Vassos; Shammas, Christos; Phelan, Marie M; Nicolaou, Stella; Phylactou, Leonidas A; Skordis, Nicos

    2016-01-01

    The onset of puberty is influenced by the interplay of stimulating and restraining factors, many of which have a genetic origin. Premature activation of the GnRH secretion in central precocious puberty (CPP) may arise either from gain-of-function mutations of the KISS1 and KISS1R genes or from loss-of-function manner mutations of the MKRN3 gene leading to MKRN3 deficiency. To explore the genetic causes responsible for CPP and the potential role of the RING finger protein 3 (MKRN3) gene. We investigated potential sequence variations in the intronless MKRN3 gene by Sanger sequencing of the entire 507 amino acid coding region of exon 1 in a family with two affected girls presented with CPP at the age of 6 and 5·7 years, respectively. A novel heterozygous g.Gly312Asp missense mutation in the MKRN3 gene was identified in these siblings. The imprinted MKRN3 missense mutation was also identified as expected in the unaffected father and followed as expected an imprinted mode of inheritance. In silico analysis of the altered missense variant using the computational algorithms Polyphen2, SIFT and Mutation Taster predicted a damage and pathogenic alteration causing CPP. The pathogenicity of the alteration at the protein level via an in silico structural model is also explored. A novel mutation in the MKRN3 gene in two sisters with CPP was identified, supporting the fundamental role of this gene in the suppression of the hypothalamic GnRH neurons. © 2015 John Wiley & Sons Ltd.

  9. Fabrication approaches for plasmon-improved photovoltaic cells

    DEFF Research Database (Denmark)

    Gritti, Claudia; Malureanu, Radu; Kardynal, B.

    During this talk we will present various fabrication approaches to improve the performance of photovoltaic (PV) cells by using metallic nanoparticles in order to generate photocurrent below the bandgap. This effect is possible due to the generation of surface plasmon polaritons (SPPs) in optimized...

  10. Genetic engineering of human NK cells to express CXCR2 improves migration to renal cell carcinoma.

    Science.gov (United States)

    Kremer, Veronika; Ligtenberg, Maarten A; Zendehdel, Rosa; Seitz, Christina; Duivenvoorden, Annet; Wennerberg, Erik; Colón, Eugenia; Scherman-Plogell, Ann-Helén; Lundqvist, Andreas

    2017-09-19

    Adoptive natural killer (NK) cell transfer is being increasingly used as cancer treatment. However, clinical responses have so far been limited to patients with hematological malignancies. A potential limiting factor in patients with solid tumors is defective homing of the infused NK cells to the tumor site. Chemokines regulate the migration of leukocytes expressing corresponding chemokine receptors. Various solid tumors, including renal cell carcinoma (RCC), readily secrete ligands for the chemokine receptor CXCR2. We hypothesize that infusion of NK cells expressing high levels of the CXCR2 chemokine receptor will result in increased influx of the transferred NK cells into tumors, and improved clinical outcome in patients with cancer. Blood and tumor biopsies from 14 primary RCC patients were assessed by flow cytometry and chemokine analysis. Primary NK cells were transduced with human CXCR2 using a retroviral system. CXCR2 receptor functionality was determined by Calcium flux and NK cell migration was evaluated in transwell assays. We detected higher concentrations of CXCR2 ligands in tumors compared with plasma of RCC patients. In addition, CXCL5 levels correlated with the intratumoral infiltration of CXCR2-positive NK cells. However, tumor-infiltrating NK cells from RCC patients expressed lower CXCR2 compared with peripheral blood NK cells. Moreover, healthy donor NK cells rapidly lost their CXCR2 expression upon in vitro culture and expansion. Genetic modification of human primary NK cells to re-express CXCR2 improved their ability to specifically migrate along a chemokine gradient of recombinant CXCR2 ligands or RCC tumor supernatants compared with controls. The enhanced trafficking resulted in increased killing of target cells. In addition, while their functionality remained unchanged compared with control NK cells, CXCR2-transduced NK cells obtained increased adhesion properties and formed more conjugates with target cells. To increase the success of NK

  11. Nanoscale dimples for improved absorption in organic solar cells

    DEFF Research Database (Denmark)

    Goszczak, Arkadiusz Jaroslaw; Rubahn, Horst-Günter; Madsen, Morten

    Organic solar cells (OSC’s) have attracted much attention in the past years due to their potential low-cost, light-weight and mechanical flexibility. A method for improving the power conversion efficiencies of the devices is by incorporating structured electrodes in the solar cell architecture......, as they can improve light absorption in the active layers of the devices. In this direction, a cheap and large-scale compatible method for structuring the electrodes in OSC’s is by the use of Anodic Alumina Oxide (AAO) membranes. In the present work, Al films of high purity and low roughness are formed via e...

  12. The small GTPase RhoA is required to maintain spinal cord neuroepithelium organization and the neural stem cell pool

    DEFF Research Database (Denmark)

    Herzog, Dominik; Loetscher, Pirmin; van Hengel, Jolanda

    2011-01-01

    ablation. We show that, in the spinal cord neuroepithelium, RhoA is essential to localize N-cadherin and ß-catenin to AJs and maintain apical-basal polarity of neural progenitor cells. Ablation of RhoA caused the loss of AJs and severe abnormalities in the organization of cells within the neuroepithelium......Dia1), does not localize to apical AJs in which it likely stabilizes intracellular adhesion by promoting local actin polymerization and microtubule organization. Furthermore, expressing a dominant-negative form of mDia1 in neural stem/progenitor cells results in a similar phenotype compared...... with that of the RhoA conditional knock-out, namely the loss of AJs and apical polarity. Together, our data show that RhoA signaling is necessary for AJ regulation and for the maintenance of mammalian neuroepithelium organization preventing precocious cell-cycle exit and differentiation....

  13. Erythrokinetics, ferrokinetics and red cell survival in sickle cell anaemia under subtropical climatic conditions

    International Nuclear Information System (INIS)

    Cardenas, R.

    1975-01-01

    Ferrokinetic parameters were evaluated with 59 Fe and red-cell survival with 51 Cr by classical techniques in a total of 17 patients with sickle-cell disease. The mean plasma 59 Fe half-disappearance time in these patients was 29.5 min as compared with a normal value of 92 min, and the t1/2 51 Cr 8.0 days as compared with a normal value of 26.0 days. The mean red-cell iron turnover rate was elevated to 9 times normal. The increased destruction of red cells appeared to take place predominantly, though not entirely, in the spleen. Eight of the 17 patients studied were identified as having intercurrent complications, but these did not significantly affect the results of the investigations. A group of 5 boys in whom the red-cell iron turnover rate was elevated to a lesser degree than in the other patients were subjected to more detailed studies of plasma 59 Fe clearance with particular reference to ineffective erythropoiesis. In these patients, the plasma 59 Fe clearance curves showed precocious humps characteristic of ineffective erythropoiesis. Detailed analysis of the results indicated ineffective erythropoiesis corresponding to 3.6, 16.0, 22.6, 32.0 and 50.0 % of the iron initially taken up by the bone marrow. It is concluded that while the anaemia in most patients with sickle-cell disease is mainly due to shortened survival of the circulating red cells, with increased destruction of red cells in the spleen, ineffective erythropoiesis may none the less be an important factor determining the actual degree of this anaemia

  14. A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fate determination.

    Science.gov (United States)

    Zhao, Chunnian; Sun, GuoQiang; Li, Shengxiu; Shi, Yanhong

    2009-04-01

    MicroRNAs have been implicated as having important roles in stem cell biology. MicroRNA-9 (miR-9) is expressed specifically in neurogenic areas of the brain and may be involved in neural stem cell self-renewal and differentiation. We showed previously that the nuclear receptor TLX is an essential regulator of neural stem cell self-renewal. Here we show that miR-9 suppresses TLX expression to negatively regulate neural stem cell proliferation and accelerate neural differentiation. Introducing a TLX expression vector that is not prone to miR-9 regulation rescued miR-9-induced proliferation deficiency and inhibited precocious differentiation. In utero electroporation of miR-9 in embryonic brains led to premature differentiation and outward migration of the transfected neural stem cells. Moreover, TLX represses expression of the miR-9 pri-miRNA. By forming a negative regulatory loop with TLX, miR-9 provides a model for controlling the balance between neural stem cell proliferation and differentiation.

  15. Improved performance in GaInNAs solar cells by hydrogen passivation

    International Nuclear Information System (INIS)

    Fukuda, M.; Whiteside, V. R.; Keay, J. C.; Meleco, A.; Sellers, I. R.; Hossain, K.; Golding, T. D.; Leroux, M.; Al Khalfioui, M.

    2015-01-01

    The effect of UV-activated hydrogenation on the performance of GaInNAs solar cells is presented. A proof-of-principle investigation was performed on non-optimum GaInNAs cells, which allowed a clearer investigation of the role of passivation on the intrinsic nitrogen-related defects in these materials. Upon optimized hydrogenation of GaInNAs, a significant reduction in the presence of defect and impurity based luminescence is observed as compared to that of unpassivated reference material. This improvement in the optical properties is directly transferred to an improved performance in solar cell operation, with a more than two-fold improvement in the external quantum efficiency and short circuit current density upon hydrogenation. Temperature dependent photovoltaic measurements indicate a strong contribution of carrier localization and detrapping processes, with non-radiative processes dominating in the reference materials, and evidence for additional strong radiative losses in the hydrogenated solar cells

  16. Culturing bone marrow cells with dexamethasone and ascorbic acid improves osteogenic cell sheet structure.

    Science.gov (United States)

    Akahane, M; Shimizu, T; Kira, T; Onishi, T; Uchihara, Y; Imamura, T; Tanaka, Y

    2016-11-01

    To assess the structure and extracellular matrix molecule expression of osteogenic cell sheets created via culture in medium with both dexamethasone (Dex) and ascorbic acid phosphate (AscP) compared either Dex or AscP alone. Osteogenic cell sheets were prepared by culturing rat bone marrow stromal cells in a minimal essential medium (MEM), MEM with AscP, MEM with Dex, and MEM with Dex and AscP (Dex/AscP). The cell number and messenger (m)RNA expression were assessed in vitro, and the appearance of the cell sheets was observed after mechanical retrieval using a scraper. β-tricalcium phosphate (β-TCP) was then wrapped with the cell sheets from the four different groups and subcutaneously implanted into rats. After mechanical retrieval, the osteogenic cell sheets from the MEM, MEM with AscP, and MEM with Dex groups appeared to be fragmented or incomplete structures. The cell sheets cultured with Dex/AscP remained intact after mechanical retrieval, without any identifiable tears. Culture with Dex/AscP increased the mRNA and protein expression of extracellular matrix proteins and cell number compared with those of the other three groups. More bridging bone formation was observed after transplantation of the β-TCP scaffold wrapped with cell sheets cultured with Dex/AscP, than in the other groups. These results suggest that culture with Dex/AscP improves the mechanical integrity of the osteogenic cell sheets, allowing retrieval of the confluent cells in a single cell sheet structure. This method may be beneficial when applied in cases of difficult tissue reconstruction, such as nonunion, bone defects, and osteonecrosis.Cite this article: M. Akahane, T. Shimizu, T. Kira, T. Onishi, Y. Uchihara, T. Imamura, Y. Tanaka. Culturing bone marrow cells with dexamethasone and ascorbic acid improves osteogenic cell sheet structure. Bone Joint Res 2016;5:569-576. DOI: 10.1302/2046-3758.511.BJR-2016-0013.R1. © 2016 Akahane et al.

  17. Juvenile hormone counteracts the bHLH-PAS transcription factors MET and GCE to prevent caspase-dependent programmed cell death in Drosophila.

    Science.gov (United States)

    Liu, Ying; Sheng, Zhentao; Liu, Hanhan; Wen, Di; He, Qianyu; Wang, Sheng; Shao, Wei; Jiang, Rong-Jing; An, Shiheng; Sun, Yaning; Bendena, William G; Wang, Jian; Gilbert, Lawrence I; Wilson, Thomas G; Song, Qisheng; Li, Sheng

    2009-06-01

    Juvenile hormone (JH) regulates many developmental and physiological events in insects, but its molecular mechanism remains conjectural. Here we report that genetic ablation of the corpus allatum cells of the Drosophila ring gland (the JH source) resulted in JH deficiency, pupal lethality and precocious and enhanced programmed cell death (PCD) of the larval fat body. In the fat body of the JH-deficient animals, Dronc and Drice, two caspase genes that are crucial for PCD induced by the molting hormone 20-hydroxyecdysone (20E), were significantly upregulated. These results demonstrated that JH antagonizes 20E-induced PCD by restricting the mRNA levels of Dronc and Drice. The antagonizing effect of JH on 20E-induced PCD in the fat body was further confirmed in the JH-deficient animals by 20E treatment and RNA interference of the 20E receptor EcR. Moreover, MET and GCE, the bHLH-PAS transcription factors involved in JH action, were shown to induce PCD by upregulating Dronc and Drice. In the Met- and gce-deficient animals, Dronc and Drice were downregulated, whereas in the Met-overexpression fat body, Dronc and Drice were significantly upregulated leading to precocious and enhanced PCD, and this upregulation could be suppressed by application of the JH agonist methoprene. For the first time, we demonstrate that JH counteracts MET and GCE to prevent caspase-dependent PCD in controlling fat body remodeling and larval-pupal metamorphosis in Drosophila.

  18. Improving the photovoltaic performance of perovskite solar cells with acetate

    Science.gov (United States)

    Zhao, Qian; Li, G. R.; Song, Jian; Zhao, Yulong; Qiang, Yinghuai; Gao, X. P.

    2016-01-01

    In an all-solid-state perovskite solar cell, methylammonium lead halide film is in charge of generating photo-excited electrons, thus its quality can directly influence the final photovoltaic performance of the solar cell. This paper accentuates a very simple chemical approach to improving the quality of a perovskite film with a suitable amount of acetic acid. With introduction of acetate ions, a homogeneous, continual and hole-free perovskite film comprised of high-crystallinity grains is obtained. UV-visible spectra, steady-state and time-resolved photoluminescence (PL) spectra reveal that the obtained perovskite film under the optimized conditions shows a higher light absorption, more efficient electron transport, and faster electron extraction to the adjoining electron transport layer. The features result in the optimized perovskite film can provide an improved short-circuit current. The corresponding solar cells with a planar configuration achieves an improved power conversion efficiency of 13.80%, and the highest power conversion efficiency in the photovoltaic measurements is up to 14.71%. The results not only provide a simple approach to optimizing perovskite films but also present a novel angle of view on fabricating high-performance perovskite solar cells. PMID:27934924

  19. Improving the photovoltaic performance of perovskite solar cells with acetate.

    Science.gov (United States)

    Zhao, Qian; Li, G R; Song, Jian; Zhao, Yulong; Qiang, Yinghuai; Gao, X P

    2016-12-09

    In an all-solid-state perovskite solar cell, methylammonium lead halide film is in charge of generating photo-excited electrons, thus its quality can directly influence the final photovoltaic performance of the solar cell. This paper accentuates a very simple chemical approach to improving the quality of a perovskite film with a suitable amount of acetic acid. With introduction of acetate ions, a homogeneous, continual and hole-free perovskite film comprised of high-crystallinity grains is obtained. UV-visible spectra, steady-state and time-resolved photoluminescence (PL) spectra reveal that the obtained perovskite film under the optimized conditions shows a higher light absorption, more efficient electron transport, and faster electron extraction to the adjoining electron transport layer. The features result in the optimized perovskite film can provide an improved short-circuit current. The corresponding solar cells with a planar configuration achieves an improved power conversion efficiency of 13.80%, and the highest power conversion efficiency in the photovoltaic measurements is up to 14.71%. The results not only provide a simple approach to optimizing perovskite films but also present a novel angle of view on fabricating high-performance perovskite solar cells.

  20. Cell phone–based health education messaging improves health ...

    African Journals Online (AJOL)

    SMS), provides new and innovative opportunities for disease prevention and health education. Objective: To explore the use of cell phone–based health education SMS to improve the health literacy of community residents in China. Methods: ...

  1. Precocious Supermassive Black Holes Challenge Theories

    Science.gov (United States)

    2004-11-01

    NASA's Chandra X-ray Observatory has obtained definitive evidence that a distant quasar formed less than a billion years after the Big Bang contains a fully-grown supermassive black hole generating energy at the rate of twenty trillion Suns. The existence of such massive black holes at this early epoch of the Universe challenges theories of the formation of galaxies and supermassive black holes. Astronomers Daniel Schwartz and Shanil Virani of the Harvard-Smithsonian Center for Astrophysics in Cambridge, MA observed the quasar, known as SDSSp J1306, which is 12.7 billion light years away. Since the Universe is estimated to be 13.7 billion years old, we see the quasar as it was a billion years after the Big Bang. They found that the distribution of X-rays with energy, or X-ray spectrum, is indistinguishable from that of nearby, older quasars. Likewise, the relative brightness at optical and X-ray wavelengths of SDSSp J1306 was similar to that of the nearby group of quasars. Optical observations suggest that the mass of the black hole is about a billion solar masses. Illustration of Quasar SDSSp J1306 Illustration of Quasar SDSSp J1306 Evidence of another early-epoch supermassive black hole was published previously by a team of scientists from the California Institute of Technology and the United Kingdom using the XMM-Newton X-ray satellite. They observed the quasar SDSSp J1030 at a distance of 12.8 billion light years and found essentially the same result for the X-ray spectrum as the Smithsonian scientists found for SDSSp J1306. Chandra's precise location and spectrum for SDSSp J1306 with nearly the same properties eliminate any lingering uncertainty that precocious supermassive black holes exist. "These two results seem to indicate that the way supermassive black holes produce X-rays has remained essentially the same from a very early date in the Universe," said Schwartz. "This implies that the central black hole engine in a massive galaxy was formed very soon

  2. Ferritin nanoparticles for improved self-renewal and differentiation of human neural stem cells.

    Science.gov (United States)

    Lee, Jung Seung; Yang, Kisuk; Cho, Ann-Na; Cho, Seung-Woo

    2018-01-01

    Biomaterials that promote the self-renewal ability and differentiation capacity of neural stem cells (NSCs) are desirable for improving stem cell therapy to treat neurodegenerative diseases. Incorporation of micro- and nanoparticles into stem cell culture has gained great attention for the control of stem cell behaviors, including proliferation and differentiation. In this study, ferritin, an iron-containing natural protein nanoparticle, was applied as a biomaterial to improve the self-renewal and differentiation of NSCs and neural progenitor cells (NPCs). Ferritin nanoparticles were added to NSC or NPC culture during cell growth, allowing for incorporation of ferritin nanoparticles during neurosphere formation. Compared to neurospheres without ferritin treatment, neurospheres with ferritin nanoparticles showed significantly promoted self-renewal and cell-cell interactions. When spontaneous differentiation of neurospheres was induced during culture without mitogenic factors, neuronal differentiation was enhanced in the ferritin-treated neurospheres. In conclusion, we found that natural nanoparticles can be used to improve the self-renewal ability and differentiation potential of NSCs and NPCs, which can be applied in neural tissue engineering and cell therapy for neurodegenerative diseases.

  3. Uterine-derived progenitor cells are immunoprivileged and effectively improve cardiac regeneration when used for cell therapy.

    Science.gov (United States)

    Ludke, Ana; Wu, Jun; Nazari, Mansoreh; Hatta, Kota; Shao, Zhengbo; Li, Shu-Hong; Song, Huifang; Ni, Nathan C; Weisel, Richard D; Li, Ren-Ke

    2015-07-01

    Cell therapy to prevent cardiac dysfunction after myocardial infarction (MI) is less effective in aged patients because aged cells have decreased regenerative capacity. Allogeneic transplanted stem cells (SCs) from young donors are usually rejected. Maintaining transplanted SC immunoprivilege may dramatically improve regenerative outcomes. The uterus has distinct immune characteristics, and we showed that reparative uterine SCs home to the myocardium post-MI. Here, we identify immunoprivileged uterine SCs and assess their effects on cardiac regeneration after allogeneic transplantation. We found more than 20% of cells in the mouse uterus have undetectable MHC I expression by flow cytometry. Uterine MHC I((neg)) and MHC I((pos)) cells were separated by magnetic cell sorting. The MHC I((neg)) population expressed the SC markers CD34, Sca-1 and CD90, but did not express MHC II or c-kit. In vitro, MHC I((neg)) and ((pos)) SCs show colony formation and endothelial differentiation capacity. In mixed leukocyte co-culture, MHC I((neg)) cells showed reduced cell death and leukocyte proliferation compared to MHC I((pos)) cells. MHC I((neg)) and ((pos)) cells had significantly greater angiogenic capacity than mesenchymal stem cells. The benefits of intramyocardial injection of allogeneic MHC I((neg)) cells after MI were comparable to syngeneic bone marrow cell transplantation, with engraftment in cardiac tissue and limited recruitment of CD4 and CD8 cells up to 21 days post-MI. MHC I((neg)) cells preserved cardiac function, decreased infarct size and improved regeneration post-MI. This new source of immunoprivileged cells can induce neovascularization and could be used as allogeneic cell therapy for regenerative medicine. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Improved genome recovery and integrated cell-size analyses of individual uncultured microbial cells and viral particles.

    Science.gov (United States)

    Stepanauskas, Ramunas; Fergusson, Elizabeth A; Brown, Joseph; Poulton, Nicole J; Tupper, Ben; Labonté, Jessica M; Becraft, Eric D; Brown, Julia M; Pachiadaki, Maria G; Povilaitis, Tadas; Thompson, Brian P; Mascena, Corianna J; Bellows, Wendy K; Lubys, Arvydas

    2017-07-20

    Microbial single-cell genomics can be used to provide insights into the metabolic potential, interactions, and evolution of uncultured microorganisms. Here we present WGA-X, a method based on multiple displacement amplification of DNA that utilizes a thermostable mutant of the phi29 polymerase. WGA-X enhances genome recovery from individual microbial cells and viral particles while maintaining ease of use and scalability. The greatest improvements are observed when amplifying high G+C content templates, such as those belonging to the predominant bacteria in agricultural soils. By integrating WGA-X with calibrated index-cell sorting and high-throughput genomic sequencing, we are able to analyze genomic sequences and cell sizes of hundreds of individual, uncultured bacteria, archaea, protists, and viral particles, obtained directly from marine and soil samples, in a single experiment. This approach may find diverse applications in microbiology and in biomedical and forensic studies of humans and other multicellular organisms.Single-cell genomics can be used to study uncultured microorganisms. Here, Stepanauskas et al. present a method combining improved multiple displacement amplification and FACS, to obtain genomic sequences and cell size information from uncultivated microbial cells and viral particles in environmental samples.

  5. Psychosexual development, maternalism, nonpromiscuity, and body image in 15 females with precocious puberty.

    Science.gov (United States)

    Money, J; Walker, P A

    1971-03-01

    Fifteen females with a history of idiopathic sexual precocity were selected without known sampling bias. They had been followed for as long as 18 years. They showed various behavioral characteristics as a group, but were also individually unique. If the IQ permitted, they benefited socially from school acceleration. Left to their own devices, the majority preferred friends nearer to them in physique age rather than chronologic age. Play interests, though influenced by the age of playmates, showed no features unique to the precocious onset of hormonal puberty. About half of the girls had occasional moody or depressed spells and wanted to be left alone. Maternalistic interests were strongly represented; only one girl was a tomboy. Masturbation and sexual play in childhood were rarely confirmed, and in no instances were totally contrary to family or community mores. No consistent progression of erotic dream content was discerned. Dreams of having a baby were rare, but antedated intercourse dreams, which were also rarely reported and did not include sensations of climax. Whereas the youngest age of having a serious boyfriend was 8 years, and the youngest age of intercourse, 11, the majority of girls did not report romantic and sexual involvements before the middle teenage years or later. In the three instances of marriage, the youngest was at age 21. Motherhood has so far been achieved by only one patient. She delivered her first child at age 11. The visible appearance of early sexual development and early advanced statural growth created a problem in childhood human relationships for most of the girls, regardless of what they said, and regardless of their skill or ineptitude in handling it. They all benefited even from minimal counseling, as did their parents. Early appearance of physical sexual development does not automatically lead to premature engagement in erotic activity or promiscuous sexual behavior. Such activity and behavior require appropriate experience

  6. The ROCK inhibitor Y-27632 improves recovery of human embryonic stem cells after fluorescence-activated cell sorting with multiple cell surface markers.

    Directory of Open Access Journals (Sweden)

    Nil Emre

    Full Text Available BACKGROUND: Due to the inherent sensitivity of human embryonic stem cells (hESCs to manipulations, the recovery and survival of hESCs after fluorescence-activated cell sorting (FACS can be low. Additionally, a well characterized and robust methodology for performing FACS on hESCs using multiple-cell surface markers has not been described. The p160-Rho-associated coiled kinase (ROCK inhibitor, Y-27632, previously has been identified as enhancing survival of hESCs upon single-cell dissociation, as well as enhancing recovery from cryopreservation. Here we examined the application of Y-27632 to hESCs after FACS to improve survival in both feeder-dependent and feeder-independent growth conditions. METHODOLOGY/PRINCIPAL FINDINGS: HESCs were sorted using markers for SSEA-3, TRA-1-81, and SSEA-1. Cells were plated after sorting for 24 hours in either the presence or the absence of Y-27632. In both feeder-dependent and feeder-independent conditions, cell survival was greater when Y-27632 was applied to the hESCs after sort. Specifically, treatment of cells with Y-27632 improved post-sort recovery up to four fold. To determine the long-term effects of sorting with and without the application of Y-27632, hESCs were further analyzed. Specifically, hESCs sorted with and without the addition of Y-27632 retained normal morphology, expressed hESC-specific markers as measured by immunocytochemistry and flow cytometry, and maintained a stable karyotype. In addition, the hESCs could differentiate into three germ layers in vitro and in vivo in both feeder-dependent and feeder-independent growth conditions. CONCLUSIONS/SIGNIFICANCE: The application of Y-27632 to hESCs after cell sorting improves cell recovery with no observed effect on pluripotency, and enables the consistent recovery of hESCs by FACS using multiple surface markers. This improved methodology for cell sorting of hESCs will aid many applications such as removal of hESCs from secondary cell types

  7. Genetic modification of embryonic stem cells with VEGF enhances cell survival and improves cardiac function.

    Science.gov (United States)

    Xie, Xiaoyan; Cao, Feng; Sheikh, Ahmad Y; Li, Zongjin; Connolly, Andrew J; Pei, Xuetao; Li, Ren-Ke; Robbins, Robert C; Wu, Joseph C

    2007-01-01

    Cardiac stem cell therapy remains hampered by acute donor cell death posttransplantation and the lack of reliable methods for tracking cell survival in vivo. We hypothesize that cells transfected with inducible vascular endothelial growth factor 165 (VEGF(165)) can improve their survival as monitored by novel molecular imaging techniques. Mouse embryonic stem (ES) cells were transfected with an inducible, bidirectional tetracycline (Bi-Tet) promoter driving VEGF(165) and renilla luciferase (Rluc). Addition of doxycycline induced Bi-Tet expression of VEGF(165) and Rluc significantly compared to baseline (p<0.05). Expression of VEGF(165) enhanced ES cell proliferation and inhibited apoptosis as determined by Annexin-V staining. For noninvasive imaging, ES cells were transduced with a double fusion (DF) reporter gene consisting of firefly luciferase and enhanced green fluorescence protein (Fluc-eGFP). There was a robust correlation between cell number and Fluc activity (R(2)=0.99). Analysis by immunostaining, histology, and RT-PCR confirmed that expression of Bi-Tet and DF systems did not affect ES cell self-renewal or pluripotency. ES cells were differentiated into beating embryoid bodies expressing cardiac markers such as troponin, Nkx2.5, and beta-MHC. Afterward, 5 x 10(5) cells obtained from these beating embryoid bodies or saline were injected into the myocardium of SV129 mice (n=36) following ligation of the left anterior descending (LAD) artery. Bioluminescence imaging (BLI) and echocardiography showed that VEGF(165) induction led to significant improvements in both transplanted cell survival and cardiac function (p<0.05). This is the first study to demonstrate imaging of embryonic stem cell-mediated gene therapy targeting cardiovascular disease. With further validation, this platform may have broad applications for current basic research and further clinical studies.

  8. Loss of niche-satellite cell interactions in syndecan-3 null mice alters muscle progenitor cell homeostasis improving muscle regeneration.

    Science.gov (United States)

    Pisconti, Addolorata; Banks, Glen B; Babaeijandaghi, Farshad; Betta, Nicole Dalla; Rossi, Fabio M V; Chamberlain, Jeffrey S; Olwin, Bradley B

    2016-01-01

    The skeletal muscle stem cell niche provides an environment that maintains quiescent satellite cells, required for skeletal muscle homeostasis and regeneration. Syndecan-3, a transmembrane proteoglycan expressed in satellite cells, supports communication with the niche, providing cell interactions and signals to maintain quiescent satellite cells. Syndecan-3 ablation unexpectedly improves regeneration in repeatedly injured muscle and in dystrophic mice, accompanied by the persistence of sublaminar and interstitial, proliferating myoblasts. Additionally, muscle aging is improved in syndecan-3 null mice. Since syndecan-3 null myofiber-associated satellite cells downregulate Pax7 and migrate away from the niche more readily than wild type cells, syxndecan-3 appears to regulate satellite cell homeostasis and satellite cell homing to the niche. Manipulating syndecan-3 provides a promising target for development of therapies to enhance muscle regeneration in muscular dystrophies and in aged muscle.

  9. Intraocular Injection of ES Cell-Derived Neural Progenitors Improve Visual Function in Retinal Ganglion Cell-Depleted Mouse Models

    Directory of Open Access Journals (Sweden)

    Mundackal S. Divya

    2017-09-01

    Full Text Available Retinal ganglion cell (RGC transplantation is a promising strategy to restore visual function resulting from irreversible RGC degeneration occurring in glaucoma or inherited optic neuropathies. We previously demonstrated FGF2 induced differentiation of mouse embryonic stem cells (ESC to RGC lineage, capable of retinal ganglion cell layer (GCL integration upon transplantation. Here, we evaluated possible improvement of visual function by transplantation of ES cell derived neural progenitors in RGC depleted glaucoma mice models. ESC derived neural progenitors (ES-NP were transplanted into N-Methyl-D-Aspartate (NMDA injected, RGC-ablated mouse models and a pre-clinical glaucoma mouse model (DBA/2J having sustained higher intra ocular pressure (IOP. Visual acuity and functional integration was evaluated by behavioral experiments and immunohistochemistry, respectively. GFP-expressing ES-NPs transplanted in NMDA-injected RGC-depleted mice differentiated into RGC lineage and possibly integrating into GCL. An improvement in visual acuity was observed after 2 months of transplantation, when compared to the pre-transplantation values. Expression of c-Fos in the transplanted cells, upon light induction, further suggests functional integration into the host retinal circuitry. However, the transplanted cells did not send axonal projections into optic nerve. Transplantation experiments in DBA/2J mouse showed no significant improvement in visual functions, possibly due to both host and transplanted retinal cell death which could be due to an inherent high IOP. We showed that, ES NPs transplanted into the retina of RGC-ablated mouse models could survive, differentiate to RGC lineage, and possibly integrate into GCL to improve visual function. However, for the survival of transplanted cells in glaucoma, strategies to control the IOP are warranted.

  10. Autosomal dominant precocious osteoarthropathy due to a mutation of the cartilage oligomeric matrix protein (COMP) gene: further expansion of the phenotypic variations of COMP defects

    Energy Technology Data Exchange (ETDEWEB)

    Kawaji, Hiroyuki [Department of Orthopaedic Surgery, Sanyudo Hospital, 6-1-219 Chuou, Yonezawa, Yamagata 992-0045 (Japan); Nishimura, Gen [Department of Radiology, Nasu Chuou Hospital, Tochigi (Japan); Watanabe, Sobei; Sasaki, Akira; Sano, Tokuhisa [Department of Orthopaedic Surgery, Tohoku Kohsei-Nenkin Hospital, Miyagi (Japan); Mabuchi, Akihiko; Ikeda, Toshiyuki; Ikegawa, Shiro [Laboratory for Bone and Joint Diseases, SNP Research Center, Tokyo (Japan); Ohashi, Hirofumi [Division of Medical Genetics, Saitama Children' s Medical Center, Saitama (Japan)

    2002-12-01

    We report on a Japanese family of four generations with an autosomal dominant precocious osteoarthropathy. The cardinal clinical manifestations of affected individuals were painful weight-bearing large joints, which started in late childhood or adolescence. The radiological hallmarks included coxa plana, mild epiphyseal dysplasia of the knee, and round talar domes with tibiotalar slant in childhood, which evolved into degenerative joint diseases in adulthood. The disease phenotype was cosegregated with a mutation of the cartilage oligomeric matrix protein (COMP) gene in the family members, who underwent molecular evaluation. COMP mutations have been reported in a mild form of multiple epiphyseal dysplasia (MED), Ribbing type, as well as allied disorders with more severe manifestations, such as MED Fairbank type and pseudoachondroplasia. Unlike previously reported cases with the Ribbing type, the present patients did not have short stature or brachydactyly. This report expands further the phenotypic variations of COMP defects. (orig.)

  11. Solid-State NMR on bacterial cells: selective cell wall signal enhancement and resolution improvement using dynamic nuclear polarization

    International Nuclear Information System (INIS)

    Takahashi, Hiroki; Bardet, Michel; De Paepe, Gael; Hediger, Sabine; Ayala, Isabel; Simorre, Jean-Pierre

    2013-01-01

    Dynamic nuclear polarization (DNP) enhanced solid-state nuclear magnetic resonance (NMR) has recently emerged as a powerful technique for the study of material surfaces. In this study, we demonstrate its potential to investigate cell surface in intact cells. Using Bacillus subtilis bacterial cells as an example, it is shown that the polarizing agent 1-(TEMPO-4-oxy)-3-(TEMPO-4-amino)propan-2-ol (TOTAPOL) has a strong binding affinity to cell wall polymers (peptidoglycan). This particular interaction is thoroughly investigated with a systematic study on extracted cell wall materials, disrupted cells, and entire cells, which proved that TOTAPOL is mainly accumulating in the cell wall. This property is used on one hand to selectively enhance or suppress cell wall signals by controlling radical concentrations and on the other hand to improve spectral resolution by means of a difference spectrum. Comparing DNP-enhanced and conventional solid-state NMR, an absolute sensitivity ratio of 24 was obtained on the entire cell sample. This important increase in sensitivity together with the possibility of enhancing specifically cell wall signals and improving resolution really opens new avenues for the use of DNP-enhanced solid-state NMR as an on-cell investigation tool. (authors)

  12. Solid-state NMR on bacterial cells: selective cell wall signal enhancement and resolution improvement using dynamic nuclear polarization.

    Science.gov (United States)

    Takahashi, Hiroki; Ayala, Isabel; Bardet, Michel; De Paëpe, Gaël; Simorre, Jean-Pierre; Hediger, Sabine

    2013-04-03

    Dynamic nuclear polarization (DNP) enhanced solid-state nuclear magnetic resonance (NMR) has recently emerged as a powerful technique for the study of material surfaces. In this study, we demonstrate its potential to investigate cell surface in intact cells. Using Bacillus subtilis bacterial cells as an example, it is shown that the polarizing agent 1-(TEMPO-4-oxy)-3-(TEMPO-4-amino)propan-2-ol (TOTAPOL) has a strong binding affinity to cell wall polymers (peptidoglycan). This particular interaction is thoroughly investigated with a systematic study on extracted cell wall materials, disrupted cells, and entire cells, which proved that TOTAPOL is mainly accumulating in the cell wall. This property is used on one hand to selectively enhance or suppress cell wall signals by controlling radical concentrations and on the other hand to improve spectral resolution by means of a difference spectrum. Comparing DNP-enhanced and conventional solid-state NMR, an absolute sensitivity ratio of 24 was obtained on the entire cell sample. This important increase in sensitivity together with the possibility of enhancing specifically cell wall signals and improving resolution really opens new avenues for the use of DNP-enhanced solid-state NMR as an on-cell investigation tool.

  13. Improving CART-Cell Therapy of Solid Tumors with Oncolytic Virus-Driven Production of a Bispecific T-cell Engager.

    Science.gov (United States)

    Wing, Anna; Fajardo, Carlos Alberto; Posey, Avery D; Shaw, Carolyn; Da, Tong; Young, Regina M; Alemany, Ramon; June, Carl H; Guedan, Sonia

    2018-05-01

    T cells expressing chimeric antigen receptors (CART) have shown significant promise in clinical trials to treat hematologic malignancies, but their efficacy in solid tumors has been limited. Oncolytic viruses have the potential to act in synergy with immunotherapies due to their immunogenic oncolytic properties and the opportunity of incorporating therapeutic transgenes in their genomes. Here, we hypothesized that an oncolytic adenovirus armed with an EGFR-targeting, bispecific T-cell engager (OAd-BiTE) would improve the outcome of CART-cell therapy in solid tumors. We report that CART cells targeting the folate receptor alpha (FR-α) successfully infiltrated preestablished xenograft tumors but failed to induce complete responses, presumably due to the presence of antigen-negative cancer cells. We demonstrated that OAd-BiTE-mediated oncolysis significantly improved CART-cell activation and proliferation, while increasing cytokine production and cytotoxicity, and showed an in vitro favorable safety profile compared with EGFR-targeting CARTs. BiTEs secreted from infected cells redirected CART cells toward EGFR in the absence of FR-α, thereby addressing tumor heterogeneity. BiTE secretion also redirected CAR-negative, nonspecific T cells found in CART-cell preparations toward tumor cells. The combinatorial approach improved antitumor efficacy and prolonged survival in mouse models of cancer when compared with the monotherapies, and this was the result of an increased BiTE-mediated T-cell activation in tumors. Overall, these results demonstrated that the combination of a BiTE-expressing oncolytic virus with adoptive CART-cell therapy overcomes key limitations of CART cells and BiTEs as monotherapies in solid tumors and encourage its further evaluation in human trials. Cancer Immunol Res; 6(5); 605-16. ©2018 AACR . ©2018 American Association for Cancer Research.

  14. Improving the efficiency of CHO cell line generation using glutamine synthetase gene knockout cells.

    Science.gov (United States)

    Fan, Lianchun; Kadura, Ibrahim; Krebs, Lara E; Hatfield, Christopher C; Shaw, Margaret M; Frye, Christopher C

    2012-04-01

    Although Chinese hamster ovary (CHO) cells, with their unique characteristics, have become a major workhorse for the manufacture of therapeutic recombinant proteins, one of the major challenges in CHO cell line generation (CLG) is how to efficiently identify those rare, high-producing clones among a large population of low- and non-productive clones. It is not unusual that several hundred individual clones need to be screened for the identification of a commercial clonal cell line with acceptable productivity and growth profile making the cell line appropriate for commercial application. This inefficiency makes the process of CLG both time consuming and laborious. Currently, there are two main CHO expression systems, dihydrofolate reductase (DHFR)-based methotrexate (MTX) selection and glutamine synthetase (GS)-based methionine sulfoximine (MSX) selection, that have been in wide industrial use. Since selection of recombinant cell lines in the GS-CHO system is based on the balance between the expression of the GS gene introduced by the expression plasmid and the addition of the GS inhibitor, L-MSX, the expression of GS from the endogenous GS gene in parental CHOK1SV cells will likely interfere with the selection process. To study endogenous GS expression's potential impact on selection efficiency, GS-knockout CHOK1SV cell lines were generated using the zinc finger nuclease (ZFN) technology designed to specifically target the endogenous CHO GS gene. The high efficiency (∼2%) of bi-allelic modification on the CHO GS gene supports the unique advantages of the ZFN technology, especially in CHO cells. GS enzyme function disruption was confirmed by the observation of glutamine-dependent growth of all GS-knockout cell lines. Full evaluation of the GS-knockout cell lines in a standard industrial cell culture process was performed. Bulk culture productivity improved two- to three-fold through the use of GS-knockout cells as parent cells. The selection stringency was

  15. Cell fusion as a tool for rice improvement

    Energy Technology Data Exchange (ETDEWEB)

    Hayashi, Y; Kyozuka, J; Terada, R; Nishibayashi, S; Shimamoto, K [Plantech Research Institute, Kamoshida, Midori-ku, Yokohama (Japan)

    1990-01-01

    Full text: Cell fusion offers a unique opportunity to hybridize sexually incompatible species and to mix cytoplasmic genomes in higher plants. Recent progress in plant regeneration from rice protoplasts facilitates an evaluation of the cell fusion method for rice improvement. By using electrofusion of protoplasts, we obtained hybrid/cybrid plants of the following combinations: Hybrids of rice x barnyard grass (E. oryzicola); Hybrids of rice x wild Oryza species; Cybrids of rice with transferred cms cytoplasm. For the latter, protoplasts irradiated with 70 krad x-rays were used. (author)

  16. Improving efficacy of cancer immunotherapy by genetic modification of natural killer cells.

    Science.gov (United States)

    Burga, Rachel A; Nguyen, Tuongvan; Zulovich, Jane; Madonna, Sarah; Ylisastigui, Loyda; Fernandes, Rohan; Yvon, Eric

    2016-11-01

    Natural killer (NK) cells are members of the innate immune system that recognize target cells via activating and inhibitory signals received through cell receptors. Derived from the lymphoid lineage, NK cells are able to produce cytokines and exert a cytotoxic effect on viral infected and malignant cells. It is their unique ability to lyse target cells rapidly and without prior education that renders NK cells a promising effector cell for adoptive cell therapy. However, both viruses and tumors employ evasion strategies to avoid attack by NK cells, which represent biological challenges that need to be harnessed to fully exploit the cytolytic potential of NK cells. Using genetic modification, the function of NK cells can be enhanced to improve their homing, cytolytic activity, in vivo persistence and safety. Examples include gene modification to express chemokine, high-affinity Fc receptor and chimeric antigen receptors, suicide genes and the forced expression of cytokines such as interleukin (IL)-2 and IL-15. Preclinical studies have clearly demonstrated that such approaches are effective in improving NK-cell function, homing and safety. In this review, we summarize the recent advances in the genetic manipulations of NK cells and their application for cellular immunotherapeutic strategies. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  17. An improved ghost-cell immersed boundary method for compressible flow simulations

    KAUST Repository

    Chi, Cheng; Lee, Bok Jik; Im, Hong G.

    2016-01-01

    This study presents an improved ghost-cell immersed boundary approach to represent a solid body in compressible flow simulations. In contrast to the commonly used approaches, in the present work ghost cells are mirrored through the boundary

  18. Bone marrow-derived cells for cardiovascular cell therapy: an optimized GMP method based on low-density gradient improves cell purity and function.

    Science.gov (United States)

    Radrizzani, Marina; Lo Cicero, Viviana; Soncin, Sabrina; Bolis, Sara; Sürder, Daniel; Torre, Tiziano; Siclari, Francesco; Moccetti, Tiziano; Vassalli, Giuseppe; Turchetto, Lucia

    2014-09-27

    Cardiovascular cell therapy represents a promising field, with several approaches currently being tested. The advanced therapy medicinal product (ATMP) for the ongoing METHOD clinical study ("Bone marrow derived cell therapy in the stable phase of chronic ischemic heart disease") consists of fresh mononuclear cells (MNC) isolated from autologous bone marrow (BM) through density gradient centrifugation on standard Ficoll-Paque. Cells are tested for safety (sterility, endotoxin), identity/potency (cell count, CD45/CD34/CD133, viability) and purity (contaminant granulocytes and platelets). BM-MNC were isolated by density gradient centrifugation on Ficoll-Paque. The following process parameters were optimized throughout the study: gradient medium density; gradient centrifugation speed and duration; washing conditions. A new manufacturing method was set up, based on gradient centrifugation on low density Ficoll-Paque, followed by 2 washing steps, of which the second one at low speed. It led to significantly higher removal of contaminant granulocytes and platelets, improving product purity; the frequencies of CD34+ cells, CD133+ cells and functional hematopoietic and mesenchymal precursors were significantly increased. The methodological optimization described here resulted in a significant improvement of ATMP quality, a crucial issue to clinical applications in cardiovascular cell therapy.

  19. Neural crest stem cell multipotency requires Foxd3 to maintain neural potential and repress mesenchymal fates.

    Science.gov (United States)

    Mundell, Nathan A; Labosky, Patricia A

    2011-02-01

    Neural crest (NC) progenitors generate a wide array of cell types, yet molecules controlling NC multipotency and self-renewal and factors mediating cell-intrinsic distinctions between multipotent versus fate-restricted progenitors are poorly understood. Our earlier work demonstrated that Foxd3 is required for maintenance of NC progenitors in the embryo. Here, we show that Foxd3 mediates a fate restriction choice for multipotent NC progenitors with loss of Foxd3 biasing NC toward a mesenchymal fate. Neural derivatives of NC were lost in Foxd3 mutant mouse embryos, whereas abnormally fated NC-derived vascular smooth muscle cells were ectopically located in the aorta. Cranial NC defects were associated with precocious differentiation towards osteoblast and chondrocyte cell fates, and individual mutant NC from different anteroposterior regions underwent fate changes, losing neural and increasing myofibroblast potential. Our results demonstrate that neural potential can be separated from NC multipotency by the action of a single gene, and establish novel parallels between NC and other progenitor populations that depend on this functionally conserved stem cell protein to regulate self-renewal and multipotency.

  20. A missense mutation in MKRN3 in a Danish girl with central precocious puberty and her brother with early puberty.

    Science.gov (United States)

    Känsäkoski, Johanna; Raivio, Taneli; Juul, Anders; Tommiska, Johanna

    2015-12-01

    Idiopathic central precocious puberty (ICPP) results from the premature reactivation of the hypothalamic-pituitary-gonadal axis leading to development of secondary sexual characteristics prior to 8 y in girls or 9 y in boys. Since the initial discovery of mutations in the maternally imprinted MKRN3 gene in 2013, several case reports have described mutations in this gene in ICPP patients from different populations, highlighting the importance of MKRN3 as a regulator of pubertal onset. We screened 29 Danish girls with ICPP for mutations in MKRN3. Expression of MKRN3 in human hypothalamic complementary DNA (cDNA) was investigated by PCR. One paternally inherited rare variant, c.1034G>A (p.Arg345His), was identified in one girl with ICPP and in her brother with early puberty. The variant is predicted to be deleterious by three different in silico prediction programs. Expression of MKRN3 was confirmed in adult human hypothalamus. Our results are in line with previous studies in which paternally inherited MKRN3 mutations have been found both in males and in females with ICPP or early puberty. Our report further expands the set of MKRN3 mutations identified in ICPP patients across diverse populations, thus supporting the major regulatory function of MKRN3 in pubertal onset.

  1. Leptin rapidly activates PPARs in C2C12 muscle cells

    International Nuclear Information System (INIS)

    Bendinelli, Paola; Piccoletti, Roberta; Maroni, Paola

    2005-01-01

    Experimental evidence suggests that leptin operates on the tissues, including skeletal muscle, also by modulating gene expression. Using electrophoretic mobility shift assays, we have shown that physiological doses of leptin promptly increase the binding of C2C12 cell nuclear extracts to peroxisome proliferator-activated receptor (PPAR) response elements in oligonucleotide probes and that all three PPAR isoforms participate in DNA-binding complexes. We pre-treated C2C12 cells with AACOCF 3 , a specific inhibitor of cytosolic phospholipase A 2 (cPLA 2 ), an enzyme that supplies ligands to PPARs, and found that it abrogates leptin-induced PPAR DNA-binding activity. Leptin treatment significantly increased cPLA 2 activity, evaluated as the release of [ 3 H]arachidonic acid from pre-labelled C2C12 cells, as well as phosphorylation. Further, using MEK1 inhibitor PD-98059 we showed that leptin activates cPLA 2 through ERK induction. These results support a direct effect of leptin on skeletal muscle cells, and suggest that the hormone may modulate muscle transcription also by precocious activation of PPARs through ERK-cPLA 2 pathway

  2. miR-137 forms a regulatory loop with nuclear receptor TLX and LSD1 in neural stem cells.

    Science.gov (United States)

    Sun, GuoQiang; Ye, Peng; Murai, Kiyohito; Lang, Ming-Fei; Li, Shengxiu; Zhang, Heying; Li, Wendong; Fu, Chelsea; Yin, Jason; Wang, Allen; Ma, Xiaoxiao; Shi, Yanhong

    2011-11-08

    miR-137 is a brain-enriched microRNA. Its role in neural development remains unknown. Here we show that miR-137 has an essential role in controlling embryonic neural stem cell fate determination. miR-137 negatively regulates cell proliferation and accelerates neural differentiation of embryonic neural stem cells. In addition, we show that the histone lysine-specific demethylase 1 (LSD1), a transcriptional co-repressor of nuclear receptor TLX, is a downstream target of miR-137. In utero electroporation of miR-137 in embryonic mouse brains led to premature differentiation and outward migration of the transfected cells. Introducing a LSD1 expression vector lacking the miR-137 recognition site rescued miR-137-induced precocious differentiation. Furthermore, we demonstrate that TLX, an essential regulator of neural stem cell self-renewal, represses the expression of miR-137 by recruiting LSD1 to the genomic regions of miR-137. Thus, miR-137 forms a feedback regulatory loop with TLX and LSD1 to control the dynamics between neural stem cell proliferation and differentiation during neural development.

  3. Stomatal development in barley as a bioassay for cell differentation: its use with X-rays and gibberellic acid

    Energy Technology Data Exchange (ETDEWEB)

    Zeiger, E; Rafalowsky, J [Chile Univ., Santiago. Departamento de Biologia y Genetica

    1976-01-01

    A bioassay for cell differentiation during stomatal development in barley (Hordeum vulgare L.) has been defined. It uses cell kinetics analysis to follow the temporal course of cell divisions in the developmental sequence. The rate of displacement of the divisions along the stomatal rows provides a measure of differentiation. Physical factors affecting differentiation may be tested with intact seedlings. The bioassay showed that X-ray irradiation inhibited the divisions leading to stomatal formation. The inhibition kinetics was similar to the one observed in root meristems. Chemical substances are tested by culturing excised shoots in a synthetic medium. Detached leaves responded to sucrose and light with increasing rates of stomatal divisions. Gibberellic acid (GA/sub 3/) was assayed for its effects on the growth of the leaf and the differentiation of stomata. GA/sub 3/ increased the overall length of the leaves without affecting the rates of cell division. The treated cells responded with increased elongation rates and a precocious initiation and completion of cell enlargement. GA/sub 3/ had no specific effect on stomatal differentiation.

  4. Mesenchymal Stem Cells Enhance Liver Regeneration via Improving Lipid Accumulation and Hippo Signaling

    Directory of Open Access Journals (Sweden)

    Yang Liu

    2018-01-01

    Full Text Available The liver has the potential to regenerate after injury. It is a challenge to improve liver regeneration (LR after liver resection in clinical practice. Bone morrow-derived mesenchymal stem cells (MSCs have shown to have a role in various liver diseases. To explore the effects of MSCs on LR, we established a model of 70% partial hepatectomy (PHx. Results revealed that infusion of MSCs could improve LR through enhancing cell proliferation and cell growth during the first 2 days after PHx, and MSCs could also restore liver synthesis function. Infusion of MSCs also improved liver lipid accumulation partly via mechanistic target of rapamycin (mTOR signaling and enhanced lipid β-oxidation support energy for LR. Rapamycin-induced inhibition of mTOR decreased liver lipid accumulation at 24 h after PHx, leading to impaired LR. And after infusion of MSCs, a proinflammatory environment formed in the liver, evidenced by increased expression of IL-6 and IL-1β, and thus the STAT3 and Hippo-YAP pathways were activated to improve cell proliferation. Our results demonstrated the function of MSCs on LR after PHx and provided new evidence for stem cell therapy of liver diseases.

  5. Improved cell activity on biodegradable photopolymer scaffolds using titanate nanotube coatings

    Energy Technology Data Exchange (ETDEWEB)

    Beke, S., E-mail: szabolcs.beke@iit.it [Nanophysics, Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova (Italy); Barenghi, R. [IEIIT, National Research Council (CNR), Via De Marini 6, 16149 Genova (Italy); Farkas, B.; Romano, I. [Nanophysics, Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova (Italy); Kőrösi, L. [Department of Biotechnology, Nanophage Therapy Center, Enviroinvest Corporation, Kertváros u. 2, H-7632 Pécs (Hungary); Scaglione, S. [IEIIT, National Research Council (CNR), Via De Marini 6, 16149 Genova (Italy); Brandi, F. [Nanophysics, Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova (Italy); Istituto Nazionale di Ottica, CNR, Via G. Moruzzi 1, 56124-Pisa (Italy)

    2014-11-01

    The development of bioactive materials is in the premise of tissue engineering. For several years, surface functionalization of scaffolds has been one of the most promising approaches to stimulate cellular activity and finally improve implant success. Herein, we describe the development of a bioactive composite scaffold composed of a biodegradable photopolymer scaffold and titanate nanotubes (TNTs). The biodegradable photopolymer scaffolds were fabricated by applying mask-projection excimer laser photocuring at 308 nm. TNTs were synthesized and then spin-coated on the porous scaffolds. Upon culturing fibroblast cells on scaffolds, we found that nanotubes coating affects cell viability and proliferation demonstrating that TNT coatings enhance cell growth on the scaffolds by further improving their surface topography. - Highlights: • Biodegradable scaffolds were produced by mask-assisted UV laser photocuring. • Titanate nanotube deposition was carried out without binding compounds or additives. • Titanate nanotube coatings enhanced cell viability and proliferation.

  6. Improved Anode for a Direct Methanol Fuel Cell

    Science.gov (United States)

    Valdez, Thomas; Narayanan, Sekharipuram

    2005-01-01

    A modified chemical composition has been devised to improve the performance of the anode of a direct methanol fuel cell. The main feature of the modified composition is the incorporation of hydrous ruthenium oxide into the anode structure. This modification can reduce the internal electrical resistance of the cell and increase the degree of utilization of the anode catalyst. As a result, a higher anode current density can be sustained with a smaller amount of anode catalyst. These improvements can translate into a smaller fuel-cell system and higher efficiency of conversion. Some background information is helpful for understanding the benefit afforded by the addition of hydrous ruthenium oxide. The anode of a direct methanol fuel cell sustains the electro-oxidation of methanol to carbon dioxide in the reaction CH3OH + H2O--->CO2 + 6H(+) + 6e(-). An electrocatalyst is needed to enable this reaction to occur. The catalyst that offers the highest activity is an alloy of approximately equal numbers of atoms of the noble metals platinum and ruthenium. The anode is made of a composite material that includes high-surface-area Pt/Ru alloy particles and a proton-conducting ionomeric material. This composite is usually deposited onto a polymer-electrolyte (proton-conducting) membrane and onto an anode gas-diffusion/current-collector sheet that is subsequently bonded to the proton-conducting membrane by hot pressing. Heretofore, the areal density of noble-metal catalyst typically needed for high performance has been about 8 mg/cm2. However, not all of the catalyst has been utilized in the catalyzed electro-oxidation reaction. Increasing the degree of utilization of the catalyst would make it possible to improve the performance of the cell for a given catalyst loading and/or reduce the catalyst loading (thereby reducing the cost of the cell). The use of carbon and possibly other electronic conductors in the catalyst layer has been proposed for increasing the utilization of the

  7. Solid polymeric electrolyte based dye-sensitized solar cell with improved stability

    Science.gov (United States)

    Prasad, Narottam; Kumar, Manish; Patel, K. R.; Roy, M. S.

    2018-05-01

    The impact of polymeric electrolyte was investigated over the performance of dye-sensitized solar cell made with Rose Bengal as sensitizer. Further, the selective influence of TiCl4 treatment and pre-sensitizer deoxycholic acid on nc-TiO2 photoanode was determined in terms of improvement in conversion efficiency of the cell. It is found that the effect of TiCl4 treatment was comparatively more than pre-sensitization with de-oxy cholic acid towards improving the efficiency of the cell. The conversion efficiency on TiCl4 treatment was 0.2% whereas on pre-sensitization with deoxy chollic acid it was 0.1%. The combined effect of both TiCl4 treatment & pre-sensitization with deoxycholic acid leads conversion efficiency to 0.33%.

  8. Leptin and adiponectin levels in girls with central precocious puberty before and during GnRH agonist treatment

    Directory of Open Access Journals (Sweden)

    Jae Won Yoo

    2016-12-01

    Full Text Available PurposeThe effects of gonadotropin-releasing hormone agonist (GnRHa treatment on the energy metabolism in girls with central precocious puberty (CPP are controversial. We focused the changes and related factors of serum levels of leptin and adiponectin in girls with CPP before and during GnRHa treatment.MethodsThirty girls with idiopathic CPP were enrolled in the study. Their auxological data and fasting blood were collected at the baseline and after six months of GnRHa treatment.ResultsAfter treatment, height (P<0.001, weight (P<0.001, and serum leptin levels (P=0.033 were significantly increased, whereas body mass index (BMI, homeostasis model of assessment-insulin resistance, serum adiponectin levels, and adiponectin/leptin ratio exhibited no significant changes. A Pearson correlation analysis showed that height, weight, BMI, and their standard deviation scores (SDSs, but not basal LH, FSH, and estradiol, were significantly correlated with serum leptin levels before and after GnRHa treatment. After a multiple linear regression analysis, only BMI was associated with serum leptin levels. Moreover, leptin SDSs adjusted for BMI were not significantly different before and after GnRHa. The Δ leptin levels (r2=0.207, P=0.012, but not with Δ leptin SDS (r2=0.019, P=0.556, during GnRHa treatment were positively correlated with Δ BMI.ConclusionThese results suggest that GnRHa treatment in girls with CPP does not affect serum levels of leptin and adiponectin and insulin resistance. Serum leptin levels were depend on the changes in BMI during GnRHa treatment.

  9. Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis

    Directory of Open Access Journals (Sweden)

    Abbas Jafari

    2017-02-01

    Full Text Available Secreted factors are a key component of stem cell niche and their dysregulation compromises stem cell function. Legumain is a secreted cysteine protease involved in diverse biological processes. Here, we demonstrate that legumain regulates lineage commitment of human bone marrow stromal cells and that its expression level and cellular localization are altered in postmenopausal osteoporotic patients. As shown by genetic and pharmacological manipulation, legumain inhibited osteoblast (OB differentiation and in vivo bone formation through degradation of the bone matrix protein fibronectin. In addition, genetic ablation or pharmacological inhibition of legumain activity led to precocious OB differentiation and increased vertebral mineralization in zebrafish. Finally, we show that localized increased expression of legumain in bone marrow adipocytes was inversely correlated with adjacent trabecular bone mass in a cohort of patients with postmenopausal osteoporosis. Our data suggest that altered proteolytic activity of legumain in the bone microenvironment contributes to decreased bone mass in postmenopausal osteoporosis.

  10. Juvenile granulosa cell ovarian tumor: a case report and review of literature.

    Science.gov (United States)

    Sivasankaran, Sujatha; Itam, Paul; Ayensu-Coker, Leslie; Sanchez, Judith; Egler, Rachel A; Anderson, Matthew L; Brandt, Mary L; Dietrich, Jennifer E

    2009-10-01

    Juvenile granulosa cell tumors (JGCT) are rare ovarian tumors that frequently present with precocious puberty. Presentation in infants less than a year of age is also rare. We describe a 10-month-old infant who presented with both premature thelarche and adrenarche due to JGCT. Laboratory evaluation revealed classic elevation of estradiol and inhibin B, and less classic elevation of total and free testosterone. Oophorectomy and staging resulted in a diagnosis of Stage IA JGCT. Survival rates are >95% among patients diagnosed under 10 years of age. Tumor recurrence is rare but can occur as late as 48 months. Therefore, tumor surveillance is warranted for patients with even a Stage IA JGCT and involves monitoring serial inhibin B levels along with intermittent imaging.

  11. Association of PAEs with Precocious Puberty in Children: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Yi Wen

    2015-12-01

    Full Text Available Background: Precocious puberty (PP currently affects 1 in 5000 children and is 10 times more common in girls. Existing studies have tried to detect an association between phathalic acid esters (PAEs and PP, but the results did not reach a consensus. Objective: To estimate the association between PAEs and children with PP based on current evidence. Methods: Databases including PubMed (1978 to March 2015, OVID (1946 to March 2015, Web of Science (1970 to March 2015, EBSCO (1976 to March 2015, CNKI (1979 to March 2015, WANFANG DATA (1987 to March 2015, CBM (1978 to March 2015 and CQVIP (1989 to March 2015 were searched to identify all case-control studies that determined the exposure and concentration of PAEs and their metabolites in children with PP. Meta-analysis of the pooled standard mean difference (SMD and odds ratio (OR with 95% confidence intervals (CI were calculated. Results: A total of 14 studies involving 2223 subjects were finally included. The pooled estimates showed that PP was associated with di-(2-ethylhexyl-phthalate (DEHP exposure (OR: 3.90, 95% CI: 2.77 to 5.49. Besides, the concentration of DEHP (SMD: 1.73, 95% CI: 0.54 to 2.91 and di-n-butyl phthalate (DBP (SMD: 4.31, 95% CI: 2.67 to 5.95 in the PP group were significantly higher than those in the control group, respectively, while no difference was detected between case and control groups in either serum or urinary concentration of mono-(2-ethylhexyl-phthalate (MEHP, monobutyl phthalate (MBP, mono(2-ethyl-5-oxohexyl phthalate(MEOHP, mono-(2-ethyl-5-carboxypentyl phthalate (MECPP, monomethyl phthalate (MMP, monobenzyl phthalate (MBzP or monoethyl phthalate (MEP. Conclusions: Exposure of DEHP and DBP might be associated with PP risk for girls, however, there is no evidence to show an association between the exposure to most PAE metabolites and PP. Given the moderate strength of the results, well-designed cohort studies with large sample size should be performed in future.

  12. COUP-TFI mitotically regulates production and migration of dentate granule cells and modulates hippocampal Cxcr4 expression.

    Science.gov (United States)

    Parisot, Joséphine; Flore, Gemma; Bertacchi, Michele; Studer, Michèle

    2017-06-01

    Development of the dentate gyrus (DG), the primary gateway for hippocampal inputs, spans embryonic and postnatal stages, and involves complex morphogenetic events. We have previously identified the nuclear receptor COUP-TFI as a novel transcriptional regulator in the postnatal organization and function of the hippocampus. Here, we dissect its role in DG morphogenesis by inactivating it in either granule cell progenitors or granule neurons. Loss of COUP-TFI function in progenitors leads to decreased granule cell proliferative activity, precocious differentiation and increased apoptosis, resulting in a severe DG growth defect in adult mice. COUP-TFI-deficient cells express high levels of the chemokine receptor Cxcr4 and migrate abnormally, forming heterotopic clusters of differentiated granule cells along their paths. Conversely, high COUP-TFI expression levels downregulate Cxcr4 expression, whereas increased Cxcr4 expression in wild-type hippocampal cells affects cell migration. Finally, loss of COUP-TFI in postmitotic cells leads to only minor and transient abnormalities, and to normal Cxcr4 expression. Together, our results indicate that COUP-TFI is required predominantly in DG progenitors for modulating expression of the Cxcr4 receptor during granule cell neurogenesis and migration. © 2017. Published by The Company of Biologists Ltd.

  13. A Hyaluronan-Based Injectable Hydrogel Improves the Survival and Integration of Stem Cell Progeny following Transplantation

    Directory of Open Access Journals (Sweden)

    Brian G. Ballios

    2015-06-01

    Full Text Available The utility of stem cells and their progeny in adult transplantation models has been limited by poor survival and integration. We designed an injectable and bioresorbable hydrogel blend of hyaluronan and methylcellulose (HAMC and tested it with two cell types in two animal models, thereby gaining an understanding of its general applicability for enhanced cell distribution, survival, integration, and functional repair relative to conventional cell delivery in saline. HAMC improves cell survival and integration of retinal stem cell (RSC-derived rods in the retina. The pro-survival mechanism of HAMC is ascribed to the interaction of the CD44 receptor with HA. Transient disruption of the retinal outer limiting membrane, combined with HAMC delivery, results in significantly improved rod survival and visual function. HAMC also improves the distribution, viability, and functional repair of neural stem and progenitor cells (NSCs. The HAMC delivery system improves cell transplantation efficacy in two CNS models, suggesting broad applicability.

  14. Improving poor fill factors for solar cells via light-induced plating

    International Nuclear Information System (INIS)

    Xing Zhao; Jia Rui; Ding Wuchang; Meng Yanlong; Jin Zhi; Liu Xinyu

    2012-01-01

    Silicon solar cells are prepared following the conventional fabrication processes, except for the metallization firing process. The cells are divided into two groups with higher and lower fill factors, respectively. After light-induced plating (LIP), the fill factors of the solar cells in both groups with different initial values reach the same level. Scanning electron microscope (SEM) images are taken under the bulk silver electrodes, which prove that the improvement for cells with a poor factor after LIP should benefit from sufficient exploitation of the high density silver crystals formed during the firing process. Moreover, the application of LIP to cells with poor electrode contact performance, such as nanowire cells and radial junction solar cells, is proposed. (semiconductor devices)

  15. MOLTEN CARBONATE FUEL CELL PRODUCT DESIGN IMPROVEMENT

    Energy Technology Data Exchange (ETDEWEB)

    H.C. Maru; M. Farooque

    2003-03-01

    The program efforts are focused on technology and system optimization for cost reduction, commercial design development, and prototype system field trials. The program is designed to advance the carbonate fuel cell technology from full-size field test to the commercial design. FuelCell Energy, Inc. (FCE) is in the later stage of the multiyear program for development and verification of carbonate fuel cell based power plants supported by DOE/NETL with additional funding from DOD/DARPA and the FuelCell Energy team. FCE has scaled up the technology to full-size and developed DFC{reg_sign} stack and balance-of-plant (BOP) equipment technology to meet product requirements, and acquired high rate manufacturing capabilities to reduce cost. FCE has designed submegawatt (DFC300A) and megawatt (DFC1500 and DFC3000) class fuel cell products for commercialization of its DFC{reg_sign} technology. A significant progress was made during the reporting period. The reforming unit design was optimized using a three-dimensional stack simulation model. Thermal and flow uniformities of the oxidant-In flow in the stack module were improved using computational fluid dynamics based flow simulation model. The manufacturing capacity was increased. The submegawatt stack module overall cost was reduced by {approx}30% on a per kW basis. An integrated deoxidizer-prereformer design was tested successfully at submegawatt scale using fuels simulating digester gas, coal bed methane gas and peak shave (natural) gas.

  16. Methods For Improving Polymeric Materials For Use In Solar Cell Applications

    Science.gov (United States)

    Hanoka, Jack I.

    2003-07-01

    A method of manufacturing a solar cell module includes the use of low cost polymeric materials with improved mechanical properties. A transparent encapsulant layer is placed adjacent a rear surface of a front support layer. Interconnected solar cells are positioned adjacent a rear surface of the transparent encapsulant layer to form a solar cell assembly. A backskin layer is placed adjacent a rear surface of the solar cell assembly. At least one of the transparent encapsulant layer and the backskin layer are predisposed to electron beam radiation.

  17. Sonic Hedgehog switches on Wnt/planar cell polarity signaling in commissural axon growth cones by reducing levels of Shisa2

    Science.gov (United States)

    Onishi, Keisuke

    2017-01-01

    Commissural axons switch on responsiveness to Wnt attraction during midline crossing and turn anteriorly only after exiting the floor plate. We report here that Sonic Hedgehog (Shh)-Smoothened signaling downregulates Shisa2, which inhibits the glycosylation and cell surface presentation of Frizzled3 in rodent commissural axon growth cones. Constitutive Shisa2 expression causes randomized turning of post-crossing commissural axons along the anterior–posterior (A–P) axis. Loss of Shisa2 led to precocious anterior turning of commissural axons before or during midline crossing. Post-crossing commissural axon turning is completely randomized along the A–P axis when Wntless, which is essential for Wnt secretion, is conditionally knocked out in the floor plate. This regulatory link between Shh and planar cell polarity (PCP) signaling may also occur in other developmental processes. PMID:28885142

  18. APC/C-Cdh1-dependent anaphase and telophase progression during mitotic slippage

    Directory of Open Access Journals (Sweden)

    Toda Kazuhiro

    2012-02-01

    Full Text Available Abstract Background The spindle assembly checkpoint (SAC inhibits anaphase progression in the presence of insufficient kinetochore-microtubule attachments, but cells can eventually override mitotic arrest by a process known as mitotic slippage or adaptation. This is a problem for cancer chemotherapy using microtubule poisons. Results Here we describe mitotic slippage in yeast bub2Δ mutant cells that are defective in the repression of precocious telophase onset (mitotic exit. Precocious activation of anaphase promoting complex/cyclosome (APC/C-Cdh1 caused mitotic slippage in the presence of nocodazole, while the SAC was still active. APC/C-Cdh1, but not APC/C-Cdc20, triggered anaphase progression (securin degradation, separase-mediated cohesin cleavage, sister-chromatid separation and chromosome missegregation, in addition to telophase onset (mitotic exit, during mitotic slippage. This demonstrates that an inhibitory system not only of APC/C-Cdc20 but also of APC/C-Cdh1 is critical for accurate chromosome segregation in the presence of insufficient kinetochore-microtubule attachments. Conclusions The sequential activation of APC/C-Cdc20 to APC/C-Cdh1 during mitosis is central to accurate mitosis. Precocious activation of APC/C-Cdh1 in metaphase (pre-anaphase causes mitotic slippage in SAC-activated cells. For the prevention of mitotic slippage, concomitant inhibition of APC/C-Cdh1 may be effective for tumor therapy with mitotic spindle poisons in humans.

  19. An Improved Ghost-cell Immersed Boundary Method for Compressible Inviscid Flow Simulations

    KAUST Repository

    Chi, Cheng

    2015-01-01

    This study presents an improved ghost-cell immersed boundary approach to represent a solid body in compressible flow simulations. In contrast to the commonly used approaches, in the present work ghost cells are mirrored through the boundary

  20. Tailoring cyanobacterial cell factory for improved industrial properties.

    Science.gov (United States)

    Luan, Guodong; Lu, Xuefeng

    Photosynthetic biomanufacturing provides a promising solution for sustainable production of biofuels and biochemicals. Cyanobacteria are among the most promising microbial platforms for the construction of photosynthetic cell factories. Metabolic engineering of cyanobacteria has enabled effective photosynthetic synthesis of diverse natural or non-natural metabolites, while commercialization of photosynthetic biomanufacturing is usually restricted by process and economic feasibilities. In actual outdoor conditions, active cell growth and product synthesis is restricted to narrow light exposure windows of the day-night cycles and is threatened by diverse physical, chemical, and biological environmental stresses. For biomass harvesting and bioproduct recovery, energy and cost consuming processing and equipment is required, which further decreases the economic and environmental competitiveness of the entire process. To facilitate scaled photosynthetic biomanufacturing, lots of efforts have been made to engineer cyanobacterial cell properties required by robust & continual cultivation and convenient & efficient recovery. In this review, we specifically summarized recently reported engineering strategies on optimizing industrial properties of cyanobacterial cells. Through systematically re-editing the metabolism, morphology, mutualism interaction of cyanobacterial chassis cells, the adaptabilities and compatibilities of the cyanobacterial cell factories to the industrial process could be significantly improved. Cell growth and product synthesis of the tailored cyanobacterial cells could be expanded and maintained at night and in stressful environments, while convenient biomass harvesting could also be expected. For developing more feasible cyanobacterial photosynthetic biomanufacturing in large scale, we here propose the importance of tailoring industrial properties of cyanobacteria and outline the directions that should be exploited in the future. Copyright © 2018

  1. Melatonin improves spermatogonial stem cells transplantation efficiency in azoospermic mice

    Directory of Open Access Journals (Sweden)

    Mohammadreza Gholami

    2014-02-01

    Conclusion: Administration of melatonin (20 mg/kg simultaneously with transplantation of spermatogonial stem cells in azoospermia mouse testis increases the efficiency of transplantation and improves structural properties of the testes tissue.

  2. An Improved Model for FE Modeling and Simulation of Closed Cell Al-Alloy Foams

    OpenAIRE

    Hasan, MD. Anwarul

    2010-01-01

    Cell wall material properties of Al-alloy foams have been derived by a combination of nanoindentation experiment and numerical simulation. Using the derived material properties in FE (finite element) modeling of foams, the existing constitutive models of closed-cell Al-alloy foams have been evaluated against experimental results. An improved representative model has been proposed for FE analysis of closed-cell Al-alloy foams. The improved model consists of a combination of spherical and cruci...

  3. Improvement of the Chinese bean [Vigna Unguiculata (L.) Walp.], through radioinduced mutagenesis

    International Nuclear Information System (INIS)

    Salmeron E, J.; Bueno J, J.E.; Valencia E, F.; Solis M, M.; Cervantes S, T.; Cruz T, E. de la

    2006-01-01

    The advances in the process of genetic improvement of the Chinese bean (Vigna Unguiculata (L.) are presented, high nutritious value that it is evaluating as alternative for marginal areas producers of the State of Guerrero. The method of improvement applied it is recurrent radiation, continued by selection cycles applying the method of progeny by plant. The applied radiation doses were 200 and 250 Gray. The established selection approaches are: resistant plants or tolerant to the plagues attack and illnesses, vigorous, with more height to the first sheath, of compact and certain growth, with short internodes, bigger number of sheaths by plant and of grains by sheath, bigger number of grain size, among others. The obtained results show that the dose that induces bigger variability and that it has propitiated the biggest quantity in possible mutants it is 200Gy. Precocious plants with more height to the first sheath, with certain growth as well as with bigger number and sheaths size have been detected. The selected plants have incorporated to an increment process by means of the progeny method by plant. (Author)

  4. Linnorm: improved statistical analysis for single cell RNA-seq expression data.

    Science.gov (United States)

    Yip, Shun H; Wang, Panwen; Kocher, Jean-Pierre A; Sham, Pak Chung; Wang, Junwen

    2017-12-15

    Linnorm is a novel normalization and transformation method for the analysis of single cell RNA sequencing (scRNA-seq) data. Linnorm is developed to remove technical noises and simultaneously preserve biological variations in scRNA-seq data, such that existing statistical methods can be improved. Using real scRNA-seq data, we compared Linnorm with existing normalization methods, including NODES, SAMstrt, SCnorm, scran, DESeq and TMM. Linnorm shows advantages in speed, technical noise removal and preservation of cell heterogeneity, which can improve existing methods in the discovery of novel subtypes, pseudo-temporal ordering of cells, clustering analysis, etc. Linnorm also performs better than existing DEG analysis methods, including BASiCS, NODES, SAMstrt, Seurat and DESeq2, in false positive rate control and accuracy. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  5. Insulin resistance, obesity, hypofibrinolysis, hyperandrogenism, and coronary heart disease risk factors in 25 pre-perimenarchal girls age < or =14 years, 13 with precocious puberty, 23 with a first-degree relative with polycystic ovary syndrome.

    Science.gov (United States)

    Glueck, Charles J; Morrison, John A; Wang, Ping

    2008-10-01

    Pre-peri-menarchal diagnosis of polycystic ovary syndrome (PCOS) is important, because intervention with metformin-diet may prevent progression to full blown PCOS. In 25 girls age PCOS, 10 pre-, 15 post-menarchal, 13 with precocious puberty, 23 with a first-degree relative with PCOS, we hypothesized that reversible coronary heart disease (CHD) risk factors, insulin resistance, clinical and biochemical hyperandrogenism, and hypofibrinolysis were already established. Fasting measures: insulin, glucose, total, LDL- (LDL-C), and HDL-cholesterol (HDL-C), triglycerides (TG), systolic and diastolic blood pressure (SBP, DBP), plasminogen activator inhibitor activity (PAI-Fx), total (T) and free testosterone (FT), androstenedione, and DHEAS. Clinical and/or biochemical hyperandrogenism was present in all 25 girls, with elevations of T or FT, or androstenedione in seven of ten pre-menarchal girls and in all 15 post-menarche. PAI-Fx was high in 28% of the 25 girls vs 6.5% in age-gender-race matched controls (p = 0.013). Categorized by race-age-specific distributions in 870 schoolgirls, the 25 girls with probable familial PCOS were more likely to have top decile body mass index (BMI), insulin, HOMA-insulin resistance (HOMA-IR), SBP, DBP, and TG, and bottom decile HDL-C. By analysis of variance, adjusting for race, age and BMI, PCOS girls had higher FT and waist circumference than controls, but did not differ for SBP, DBP, HDL-C, or TG (p>0.05). Pre-peri-menarchal acquisition of centripetal obesity amplifies CHD risk factors and hypofibrinolysis in hyperandrogenemic girls with probable familial PCOS and precocious puberty. When schoolgirls become as obese as girls with probable familial PCOS, they acquire the same CHD risk factors, and differ only by lower free T and less centripetal obesity.

  6. Development of CAR T cells designed to improve antitumor efficacy and safety

    OpenAIRE

    Jaspers, Janneke E.; Brentjens, Renier J.

    2017-01-01

    Chimeric antigen receptor (CAR) T cell therapy has shown promising efficacy against hematologic malignancies. Antitumor activity of CAR T cells, however, needs to be improved to increase therapeutic efficacy in both hematologic and solid cancers. Limitations to overcome are ‘on-target, off-tumor’ toxicity, antigen escape, short CAR T cell persistence, little expansion, trafficking to the tumor and inhibition of T cell activity by an inhibitory tumor microenvironment. Here we will discuss how ...

  7. Methods for Using Small Non-Coding RNAs to Improve Recombinant Protein Expression in Mammalian Cells

    Directory of Open Access Journals (Sweden)

    Sarah Inwood

    2018-01-01

    Full Text Available The ability to produce recombinant proteins by utilizing different “cell factories” revolutionized the biotherapeutic and pharmaceutical industry. Chinese hamster ovary (CHO cells are the dominant industrial producer, especially for antibodies. Human embryonic kidney cells (HEK, while not being as widely used as CHO cells, are used where CHO cells are unable to meet the needs for expression, such as growth factors. Therefore, improving recombinant protein expression from mammalian cells is a priority, and continuing effort is being devoted to this topic. Non-coding RNAs are RNA segments that are not translated into a protein and often have a regulatory role. Since their discovery, major progress has been made towards understanding their functions. Non-coding RNA has been investigated extensively in relation to disease, especially cancer, and recently they have also been used as a method for engineering cells to improve their protein expression capability. In this review, we provide information about methods used to identify non-coding RNAs with the potential of improving recombinant protein expression in mammalian cell lines.

  8. GA 3 improves flower yield in some cucurbits treated with lead and ...

    African Journals Online (AJOL)

    Present study reveals florigenic effects of growth hormones (i.e. gibberellic acid, GA3) and heavy metals (i.e., Pb(NO3)2 and HgCl2) in Cucumis sativus L. and Momordica charantia L. Applied GA3 at 400 ppm caused precocious flowering, increasing the number of pistillate and staminate flowers in both plants. Application of ...

  9. Use of piracetam improves sickle cell deformability in vitro and in vivo.

    Science.gov (United States)

    Gini, E K; Sonnet, J

    1987-01-01

    Microsieving diluted suspensions of oxygenated sickle cell anaemia (HbSS) cells on polycarbonate filters shows that piracetam improves the red cell deformability in vitro. In vivo an oral intake of 160 mg/kg/day divided in four doses enhances the HbSS cell deformability as actively as it does in in vitro experiments. The drug is also able partially to restore the impaired deformability of physiologically deoxygenated HbSS cells. These findings are consistent with the results of clinical trials, which show that continuous treatment with piracetam reduces the incidence of vaso-occlusive crises in patients with sickle cell disease. PMID:3818978

  10. Improvement of mammalian cell culture performance through surfactant enabled concentrated feed media.

    Science.gov (United States)

    Hossler, Patrick; McDermott, Sean; Racicot, Christopher; Fann, John C H

    2013-01-01

    The design of basal and feed media in mammalian cell culture is paramount towards ensuring acceptable upstream process performance in various operation modes, especially fed-batch culture. Mammalian cell culture media designs have evolved from the classical formulations designed by Eagle and Ham, to today's formulations designed from continuous improvement and statistical frameworks. Feed media is especially important for ensuring robust cell growth, productivity, and ensuring the product quality of recombinant therapeutics are within acceptable ranges. Numerous studies have highlighted the benefit of various media designs, supplements, and feed addition strategies towards the resulting cell culture process. In this work we highlight the use of a top-down level approach towards feed media design enabled by the use of select surfactants for the targeted enrichment of a chemically defined feed media. The use of the enriched media was able to improve product titers at g/L levels, without adversely impacting the growth of multiple Chinese Hamster Ovary cell lines or the product quality of multiple recombinant antibodies. © 2013 American Institute of Chemical Engineers.

  11. Nanoscale Dimples for Improved Absorption in and Efficiency of Organic Solar Cells

    DEFF Research Database (Denmark)

    Goszczak, Arkadiusz Jaroslaw; Adam, Jost; Cielecki, Pawel Piotr

    Organic solar cells (OSC’s) have attracted much attention in the past years due to their low costs, light weight and mechanical flexibility. A promising method for improving the power conversion efficiencies of the devices is by incorporating structured electrodes in the solar cell architecture....... That way light absorption in the active layers of the devices can be improved. A cheap and large-scale production compatible method for structuring the electrodes in OSC’s is by the use of Anodic Alumina Oxide (AAO) membranes. Here, nano-scale pores of controlled dimensions are formed through anodic...

  12. LIN28B polymorphisms are associated with central precocious puberty and early puberty in girls

    Directory of Open Access Journals (Sweden)

    Sung Won Park

    2012-10-01

    Full Text Available &lt;B&gt;Purpose:&lt;/B&gt; Single-nucleotide polymorphism (SNP markers within &lt;i&gt;LIN28B&lt;/i&gt; have been reported to be related to the timing of pubertal growth. However, no study has investigated the frequency of genetic markers in girls with precocious puberty (PP or early puberty (EP. This study aimed to determine the frequency of putative genetic markers in girls with PP or EP. &lt;B&gt;Methods:&lt;/B&gt; Genomic DNAs were obtained from 77 and 109 girls that fulfilled the criteria for PP and EP, respectively. The controls in this study were 144 healthy volunteers between 20 and 30 years of age. The haplotypes were reconstructed using 11 SNPs of &lt;i&gt;LIN28B&lt;/i&gt;, and haplotype association analysis was performed. The haplotype frequencies were compared. Differences in the clinical and laboratory parameters were analyzed according to the haplotype dosage. &lt;B&gt;Results:&lt;/B&gt; Eleven SNPs in &lt;i&gt;LIN28B&lt;/i&gt; were all located in a block that was in linkage disequilibrium. The haplotype could be reconstructed using 2 representative SNPs, rs4946651 and rs369065. The AC haplotype was less frequently observed in the PP group than in the controls (0.069 vs. 0.144, &lt;I&gt;P&lt;/I&gt;=0.010. The trend that girls with non-AC haplotypes tended to have earlier puberty onset (&lt;I&gt;P&lt;/I&gt;=0.037 was illustrated even in the EP+PP patient group by Kaplan-Meier analysis. &lt;B&gt;Conclusion:&lt;/B&gt; The results of the present study showed that non-AC haplotypes of &lt;i&gt;LIN28B&lt;/i&gt;had a significant association with PP in girls.

  13. PhEXPA1, a Petunia hybrida expansin, is involved in cell wall metabolism and in plant architecture specification.

    Science.gov (United States)

    Dal Santo, Silvia; Fasoli, Marianna; Cavallini, Erika; Tornielli, Giovanni Battista; Pezzotti, Mario; Zenoni, Sara

    2011-12-01

    Expansins are wall-loosening proteins that induce wall stress relaxation and irreversible wall extension in a pH-dependent manner. Despite a substantial body of work has been performed on the characterization of many expansins genes in different plant species, the knowledge about their precise biological roles during plant development remains scarce. To yield insights into the expansion process in Petunia hybrida, PhEXPA1, an expansin gene preferentially expressed in petal limb, has been characterized. The constitutive overexpression of PhEXPA1 significantly increased expansin activity, cells size and organ dimensions. Moreover, 35S::PhEXPA1 transgenic plants exhibited an altered cell wall polymer composition and a precocious timing of axillary meristem development compared with wild-type plants. These findings supported a previous hypothesis that expansins are not merely structural proteins involved in plant cell wall metabolism but they also take part in many plant development processes. Here, to support this expansins dual role, we discuss about differential cell wall-related genes expressed in PhEXPA1 expression mutants and gradients of altered petunia branching pattern. © 2011 Landes Bioscience

  14. Fine-tuning the CAR spacer improves T-cell potency

    Science.gov (United States)

    Watanabe, Norihiro; Bajgain, Pradip; Sukumaran, Sujita; Ansari, Salma; Heslop, Helen E.; Rooney, Cliona M.; Brenner, Malcolm K.; Leen, Ann M.; Vera, Juan F.

    2016-01-01

    ABSTRACT The adoptive transfer of genetically engineered T cells expressing chimeric antigen receptors (CARs) has emerged as a transformative cancer therapy with curative potential, precipitating a wave of preclinical and clinical studies in academic centers and the private sector. Indeed, significant effort has been devoted to improving clinical benefit by incorporating accessory genes/CAR endodomains designed to enhance cellular migration, promote in vivo expansion/persistence or enhance safety by genetic programming to enable the recognition of a tumor signature. However, our efforts centered on exploring whether CAR T-cell potency could be enhanced by modifying pre-existing CAR components. We now demonstrate how molecular refinements to the CAR spacer can impact multiple biological processes including tonic signaling, cell aging, tumor localization, and antigen recognition, culminating in superior in vivo antitumor activity. PMID:28180032

  15. Tumor-Infiltrating Merkel Cell Polyomavirus-Specific T Cells Are Diverse and Associated with Improved Patient Survival. | Office of Cancer Genomics

    Science.gov (United States)

    Tumor-infiltrating CD8+ T cells are associated with improved survival of patients with Merkel cell carcinoma (MCC), an aggressive skin cancer causally linked to Merkel cell polyomavirus (MCPyV). However, CD8+ T-cell infiltration is robust in only 4% to 18% of MCC tumors. We characterized the T-cell receptor (TCR) repertoire restricted to one prominent epitope of MCPyV (KLLEIAPNC, "KLL") and assessed whether TCR diversity, tumor infiltration, or T-cell avidity correlated with clinical outcome.

  16. Improving the Efficiency of Organic Solar Cells upon Addition of Polyvinylpyridine

    Directory of Open Access Journals (Sweden)

    Rita Rodrigues

    2014-12-01

    Full Text Available We report on the efficiency improvement of organic solar cells (OPVs based on the low energy gap polyfluorene derivative, APFO-3, and the soluble C60 fullerene PCBM, upon addition of a residual amount of poly (4-vinylpyridine (PVP. We find that the addition of 1% by weight of PVP with respect to the APFO-3 content leads to an increase of efficiency from 2.4% to 2.9%. Modifications in the phase separation details of the active layer were investigated as a possible origin of the efficiency increase. At high concentrations of PVP, the blend morphology is radically altered as observed by Atomic Force Microscopy. Although the use of low molecular weight additives is a routine method to improve OPVs efficiency, this report shows that inert polymers, in terms of optical and charge transport properties, may also improve the performance of polymer-based solar cells.

  17. Improved contact metallization for high efficiency EFG polycrystalline silicon solar cells

    International Nuclear Information System (INIS)

    Dube, C.E.; Gonsiorawski, R.C.

    1990-01-01

    Improvements in the performance of polycrystalline silicon solar cells based on a novel, laser patterned contact process are described. Small lots of cells having an average conversion efficiency of 14 + %, with several cells approaching 15%, are reported for cells of 45 cm 2 area. The high efficiency contact design is based on YAG laser patterning of the silicon nitride anti-reflection coating. The Cu metallization is done using light-induced plating, with the cell providing the driving voltage for the plating process. The Cu electrodeposits into the laser defined windows in the AR coating for reduced contact area, following which the Cu bridges on top of the Ar coating to form a continuous finger pattern. The higher cell conversion efficiency is attributed to reduced shadow loss, higher junction quality, and reduced metal-semiconductor interfacial area

  18. Giant Cell Fibroma in a Two-Year-Old Child

    Directory of Open Access Journals (Sweden)

    Anna Carolina Volpi Mello-Moura

    2016-01-01

    Full Text Available The giant cell fibroma is a benign nonneoplastic fibrous tumor of the oral mucosa. It occurs in the first three decades of life in the mandibular gingiva, predominantly, showing predilection for females. This article reports a case of giant cell fibroma in a 2-year-old girl, which is an uncommon age for this lesion. The patient was brought for treatment at the Research and Clinical Center of Dental Trauma in Primary Teeth, where practice for the Discipline of Pediatric Dentistry (Faculty of Dentistry, University of São Paulo, Brazil takes place. During clinical examination, a tissue growth was detected on the lingual gingival mucosa of the lower right primary incisors teeth. The lesion was excised under local anesthesia and submitted to histological examination at the Oral Pathology Department of the Faculty of Dentistry, University of São Paulo, which confirmed the diagnosis of giant cell fibroma. There was no recurrence after 20 months of monitoring. This instance reinforces the importance of oral care from the very first months of life in order to enable doctors to make precocious diagnosis and offer more appropriate treatments for oral diseases, as well as to promote more efficient oral health in the community.

  19. Improving B-cell depletion in systemic lupus erythematosus and rheumatoid arthritis.

    Science.gov (United States)

    Mota, Pedro; Reddy, Venkat; Isenberg, David

    2017-07-01

    Rituximab-based B-cell depletion (BCD) therapy is effective in refractory rheumatoid arthritis (RA) and although used to treat patients with refractory systemic lupus erythematosus (SLE) in routine clinical practice, rituximab failed to meet the primary endpoints in two large randomised controlled trials (RCTs) of non-renal (EXPLORER) and renal (LUNAR) SLE. Areas covered: We review how BCD could be improved to achieve better clinical responses in RA and SLE. Insights into the variability in clinical response to BCD in RA and SLE may help develop new therapeutic strategies. To this end, a literature search was performed using the following terms: rheumatoid arthritis, systemic erythematosus lupus, rituximab and B-cell depletion. Expert commentary: Poor trial design may have, at least partly, contributed to the apparent lack of response to BCD in the two RCTs of patients with SLE. Enhanced B-cell depletion and/or sequential therapy with belimumab may improve clinical response at least in some patients with SLE.

  20. Lanthanide-Doped Ceria Nanoparticles as Backside Coaters to Improve Silicon Solar Cell Efficiency.

    Science.gov (United States)

    Hajjiah, Ali; Samir, Effat; Shehata, Nader; Salah, Mohamed

    2018-05-23

    This paper introduces lanthanide-doped ceria nanoparticles as silicon solar cell back-side coaters, showing their influence on the solar cell efficiency. Ceria nanoparticles can be synthesized to have formed oxygen vacancies (O-vacancies), which are associated with converting cerium ions from the Ce 4+ state ions to the Ce 3+ ones. These O-vacancies follow the rule of improving silicon solar cell conductivity through a hopping mechanism. Besides, under near-ultra violet (near-UV) excitation, the reduced trivalent cerium Ce 3+ ions are directly responsible for down converting the un-absorbed UV wavelengths to a resultant green photo-luminescence emission at ~520 nm, which is absorbed through the silicon solar cell’s active layer. Adding lanthanide elements such as Neodymium “Nd” as ceria nanoparticle dopants helps in forming extra oxygen vacancies (O-vacancies), followed by an increase in the number of Ce 4+ to Ce 3+ ion reductions, thus enhancing the conductivity and photoluminescence down conversion mechanisms. After introducing lanthanide-doped ceria nanoparticles on a silicon solar cell surface, a promising enhancement in the behavior of the solar cell current-voltage curve is observed, and the efficiency is improved by about 25% of its initial value due to the mutual impact of improving both electric conductivity and optical conversions.

  1. Cell Line Data Base: structure and recent improvements towards molecular authentication of human cell lines.

    Science.gov (United States)

    Romano, Paolo; Manniello, Assunta; Aresu, Ottavia; Armento, Massimiliano; Cesaro, Michela; Parodi, Barbara

    2009-01-01

    The Cell Line Data Base (CLDB) is a well-known reference information source on human and animal cell lines including information on more than 6000 cell lines. Main biological features are coded according to controlled vocabularies derived from international lists and taxonomies. HyperCLDB (http://bioinformatics.istge.it/hypercldb/) is a hypertext version of CLDB that improves data accessibility by also allowing information retrieval through web spiders. Access to HyperCLDB is provided through indexes of biological characteristics and navigation in the hypertext is granted by many internal links. HyperCLDB also includes links to external resources. Recently, an interest was raised for a reference nomenclature for cell lines and CLDB was seen as an authoritative system. Furthermore, to overcome the cell line misidentification problem, molecular authentication methods, such as fingerprinting, single-locus short tandem repeat (STR) profile and single nucleotide polymorphisms validation, were proposed. Since this data is distributed, a reference portal on authentication of human cell lines is needed. We present here the architecture and contents of CLDB, its recent enhancements and perspectives. We also present a new related database, the Cell Line Integrated Molecular Authentication (CLIMA) database (http://bioinformatics.istge.it/clima/), that allows to link authentication data to actual cell lines.

  2. An improved out-cell to in-cell rapid transfer system at the HFEF-south

    International Nuclear Information System (INIS)

    Bacca, J.P.; Sherman, E.K.

    1990-01-01

    The Argonne National Laboratory (ANL) Hot Fuel Examination Facility-South (HFEF-S), located at the ANL-West site of the Idaho National Engineering Laboratory, is currently undergoing extensive refurbishment and modifications in preparation for its use, beginning in 1991, in demonstrating remote recycling of fast reactor, metal-alloy fuel as part of the US Department of Energy liquid-metal reactor, Integral Fast Reactor (IFR) program. Included in these improvements to HFEF-S is a new, small-item, rapid transfer system (RTS). When installed, this system will enable the rapid transfer of small items from the hot-cell exterior into the argon cell (argon-gas atmosphere) of the facility without necessitating the use of time-consuming and laborious procedures. The new RTS will also provide another important function associated with HFEF-S hot-cell operation in the IFR Fuel Recycle Program; namely, the rapid insertion of clean, radioactive contamination-measuring smear paper specimens into the hot cells for area surveys, and the expedited removal of these contaminated (including alpha as well as beta/gamma contamination) smears from the argon cell for transfer to an adjacent health physics field laboratory in the facility for nuclear contamination/radiation counting

  3. Evidence Supporting Intralesional Stem Cell Therapy to Improve Equine Flexor Tendon Healing

    Directory of Open Access Journals (Sweden)

    Sushmitha Durgam

    2017-01-01

    Full Text Available Clinical bottom lineCurrent experimental evidence suggests that intralesional stem cell administration improves the histological characteristics and matrix organisation of healing equine superficial digital flexor tendons (SDFT; however, the clinical relevance of these findings are not clear. Current case-based evidence suggests that cell-based therapies improve the quality of tendon healing and reduce the recurrence rates of SDFT injuries but the lack of any randomised, controlled prospective studies with function-based outcomes is still concerning, given the widespread advocacy for and use of ‘stem cell’ therapies for the treatment of equine tendon injuries. 

  4. Modular Approach for Continuous Cell-Level Balancing to Improve Performance of Large Battery Packs: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Muneed ur Rehman, M.; Evzelman, M.; Hathaway, K.; Zane, R.; Plett, G. L.; Smith, K.; Wood, E.; Maksimovic, D.

    2014-10-01

    Energy storage systems require battery cell balancing circuits to avoid divergence of cell state of charge (SOC). A modular approach based on distributed continuous cell-level control is presented that extends the balancing function to higher level pack performance objectives such as improving power capability and increasing pack lifetime. This is achieved by adding DC-DC converters in parallel with cells and using state estimation and control to autonomously bias individual cell SOC and SOC range, forcing healthier cells to be cycled deeper than weaker cells. The result is a pack with improved degradation characteristics and extended lifetime. The modular architecture and control concepts are developed and hardware results are demonstrated for a 91.2-Wh battery pack consisting of four series Li-ion battery cells and four dual active bridge (DAB) bypass DC-DC converters.

  5. Cell-laden hydrogel/titanium microhybrids: Site-specific cell delivery to metallic implants for improved integration.

    Science.gov (United States)

    Koenig, Geraldine; Ozcelik, Hayriye; Haesler, Lisa; Cihova, Martina; Ciftci, Sait; Dupret-Bories, Agnes; Debry, Christian; Stelzle, Martin; Lavalle, Philippe; Vrana, Nihal Engin

    2016-03-01

    Porous titanium implants are widely used in dental, orthopaedic and otorhinolaryngology fields to improve implant integration to host tissue. A possible step further to improve the integration with the host is the incorporation of autologous cells in porous titanium structures via cell-laden hydrogels. Fast gelling hydrogels have advantageous properties for in situ applications such as localisation of specific cells and growth factors at a target area without dispersion. The ability to control the cell types in different regions of an implant is important in applications where the target tissue (i) has structural heterogeneity (multiple cell types with a defined spatial configuration with respect to each other); (ii) has physical property gradients essential for its function (such as in the case of osteochondral tissue transition). Due to their near immediate gelation, such gels can also be used for site-specific modification of porous titanium structures, particularly for implants which would face different tissues at different locations. Herein, we describe a step by step design of a model system: the model cell-laden gel-containing porous titanium implants in the form of titanium microbead/hydrogel (maleimide-dextran or maleimide-PVA based) microhybrids. These systems enable the determination of the effect of titanium presence on gel properties and encapsulated cell behaviour as a miniaturized version of full-scale implants, providing a system compatible with conventional analysis methods. We used a fibroblast/vascular endothelial cell co-cultures as our model system and by utilising single microbeads we have quantified the effect of gel microenvironment (degradability, presence of RGD peptides within gel formulation) on cell behaviour and the effect of the titanium presence on cell behaviour and gel formation. Titanium presence slightly changed gel properties without hindering gel formation or affecting cell viability. Cells showed a preference to move towards

  6. Basic aspects for improving the energy conversion efficiency of hetero-junction organic photovoltaic cells.

    Science.gov (United States)

    Ryuzaki, Sou; Onoe, Jun

    2013-01-01

    Hetero-junction organic photovoltaic (OPV) cells consisting of donor (D) and acceptor (A) layers have been regarded as next-generation PV cells, because of their fascinating advantages, such as lightweight, low fabrication cost, resource free, and flexibility, when compared to those of conventional PV cells based on silicon and semiconductor compounds. However, the power conversion efficiency (η) of the OPV cells has been still around 8%, though more than 10% efficiency has been required for their practical use. To fully optimize these OPV cells, it is necessary that the low mobility of carriers/excitons in the OPV cells and the open circuit voltage (V OC), of which origin has not been understood well, should be improved. In this review, we address an improvement of the mobility of carriers/excitons by controlling the crystal structure of a donor layer and address how to increase the V OC for zinc octaethylporphyrin [Zn(OEP)]/C60 hetero-junction OPV cells [ITO/Zn(OEP)/C60/Al]. It was found that crystallization of Zn(OEP) films increases the number of inter-molecular charge transfer (IMCT) excitons and enlarges the mobility of carriers and IMCT excitons, thus significantly improving the external quantum efficiency (EQE) under illumination of the photoabsorption band due to the IMCT excitons. Conversely, charge accumulation of photo-generated carriers in the vicinity of the donor/acceptor (D/A) interface was found to play a key role in determining the V OC for the OPV cells.

  7. Disintegration of Nannochloropsis sp. cells in an improved turbine bead mill.

    Science.gov (United States)

    Pan, Zhidong; Huang, Ying; Wang, Yanmin; Wu, Zhiwei

    2017-12-01

    The Nannochloropsis sp. cells in aqueous solution were disintegrated in an improved bead mill with turbine agitator. The disintegration rates of cell samples disrupted under various operating parameters (i.e., circumferential speed, bead size, disintegration time, and cell concentration) were analyzed. An experimental strategy to optimize the parameters affecting the cell disintegration process was proposed. The results show that Nannochloropsis sp. cells can be effectively disintegrated in the turbine stirred bead mill under the optimum condition (i.e., circumferential speed of 2.3m/s, concentration of 15vol.%, disintegration time of 40min and bead size of 0.3-0.4mm). The disintegration mechanism was discussed via the selection and breakage functions from population balance modelling. It is revealed that the impact and compression effects of stirring beads are more effective for the disruption of coarser fraction of cells, and the shear effect dominates the production of finer fractions of disintegrated cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. MOLTEN CARBONATE FUEL CELL PRODUCT DESIGN IMPROVEMENT

    Energy Technology Data Exchange (ETDEWEB)

    H.C. Maru; M. Farooque

    2005-03-01

    The program was designed to advance the carbonate fuel cell technology from full-size proof-of-concept field test to the commercial design. DOE has been funding Direct FuelCell{reg_sign} (DFC{reg_sign}) development at FuelCell Energy, Inc. (FCE, formerly Energy Research Corporation) from an early state of development for stationary power plant applications. The current program efforts were focused on technology and system development, and cost reduction, leading to commercial design development and prototype system field trials. FCE, in Danbury, CT, is a world-recognized leader for the development and commercialization of high efficiency fuel cells that can generate clean electricity at power stations, or at distributed locations near the customers such as hospitals, schools, universities, hotels and other commercial and industrial applications. FCE has designed three different fuel cell power plant models (DFC300A, DFC1500 and DFC3000). FCE's power plants are based on its patented DFC{reg_sign} technology, where a hydrocarbon fuel is directly fed to the fuel cell and hydrogen is generated internally. These power plants offer significant advantages compared to the existing power generation technologies--higher fuel efficiency, significantly lower emissions, quieter operation, flexible siting and permitting requirements, scalability and potentially lower operating costs. Also, the exhaust heat by-product can be used for cogeneration applications such as high-pressure steam, district heating and air conditioning. Several sub-MW power plants based on the DFC design are currently operating in Europe, Japan and the US. Several one-megawatt power plant design was verified by operation on natural gas at FCE. This plant is currently installed at a customer site in King County, WA under another US government program and is currently in operation. Because hydrogen is generated directly within the fuel cell module from readily available fuels such as natural gas and

  9. Cell surface glycan engineering of neural stem cells augments neurotropism and improves recovery in a murine model of multiple sclerosis

    KAUST Repository

    Merzaban, Jasmeen S.

    2015-09-13

    Neural stem cell (NSC)-based therapies offer potential for neural repair in central nervous system (CNS) inflammatory and degenerative disorders. Typically, these conditions present with multifocal CNS lesions making it impractical to inject NSCs locally, thus mandating optimization of vascular delivery of the cells to involved sites. Here, we analyzed NSCs for expression of molecular effectors of cell migration and found that these cells are natively devoid of E-selectin ligands. Using glycosyltransferase-programmed stereosubstitution (GPS), we glycan engineered the cell surface of NSCs ("GPS-NSCs") with resultant enforced expression of the potent E-selectin ligand HCELL (hematopoietic cell E-/L-selectin ligand) and of an E-selectin-binding glycoform of neural cell adhesion molecule ("NCAM-E"). Following intravenous (i.v.) injection, short-term homing studies demonstrated that, compared with buffer-treated (control) NSCs, GPS-NSCs showed greater neurotropism. Administration of GPS-NSC significantly attenuated the clinical course of experimental autoimmune encephalomyelitis (EAE), with markedly decreased inflammation and improved oligodendroglial and axonal integrity, but without evidence of long-term stem cell engraftment. Notably, this effect of NSC is not a universal property of adult stem cells, as administration of GPS-engineered mouse hematopoietic stem/progenitor cells did not improve EAE clinical course. These findings highlight the utility of cell surface glycan engineering to boost stem cell delivery in neuroinflammatory conditions and indicate that, despite the use of a neural tissue-specific progenitor cell population, neural repair in EAE results from endogenous repair and not from direct, NSC-derived cell replacement.

  10. Carbon nanotube-incorporated collagen hydrogels improve cell alignment and the performance of cardiac constructs

    Science.gov (United States)

    Sun, Hongyu; Zhou, Jing; Huang, Zhu; Qu, Linlin; Lin, Ning; Liang, Chengxiao; Dai, Ruiwu; Tang, Lijun; Tian, Fuzhou

    2017-01-01

    Carbon nanotubes (CNTs) provide an essential 2-D microenvironment for cardiomyocyte growth and function. However, it remains to be elucidated whether CNT nanostructures can promote cell–cell integrity and facilitate the formation of functional tissues in 3-D hydrogels. Here, single-walled CNTs were incorporated into collagen hydrogels to fabricate (CNT/Col) hydrogels, which improved mechanical and electrical properties. The incorporation of CNTs (up to 1 wt%) exhibited no toxicity to cardiomyocytes and enhanced cell adhesion and elongation. Through the use of immunohistochemical staining, transmission electron microscopy, and intracellular calcium-transient measurement, the incorporation of CNTs was found to improve cell alignment and assembly remarkably, which led to the formation of engineered cardiac tissues with stronger contraction potential. Importantly, cardiac tissues based on CNT/Col hydrogels were noted to have better functionality. Collectively, the incorporation of CNTs into the Col hydrogels improved cell alignment and the performance of cardiac constructs. Our study suggests that CNT/Col hydrogels offer a promising tissue scaffold for cardiac constructs, and might serve as injectable biomaterials to deliver cell or drug molecules for cardiac regeneration following myocardial infarction in the near future. PMID:28450785

  11. Improving Perovskite Solar Cells: Insights From a Validated Device Model

    NARCIS (Netherlands)

    Sherkar, Tejas S.; Momblona, Cristina; Gil-Escrig, Lidon; Bolink, Henk J.; Koster, L. Jan Anton

    2017-01-01

    To improve the efficiency of existing perovskite solar cells (PSCs), a detailed understanding of the underlying device physics during their operation is essential. Here, a device model has been developed and validated that describes the operation of PSCs and quantitatively explains the role of

  12. Linking incomplete reprogramming to the improved pluripotency of murine embryonal carcinoma cell-derived pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Gang Chang

    Full Text Available Somatic cell nuclear transfer (SCNT has been proved capable of reprogramming various differentiated somatic cells into pluripotent stem cells. Recently, induced pluripotent stem cells (iPS have been successfully derived from mouse and human somatic cells by the over-expression of a combination of transcription factors. However, the molecular mechanisms underlying the reprogramming mediated by either the SCNT or iPS approach are poorly understood. Increasing evidence indicates that many tumor pathways play roles in the derivation of iPS cells. Embryonal carcinoma (EC cells have the characteristics of both stem cells and cancer cells and thus they might be the better candidates for elucidating the details of the reprogramming process. Although previous studies indicate that EC cells cannot be reprogrammed into real pluripotent stem cells, the reasons for this remain unclear. Here, nuclei from mouse EC cells (P19 were transplanted into enucleated oocytes and pluripotent stem cells (P19 NTES cells were subsequently established. Interestingly, P19 NTES cells prolonged the development of tetraploid aggregated embryos compared to EC cells alone. More importantly, we found that the expression recovery of the imprinted H19 gene was dependent on the methylation state in the differential methylation region (DMR. The induction of Nanog expression, however, was independent of the promoter region DNA methylation state in P19 NTES cells. A whole-genome transcriptome analysis further demonstrated that P19 NTES cells were indeed the intermediates between P19 cells and ES cells and many interesting genes were uncovered that may be responsible for the failed reprogramming of P19 cells. To our knowledge, for the first time, we linked incomplete reprogramming to the improved pluripotency of EC cell-derived pluripotent stem cells. The candidate genes we discovered may be useful not only for understanding the mechanisms of reprogramming, but also for deciphering the

  13. Corrugated round fibers to improve cell adhesion and proliferation in tissue engineering scaffolds

    NARCIS (Netherlands)

    Bettahalli Narasimha, M.S.; Arkesteijn, I.T.M.; Wessling, Matthias; Poot, Andreas A.; Stamatialis, Dimitrios

    2013-01-01

    Optimal cell interaction with biomaterial scaffolds is one of the important requirements for the development of successful in vitro tissue-engineered tissues. Fast, efficient and spatially uniform cell adhesion can improve the clinical potential of engineered tissue. Three-dimensional (3-D) solid

  14. Introducing catalyst in alkaline membrane for improved performance direct borohydride fuel cells

    Science.gov (United States)

    Qin, Haiying; Lin, Longxia; Chu, Wen; Jiang, Wei; He, Yan; Shi, Qiao; Deng, Yonghong; Ji, Zhenguo; Liu, Jiabin; Tao, Shanwen

    2018-01-01

    A catalytic material is introduced into the polymer matrix to prepare a novel polymeric alkaline electrolyte membrane (AEM) which simultaneously increases ionic conductivity, reduces the fuel cross-over. In this work, the hydroxide anion exchange membrane is mainly composed of poly(vinylalcohol) and alkaline exchange resin. CoCl2 is added into the poly(vinylalcohol) and alkaline exchange resin gel before casting the membrane to introduce catalytic materials. CoCl2 is converted into CoOOH after the reaction with KOH solution. The crystallinity of the polymer matrix decreases and the ionic conductivity of the composite membrane is notably improved by the introduction of Co-species. A direct borohydride fuel cell using the composite membrane exhibits an open circuit voltage of 1.11 V at 30 °C, which is notably higher than that of cells using other AEMs. The cell using the composite membrane achieves a maximum power density of 283 mW cm-2 at 60 °C while the cell using the membrane without Co-species only reaches 117 mW cm-2 at the same conditions. The outstanding performance of the cell using the composite membrane benefits from impregnation of the catalytic Co-species in the membrane, which not only increases the ionic conductivity but also reduces electrode polarization thus improves the fuel cell performance. This work provides a new approach to develop high-performance fuel cells through adding catalysts in the electrolyte membrane.

  15. Incorporation of bone marrow cells in pancreatic pseudoislets improves posttransplant vascularization and endocrine function.

    Directory of Open Access Journals (Sweden)

    Christine Wittig

    Full Text Available Failure of revascularization is known to be the major reason for the poor outcome of pancreatic islet transplantation. In this study, we analyzed whether pseudoislets composed of islet cells and bone marrow cells can improve vascularization and function of islet transplants. Pancreatic islets isolated from Syrian golden hamsters were dispersed into single cells for the generation of pseudoislets containing 4×10(3 cells. To create bone marrow cell-enriched pseudoislets 2×10(3 islet cells were co-cultured with 2×10(3 bone marrow cells. Pseudoislets and bone marrow cell-enriched pseudoislets were transplanted syngeneically into skinfold chambers to study graft vascularization by intravital fluorescence microscopy. Native islet transplants served as controls. Bone marrow cell-enriched pseudoislets showed a significantly improved vascularization compared to native islets and pseudoislets. Moreover, bone marrow cell-enriched pseudoislets but not pseudoislets normalized blood glucose levels after transplantation of 1000 islet equivalents under the kidney capsule of streptozotocin-induced diabetic animals, although the bone marrow cell-enriched pseudoislets contained only 50% of islet cells compared to pseudoislets and native islets. Fluorescence microscopy of bone marrow cell-enriched pseudoislets composed of bone marrow cells from GFP-expressing mice showed a distinct fraction of cells expressing both GFP and insulin, indicating a differentiation of bone marrow-derived cells to an insulin-producing cell-type. Thus, enrichment of pseudoislets by bone marrow cells enhances vascularization after transplantation and increases the amount of insulin-producing tissue. Accordingly, bone marrow cell-enriched pseudoislets may represent a novel approach to increase the success rate of islet transplantation.

  16. Apospory appears to accelerate onset of meiosis and sexual embryo sac formation in sorghum ovules

    Directory of Open Access Journals (Sweden)

    Elliott Estella

    2011-01-01

    Full Text Available Abstract Background Genetically unreduced (2n embryo sacs (ES form in ovules of gametophytic apomicts, the 2n eggs of which develop into embryos parthenogenetically. In many apomicts, 2n ES form precociously during ovule development. Whether meiosis and sexual ES formation also occur precociously in facultative apomicts (capable of apomictic and sexual reproduction has not been studied. We determined onset timing of meiosis and sexual ES formation for 569 Sorghum bicolor genotypes, many of which produced 2n ES facultatively. Results Genotype differences for onset timing of meiosis and sexual ES formation, relative to ovule development, were highly significant. A major source of variation in timing of sexual germline development was presence or absence of apomictic ES, which formed from nucellar cells (apospory in some genotypes. Genotypes that produced these aposporous ES underwent meiosis and sexual ES formation precociously. Aposporous ES formation was most prevalent in subsp. verticilliflorum and in breeding lines of subsp. bicolor. It was uncommon in land races. Conclusions The present study adds meiosis and sexual ES formation to floral induction, apomictic ES formation, and parthenogenesis as processes observed to occur precociously in apomictic plants. The temporally diverse nature of these events suggests that an epigenetic memory of the plants' apomixis status exists throughout its life cycle, which triggers, during multiple life cycle phases, temporally distinct processes that accelerate reproduction.

  17. Rac1 selective activation improves retina ganglion cell survival and regeneration.

    Directory of Open Access Journals (Sweden)

    Erika Lorenzetto

    Full Text Available In adult mammals, after optic nerve injury, retinal ganglion cells (RGCs do not regenerate their axons and most of them die by apoptosis within a few days. Recently, several strategies that activate neuronal intracellular pathways were proposed to prevent such degenerative processes. The rho-related small GTPase Rac1 is part of a complex, still not fully understood, intracellular signaling network, mediating in neurons many effects, including axon growth and cell survival. However, its role in neuronal survival and regeneration in vivo has not yet been properly investigated. To address this point we intravitreally injected selective cell-penetrating Rac1 mutants after optic nerve crush and studied the effect on RGC survival and axonal regeneration. We injected two well-characterized L61 constitutively active Tat-Rac1 fusion protein mutants, in which a second F37A or Y40C mutation confers selectivity in downstream signaling pathways. Results showed that, 15 days after crush, both mutants were able to improve survival and to prevent dendrite degeneration, while the one harboring the F37A mutation also improved axonal regeneration. The treatment with F37A mutant for one month did not improve the axonal elongation respect to 15 days. Furthermore, we found an increase of Pak1 T212 phosphorylation and ERK1/2 expression in RGCs after F37A treatment, whereas ERK1/2 was more activated in glial cells after Y40C administration. Our data suggest that the selective activation of distinct Rac1-dependent pathways could represent a therapeutic strategy to counteract neuronal degenerative processes in the retina.

  18. Change in body mass index and insulin resistance after 1-year treatment with gonadotropin-releasing hormone agonists in girls with central precocious puberty.

    Science.gov (United States)

    Park, Jina; Kim, Jae Hyun

    2017-03-01

    Gonadotropin-releasing hormone agonist (GnRHa) is used as a therapeutic agent for central precocious puberty (CPP); however, increased obesity may subsequently occur. This study compared body mass index (BMI) and insulin resistance during the first year of GnRHa treatment for CPP. Patient group included 83 girls (aged 7.0-8.9 years) with developed breasts and a peak luteinizing hormone level of ≥5 IU/L after GnRH stimulation. Control group included 48 prepubertal girls. BMI and insulin resistance-related indices (homeostasis model assessment of insulin resistance [HOMA-IR] and quantitative insulin sensitivity check index [QUICKI]) were used to compare the groups before treatment, and among the patient group before and after GnRHa treatment. No statistical difference in BMI z -score was detected between the 2 groups before treatment. Fasting insulin and HOMA-IR were increased in the patient group; fasting glucose-to-insulin ratio and QUICKI were increased in the control group (all P resistance compared to the control group. During GnRHa treatment, normal-weight individuals showed increased BMI z -scores without increased insulin resistance; the overweight group demonstrated increased insulin resistance without significantly altered BMI z -scores. Long-term follow-up of BMI and insulin resistance changes in patients with CPP is required.

  19. Imatinib prevents beta cell death in vitro but does not improve islet transplantation outcome.

    Science.gov (United States)

    King, Aileen J F; Griffiths, Lisa A; Persaud, Shanta J; Jones, Peter M; Howell, Simon L; Welsh, Nils

    2016-05-01

    Introduction Improving islet transplantation outcome could not only bring benefits to individual patients but also widen the patient pool to which this life-changing treatment is available. Imatinib has previously been shown to protect beta cells from apoptosis in a variety of in vitro and in vivo models. The aim of this study was to investigate whether imatinib could be used to improve islet transplantation outcome. Methods Islets were isolated from C57Bl/6 mice and pre-cultured with imatinib prior to exposure to streptozotocin and cytokines in vitro. Cell viability and glucose-induced insulin secretion were measured. For transplantation experiments, islets were pre-cultured with imatinib for either 72 h or 24 h prior to transplantation into streptozotocin-diabetic C57Bl/6 mice. In one experimental series mice were also administered imatinib after islet transplantation. Results Imatinib partially protected islets from beta cell death in vitro. However, pre-culturing islets in imatinib or administering the drug to the mice in the days following islet transplantation did not improve blood glucose concentrations more than control-cultured islets. Conclusion Although imatinib protected against beta cell death from cytokines and streptozotocin in vitro, it did not significantly improve syngeneic islet transplantation outcome.

  20. Parameter estimation of photovoltaic cells using an improved chaotic whale optimization algorithm

    International Nuclear Information System (INIS)

    Oliva, Diego; Abd El Aziz, Mohamed; Ella Hassanien, Aboul

    2017-01-01

    Highlights: •We modify the whale algorithm using chaotic maps. •We apply a chaotic algorithm to estimate parameter of photovoltaic cells. •We perform a study of chaos in whale algorithm. •Several comparisons and metrics support the experimental results. •We test the method with data from real solar cells. -- Abstract: The using of solar energy has been increased since it is a clean source of energy. In this way, the design of photovoltaic cells has attracted the attention of researchers over the world. There are two main problems in this field: having a useful model to characterize the solar cells and the absence of data about photovoltaic cells. This situation even affects the performance of the photovoltaic modules (panels). The characteristics of the current vs. voltage are used to describe the behavior of solar cells. Considering such values, the design problem involves the solution of the complex non-linear and multi-modal objective functions. Different algorithms have been proposed to identify the parameters of the photovoltaic cells and panels. Most of them commonly fail in finding the optimal solutions. This paper proposes the Chaotic Whale Optimization Algorithm (CWOA) for the parameters estimation of solar cells. The main advantage of the proposed approach is using the chaotic maps to compute and automatically adapt the internal parameters of the optimization algorithm. This situation is beneficial in complex problems, because along the iterative process, the proposed algorithm improves their capabilities to search for the best solution. The modified method is able to optimize complex and multimodal objective functions. For example, the function for the estimation of parameters of solar cells. To illustrate the capabilities of the proposed algorithm in the solar cell design, it is compared with other optimization methods over different datasets. Moreover, the experimental results support the improved performance of the proposed approach

  1. Induced Human Decidual NK-Like Cells Improve Utero-Placental Perfusion in Mice.

    Directory of Open Access Journals (Sweden)

    Ricardo C Cavalli

    Full Text Available Decidual NK (dNK cells, a distinct type of NK cell, are thought to regulate uterine spiral artery remodeling, a process that allows for increased blood delivery to the fetal-placental unit. Impairment of uterine spiral artery remodeling is associated with decreased placental perfusion, increased uterine artery resistance, and obstetric complications such as preeclampsia and intrauterine growth restriction. Ex vivo manipulation of human peripheral blood NK (pNK cells by a combination of hypoxia, TGFß-1 and 5-aza-2'-deoxycytidine yields cells with phenotypic and in vitro functional similarities to dNK cells, called idNK cells. Here, gene expression profiling shows that CD56Bright idNK cells derived ex vivo from human pNK cells, and to a lesser extent CD56Dim idNK cells, are enriched in the gene expression signature that distinguishes dNK cells from pNK cells. When injected into immunocompromised pregnant mice with elevated uterine artery resistance, idNK cells homed to the uterus and reduced the uterine artery resistance index, suggesting improved placental perfusion.

  2. Dual Functional Capability of Dendritic Cells - Cytokine-Induced Killer Cells in Improving Side Effects of Colorectal Cancer Therapy.

    Science.gov (United States)

    Mosińska, Paula; Gabryelska, Agata; Zasada, Malwina; Fichna, Jakub

    2017-01-01

    The aim of cancer therapy is to eradicate cancer without affecting healthy tissues. Current options available for treating colorectal cancer (CRC), including surgery, chemotherapy or radiotherapy, usually elicit multiple adverse effects and frequently fail to completely remove the tumor cells. Thus, there is a constant need for seeking cancer cell-specific therapeutics to improve the course of cancer therapy and reduce the risk of relapse. In this review we elaborate on the mechanisms underlying the immunotherapy with dendritic cells (DCs) and cytokine-induced killer (CIK) cells, and summarize their effectiveness and tolerability available clinical studies. Finally, we discuss the up-to-date combinatorial adoptive anti-cancer immunotherapy with CIK cells co-cultured with DCs that recently showed encouraging efficacy and usefulness in treating malignant disease, including CRC.

  3. Synthesis and characterization of Ag nanowires: Improved performance in dye sensitized solar cells

    Directory of Open Access Journals (Sweden)

    Safia A. Kazmi

    2016-09-01

    Full Text Available Development of highly efficient dye-sensitized solar cells (DSSCs with good photovoltaic parameters is an active research area of current global interest. Recently, one dimensional nanomaterial, such as nanorods and nanotubes has replaced the nanoparticles used in DSSCs anode because of their ability to improve the electron transport leading to enhanced electron collection efficiency. In the present work, rapid synthesis of silver nanowires (AgNWs was done. The XRD characterization was performed to confirm the formation and size of synthesized AgNWs. It was observed that FWHM of the diffraction peaks was increased with AgNWs concentration in TiO2. The synthesized TiO2AgNWs nanocomposite was used as the photo anode of Dye sensitized solar cell. The I–V characteristics of the solar cell were drawn using standard conditions. It was observed that TiO2AgNWs based solar cells have significantly increased photocurrent density resulting in improved conversion efficiency as compared to pure TiO2 based DSSC.

  4. IL-15 improves the cytotoxicity of cytokine-induced killer cells against leukemia cells by upregulating CD3+CD56+ cells and downregulating regulatory T cells as well as IL-35.

    Science.gov (United States)

    Tao, Qianshan; Chen, Tianping; Tao, Lili; Wang, Huiping; Pan, Ying; Xiong, Shudao; Zhai, Zhimin

    2013-01-01

    Cytokine-induced killer (CIK) cells are usually generated from peripheral blood mononuclear cells with the stimulation of IL-2 in vitro. Unlike the conventional IL-2-stimulated CIK cells (IL-2-CIK cells), we investigated the characteristics and potential mechanism of IL-15-stimulated CIK cells (IL-15-CIK cells) in this study. Compared with IL-2-CIK cells, the percentage of CD3CD56 cells was significantly increased in IL-15-CIK cells, but the expression of regulatory T (Treg) cells and IL-35 was significantly decreased in IL-15-CIK cells. Meanwhile, the in vitro cytotoxicity against human myeloid leukemia cells K562 of IL-15-CIK cells was significantly augmented compared with IL-2-CIK cells. These data suggest that IL-15 may improve the cytotoxicity of CIK cells against leukemia cells by upregulating CD3CD56 cells and downregulating Treg cells and IL-35.

  5. Slow-Adhering Stem Cells Derived from Injured Skeletal Muscle Have Improved Regenerative Capacity

    Science.gov (United States)

    2011-08-01

    stress urinary incontinence . Urology 2006, 68:449–454 15. Chermansky CJ, Tarin T, Kwon DD, Jankowski RJ, Cannon TW, de Groat WC, Huard J, Chancellor...from control noninjured muscle. These data suggest that traumatic injury may modify stem cell characteristics through trophic factors and improve the...alter the microenvironment of resident muscle cells (ie, stimu- lating cell dedifferentiation on various trophic factors )20,21 and result in profound

  6. Considerably improved photovoltaic performance of carbon nanotube-based solar cells using metal oxide layers

    Science.gov (United States)

    Wang, Feijiu; Kozawa, Daichi; Miyauchi, Yuhei; Hiraoka, Kazushi; Mouri, Shinichiro; Ohno, Yutaka; Matsuda, Kazunari

    2015-02-01

    Carbon nanotube-based solar cells have been extensively studied from the perspective of potential application. Here we demonstrated a significant improvement of the carbon nanotube solar cells by the use of metal oxide layers for efficient carrier transport. The metal oxides also serve as an antireflection layer and an efficient carrier dopant, leading to a reduction in the loss of the incident solar light and an increase in the photocurrent, respectively. As a consequence, the photovoltaic performance of both p-single-walled carbon nanotube (SWNT)/n-Si and n-SWNT/p-Si heterojunction solar cells using MoOx and ZnO layers is improved, resulting in very high photovoltaic conversion efficiencies of 17.0 and 4.0%, respectively. These findings regarding the use of metal oxides as multifunctional layers suggest that metal oxide layers could improve the performance of various electronic devices based on carbon nanotubes.

  7. Considerably improved photovoltaic performance of carbon nanotube-based solar cells using metal oxide layers.

    Science.gov (United States)

    Wang, Feijiu; Kozawa, Daichi; Miyauchi, Yuhei; Hiraoka, Kazushi; Mouri, Shinichiro; Ohno, Yutaka; Matsuda, Kazunari

    2015-02-18

    Carbon nanotube-based solar cells have been extensively studied from the perspective of potential application. Here we demonstrated a significant improvement of the carbon nanotube solar cells by the use of metal oxide layers for efficient carrier transport. The metal oxides also serve as an antireflection layer and an efficient carrier dopant, leading to a reduction in the loss of the incident solar light and an increase in the photocurrent, respectively. As a consequence, the photovoltaic performance of both p-single-walled carbon nanotube (SWNT)/n-Si and n-SWNT/p-Si heterojunction solar cells using MoOx and ZnO layers is improved, resulting in very high photovoltaic conversion efficiencies of 17.0 and 4.0%, respectively. These findings regarding the use of metal oxides as multifunctional layers suggest that metal oxide layers could improve the performance of various electronic devices based on carbon nanotubes.

  8. Developments for improved direct methanol fuel cell stacks for portable power

    Energy Technology Data Exchange (ETDEWEB)

    Cremers, C.; Stimming, U. [Bavarian Center for Applied Energy Research, ZAE Bayern, Abteilung 1, Walther-Meissner-Str. 6, D-85748 Garching (Germany); Technische Universitaet Muenchen, Department of Physics E19, James-Franck-Str. 1, D-85748 Garching (Germany); Scholz, M.; Seliger, W. [Bavarian Center for Applied Energy Research, ZAE Bayern, Abteilung 1, Walther-Meissner-Str. 6, D-85748 Garching (Germany); Racz, A. [Technische Universitaet Muenchen, Department of Physics E19, James-Franck-Str. 1, D-85748 Garching (Germany); Knechtel, W.; Rittmayr, J.; Grafwallner, F.; Peller, H. [ET EnergieTechnologie GmbH, Eugen-Saenger-Ring 4, D-85649 Brunnthal-Nord (Germany)

    2007-02-15

    Different aspects of the improvement of direct methanol fuel cell (DMFC) systems for portable power generation are investigated, in a project funded by the Bavarian state. The materials research focuses on the development of improved catalysts, in particular for the oxygen reduction reaction. Some recent results on supported ruthenium selenium catalysts are reported. In parallel, tests on other fuel cell materials are performed using MEAs made from industrial unsupported catalysts as the reference. These standard MEAs have catalyst loadings of about 11 mg cm{sup -2} and, at high air flux, can deliver current densities of about 500 mA cm{sup -2} and 100 mA cm{sup -2} at 110 C and 50 C, respectively. At low air flux and 50 C, current densities between 60 and 80 mA cm{sup -2} are possible rate at 500 mV. Using these MEAs, different commercial gas diffusion materials are tested as the cathode backing. Thus, it is found that the Sigracet materials by SGL Carbon are the most suitable for operation at a low air flux. Finally, a demonstration stack, comprised of up to ten cells, is developed using graphite PVDF compound bipolar plates by SGL Carbon. As will be reported, this stack shows a high homogeneity of cell voltages and stable operation under relevant conditions, using standard MEAs. (Abstract Copyright [2007], Wiley Periodicals, Inc.)

  9. Suspension Matrices for Improved Schwann-Cell Survival after Implantation into the Injured Rat Spinal Cord

    Science.gov (United States)

    Patel, Vivek; Joseph, Gravil; Patel, Amit; Patel, Samik; Bustin, Devin; Mawson, David; Tuesta, Luis M.; Puentes, Rocio; Ghosh, Mousumi

    2010-01-01

    Abstract Trauma to the spinal cord produces endogenously irreversible tissue and functional loss, requiring the application of therapeutic approaches to achieve meaningful restoration. Cellular strategies, in particular Schwann-cell implantation, have shown promise in overcoming many of the obstacles facing successful repair of the injured spinal cord. Here, we show that the implantation of Schwann cells as cell suspensions with in-situ gelling laminin:collagen matrices after spinal-cord contusion significantly enhances long-term cell survival but not proliferation, as well as improves graft vascularization and the degree of axonal in-growth over the standard implantation vehicle, minimal media. The use of a matrix to suspend cells prior to implantation should be an important consideration for achieving improved survival and effectiveness of cellular therapies for future clinical application. PMID:20144012

  10. Improving the efficacy and safety of engineered T cell therapy for cancer.

    Science.gov (United States)

    Shi, Huan; Liu, Lin; Wang, Zhehai

    2013-01-28

    Adoptive T-cell therapy (ACT) using tumor-infiltrating lymphocytes (TILs) is a powerful immunotherapeutics approach against metastatic melanoma. The success of TIL therapy has led to novel strategies for redirecting normal T cells to recognize tumor-associated antigens (TAAs) by genetically engineering tumor antigen-specific T cell receptors (TCRs) or chimeric antigen receptor (CAR) genes. In this manner, large numbers of antigen-specific T cells can be rapidly generated compared with the longer term expansion of TILs. Great efforts have been made to improve these approaches. Initial clinical studies have demonstrated that genetically engineered T cells can mediate tumor regression in vivo. In this review, we discuss the development of TCR and CAR gene-engineered T cells and the safety concerns surrounding the use of these T cells in patients. We highlight the importance of judicious selection of TAAs for modified T cell therapy and propose solutions for potential "on-target, off-organ" toxicity. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  11. Macrophages improve survival, proliferation and migration of engrafted myogenic precursor cells into MDX skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Pierre-François Lesault

    Full Text Available Transplantation of muscle precursor cells is of therapeutic interest for focal skeletal muscular diseases. However, major limitations of cell transplantation are the poor survival, expansion and migration of the injected cells. The massive and early death of transplanted myoblasts is not fully understood although several mechanisms have been suggested. Various attempts have been made to improve their survival or migration. Taking into account that muscle regeneration is associated with the presence of macrophages, which are helpful in repairing the muscle by both cleansing the debris and deliver trophic cues to myoblasts in a sequential way, we attempted in the present work to improve myoblast transplantation by coinjecting macrophages. The present data showed that in the 5 days following the transplantation, macrophages efficiently improved: i myoblast survival by limiting their massive death, ii myoblast expansion within the tissue and iii myoblast migration in the dystrophic muscle. This was confirmed by in vitro analyses showing that macrophages stimulated myoblast adhesion and migration. As a result, myoblast contribution to regenerating host myofibres was increased by macrophages one month after transplantation. Altogether, these data demonstrate that macrophages are beneficial during the early steps of myoblast transplantation into skeletal muscle, showing that coinjecting these stromal cells may be used as a helper to improve the efficiency of parenchymal cell engraftment.

  12. Carbon nanotube-incorporated collagen hydrogels improve cell alignment and the performance of cardiac constructs

    Directory of Open Access Journals (Sweden)

    Sun HY

    2017-04-01

    Full Text Available Hongyu Sun,* Jing Zhou,* Zhu Huang,* Linlin Qu,* Ning Lin,* Chengxiao Liang, Ruiwu Dai, Lijun Tang, Fuzhou Tian General Surgery Center, Chengdu Military General Hospital, Chengdu, China *These authors contributed equally to this work Abstract: Carbon nanotubes (CNTs provide an essential 2-D microenvironment for cardiomyocyte growth and function. However, it remains to be elucidated whether CNT nanostructures can promote cell–cell integrity and facilitate the formation of functional tissues in 3-D hydrogels. Here, single-walled CNTs were incorporated into collagen hydrogels to fabricate (CNT/Col hydrogels, which improved mechanical and electrical properties. The incorporation of CNTs (up to 1 wt% exhibited no toxicity to cardiomyocytes and enhanced cell adhesion and elongation. Through the use of immunohistochemical staining, transmission electron microscopy, and intracellular calcium-transient measurement, the incorporation of CNTs was found to improve cell alignment and assembly remarkably, which led to the formation of engineered cardiac tissues with stronger contraction potential. Importantly, cardiac tissues based on CNT/Col hydrogels were noted to have better functionality. Collectively, the incorporation of CNTs into the Col hydrogels improved cell alignment and the performance of cardiac constructs. Our study suggests that CNT/Col hydrogels offer a promising tissue scaffold for cardiac constructs, and might serve as injectable biomaterials to deliver cell or drug molecules for cardiac regeneration following myocardial infarction in the near future. Keywords: carbon nanotubes, collagen hydrogel, cardiac constructs, cell alignment, tissue functionality

  13. Improved Performance in Mammalian Cell Perfusion Cultures by Growth Inhibition.

    Science.gov (United States)

    Wolf, Moritz K F; Closet, Aurélie; Bzowska, Monika; Bielser, Jean-Marc; Souquet, Jonathan; Broly, Hervé; Morbidelli, Massimo

    2018-05-21

    Mammalian cell perfusion cultures represent a promising alternative to the current fed-batch technology for the production of various biopharmaceuticals. Long-term operation at a fixed viable cell density (VCD) requires a viable culture and a constant removal of excessive cells. Product loss in the cell removing bleed stream deteriorates the process yield. In this study, the authors investigate the use of chemical and environmental growth inhibition on culture performance by either adding valeric acid (VA) to the production media or by reducing the culture temperature (33.0 °C) with respect to control conditions (36.5 °C, no VA). Low temperature significantly reduces cellular growth, thus, resulting in lower bleed rates accompanied by a reduced product loss of 11% compared to 26% under control conditions. Additionally, the cell specific productivity of the target protein improves and maintained stable leading to media savings per mass of product. VA shows initially an inhibitory effect on cellular growth. However, cells seemed to adapt to the presence of the inhibitor resulting in a recovery of the cellular growth. Cell cycle and Western blot analyses support the observed results. This work underlines the role of temperature as a key operating variable for the optimization of perfusion cultures. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Distinct Responses of Stem Cells to Telomere Uncapping-A Potential Strategy to Improve the Safety of Cell Therapy.

    Science.gov (United States)

    Liu, Chang Ching; Ma, Dong Liang; Yan, Ting-Dong; Fan, XiuBo; Poon, Zhiyong; Poon, Lai-Fong; Goh, Su-Ann; Rozen, Steve G; Hwang, William Ying Khee; Tergaonkar, Vinay; Tan, Patrick; Ghosh, Sujoy; Virshup, David M; Goh, Eyleen L K; Li, Shang

    2016-10-01

    In most human somatic cells, the lack of telomerase activity results in progressive telomere shortening during each cell division. Eventually, DNA damage responses triggered by critically short telomeres induce an irreversible cell cycle arrest termed replicative senescence. However, the cellular responses of human pluripotent stem cells to telomere uncapping remain unknown. We generated telomerase knockout human embryonic stem (ES) cells through gene targeting. Telomerase inactivation in ES cells results in progressive telomere shortening. Telomere DNA damage in ES cells and neural progenitor cells induces rapid apoptosis when telomeres are uncapped, in contrast to fibroblast cells that enter a state of replicative senescence. Significantly, telomerase inactivation limits the proliferation capacity of human ES cells without affecting their pluripotency. By targeting telomerase activity, we can functionally separate the two unique properties of human pluripotent stem cells, namely unlimited self-renewal and pluripotency. We show that the potential of ES cells to form teratomas in vivo is dictated by their telomere length. By controlling telomere length of ES cells through telomerase inactivation, we can inhibit teratoma formation and potentially improve the safety of cell therapies involving terminally differentiated cells as well as specific progenitor cells that do not require sustained cellular proliferation in vivo, and thus sustained telomerase activity. Stem Cells 2016;34:2471-2484. © 2016 AlphaMed Press.

  15. Adult height in girls with central precocious puberty treated with gonadotropin-releasing hormone agonist with or without growth hormone

    Directory of Open Access Journals (Sweden)

    Mo Kyung Jung

    2014-12-01

    Full Text Available PurposeThere is controversy surrounding the growth outcomes of treatment with gonadotropin-releasing hormone agonist (GnRHa in central precocious puberty (CPP. We analyzed height preservation after treatment with GnRHa with and without growth hormone (GH in girls with CPP.MethodsWe reviewed the medical records of 82 girls with idiopathic CPP who had been treated with GnRHa at Severance Children's Hospital from 2004 to 2014. We assessed the changes in height standard deviation score (SDS for bone age (BA, and compared adult height (AH with midparental height (MPH and predicted adult height (PAH during treatment in groups received GnRHa alone (n=59 or GnRHa plus GH (n=23.ResultsIn the GnRHa alone group, the height SDS for BA was increased during treatment. AH (160.4±4.23 cm was significantly higher than the initial PAH (156.6±3.96 cm (P<0.001, and it was similar to the MPH (159.9±3.52 cm. In the GnRHa plus GH group, the height SDS for BA was also increased during treatment. AH (159.3±5.33 cm was also higher than the initial PAH (154.6±2.55 cm (P<0.001, which was similar to the MPH (158.1±3.31 cm. Height gain was slightly higher than that in the GnRHa alone group, however it statistically showed no significant correlation with GH treatment.ConclusionIn CPP girls treated with GnRHa, the height SDS for BA was increased, and the AH was higher than the initial PAH. Combined GH treatment showed a limited increase in height gain.

  16. Improvements in numerical modelling of highly injected crystalline silicon solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Altermatt, P.P. [University of New South Wales, Centre for Photovoltaic Engineering, 2052 Sydney (Australia); Sinton, R.A. [Sinton Consulting, 1132 Green Circle, 80303 Boulder, CO (United States); Heiser, G. [University of NSW, School of Computer Science and Engineering, 2052 Sydney (Australia)

    2001-01-01

    We numerically model crystalline silicon concentrator cells with the inclusion of band gap narrowing (BGN) caused by injected free carriers. In previous studies, the revised room-temperature value of the intrinsic carrier density, n{sub i}=1.00x10{sup 10}cm{sup -3}, was inconsistent with the other material parameters of highly injected silicon. In this paper, we show that high-injection experiments can be described consistently with the revised value of n{sub i} if free-carrier induced BGN is included, and that such BGN is an important effect in silicon concentrator cells. The new model presented here significantly improves the ability to model highly injected silicon cells with a high level of precision.

  17. Improved Diffuse Fluorescence Flow Cytometer Prototype for High Sensitivity Detection of Rare Circulating Cells In Vivo

    Science.gov (United States)

    Pestana, Noah Benjamin

    Accurate quantification of circulating cell populations is important in many areas of pre-clinical and clinical biomedical research, for example, in the study of cancer metastasis or the immune response following tissue and organ transplants. Normally this is done "ex-vivo" by drawing and purifying a small volume of blood and then analyzing it with flow cytometry, hemocytometry or microfludic devices, but the sensitivity of these techniques are poor and the process of handling samples has been shown to affect cell viability and behavior. More recently "in vivo flow cytometry" (IVFC) techniques have been developed where fluorescently-labeled cells flowing in a small blood vessel in the ear or retina are analyzed, but the sensitivity is generally poor due to the small sampling volume. To address this, our group recently developed a method known as "Diffuse Fluorescence Flow Cytometry" (DFFC) that allows detection and counting of rare circulating cells with diffuse photons, offering extremely high single cell counting sensitivity. In this thesis, an improved DFFC prototype was designed and validated. The chief improvements were three-fold, i) improved optical collection efficiency, ii) improved detection electronics, and iii) development of a method to mitigate motion artifacts during in vivo measurements. In combination, these improvements yielded an overall instrument detection sensitivity better than 1 cell/mL in vivo, which is the most sensitive IVFC system reported to date. Second, development and validation of a low-cost microfluidic device reader for analysis of ocular fluids is described. We demonstrate that this device has equivalent or better sensitivity and accuracy compared a fluorescence microscope, but at an order-of-magnitude reduced cost with simplified operation. Future improvements to both instruments are also discussed.

  18. Natural Killer Cells Improve Hematopoietic Stem Cell Engraftment by Increasing Stem Cell Clonogenicity In Vitro and in a Humanized Mouse Model.

    Science.gov (United States)

    Escobedo-Cousin, Michelle; Jackson, Nicola; Laza-Briviesca, Raquel; Ariza-McNaughton, Linda; Luevano, Martha; Derniame, Sophie; Querol, Sergio; Blundell, Michael; Thrasher, Adrian; Soria, Bernat; Cooper, Nichola; Bonnet, Dominique; Madrigal, Alejandro; Saudemont, Aurore

    2015-01-01

    Cord blood (CB) is increasingly used as a source of hematopoietic stem cells (HSC) for transplantation. Low incidence and severity of graft-versus-host disease (GvHD) and a robust graft-versus-leukemia (GvL) effect are observed following CB transplantation (CBT). However, its main disadvantages are a limited number of HSC per unit, delayed immune reconstitution and a higher incidence of infection. Unmanipulated grafts contain accessory cells that may facilitate HSC engraftment. Therefore, the effects of accessory cells, particularly natural killer (NK) cells, on human CB HSC (CBSC) functions were assessed in vitro and in vivo. CBSC cultured with autologous CB NK cells showed higher levels of CXCR4 expression, a higher migration index and a higher number of colony forming units (CFU) after short-term and long-term cultures. We found that CBSC secreted CXCL9 following interaction with CB NK cells. In addition, recombinant CXCL9 increased CBSC clonogenicity, recapitulating the effect observed of CB NK cells on CBSC. Moreover, the co-infusion of CBSC with CB NK cells led to a higher level of CBSC engraftment in NSG mouse model. The results presented in this work offer the basis for an alternative approach to enhance HSC engraftment that could improve the outcome of CBT.

  19. Cellular targets for improved manufacturing of virus-based biopharmaceuticals in animal cells.

    Science.gov (United States)

    Rodrigues, Ana F; Carrondo, Manuel J T; Alves, Paula M; Coroadinha, Ana S

    2014-12-01

    The past decade witnessed the entry into the market of new virus-based biopharmaceuticals produced in animal cells such as oncolytic vectors, virus-like particle vaccines, and gene transfer vectors. Therefore, increased attention and investment to optimize cell culture processes towards enhanced manufacturing of these bioproducts is anticipated. Herein, we review key findings on virus-host interactions that have been explored in cell culture optimization. Approaches supporting improved productivity or quality of vector preparations are discussed, mainly focusing on medium design and genetic manipulation. This review provides an integrated outline for current and future efforts in exploring cellular targets for the optimization of cell culture manufacturing of virus-based biopharmaceuticals. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Improved premises for cell factory development

    DEFF Research Database (Denmark)

    Søgaard, Karina Marie

    The sustainable manufacturing of medicines, materials and chemicals is enabled with biotechnology, and the key to the development of new processes, as well as improvement of existing ones, lies in our fundamental understanding of the biological systems we manipulate. Recombinant protein production...... is at the core of biotechnology and numerous molecular tools and bacterial strains have been developed over the past four decades for this purpose. Understanding of the genetic code and our ability to manipulate genetic material, paves the way for the microbial cell factory development that enables production......, and building a platform for enhanced expression of certain plant genes in bacteria. The relevance of the conducted research to the field of biotechnology is covered, as well as necessary scientific background and history. Specifically, the surprisingly minor effects of tRNA overexpression on the production...

  1. Improved method and apparatus for electrostatically sorting biological cells. [DOE patent application

    Science.gov (United States)

    Merrill, J.T.

    An improved method of sorting biological cells in a conventional cell sorter apparatus includes generating a fluid jet containing cells to be sorted, measuring the distance between the centers of adjacent droplets in a zone thereof defined at the point where the fluid jet separates into descrete droplets, setting the distance between the center of a droplet in said separation zone and the position along said fluid jet at which the cell is optically sensed for specific characteristics to be an integral multiple of said center-to-center distance, and disabling a charger from electrically charging a specific droplet if a cell is detected by the optical sensor in a position wherein it will be in the neck area between droplets during droplet formation rather than within a predetermined distance from the droplet center.

  2. Cell phone-based health education messaging improves health literacy.

    Science.gov (United States)

    Zhuang, Runsen; Xiang, Yueying; Han, Tieguang; Yang, Guo-An; Zhang, Yuan

    2016-03-01

    The ubiquity of cell phones, which allow for short message service (SMS), provides new and innovative opportunities for disease prevention and health education. To explore the use of cell phone-based health education SMS to improve the health literacy of community residents in China. A multi-stage random sampling method was used to select representative study communities and participants ≥ 18 years old. Intervention participants were sent health education SMSs once a week for 1 year and controls were sent conventional, basic health education measures. Health literacy levels of the residents before and after the intervention were evaluated between intervention and control groups. Public health literacy scores increased 1.5 points, from 61.8 to 63.3, after SMS intervention for 1 year (P<0.01); the increase was greater for males than females (2.01 vs. 1.03; P<0.01) and for Shenzhen local residents than non-permanent residents (2.56 vs. 1.14; P<0.01). The frequency of high health literacy scores was greater for the intervention than control group (22.03% to 30.93% vs. 22.07% to 20.82%). With health literacy as a cost-effective index, the cost-effectiveness per intervention was 0.54. SMS may be a useful tool for improving health literacy.

  3. Improved performance of silicon-nanoparticle film-coated dye-sensitized solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, Ravindra Kumar; Bedja, Idriss M. [CRC, Department of Optometry, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh 11433 (Saudi Arabia); Aldwayyan, Abdullah Saleh [Department of Physics and Astronomy, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451 (Saudi Arabia)

    2012-11-15

    Silicon (Si) nanoparticles with average size of 13 nm and orange-red luminescence under UV absorption were synthesized using electrochemical etching of silicon wafers. A film of Si nanoparticles with thickness of 0.75 {mu}m to 2.6 {mu}m was coated on the glass (TiO{sub 2} side) of a dye-sensitized solar cell (DSSC). The cell exhibited nearly 9% enhancement in power conversion efficiency ({eta}) at film thickness of {proportional_to}2.4 {mu}m under solar irradiation of 100 mW/cm{sup 2} (AM 1.5) with improved fill factor and short-circuit current density. This study revealed for the first time that the Si-nanoparticle film converting UV into visible light and helping in homogeneous irradiation, can be utilized for improving the efficiency of the DSSCs. (copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  4. Early and late endocrine effects in pediatric central nervous system diseases.

    Science.gov (United States)

    Aslan, Ivy R; Cheung, Clement C

    2014-01-01

    Endocrinopathies are frequently linked to central nervous system disease, both as early effects prior to the disease diagnosis and/or late effects after the disease has been treated. In particular, tumors and infiltrative diseases of the brain and pituitary, such as craniopharyngioma, optic pathway and hypothalamic gliomas, intracranial germ cell tumor, and Langerhans cell histiocytosis, can present with abnormal endocrine manifestations that precede the development of neurological symptoms. Early endocrine effects include diabetes insipidus, growth failure, obesity, and precocious or delayed puberty. With improving prognosis and treatment of childhood brain tumors, many survivors experience late endocrine effects related to medical and surgical interventions. Chemotherapeutic agents and radiation therapy can affect the hypothalamic-pituitary axes governing growth, thyroid, gonadal, and adrenal function. In addition, obesity and metabolic alterations are frequent late manifestations. Diagnosing and treating both early and late endocrine manifestations can dramatically improve the growth, well-being, and quality of life of patients with childhood central nervous system diseases.

  5. Combined strategy of endothelial cells coating, Sertoli cells coculture and infusion improves vascularization and rejection protection of islet graft.

    Directory of Open Access Journals (Sweden)

    Yang Li

    Full Text Available Improving islet graft revascularization and inhibiting rejection become crucial tasks for prolonging islet graft survival. Endothelial cells (ECs are the basis of islet vascularization and Sertoli cells (SCs have the talent to provide nutritional support and exert immunosuppressive effects. We construct a combined strategy of ECs coating in the presence of nutritious and immune factors supplied by SCs in a co-culture system to investigate the effect of vascularization and rejection inhibition for islet graft. In vivo, the combined strategy improved the survival and vascularization as well as inhibited lymphocytes and inflammatory cytokines. In vitro, we found the combinatorial strategy improved the function of islets and the effect of ECs-coating on islets. Combined strategy treated islets revealed higher levels of anti-apoptotic signal molecules (Bcl-2 and HSP-32, survival and function related molecules (PDX-1, Ki-67, ERK1/2 and Akt and demonstrated increased vascular endothelial growth factor receptor 2 (KDR and angiogenesis signal molecules (FAk and PLC-γ. SCs effectively inhibited the activation of lymphocyte stimulated by islets and ECs. Predominantly immunosuppressive cytokines could be detected in culture supernatants of the SCs coculture group. These results suggest that ECs-coating and Sertoli cells co-culture or infusion synergistically enhance islet survival and function after transplantation.

  6. Lipofection of insulin-producing RINm5F cells: methodological improvements.

    Science.gov (United States)

    Barbu, Andreea; Welsh, Nils

    2007-01-01

    Cationic lipid/DNA-complexes have been widely used as gene transfer vectors because they are less toxic and immunogenic than viral vectors. The aim of the present study was to improve and characterize lipofection of an insulin-producing cell line. We compared the transfection efficiency of seven commercially available lipid formulations (Lipotaxi, SuperFect, Fugene, TransFast, Dosper, GenePORTER and LipofectAMINE) by flow cytometry analysis of GFP-expression. In addition, we have determined the influences of centrifugation, serum and a nuclear localization signal peptide on the lipofection efficiency. We observed that two lipid formulations, GenePORTER and LipofectAMINE, were able to promote efficient gene transfer in RINm5F cells. However, GenePORTER exhibited the important advantage of being able to transfect cells in the presence of serum and with less cytotoxicity than LipofectAMINE. LipofectAMINE-induced RINm5F cell death could partially be counteracted by TPA, forskolin or fumonisin beta(1). Finally, both centrifugation and a nuclear localization signal peptide increased transfection efficiency.

  7. Improved Structure and Function in Autosomal Recessive Polycystic Rat Kidneys with Renal Tubular Cell Therapy.

    Science.gov (United States)

    Kelly, K J; Zhang, Jizhong; Han, Ling; Kamocka, Malgorzata; Miller, Caroline; Gattone, Vincent H; Dominguez, Jesus H

    2015-01-01

    Autosomal recessive polycystic kidney disease is a truly catastrophic monogenetic disease, causing death and end stage renal disease in neonates and children. Using PCK female rats, an orthologous model of autosomal recessive polycystic kidney disease harboring mutant Pkhd1, we tested the hypothesis that intravenous renal cell transplantation with normal Sprague Dawley male kidney cells would improve the polycystic kidney disease phenotype. Cytotherapy with renal cells expressing wild type Pkhd1 and tubulogenic serum amyloid A1 had powerful and sustained beneficial effects on renal function and structure in the polycystic kidney disease model. Donor cell engraftment and both mutant and wild type Pkhd1 were found in treated but not control PCK kidneys 15 weeks after the final cell infusion. To examine the mechanisms of global protection with a small number of transplanted cells, we tested the hypothesis that exosomes derived from normal Sprague Dawley cells can limit the cystic phenotype of PCK recipient cells. We found that renal exosomes originating from normal Sprague Dawley cells carried and transferred wild type Pkhd1 mRNA to PCK cells in vivo and in vitro and restricted cyst formation by cultured PCK cells. The results indicate that transplantation with renal cells containing wild type Pkhd1 improves renal structure and function in autosomal recessive polycystic kidney disease and may provide an intra-renal supply of normal Pkhd1 mRNA.

  8. Resveratrol Improves Cell Cycle Arrest in Chronic Prostatitis Rats, by C-kit/SCF Suppression.

    Science.gov (United States)

    He, Yi; Zeng, Huizhi; Yu, Yang; Zhang, Jiashu; Zeng, Xiaona; Gong, Fengtao; Liu, Qi; Yang, Bo

    2017-08-01

    Chronic prostatitis (CP) with complex pathogenesis is difficult for treatment. c-kit has been associated with the control of cell proliferation of prostate cells. This study aims to evaluate the role of resveratrol, an activator of Sirt1, in regulating the expression of c-kit in CP and investigate the consequent effects on cell cycle. Rat model of CP was established through subcutaneous injections of diphtheria-pertussis-tetanus vaccine and subsequently treated with resveratrol. Hematoxylin and eosin staining was performed to identify the histopathological changes in prostates. Western blotting and immunohistochemical staining examined the expression level of c-kit, stem cell factor (SCF), Sirt1, and cell cycle-associated proteins. The model group exhibited severe diffuse chronic inflammation, characterized by leukocyte infiltration and papillary frond protrusion into the gland cavities, and a notable increase in prostatic epithelial height. Gland lumen diameter was also significantly smaller; the activity of c-kit/SCF in the CP rats was increased significantly compared to the control group. Meanwhile, the cell cycle proteins are dysregulated significantly in CP rats. Resveratrol treatment significantly improved these factors by Sirt1 activation. Dysregulation of cell cycle was involved in the pathological processes of CP, which was improved after resveratrol treatment by the downregulation of c-kit/SCF by activating Sirt1.

  9. Improved performance of mesostructured perovskite solar cells via an anti-solvent method

    Science.gov (United States)

    Hao, Jiabin; Hao, Huiying; Cheng, Feiyu; Li, Jianfeng; Zhang, Haiyu; Dong, Jingjing; Xing, Jie; Liu, Hao; Wu, Jian

    2018-06-01

    One-step solution process is a facile and widely used procedure to prepare organic-inorganic perovskite materials. However, the poor surface morphology of the films attributed to the uncontrollable nucleation and crystal growth in the process is unfavorable to solar cells. In this study, an anti-solvent treatment during the one-step solution process, in which ethyl acetate (EA) was dropped on the sample during spinning the precursor solution containing CH3NH3Cl, was adopted to fabricate perovskite materials and solar cells. It was found that the morphology of the perovskite film was significantly improved due to the rapid nucleation and slow crystal growth process. The modified process enabled us to fabricate the mesoporous solar cell with power conversion efficiency of 14%, showing an improvement of 40% over the efficiency of 9.7% of the device prepared by conventional one-step method. The controlling effect of annealing time on the morphology, crystal structure and transport properties of perovskite layer as well as the performance of device fabricated by the anti-solvent method were investigated and the possible mechanism was discussed.

  10. Collagen Type I Improves the Differentiation of Human Embryonic Stem Cells towards Definitive Endoderm

    DEFF Research Database (Denmark)

    Rasmussen, Camilla Holzmann; Petersen, Dorthe Roenn; Møller, Jonas Bech

    2015-01-01

    Human embryonic stem cells have the ability to generate all cell types in the body and can potentially provide an unlimited source of cells for cell replacement therapy to treat degenerative diseases such as diabetes. Current differentiation protocols of human embryonic stem cells towards insulin...... and consistent differentiation of stem cells to definitive endoderm. The results shed light on the importance of extracellular matrix proteins for differentiation and also points to a cost effective and easy method to improve differentiation....... embryonic stem cells to the definitive endoderm lineage. The percentage of definitive endoderm cells after differentiation on collagen I and fibronectin was >85% and 65%, respectively. The cells on collagen I substrates displayed different morphology and gene expression during differentiation as assessed...

  11. Repression of COUP-TFI Improves Bone Marrow-Derived Mesenchymal Stem Cell Differentiation into Insulin-Producing Cells

    Directory of Open Access Journals (Sweden)

    Tao Zhang

    2017-09-01

    Full Text Available Identifying molecular mechanisms that regulate insulin expression in bone marrow-derived mesenchymal stem cells (bmMSCs can provide clues on how to stimulate the differentiation of bmMSCs into insulin-producing cells (IPCs, which can be used as a therapeutic approach against type 1 diabetes (T1D. As repression factors may inhibit differentiation, the efficiency of this process is insufficient for cell transplantation. In this study, we used the mouse insulin 2 (Ins2 promoter sequence and performed a DNA affinity precipitation assay combined with liquid chromatography-mass spectrometry to identify the transcription factor, chicken ovalbumin upstream promoter transcriptional factor I (COUP-TFI. Functionally, bmMSCs were reprogrammed into IPCs via COUP-TFI suppression and MafA overexpression. The differentiated cells expressed higher levels of genes specific for islet endocrine cells, and they released C-peptide and insulin in response to glucose stimulation. Transplantation of IPCs into streptozotocin-induced diabetic mice caused a reduction in hyperglycemia. Mechanistically, COUP-TFI bound to the DR1 (direct repeats with 1 spacer element in the Ins2 promoter, thereby negatively regulating promoter activity. Taken together, the data provide a novel mechanism by which COUP-TFI acts as a negative regulator in the Ins2 promoter. The differentiation of bmMSCs into IPCs could be improved by knockdown of COUP-TFI, which may provide a novel stem cell-based therapy for T1D. Keywords: siRNAs, differentiation, stem cell transplantation, diabetes, mesenchymal stem cells

  12. An improved ontological representation of dendritic cells as a paradigm for all cell types

    Directory of Open Access Journals (Sweden)

    Mungall Chris

    2009-02-01

    Full Text Available Abstract Background Recent increases in the volume and diversity of life science data and information and an increasing emphasis on data sharing and interoperability have resulted in the creation of a large number of biological ontologies, including the Cell Ontology (CL, designed to provide a standardized representation of cell types for data annotation. Ontologies have been shown to have significant benefits for computational analyses of large data sets and for automated reasoning applications, leading to organized attempts to improve the structure and formal rigor of ontologies to better support computation. Currently, the CL employs multiple is_a relations, defining cell types in terms of histological, functional, and lineage properties, and the majority of definitions are written with sufficient generality to hold across multiple species. This approach limits the CL's utility for computation and for cross-species data integration. Results To enhance the CL's utility for computational analyses, we developed a method for the ontological representation of cells and applied this method to develop a dendritic cell ontology (DC-CL. DC-CL subtypes are delineated on the basis of surface protein expression, systematically including both species-general and species-specific types and optimizing DC-CL for the analysis of flow cytometry data. We avoid multiple uses of is_a by linking DC-CL terms to terms in other ontologies via additional, formally defined relations such as has_function. Conclusion This approach brings benefits in the form of increased accuracy, support for reasoning, and interoperability with other ontology resources. Accordingly, we propose our method as a general strategy for the ontological representation of cells. DC-CL is available from http://www.obofoundry.org.

  13. Haptic shared control improves hot cell remote handling despite controller inaccuracies

    NARCIS (Netherlands)

    van Oosterhout, J.; Abbink, D. A.; Koning, J. F.; Boessenkool, H.; Wildenbeest, J. G. W.; Heemskerk, C. J. M.

    2013-01-01

    A promising solution to improve task performance in ITER hot cell remote handling is the use of haptic shared control. Haptic shared control can assist the human operator along a safe and optimal path with continuous guiding forces from an intelligent autonomous controller. Previous research tested

  14. Improvements to the solar cell efficiency and production yields of low-lifetime wafers with effective phosphorus gettering

    International Nuclear Information System (INIS)

    Lu, Jiunn-Chenn; Chen, Ping-Nan; Chen, Chih-Min; Wu, Chung-Han

    2013-01-01

    Highlights: • Variable-temperature gettering improves efficiencies when the wafer quality is poor. • High-quality wafers need not be used for variable-temperature gettering. • The proposed gettering method is based on an existing diffusion process. • It has a potential interest for hot-spot prevention. -- Abstract: This research focuses on the improvement of solar cell efficiencies in low-lifetime wafers by implementing an appropriate gettering method of the diffusion process. The study also considers a reduction in the value of the reverse current at −12 V, an important electrical parameter related to the hot-spot heating of solar cells and modules, to improve the product's quality during commercial mass production. A practical solar cell production case study is examined to illustrate the use of the proposed method. The results of this case study indicate that variable-temperature gettering significantly improves solar cell efficiencies by 0.14% compared to constant-temperature methods when the wafer quality is poor. Moreover, this study finds that variable-temperature gettering raises production yields of low quality wafers by more than 30% by restraining the measurement value of the reverse current at −12 V during solar cell manufacturing

  15. Multipotent human stromal cells improve cardiac function after myocardial infarction in mice without long-term engraftment

    International Nuclear Information System (INIS)

    Iso, Yoshitaka; Spees, Jeffrey L.; Serrano, Claudia; Bakondi, Benjamin; Pochampally, Radhika; Song, Yao-Hua; Sobel, Burton E.; Delafontaine, Patrick; Prockop, Darwin J.

    2007-01-01

    The aim of this study was to determine whether intravenously administered multipotent stromal cells from human bone marrow (hMSCs) can improve cardiac function after myocardial infarction (MI) without long-term engraftment and therefore whether transitory paracrine effects or secreted factors are responsible for the benefit conferred. hMSCs were injected systemically into immunodeficient mice with acute MI. Cardiac function and fibrosis after MI in the hMSC-treated group were significantly improved compared with controls. However, despite the cardiac improvement, there was no evident hMSC engraftment in the heart 3 weeks after MI. Microarray assays and ELISAs demonstrated that multiple protective factors were expressed and secreted from the hMSCs in culture. Factors secreted by hMSCs prevented cell death of cultured cardiomyocytes and endothelial cells under conditions that mimicked tissue ischemia. The favorable effects of hMSCs appear to reflect the impact of secreted factors rather than engraftment, differentiation, or cell fusion

  16. Cell adhesion-mediated radioresistance (CAM-RR). Extracellular matrix-dependent improvement of cell survival in human tumor and normal cells in vitro

    International Nuclear Information System (INIS)

    Cordes, N.; Meineke, V.

    2003-01-01

    Background: Cell-extracellular matrix (ECM) contact is thought to have great impact on cellular mechanisms resulting in increased cell survival upon exposure to ionizing radiation. Several human tumor cell lines and normal human fibroblastic cell strains of different origin, all of them expressing the wide-spread and important integrin subunit β1, were irradiated, and clonogenic cell survival, β1-integrin cell surface expression, and adhesive functionality were investigated. Material and Methods: Human tumor cell lines A172 (glioblastoma), PATU8902 (pancreas carcinoma), SKMES1 (lung carcinoma), A549 (lung carcinoma), and IPC298 (melanoma) as well as normal human skin (HSF1) and lung fibroblasts (CCD32) and human keratinocytes (HaCaT) were irradiated with 0-8 Gy. Besides colony formation assays, β1-integrin cell surface expression by flow cytometry and adhesive functionality by adhesion assays were analyzed. Results: All cell lines showed improved clonogenic survival after irradiation in the presence of fibronectin as compared to plastic. Irradiated cells exhibited a significant, dose-dependent increase in β1-integrin cell surface expression following irradiation. As a parameter of the adhesive functionality of the β1-integrin, a radiation-dependent elevation of cell adhesion to fibronectin in comparison with adhesion to plastic was demonstrated. Conclusion: The in vitro cellular radiosensitivity is highly influenced by fibronectin according to the phenomenon of cell adhesion-mediated radioresistance. Additionally, our emerging data question the results of former and current in vitro cytotoxicity studies performed in the absence of an ECM. These findings might also be important for the understanding of malignant transformation, anchorage-independent cell growth, optimization of radiotherapeutic regimes and the prevention of normal tissue side effects on the basis of experimental radiobiological data. (orig.)

  17. An improved single cell ultrahigh throughput screening method based on in vitro compartmentalization.

    Directory of Open Access Journals (Sweden)

    Fuqiang Ma

    Full Text Available High-throughput screening is a key technique in discovery and engineering of enzymes. In vitro compartmentalization based fluorescence-activated cell sorting (IVC-FACS has recently emerged as a powerful tool for ultrahigh-throughput screening of biocatalysts. However, the accuracy of current IVC-FACS assays is severely limited by the wide polydispersity of micro-reactors generated by homogenizing. Here, an improved protocol based on membrane-extrusion technique was reported to generate the micro-reactors in a more uniform manner. This crucial improvement enables ultrahigh-throughput screening of enzymatic activity at a speed of >10⁸ clones/day with an accuracy that could discriminate as low as two-fold differences in enzymatic activity inside the micro-reactors, which is higher than similar IVC-FACS systems ever have reported. The enzymatic reaction in the micro-reactors has very similar kinetic behavior compared to the bulk reaction system and shows wide dynamic range. By using the modified IVC-FACS, E. coli cells with esterase activity could be enriched 330-fold from large excesses of background cells through a single round of sorting. The utility of this new IVC-FACS system was further illustrated by the directed evolution of thermophilic esterase AFEST. The catalytic activity of the very efficient esterase was further improved by ∼2-fold, resulting in several improved mutants with k(cat/K(M values approaching the diffusion-limited efficiency of ∼10⁸ M⁻¹s⁻¹.

  18. Lipofectamine and related cationic lipids strongly improve adenoviral infection efficiency of primitive human hematopoietic cells.

    Science.gov (United States)

    Byk, T; Haddada, H; Vainchenker, W; Louache, F

    1998-11-20

    Adenoviral vectors have the potential to infect a large number of cell types including quiescent cells. Their use in hematopoietic cells is limited by the episomal form of their DNA, leading to transgene loss in the progeny cells. However, the use of this vector may be interesting for short-term in vitro modifications of primitive human hematopoietic cells. Therefore, we have investigated the ability of adenovirus to transduce cord blood CD34+ cells. Several promoters were tested using the lacZ reporter gene. The PGK and CMV promoters induced transgene expression in 18-25% of the cells, whereas the HTLV-I and especially the RSV promoter were almost inactive. To improve infection efficiency, adenovirus was complexed with cationic lipids. Lipofectamine, Cellfectin, and RPR120535b, but not Lipofectin, Lipofectace, or DOTAP, markedly improved transgene expression in CD34+ cells (from 19 to 35%). Lipofectamine strongly enhanced infection efficiency of the poorly infectable primitive CD34+CD38low cells (from 11 to 28%) whereas the more mature CD34+CD38+ cells were only slightly affected (from 24 to 31%). Lipofectamine tripled the infection of CFU-GMs and LTC-ICs derived from the CD34+CD38low cell fraction (from 4 to 12% and from 5 to 16%, respectively) and doubled that of BFU-Es (from 13 to 26%). We conclude that cationic lipids can markedly increase the efficiency of adenovirus-mediated gene transfer into primitive hematopoietic cells.

  19. Using silicon nanostructures for the improvement of silicon solar cells' efficiency

    International Nuclear Information System (INIS)

    Torre, J. de la; Bremond, G.; Lemiti, M.; Guillot, G.; Mur, P.; Buffet, N.

    2006-01-01

    Silicon nanostructures (ns-Si) show interesting optical and electrical properties as a result of the band gap widening caused by quantum confinement effects. Along with their potential utilization for silicon-based light emitters' fabrication, they could also represent an appealing option for the improvement of energy conversion efficiency in silicon-based solar cells whether by using their luminescence properties (photon down-conversion) or the excess photocurrent produced by an improved high-energy photon's absorption. In this work, we report on the morphological and optical studies of non-stoichiometric silica (SiO x ) and silicon nitride (SiN x ) layers containing silicon nanostructures (ns-Si) in view of their application for solar cell's efficiency improvement. The morphological studies of the samples performed by transmission electron microscopy (TEM) unambiguously show the presence of ns-Si in a crystalline form for high temperature-annealed SiO x layers and for low temperature deposition of SiN x layers. The photoluminescence emission (PL) shows a rather high efficiency in both kind of layers with an intensity of only a factor ∼ 100 lower than that of porous silicon (pi-Si). The photocurrent spectroscopy (PC) shows a significant increase of absorption at high photon energy excitation most probably related to photon absorption within ns-Si quantized states. Moreover, the absorption characteristics obtained from PC spectra show a good agreement with the PL emission states unambiguously demonstrating a same origin, related to Q-confined excitons within ns-Si. Finally, the major asset of this material is the possibility to incorporate it to solar cells manufacturing processing for an insignificant cost

  20. Effects of the prescription of reinforcing kidney, nourishing blood, improving eyesight on ARPE-19 cells induced by acrolein

    Directory of Open Access Journals (Sweden)

    Man Li

    2015-05-01

    Full Text Available AIM: To explore the effects of the prescription of reinforcing kidney, nourishing blood, improving eyesight on the oxidative stress model of ARPE-19 cells induced by acrolein. METHODS: SD rats serum containing the prescription of reinforcing kidney, nourishing blood, improving eyesight and the content of distilled water in serum were prepared. The effects of the prescription and distilled water in serum at different concentration(2.5%, 5%, 10%, 20% and 40%on cell vitality was observed by cell counting kit(CCK-8assay. the logarithmic phase of ARPE-19 cells were pretreated by different concentrations(1.25%, 2.5% and 5%of the prescription serum and distilled water in serum for 24h. Then it was treated with 75μmol/L acrolein for 24h. Cell vitality was observed by CCK-8 assay. The change of cell nucleus was detected by DAPI staining.RESULTS: 2.5% and 5% serum had no effect on cell viability(P>0.05, while 10%, 20%, 40% serum could inhibit cell viability(PPCONCLUSION: The prescription of reinforcing kidney, nourishing blood, improving eyesight has the protective effect on ARPE-19 cell damage induced by acrolein.

  1. Improvements to the hierarchically structured ZnO nanosphere based dye-sensitized solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Yongzhe; Wu Lihui; Liu Yanping; Xie Erqing, E-mail: zhangyzh04@126.co, E-mail: xieeq@lzu.edu.c [School of Physical Science and Technology, Lanzhou University, Lanzhou 730000 (China)

    2009-04-21

    Hierarchically structured ZnO nanospheres are synthesized by a wet-chemical method and ZnO sphere-consisting films are applied to dye-sensitized solar cells (DSSCs). It is found that the overall light-to-electricity conversion efficiency ({eta}) is significantly enhanced from 0.474% to 1.03% due to light scattering compared with the ZnO nanoparticle-based DSSC. However, the fill factor (FF) and open-circuit voltage (V{sub oc}) decrease obviously. After annealing the films in an oxygen environment and placing a ZnO blocking layer on the fluorine-doped SnO{sub 2} (FTO) conducting substrate, the FF and V{sub oc} are greatly improved and {eta} increases from 1.03% to 1.59% and 2.25%, respectively. According to the results of x-ray diffraction and photoluminescence, the significant improvements in the cell performances might be due to the suppression of the recombination and the decrease in the resistances existing in the cell.

  2. Design of magnetic flywheel control for performance improvement of fuel cells used in vehicles

    International Nuclear Information System (INIS)

    Huang, Chung-Neng; Chen, Yui-Sung

    2017-01-01

    Because hydrogen can be extracted naturally and stored for a long time, different types of fuel cells have been developed to generate clean power, particularly for use in vehicles. However, the power demand of a running vehicle leads to unstable and irregular loading of fuel cells. This not only reduces fuel cell lifespan and efficiency but also affects driving safety when the slow output response cannot satisfy an abrupt increase in power demand. Magnetic flywheels with characteristics such as high energy density, high-speed charging ability, and low loss have been extensively used in Formula One cars. This study developed a hybrid powertrain in which a magnetic flywheel system (MFS) is integrated with the fuel cells to solve the aforementioned problems. Moreover, an auto-tuning proportional–integral–derivative (PID) controller based on the controls of a multiple adaptive neuro-fuzzy interference system and particle swarm optimization was designed for MFS control. Furthermore, MATLAB/Simulink simulations considering an FTP-75 urban driving cycle were conducted, and a variability improvement of approximately 27.3% in fuel cell output was achieved. - Highlights: • A hybrid powertrain integrating the magnetic flywheel and fuel cells is proposed. • An auto-tuning PID controller is designed for MFS control. • The MIMO-ANFIS and PSO based optimal control is realized. • A 27.3% improvement in the output variability of fuel cell is achieved under control.

  3. Stem Cells as a Tool to Improve Outcomes of Islet Transplantation

    Directory of Open Access Journals (Sweden)

    Emily Sims

    2012-01-01

    Full Text Available The publication of the promising results of the Edmonton protocol in 2000 generated optimism for islet transplantation as a potential cure for Type 1 Diabetes Mellitus. Unfortunately, follow-up data revealed that less than 10% of patients achieved long-term insulin independence. More recent data from other large trials like the Collaborative Islet Transplant Registry show incremental improvement with 44% of islet transplant recipients maintaining insulin independence at three years of follow-up. Multiple underlying issues have been identified that contribute to islet graft failure, and newer research has attempted to address these problems. Stem cells have been utilized not only as a functional replacement for β cells, but also as companion or supportive cells to address a variety of different obstacles that prevent ideal graft viability and function. In this paper, we outline the manners in which stem cells have been applied to address barriers to the achievement of long-term insulin independence following islet transplantation.

  4. Improved isolation protocol for equine cord blood-derived mesenchymal stromal cells

    DEFF Research Database (Denmark)

    Koch, Thomas Gadegaard; Thomsen, Preben Dybdahl; Betts, Dean H.

    2009-01-01

      BACKGROUND AIMS: A robust methodology for the isolation of cord blood-derived multipotent mesenchymal stromal cells (CB-MSCs) from fresh umbilical cord blood has not been reported in any species. The objective of this study was to improve the isolation procedure for equine CB-MSCs. METHODS: Pre......-culture separation of red and white blood cells was done using either PrepaCyte?-EQ medium or Ficoll-Paque? PREMIUM density medium. Regular FBS and MSC-qualified FBS were compared for their ability to support the establishment of putative primary MSC colonies. RESULTS AND CONCLUSIONS: Our results indicate that Prepa...

  5. Improved mass-measurement accuracy using a PNB Load Cell Scale

    International Nuclear Information System (INIS)

    Suda, S.; Pontius, P.; Schoonover, R.

    1981-08-01

    The PNB Load Cell Scale is a Preloaded, Narrow-Band calibration mass comparator. It consists of (1) a frame and servo-mechanism that maintains a preload tension on the load cell until the load, an unknown mass, is sensed, and (2) a null-balance digital instrument that suppresses the cell response associated with the preload, thereby improving the precision and accuracy of the measurements. Ideally, the objects used to set the preload should be replica mass standards that closely approximate the density and mass of the unknowns. The advantages of the PNB scale are an expanded output signal over the range of interest which increases both the sensitivity and resolution, and minimizes the transient effects associated with loading of load cells. An area of immediate and practical application of this technique to nuclear material safeguards is the weighing of UF 6 cyliners where in-house mass standards are currently available and where the mass values are typically assigned on the basis of comparison weighings. Several prototypical versions of the PNB scale have been assembled at the US National Bureau of Standards. A description of the instrumentation, principles of measurements, and applications are presented in this paper

  6. Hydrophobic Polystyrene Passivation Layer for Simultaneously Improved Efficiency and Stability in Perovskite Solar Cells.

    Science.gov (United States)

    Li, Minghua; Yan, Xiaoqin; Kang, Zhuo; Huan, Yahuan; Li, Yong; Zhang, Ruxiao; Zhang, Yue

    2018-06-06

    The major restraint for the commercialization of the high-performance hybrid metal halide perovskite solar cells is the long-term stability, especially at the infirm interface between the perovskite film and organic charge-transfer layer. Recently, engineering the interface between the perovskite and spiro-OMeTAD becomes an effective strategy to simultaneously improve the efficiency and stability in the perovskite solar cells. In this work, we demonstrated that introducing an interfacial polystyrene layer between the perovskite film and spiro-OMeTAD layer can effectively improve the perovskite solar cells photovoltaic performance. The inserted polystyrene layer can passivate the interface traps and defects effectively and decrease the nonradiative recombination, leading to enhanced photoluminescence intensity and carrier lifetime, without compromising the carrier extraction and transfer. Under the optimized condition, the perovskite solar cells with the polystyrene layer achieve an enhanced average power efficiency of about 19.61% (20.46% of the best efficiency) from about 17.63% with negligible current density-voltage hysteresis. Moreover, the optimized perovskite solar cells with the hydrophobic polystyrene layer can maintain about 85% initial efficiency after 2 months storage in open air conditions without encapsulation.

  7. Improving the Quality of the Deteriorated Regions of Multicrystalline Silicon Ingots during General Solar Cell Processes

    International Nuclear Information System (INIS)

    Wu Shan-Shan; Wang Lei; Yang De-Ren

    2011-01-01

    The behavior of wafers and solar cells from the border of a multicrystalline silicon (mc-Si) ingot, which contain deteriorated regions, is investigated. It is found that the diffusion length distribution of minority carriers in the cells is uniform, and high efficiency of the solar cells (about 16%) is achieved. It is considered that the quality of the deteriorated regions could be improved to be similar to that of adjacent regions. Moreover, it is indicated that during general solar cell fabrication, phosphorus gettering and hydrogen passivation could significantly improve the quality of deteriorated regions, while aluminum gettering by RTP could not. Therefore, it is suggested that the border of a mc-Si ingot could be used to fabricate high efficiency solar cells, which will increase mc-Si utilization effectively. (condensed matter: structure, mechanical and thermal properties)

  8. Improved methods for binding acma-type protein anchor fusions yo cell-wall material of micro-organisms

    NARCIS (Netherlands)

    Leenhouts, Cornelis; Ramasamy, R.; Steen, Anton; Kok, Jan; Buist, Girbe; Kuipers, Oscar

    2002-01-01

    The invention provides a method for improving binding of a proteinaceous substance to cell-wall material of a Gram-positive bacterium, said substance comprising an AcmA cell wall binding domain or homolog or functional derivative thereof, said method comprising treating said cell-wall material with

  9. Nanostructural optimization of silicon/PEDOT:PSS hybrid solar cells for performance improvement

    International Nuclear Information System (INIS)

    Wang, Yanzhou; Shao, Pengfei; Li, Yali; Li, Junshuai; He, Deyan; Chen, Qiang

    2017-01-01

    In this paper, an inverted silicon (Si) nanopyramid (iSiNP) surface structure with low aspect ratio and remarkable antireflection is developed through sequential treatments of NaOH and HF/CH 3 COOH/HNO 3 solutions to Si nanowire (SiNW)-textured Si wafers, which are prepared by traditional electroless chemical etching. The iSiNP/PEDOT:PSS hybrid solar cell is fabricated through conformally spin-coating poly(3.4-ethylene dioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) onto the iSiNPs; it exhibits enhanced device performance owing to the improved junction and contact quality as compared to the SiNW/PEDOT:PSS counterpart. A power conversion efficiency (PCE) of 9.6% mainly contributed from an increased fill factor (FF) of 0.61 and improved open circuit voltage ( V oc ) of 0.53 V is delivered by the iSiNP/PEDOT:PSS solar cell. As a comparison, the SiNW/PEDOT:PSS structure delivers a 7.1% PCE with a FF of 0.45 and V oc of 0.46 V. Considering the submicro-scale characteristic dimensions, iSiNPs are expected to be applicable to highly efficient thin film Si/PEDOT:PSS hybrid solar cells. (paper)

  10. Genetic damage induced by a food coloring dye (sunset yellow) on meristematic cells of Brassica campestris L.

    Science.gov (United States)

    Dwivedi, Kshama; Kumar, Girjesh

    2015-01-01

    We have performed the present piece of work to evaluate the effect of synthetic food coloring azo dye (sunset yellow) on actively dividing root tip cells of Brassica campestris L. Three doses of azo dye were administered for the treatment of actively dividing root tip cells, namely, 1%, 3%, and 5%, for 6-hour duration along with control. Mitotic analysis clearly revealed the azo dye induced endpoint deviation like reduction in the frequency of normal divisions in a dose dependent manner. Mitotic divisions in the control sets were found to be perfectly normal while dose based reduction in MI was registered in the treated sets. Azo dye has induced several chromosomal aberrations (genotoxic effect) at various stages of cell cycle such as stickiness of chromosomes, micronuclei formation, precocious migration of chromosome, unorientation, forward movement of chromosome, laggards, and chromatin bridge. Among all, stickiness of chromosomes was present in the highest frequency followed by partial genome elimination as micronuclei. The present study suggests that extensive use of synthetic dye should be forbidden due to genotoxic and cytotoxic impacts on living cells. Thus, there is an urgent need to assess potential hazardous effects of these dyes on other test systems like human and nonhuman biota for better scrutiny.

  11. Mesenchymal stem cells increase T-regulatory cells and improve healing following trauma and hemorrhagic shock.

    Science.gov (United States)

    Gore, Amy V; Bible, Letitia E; Song, Kimberly; Livingston, David H; Mohr, Alicia M; Sifri, Ziad C

    2015-07-01

    Rodent lungs undergo full histologic recovery within 1 week following unilateral lung contusion (LC). However, when LC is followed by hemorrhagic shock (HS), healing is impaired. We hypothesize that the intravenous administration of mesenchymal stem cells (MSCs) in animals undergoing combined LC followed by HS (LCHS) will improve wound healing. Male Sprague-Dawley rats (n = 5-6 per group) were subjected to LCHS with or without the injection of a single intravenous dose of 5 × 10 MSCs following return of shed blood after HS. Rats were sacrificed 7 days following injury. Flow cytometry was used to determine the T-regulatory cell (Treg) population in peripheral blood. Lung histology was graded using a well-established lung injury score (LIS). Components of the LIS include average inflammatory cells per high-power field over 30 fields, interstitial edema, pulmonary edema, and alveolar integrity, with total scores ranging from 0 to 11. Data were analyzed by analysis of variance followed by Tukey's multiple comparison test, expressed as mean (SD). p healing with an LIS unchanged from naive. The addition of HS resulted in a persistently elevated LIS score, whereas the addition of MSCs to LCHS decreased the LIS score back to naive levels. The change in LIS was driven by a significant decrease in edema scores. In rats undergoing LC alone, 10.5% (3.3%) of CD4 cells were Tregs. The addition of HS caused no significant change in Treg population (9.3% [0.7%]), whereas LCHS + MSC significantly increased the population to 18.2% (6.8%) in peripheral blood (p healing following trauma and HS is improved by a single dose of MSCs given immediately after injury. This enhanced healing is associated with an increase in the Treg population and a significant decrease in lung edema score as compared with animals undergoing LCHS. Further study into the role of Tregs in MSC-mediated wound healing is warranted.

  12. Rational design of nanoparticles towards targeting antigen-presenting cells and improved T cell priming.

    Science.gov (United States)

    Zupančič, Eva; Curato, Caterina; Paisana, Maria; Rodrigues, Catarina; Porat, Ziv; Viana, Ana S; Afonso, Carlos A M; Pinto, João; Gaspar, Rogério; Moreira, João N; Satchi-Fainaro, Ronit; Jung, Steffen; Florindo, Helena F

    2017-07-28

    -like receptor (TLR) ligand CpG, induced the most profound antigen-specific T cell response, by both CD4 + and CD8 + T cells, in vivo. Overall, our data reveal the impact of NP composition and surface properties on the type and extension of induced immune responses. Deeper understanding on the NP-immune cell crosstalk can guide the rational development of nano-immunotherapeutic systems with improved and specific therapeutic efficacy and avoiding off-target effects. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Cysteine modified polyaniline films improve biocompatibility for two cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Yslas, Edith I., E-mail: eyslas@exa.unrc.edu.ar [Departamento de Biología Molecular, Universidad Nacional de Río Cuarto, Agencia Postal Nro3, X580BYA Río Cuarto (Argentina); Cavallo, Pablo; Acevedo, Diego F.; Barbero, César A. [Departamento de Química, Universidad Nacional de Río Cuarto, Agencia Postal Nro3, X580BYA Río Cuarto (Argentina); Rivarola, Viviana A. [Departamento de Biología Molecular, Universidad Nacional de Río Cuarto, Agencia Postal Nro3, X580BYA Río Cuarto (Argentina)

    2015-06-01

    This work focuses on one of the most exciting application areas of conjugated conducting polymers, which is cell culture and tissue engineering. To improve the biocompatibility of conducting polymers we present an easy method that involves the modification of the polymer backbone using L-cysteine. In this publication, we show the synthesis of polyaniline (PANI) films supported onto Polyethylene terephthalate (PET) films, and modified using cysteine (PANI-Cys) in order to generate a biocompatible substrate for cell culture. The PANI-Cys films are characterized by Fourier Transform infrared and UV–visible spectroscopy. The changes in the hydrophilicity of the polymer films after and before the modification were tested using contact angle measurements. After modification the contact angle changes from 86° ± 1 to 90° ± 1, suggesting a more hydrophylic surface. The adhesion properties of LM2 and HaCaT cell lines on the surface of PANI-Cys films in comparison with tissue culture plastic (TCP) are studied. The PANI-Cys film shows better biocompatibility than PANI film for both cell lines. The cell morphologies on the TCP and PANI-Cys film were examined by florescence and Atomic Force Microscopy (AFM). Microscopic observations show normal cellular behavior when PANI-Cys is used as a substrate of both cell lines (HaCaT and LM2) as when they are cultured on TCP. The ability of these PANI-Cys films to support cell attachment and growth indicates their potential use as biocompatible surfaces and in tissue engineering. - Highlights: • A new surface PANI-Cys was produced on films of polyethylene terephthalate. • The relationship between surface characteristics and biocompatibility is analyzed. • The PANI-Cys film presents good biocompatibility for two cell lines.

  14. Progenitor Hematopoietic Cells Implantation Improves Functional Capacity of End Stage Coronary Artery Disease Patients with Advanced Heart Failure

    Directory of Open Access Journals (Sweden)

    Yoga Yuniadi

    2016-01-01

    Full Text Available Background. Proangiogenic Hematopoietic Cells (PHC which comprise diverse mixture of cell types are able to secrete proangiogenic factors and interesting candidate for cell therapy. The aim of this study was to seek for benefit in implantation of PHC on functional improvement in end stage coronary artery disease patients with advanced heart failure. Methods. Patients with symptomatic heart failure despite guideline directed medical therapy and LVEF less than 35% were included. Peripheral blood mononuclear cells were isolated, cultivated for 5 days, and then harvested. Flow cytometry and cell surface markers were used to characterize PHC. The PHC were delivered retrogradely via sinus coronarius. Echocardiography, myocardial perfusion, and clinical and functional data were analyzed up to 1-year observation. Results. Of 30 patients (56.4±7.40 yo preimplant NT proBNP level is 5124.5±4682.50 pmol/L. Harvested cells characterized with CD133, CD34, CD45, and KDR showed 0.87±0.41, 0.63±0.66, 99.00±2.60, and 3.22±3.79%, respectively. LVEF was improved (22±5.68 versus 26.8±7.93, p<0.001 during short and long term observation. Myocardial perfusion significantly improved 6 months after treatment. NYHA Class and six-minute walk test are improved during short term and long term follow-up. Conclusion. Expanded peripheral blood PHC implantation using retrograde delivery approach improved LV systolic function, myocardial perfusion, and functional capacity.

  15. Improving Performance of CIGS Solar Cells by Annealing ITO Thin Films Electrodes

    Directory of Open Access Journals (Sweden)

    Chuan Lung Chuang

    2015-01-01

    Full Text Available Indium tin oxide (ITO thin films were grown on glass substrates by direct current (DC reactive magnetron sputtering at room temperature. Annealing at the optimal temperature can considerably improve the composition, structure, optical properties, and electrical properties of the ITO film. An ITO sample with a favorable crystalline structure was obtained by annealing in fixed oxygen/argon ratio of 0.03 at 400°C for 30 min. The carrier concentration, mobility, resistivity, band gap, transmission in the visible-light region, and transmission in the near-IR regions of the ITO sample were -1.6E+20 cm−3, 2.7E+01 cm2/Vs, 1.4E-03 Ohm-cm, 3.2 eV, 89.1%, and 94.7%, respectively. Thus, annealing improved the average transmissions (400–1200 nm of the ITO film by 16.36%. Moreover, annealing a copper-indium-gallium-diselenide (CIGS solar cell at 400°C for 30 min in air improved its efficiency by 18.75%. The characteristics of annealing ITO films importantly affect the structural, morphological, electrical, and optical properties of ITO films that are used in solar cells.

  16. Development of improved methods for the LWR lattice physics code EPRI-CELL

    International Nuclear Information System (INIS)

    Williams, M.L.; Wright, R.Q.; Barhen, J.

    1982-07-01

    A number of improvements have been made by ORNL to the lattice physics code EPRI-CELL (E-C) which is widely used by utilities for analysis of power reactors. The code modifications were made mainly in the thermal and epithermal routines and resulted in improved reactor physics approximations and more efficient running times. The improvements in the thermal flux calculation included implementation of a group-dependent rebalance procedure to accelerate the iterative process and a more rigorous calculation of interval-to-interval collision probabilities. The epithermal resonance shielding methods used in the code have been extensively studied to determine its major approximations and to examine the sensitivity of computed results to these approximations. The study has resulted in several improvements in the original methodology

  17. Polyvinylpyrrolidone-Based Bio-Ink Improves Cell Viability and Homogeneity during Drop-On-Demand Printing

    Directory of Open Access Journals (Sweden)

    Wei Long Ng

    2017-02-01

    Full Text Available Drop-on-demand (DOD bioprinting has attracted huge attention for numerous biological applications due to its precise control over material volume and deposition pattern in a contactless printing approach. 3D bioprinting is still an emerging field and more work is required to improve the viability and homogeneity of printed cells during the printing process. Here, a general purpose bio-ink was developed using polyvinylpyrrolidone (PVP macromolecules. Different PVP-based bio-inks (0%–3% w/v were prepared and evaluated for their printability; the short-term and long-term viability of the printed cells were first investigated. The Z value of a bio-ink determines its printability; it is the inverse of the Ohnesorge number (Oh, which is the ratio between the Reynolds number and a square root of the Weber number, and is independent of the bio-ink velocity. The viability of printed cells is dependent on the Z values of the bio-inks; the results indicated that the cells can be printed without any significant impairment using a bio-ink with a threshold Z value of ≤9.30 (2% and 2.5% w/v. Next, the cell output was evaluated over a period of 30 min. The results indicated that PVP molecules mitigate the cell adhesion and sedimentation during the printing process; the 2.5% w/v PVP bio-ink demonstrated the most consistent cell output over a period of 30 min. Hence, PVP macromolecules can play a critical role in improving the cell viability and homogeneity during the bioprinting process.

  18. Improving Gene Therapy Efficiency through the Enrichment of Human Hematopoietic Stem Cells.

    Science.gov (United States)

    Masiuk, Katelyn E; Brown, Devin; Laborada, Jennifer; Hollis, Roger P; Urbinati, Fabrizia; Kohn, Donald B

    2017-09-06

    Lentiviral vector (LV)-based hematopoietic stem cell (HSC) gene therapy is becoming a promising clinical strategy for the treatment of genetic blood diseases. However, the current approach of modifying 1 × 10 8 to 1 × 10 9 CD34 + cells per patient requires large amounts of LV, which is expensive and technically challenging to produce at clinical scale. Modification of bulk CD34 + cells uses LV inefficiently, because the majority of CD34 + cells are short-term progenitors with a limited post-transplant lifespan. Here, we utilized a clinically relevant, immunomagnetic bead (IB)-based method to purify CD34 + CD38 - cells from human bone marrow (BM) and mobilized peripheral blood (mPB). IB purification of CD34 + CD38 - cells enriched severe combined immune deficiency (SCID) repopulating cell (SRC) frequency an additional 12-fold beyond standard CD34 + purification and did not affect gene marking of long-term HSCs. Transplant of purified CD34 + CD38 - cells led to delayed myeloid reconstitution, which could be rescued by the addition of non-transduced CD38 + cells. Importantly, LV modification and transplantation of IB-purified CD34 + CD38 - cells/non-modified CD38 + cells into immune-deficient mice achieved long-term gene-marked engraftment comparable with modification of bulk CD34 + cells, while utilizing ∼7-fold less LV. Thus, we demonstrate a translatable method to improve the clinical and commercial viability of gene therapy for genetic blood cell diseases. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  19. Improving the Post-Stroke Therapeutic Potency of Mesenchymal Multipotent Stromal Cells by Cocultivation With Cortical Neurons: The Role of Crosstalk Between Cells.

    Science.gov (United States)

    Babenko, Valentina A; Silachev, Denis N; Zorova, Ljubava D; Pevzner, Irina B; Khutornenko, Anastasia A; Plotnikov, Egor Y; Sukhikh, Gennady T; Zorov, Dmitry B

    2015-09-01

    The goal of the present study was to maximally alleviate the negative impact of stroke by increasing the therapeutic potency of injected mesenchymal multipotent stromal cells (MMSCs). To pursue this goal, the intercellular communications of MMSCs and neuronal cells were studied in vitro. As a result of cocultivation of MMSCs and rat cortical neurons, we proved the existence of intercellular contacts providing transfer of cellular contents from one cell to another. We present evidence of intercellular exchange with fluorescent probes specifically occupied by cytosol with preferential transfer from neurons toward MMSCs. In contrast, we observed a reversed transfer of mitochondria (from MMSCs to neural cells). Intravenous injection of MMSCs in a postischemic period alleviated the pathological indexes of a stroke, expressed as a lower infarct volume in the brain and partial restoration of neurological status. Also, MMSCs after cocultivation with neurons demonstrated more profound neuroprotective effects than did unprimed MMSCs. The production of the brain-derived neurotrophic factor was slightly increased in MMSCs, and the factor itself was redistributed in these cells after cocultivation. The level of Miro1 responsible for intercellular traffic of mitochondria was increased in MMSCs after cocultivation. We conclude that the exchange by cellular compartments between neural and stem cells improves MMSCs' protective abilities for better rehabilitation after stroke. This could be used as an approach to enhance the therapeutic benefits of stem cell therapy to the damaged brain. The idea of priming stem cells before practical use for clinical purposes was applied. Thus, cells were preconditioned by coculturing them with the targeted cells (i.e., neurons for the treatment of brain pathological features) before the transfusion of stem cells to the organism. Such priming improved the capacity of stem cells to treat stroke. Some additional minimal study will be required to

  20. Precocious puberty

    Science.gov (United States)

    ... Surgery to remove a tumor. Children with early sexual development may have psychological and social problems. Children and ... to be the same as their peers. Early sexual development can make them appear different. Parents can support ...

  1. Improving photovoltaic performance of silicon solar cells using a combination of plasmonic and luminescent downshifting effects

    Science.gov (United States)

    Ho, Wen-Jeng; Feng, Sheng-Kai; Liu, Jheng-Jie; Yang, Yun-Chie; Ho, Chun-Hung

    2018-05-01

    This paper reports on efforts to improve the photovoltaic performance of crystalline silicon solar cells by combining the plasmonic scattering of silver nanoparticles (Ag NPs) with the luminescent downshifting (LDS) effects of Eu-doped phosphors. The surface morphology was examined using a scanning electron microscope in conjunction with ImageJ software. Raman scattering and absorbance measurements were used to examine the surface plasmon resonance of Ag NPs of various dimensions in various dielectric environments. The fluorescence emission of the Eu-doped phosphors was characterized via photoluminescence measurements at room temperature. We examined the combination of plasmonic and LDS effects by measuring the optical reflectance and external quantum efficiency. Improvements in the photovoltaic performance of the solar cells were determined by photovoltaic current density-voltage under AM 1.5G illumination. A combination of plasmonic and LDS effects led to an impressive 26.17% improvement in efficiency, whereas plasmonic effects resulted in a 22.63% improvement compared to the cell with a SiO2 ARC of 17.33%.

  2. Control of the first flowering in forest trees

    Energy Technology Data Exchange (ETDEWEB)

    Chalupka, W. [Inst. od Dendrology, Kornik (Poland); Cecich, R.A. [U.S.D.A.-Forest Service, Columbia, MO (United States). North Central Forest Experiment Station

    1997-04-01

    Precocious flowering provides opportunities to shorten a breeding cycle. A tree may flower for the first time when sufficient crown development has occurred and there are enough meristems to support both vegetative and reproductive buds. Precocious flowering can be promoted through the use of cultural techniques, such as photoperiod, accelerated growth, gibberellins and water stress. The length of the juvenile phase is dependent on genetic and environmental variables that affect achievement of a minimum size, and is positively correlated with the height of the plants within a family. Selection pressure can be applied successfully to the precocious flowering character, and crossed or inbred lines of precocious flowering progeny can be developed. Various levels and amounts of genetic control have been implicated in the control of precocious flowering. 90 refs, 1 tab

  3. Room temperature electrocompetent bacterial cells improve DNA transformation and recombineering efficiency.

    Science.gov (United States)

    Tu, Qiang; Yin, Jia; Fu, Jun; Herrmann, Jennifer; Li, Yuezhong; Yin, Yulong; Stewart, A Francis; Müller, Rolf; Zhang, Youming

    2016-04-20

    Bacterial competent cells are essential for cloning, construction of DNA libraries, and mutagenesis in every molecular biology laboratory. Among various transformation methods, electroporation is found to own the best transformation efficiency. Previous electroporation methods are based on washing and electroporating the bacterial cells in ice-cold condition that make them fragile and prone to death. Here we present simple temperature shift based methods that improve DNA transformation and recombineering efficiency in E. coli and several other gram-negative bacteria thereby economizing time and cost. Increased transformation efficiency of large DNA molecules is a significant advantage that might facilitate the cloning of large fragments from genomic DNA preparations and metagenomics samples.

  4. An improved model for nucleation-limited ice formation in living cells during freezing.

    Directory of Open Access Journals (Sweden)

    Jingru Yi

    Full Text Available Ice formation in living cells is a lethal event during freezing and its characterization is important to the development of optimal protocols for not only cryopreservation but also cryotherapy applications. Although the model for probability of ice formation (PIF in cells developed by Toner et al. has been widely used to predict nucleation-limited intracellular ice formation (IIF, our data of freezing Hela cells suggest that this model could give misleading prediction of PIF when the maximum PIF in cells during freezing is less than 1 (PIF ranges from 0 to 1. We introduce a new model to overcome this problem by incorporating a critical cell volume to modify the Toner's original model. We further reveal that this critical cell volume is dependent on the mechanisms of ice nucleation in cells during freezing, i.e., surface-catalyzed nucleation (SCN and volume-catalyzed nucleation (VCN. Taken together, the improved PIF model may be valuable for better understanding of the mechanisms of ice nucleation in cells during freezing and more accurate prediction of PIF for cryopreservation and cryotherapy applications.

  5. Surface modification of hydrophobic polymers for improvement of endothelial cell-surface interactions

    NARCIS (Netherlands)

    Dekker, A.; Dekker, A.; Reitsma, K.; Beugeling, T.; Beugeling, T.; Bantjes, A.; Bantjes, A.; Feijen, Jan; Kirkpatrick, C.J.; van Aken, W.G.

    1992-01-01

    The aim of this study is to improve the interaction of endothelial cells with polymers used in vascular prostheses. Polytetrafluoroethylene (PTFE; Teflon) films were treated by means of nitrogen and oxygen plasmas. Depending on the plasma exposure time, modified PTFE surfaces showed water-contact

  6. STUDY OF CLINICAL PROFILE OF PATIENTS PRESENTING WITH SEXUAL PRECOCITY TO A TERTIARY CARE HOSPITAL

    Directory of Open Access Journals (Sweden)

    Binoy Kumar Mohanty

    2016-07-01

    Full Text Available BACKGROUND Precocious puberty is a common paediatric endocrine disorder seen in clinical practice. OBJECTIVE To study the various aetiologies and clinical presentations of patients presenting with sexual precocity to a tertiary care hospital. DESIGN Cross sectional study. MATERIAL AND METHODS We collected and analysed the clinical data including hormonal status of 24 consecutive patients who presented to our department from January 2014 to December 2015 for evaluation of sexual precocity. RESULTS Most of the patients presenting to us had evidence of precocious puberty (n=16, followed by premature adrenarche (n=5 and premature thelarche (n=3 respectively. The females outnumbered males in our study (68.75% of total cases. Females presenting with central precocious puberty had no appreciable cause (idiopathic in majority (85.72% of cases. While, males presenting with central precocious puberty had an organic cause (60% in majority of cases. CONCLUSIONS Precocious puberty is more common among females as compared to males. Organic lesion must be ruled out in all patients presenting with central precocious puberty especially in males.

  7. Use of a small molecule cell cycle inhibitor to control cell growth and improve specific productivity and product quality of recombinant proteins in CHO cell cultures.

    Science.gov (United States)

    Du, Zhimei; Treiber, David; McCarter, John D; Fomina-Yadlin, Dina; Saleem, Ramsey A; McCoy, Rebecca E; Zhang, Yuling; Tharmalingam, Tharmala; Leith, Matthew; Follstad, Brian D; Dell, Brad; Grisim, Brent; Zupke, Craig; Heath, Carole; Morris, Arvia E; Reddy, Pranhitha

    2015-01-01

    The continued need to improve therapeutic recombinant protein productivity has led to ongoing assessment of appropriate strategies in the biopharmaceutical industry to establish robust processes with optimized critical variables, that is, viable cell density (VCD) and specific productivity (product per cell, qP). Even though high VCD is a positive factor for titer, uncontrolled proliferation beyond a certain cell mass is also undesirable. To enable efficient process development to achieve consistent and predictable growth arrest while maintaining VCD, as well as improving qP, without negative impacts on product quality from clone to clone, we identified an approach that directly targets the cell cycle G1-checkpoint by selectively inhibiting the function of cyclin dependent kinases (CDK) 4/6 with a small molecule compound. Results from studies on multiple recombinant Chinese hamster ovary (CHO) cell lines demonstrate that the selective inhibitor can mediate a complete and sustained G0/G1 arrest without impacting G2/M phase. Cell proliferation is consistently and rapidly controlled in all recombinant cell lines at one concentration of this inhibitor throughout the production processes with specific productivities increased up to 110 pg/cell/day. Additionally, the product quality attributes of the mAb, with regard to high molecular weight (HMW) and glycan profile, are not negatively impacted. In fact, high mannose is decreased after treatment, which is in contrast to other established growth control methods such as reducing culture temperature. Microarray analysis showed major differences in expression of regulatory genes of the glycosylation and cell cycle signaling pathways between these different growth control methods. Overall, our observations showed that cell cycle arrest by directly targeting CDK4/6 using selective inhibitor compound can be utilized consistently and rapidly to optimize process parameters, such as cell growth, qP, and glycosylation profile in

  8. Improved Power Conversion Efficiency of Inverted Organic Solar Cells by Incorporating Au Nanorods into Active Layer.

    Science.gov (United States)

    He, Yeyuan; Liu, Chunyu; Li, Jinfeng; Zhang, Xinyuan; Li, Zhiqi; Shen, Liang; Guo, Wenbin; Ruan, Shengping

    2015-07-29

    This Research Article describes a cooperative plasmonic effect on improving the performance of organic solar cells. When Au nanorods(NRs) are incorporated into the active layers, the designed project shows superior enhanced light absorption behavior comparing with control devices, which leads to the realization of organic solar cell with power conversion efficiency of 6.83%, accounting for 18.9% improvement. Further investigations unravel the influence of plasmonic nanostructures on light trapping, exciton generation, dissociation, and charge recombination and transport inside the thin films devices. Moreover, the introduction of high-conductivity Au NRs improves electrical conductivity of the whole device, which contributes to the enhanced fill factor.

  9. Florigenic effects of IAA for improving pistillate and staminate flowering in some cucurbits under Pb stress

    International Nuclear Information System (INIS)

    Khan, A.S.; Chaudhary, N.Y.

    2010-01-01

    This study contributes to the enhancement of on knowledge about behaviour of cucurbits with heavy metal i.e., Pb (NO/sub 3/)/sub 2/ and/or their combination with growth hormones (IAA). Effects of Pb and IAA were studied on flowering in Cucumis sativus L. and Momordica charantia L. There is very little information on the effects of heavy metals on the flowering in plants particularly in cucurbits; this in itself makes the issue of interest apart from the interaction of heavy metals with hormones. Plant under the stress of heavy metals can be treated with growth hormones to improve growth parameters, to avoid delay in flowering and likewise quality of fruit can be improved. Applied 400 mg/l IAA caused precocious flowering, increasing the number of flowers in both the plants. Lead caused significant delay in flowering, consequently leading to reduction in the number of pistillate and staminate flowers. However, when IAA was applied with Pb (NO/sub 3/)/sub 2/, there was less decrease in staminate and pistillate flowers, revealing the dominant effect of IAA. Current study reveals that inhibitory effects of heavy metals on flowering were partially restored by IAA applications. (author)

  10. Thermal and mechanical improvement of aluminum open-cells foams through electrodeposition of copper and graphene

    Directory of Open Access Journals (Sweden)

    Simoncini Alessandro

    2016-01-01

    Full Text Available Thanks to its planar structure, graphene is characterized by unique properties, such as excellent chemical inactivity, high electrical and thermal conductivity, high optical transparency, extraordinary flexibility and high mechanical resistance, which make it suitable in a very wide range of applications. This paper details the state of the art in graphene coating applied to aluminum open-cells foams for the improvement of their mechanical and thermal behavior. Metallic foams are highly porous materials with extremely high convective heat transfer coefficients, thanks to their complex structure of three-dimensional open-cells. Graphene nanoplatelets have been used to improve thermal conductivity of aluminum foams, to make them better suitable during heat transfer in transient state. Also, an improvement of mechanical resistance has been observed. Before electrodeposition, all the samples have been subjected to sandblasting process, to eliminate the oxide layer on the surface, enabling a better adhesion of the coating. Different nanoparticles of graphene have been used. The experimental findings revealed a higher thermal conductivity for aluminum open cells foams electroplated with graphene. Considered the relatively low process costs and the improvements obtainable, these materials are very promising in many technological fields. The topics covered include surface modification, electrochemical plating, thermo-graphic analysis.

  11. New mounting improves solar-cell efficiency

    Science.gov (United States)

    Shepard, N. F., Jr.

    1980-01-01

    Method boosts output by about 20 percent by trapping and redirecting solar radiation without increasing module depth. Mounted solar-cell array is covered with internally reflecting plate. Plate is attached to each cell by transparent adhesive, and space between cells is covered with layer of diffusely reflecting material. Solar energy falling on space between cells is diffused and reflected internally by plate until it is reflected onto solar cell.

  12. Use of Eltrombopag in Improving Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Samip Master

    2018-03-01

    Full Text Available Eltrombopag is a thrombopoietin agonist and has been used in aplastic anemia and post-transplantation thrombocytopenia. The c-MPL receptor is present on hematopoietic stem cells. There are no reports of eltrombopag utilization for improving poor graft function in the post-transplant setting. Here were report a case of a young female with post-transplant poor graft function as evident from the low absolute neutrophil count, anemia, and thrombocytopenia on day 60. Eltrombopag was started on day 72 and resulted in improvement in all 3 cell lines. The counts continued to be stable even after eltrombopag was discontinued. The patient tolerated the drug without significant side effects for 1 year.

  13. Significant adverse reactions to long-acting gonadotropin-releasing hormone agonists for the treatment of central precocious puberty and early onset puberty

    Directory of Open Access Journals (Sweden)

    Ji Woo Lee

    2014-09-01

    Full Text Available PurposeLong-acting gonadotropin-releasing hormone agonists (GnRHa are commonly used to treat central precocious puberty (CPP in Korea. Although rare, there have been reports on the characteristic of adverse reactions of GnRHa in CPP among the Korean population. This study was intended to report on our clinical experience regarding significant adverse reactions to long-acting GnRHa in CPP and early onset puberty and to evaluate the prevalence rate of serious side effects.MethodsThis retrospective study included children with CPP and early onset puberty, who were administered monthly with long-acting GnRHa (leuprolide acetate, triptorelin acetate at the outpatient clinic of Department of Pediatrics, at Inha University Hospital, between January 2011 and December 2013. We analyzed the clinical characteristics of patients who experienced significant adverse reactions and evaluated the prevalence rate.ResultsSix serious side effects (0.9% were observed among total of 621 CPP and early onset puberty children with GnRHa therapy. The number of sterile abscess formation was four in three patients (4 events of 621. Anaphylaxis occurred in only one patient, and unilateral slipped capital femoral epiphysis (SCFE in another one patient. Anaphylaxis occurred after the 6th administration of the monthly depot triptorelin acetate. Unilateral SCFE developed in GnRHa therapy.ConclusionSterile abscess formation occurred in 0.6% of CPP and early onset puberty patients from the administration of a monthly depot GnRHa therapy. The occurrences of anaphylaxis and SCFE are extremely rare, but can have serious implications on patients. Clinicians should be aware of these potential adverse effects related to GnRHa therapy in CPP.

  14. Improving Efficiency of Multicrystalline Silicon and CIGS Solar Cells by Incorporating Metal Nanoparticles

    Directory of Open Access Journals (Sweden)

    Ming-Jer Jeng

    2015-10-01

    Full Text Available This work studies the use of gold (Au and silver (Ag nanoparticles in multicrystalline silicon (mc-Si and copper-indium-gallium-diselenide (CIGS solar cells. Au and Ag nanoparticles are deposited by spin-coating method, which is a simple and low cost process. The random distribution of nanoparticles by spin coating broadens the resonance wavelength of the transmittance. This broadening favors solar cell applications. Metal shadowing competes with light scattering in a manner that varies with nanoparticle concentration. Experimental results reveal that the mc-Si solar cells that incorporate Au nanoparticles outperform those with Ag nanoparticles. The incorporation of suitable concentration of Au and Ag nanoparticles into mc-Si solar cells increases their efficiency enhancement by 5.6% and 4.8%, respectively. Incorporating Au and Ag nanoparticles into CIGS solar cells improve their efficiency enhancement by 1.2% and 1.4%, respectively. The enhancement of the photocurrent in mc-Si solar cells is lower than that in CIGS solar cells, owing to their different light scattering behaviors and material absorption coefficients.

  15. Berkeley Lab Sheds Light on Improving Solar Cell Efficiency

    International Nuclear Information System (INIS)

    Lawrence Berkeley National Laboratory

    2007-01-01

    Typical manufacturing methods produce solar cells with an efficiency of 12-15%; and 14% efficiency is the bare minimum for achieving a profit. In work performed at the Ernest Orlando Lawrence Berkeley National Laboratory (Berkeley, CA, 5 10-486-577 1)--a US Department of Energy national laboratory that conducts unclassified scientific research and is managed by the University of California--scientist Scott McHugo has obtained keen insights into the impaired performance of solar cells manufactured from polycrystalline silicon. The solar cell market is potentially vast, according to Berkeley Lab. Lightweight solar panels are highly beneficial for providing electrical power to remote locations in developing nations, since there is no need to build transmission lines or truck-in generator fuel. Moreover, industrial nations confronted with diminishing resources have active programs aimed at producing improved, less expensive solar cells. 'In a solar cell, there is a junction between p-type silicon and an n-type layer, such as diffused-in phosphorous', explained McHugo, who is now with Berkeley Lab's Accelerator and Fusion Research Division. 'When sunlight is absorbed, it frees electrons, which start migrating in a random-walk fashion toward that junction. If the electrons make it to the junction; they contribute to the cell's output of electric current. Often, however, before they reach the junction, they recombine at specific sites in the crystal' (and, therefore, cannot contribute to current output). McHugo scrutinized a map of a silicon wafer in which sites of high recombination appeared as dark regions. Previously, researchers had shown that such phenomena occurred not primarily at grain boundaries in the polycrystalline material, as might be expected, but more often at dislocations in the crystal. However, the dislocations themselves were not the problem. Using a unique heat treatment technique, McHugo performed electrical measurements to investigate the material

  16. Further Improvement and System Integration of High Temperature Polymer Electrolyte Membrane Fuel Cells

    DEFF Research Database (Denmark)

    Li, Qingfeng; Jensen, Jens Oluf

    The strategic developments of the FURIM are in three steps: (1) further improvement of the high temperature polymer membranes and related materials; (2) development of technological units including fuel cell stack, hydrocarbon reformer and afterburner, that are compatible with the HT-PEMFC; and (3......) integration of the HT-PEMFC stack with these compatible subunits. The main goal of the project is a 2kWel HT-PEMFC stack operating in a temperature range of 150-200°C, with a single cell performance target of 0.7 A/cm² at a cell voltage around 0.6 V. The target durability is more than 5,000 hours...

  17. Improving Energy Efficiency and Enabling Water Recycle in Biorefineries Using Bioelectrochemical Cells

    International Nuclear Information System (INIS)

    Borole, Abhijeet P.

    2010-01-01

    Improving biofuel yield and water reuse are two important issues in further development of biorefineries. The total energy content of liquid fuels (including ethanol and hydrocarbon) produced from cellulosic biomass via biochemical or hybrid bio-thermochemical routes can vary from 49% to 70% of the biomass entering the biorefinery, on an energy basis. Use of boiler for combustion of residual organics and lignin results in significant energy and water losses. An alternate process to improve energy recovery from the residual organic streams is via use of bioelectrochemical systems such as microbial fuel cells (MFCs) microbial electrolysis cells (MECs). The potential advantages of this alternative scheme in a biorefinery include minimization of heat loss and generation of a higher value product, hydrogen. The need for 5-15 gallons of water per gallon of ethanol can be reduced significantly via recycle of water after MEC treatment. Removal of inhibitory byproducts such as furans, phenolics and acetate in MFC/MECs to generate energy, thus, has dual advantages including improvements in energy efficiency and ability to recycle water. Conversion of the sugar- and lignin- degradation products to hydrogen is synergistic with biorefinery hydrogen requirements for upgrading F-T liquids and other byproducts to high-octane fuels and/or high value products. Some of these products include sorbitol, succinic acid, furan and levulinate derivatives, glycols, polyols, 1,4-butenadiol, phenolics polymers, etc. Potential process alternatives utilizing MECs in biorefineries capable of improving energy efficiency by up to 30% are discussed.

  18. A Francisella tularensis live vaccine strain that improves stimulation of antigen-presenting cells does not enhance vaccine efficacy.

    Directory of Open Access Journals (Sweden)

    Deanna M Schmitt

    Full Text Available Vaccination is a proven strategy to mitigate morbidity and mortality of infectious diseases. The methodology of identifying and testing new vaccine candidates could be improved with rational design and in vitro testing prior to animal experimentation. The tularemia vaccine, Francisella tularensis live vaccine strain (LVS, does not elicit complete protection against lethal challenge with a virulent type A Francisella strain. One factor that may contribute to this poor performance is limited stimulation of antigen-presenting cells. In this study, we examined whether the interaction of genetically modified LVS strains with human antigen-presenting cells correlated with effectiveness as tularemia vaccine candidates. Human dendritic cells infected with wild-type LVS secrete low levels of proinflammatory cytokines, fail to upregulate costimulatory molecules, and activate human T cells poorly in vitro. One LVS mutant, strain 13B47, stimulated higher levels of proinflammatory cytokines from dendritic cells and macrophages and increased costimulatory molecule expression on dendritic cells compared to wild type. Additionally, 13B47-infected dendritic cells activated T cells more efficiently than LVS-infected cells. A deletion allele of the same gene in LVS displayed similar in vitro characteristics, but vaccination with this strain did not improve survival after challenge with a virulent Francisella strain. In vivo, this mutant was attenuated for growth and did not stimulate T cell responses in the lung comparable to wild type. Therefore, stimulation of antigen-presenting cells in vitro was improved by genetic modification of LVS, but did not correlate with efficacy against challenge in vivo within this model system.

  19. REMOTE IN-CELL SAMPLING IMPROVEMENTS PROGRAM AT THESAVANNAH RIVER SITE (SRS) DEFENSE WASTE PROCESSING FACILITY (DWPF)

    International Nuclear Information System (INIS)

    Marzolf, A

    2007-01-01

    Remote Systems Engineering (RSE) of the Savannah River National Lab (SRNL) in combination with the Defense Waste Processing Facility(DWPF) Engineering and Operations has evaluated the existing equipment and processes used in the facility sample cells for 'pulling' samples from the radioactive waste stream and performing equipment in-cell repairs/replacements. RSE has designed and tested equipment for improving remote in-cell sampling evolutions and reducing the time required for in-cell maintenance of existing equipment. The equipment within the present process tank sampling system has been in constant use since the facility start-up over 17 years ago. At present, the method for taking samples within the sample cells produces excessive maintenance and downtime due to frequent failures relative to the sampling station equipment and manipulator. Location and orientation of many sampling stations within the sample cells is not conducive to manipulator operation. The overextension of manipulators required to perform many in-cell operations is a major cause of manipulator failures. To improve sampling operations and reduce downtime due to equipment maintenance, a Portable Sampling Station (PSS), wireless in-cell cameras, and new commercially available sampling technology has been designed, developed and/or adapted and tested. The uniqueness of the design(s), the results of the scoping tests, and the benefits relative to in-cell operation and reduction of waste are presented

  20. DOT1L inhibitor improves early development of porcine somatic cell nuclear transfer embryos

    DEFF Research Database (Denmark)

    Tao, Jia; Zhang, Yu; Zuo, Xiaoyuan

    2017-01-01

    Incomplete epigenetic reprogramming of the genome of donor cells causes poor early and full-term developmental efficiency of somatic cell nuclear transfer (SCNT) embryos. Previous research indicate that inhibition of the histone H3 K79 methyltransferase DOT1L, using a selective pharmacological...... inhibitor EPZ004777 (EPZ), significantly improved reprogramming efficiency during the generation of mouse induced pluripotent stem cells. However, the roles of DOT1L in porcine nuclear transfer-mediated cellular reprogramming are not yet known. Here we showed that DOT1L inhibition via 0.5 nM EPZ treatment...

  1. Cognitive, emotional and psychosocial functioning of girls treated with pharmacological puberty blockage for idiopathic central precocious puberty

    Directory of Open Access Journals (Sweden)

    Slawomir Wojniusz

    2016-07-01

    Full Text Available Central precocious puberty (CPP develops due to premature activation of the hypothalamic-pituitary-gonadal (HPG axis, resulting in early pubertal changes and rapid bone maturation. CPP is associated with lower adult height and increased risk for development of psychological problems. Standard treatment of CPP is based on postponement of pubertal development by blockade of the HPG axis with gonadotropin releasing hormone analogs (GnRHa leading to abolition of gonadal sex hormones synthesis. Whereas the hormonal and auxological effects of GnRHa are well researched, there is a lack of knowledge whether GnRHa treatment influences psychological functioning of treated children, despite the fact that prevention of psychological problems is used as one of the main reasons for treatment initiation. In the present study we seek to address this issue by exploring differences in cognitive function, behavior, emotional reactivity, and psychosocial problems between GnRHa treated CPP girls and age-matched controls.Fifteen girls with idiopathic CPP; median age 10.4 years, treated with slow-release GnRHa (triptorelin acetate – Decapeptyl SR ® 11.25 and 15 age-matched controls, were assessed with a comprehensive test battery consisting of paper and pencil tests, computerized tasks, behavioral paradigms, heart rate variability, and questionnaires filled in by the children’s parents. Both groups showed very similar scores with regard to cognitive performance, behavioral and psychosocial problems. Compared to controls, treated girls displayed significantly higher emotional reactivity (p = 0.016; Cohen’s d = 1.04 on one of the two emotional reactivity task conditions. Unexpectedly, the CPP group showed significantly lower resting heart rates than the controls (p = 0.004; Cohen’s d = 1.03; lower heart rate was associated with longer treatment duration (r = - 0.582, p = 0.037. The results suggest that GnRHa treated CPP girls do not differ in their cognitive or

  2. Colonic inflammation in mice is improved by cigarette smoke through iNKT cells recruitment.

    Directory of Open Access Journals (Sweden)

    Muriel Montbarbon

    Full Text Available Cigarette smoke (CS protects against intestinal inflammation during ulcerative colitis. Immunoregulatory mechanisms sustaining this effect remain unknown. The aim of this study was to assess the effects of CS on experimental colitis and to characterize the intestinal inflammatory response at the cellular and molecular levels. Using the InExpose® System, a smoking device accurately reproducing human smoking habit, we pre-exposed C57BL/6 mice for 2 weeks to CS, and then we induced colitis by administration of dextran sodium sulfate (DSS. This system allowed us to demonstrate that CS exposure improved colonic inflammation (significant decrease in clinical score, body weight loss and weight/length colonic ratio. This improvement was associated with a significant decrease in colonic proinflammatory Th1/Th17 cytokine expression, as compared to unexposed mice (TNF (p=0.0169, IFNγ (p<0.0001, and IL-17 (p=0.0008. Smoke exposure also induced an increased expression of IL-10 mRNA (p=0.0035 and a marked recruitment of iNKT (invariant Natural Killer T; CD45+ TCRβ+ CD1d tetramer+ cells in the colon of DSS-untreated mice. Demonstration of the role of iNKT cells in CS-dependent colitis improvement was performed using two different strains of NKT cells deficient mice. Indeed, in Jα18KO and CD1dKO animals, CS exposure failed to induce significant regulation of DSS-induced colitis both at the clinical and molecular levels. Thus, our study demonstrates that iNKT cells are pivotal actors in the CS-dependent protection of the colon. These results highlight the role of intestinal iNKT lymphocytes and their responsiveness to environmental stimuli. Targeting iNKT cells would represent a new therapeutic way for inflammatory bowel diseases.

  3. Improving chemotherapy for patients with advanced non-small cell lung cancer

    DEFF Research Database (Denmark)

    von Plessen, Christian

    2011-01-01

    INTRODUCTION: Lung cancer is the third most common mortal disease in industrialised countries and the prognosis has been slow to improve. The largest subgroup has locally advanced or metastatic non-small cell lung cancer (NSCLC). Unfortunately, these patients can usually not be cured and the main...... project. The description of the experiences can serve as an example for the improvement of microsystems in settings with similar problems. Finally, in the registry study of Norwegian patients with lung cancer, we found significant geographical and temporal variations of the utilisation of chemotherapy...... that were related to survival. Potential areas of improvement in the system of care for lung cancer are recruitment of patients in clinical studies, standardisation of the processes of care in outpatient clinics, definition of strategic aims of quality, development of balanced quality indicators, as well...

  4. Improvement of Heart Failure by Human Amniotic Mesenchymal Stromal Cell Transplantation in Rats.

    Science.gov (United States)

    Razavi Tousi, Seyed Mohammad Taghi; Faghihi, Mahdieh; Nobakht, Maliheh; Molazem, Mohammad; Kalantari, Elham; Darbandi Azar, Amir; Aboutaleb, Nahid

    2016-07-06

    Background: Recently, stem cells have been considered for the treatment of heart diseases, but no marked improvement has been recorded. This is the first study to examine the functional and histological effects of the transplantation of human amniotic mesenchymal stromal cells (hAMSCs) in rats with heart failure (HF). Methods: This study was conducted in the years 2014 and 2015. 35 male Wistar rats were randomly assigned into 5 equal experimental groups (7 rats each) as 1- Control 2- Heart Failure (HF) 3- Sham 4- Culture media 5- Stem Cell Transplantation (SCT). Heart failure was induced using 170 mg/kg/d of isoproterenol subcutaneously injection in 4 consecutive days. The failure confirmed by the rat cardiac echocardiography on day 28. In SCT group, 3×10 6 cells in 150 µl of culture media were transplanted to the myocardium. At the end, echocardiographic and hemodynamic parameters together with histological evaluation were done. Results: Echocardiography results showed that cardiac ejection fraction in HF group increased from 58/73 ± 9% to 81/25 ± 6/05% in SCT group (p value < 0.001). Fraction shortening in HF group was increased from 27/53 ± 8/58% into 45/55 ± 6/91% in SCT group (p value < 0.001). Furthermore, hAMSCs therapy significantly improved mean diastolic blood pressure, mean arterial pressure, left ventricular systolic pressure, rate pressure product, and left ventricular end-diastolic pressure compared to those in the HF group, with the values reaching the normal levels in the control group. A marked reduction in fibrosis tissue was also found in the SCT group (p value < 0.001) compared with the animals in the HF group. Conclusion: The transplantation of hAMSCs in rats with heart failure not only decreased the level of fibrosis but also conferred significant improvement in heart performance in terms of echocardiographic and hemodynamic parameters.

  5. Improving washing strategies of human mesenchymal stem cells using negative mode expanded bed chromatography.

    Science.gov (United States)

    Cunha, Bárbara; Silva, Ricardo J S; Aguiar, Tiago; Serra, Margarida; Daicic, John; Maloisel, Jean-Luc; Clachan, John; Åkerblom, Anna; Carrondo, Manuel J T; Peixoto, Cristina; Alves, Paula M

    2016-01-15

    The use of human mesenchymal stem cells (hMSC) in clinical applications has been increasing over the last decade. However, to be applied in a clinical setting hMSC need to comply with specific requirements in terms of identity, potency and purity. This study reports the improvement of established tangential flow filtration (TFF)-based washing strategies, further increasing hMSC purity, using negative mode expanded bed adsorption (EBA) chromatography with a new multimodal prototype matrix based on core-shell bead technology. The matrix was characterized and a stable, expanded bed could be obtained using standard equipment adapted from what is used for conventional packed bed chromatography processes. The effect of different expansion rates on cell recovery yield and protein removal capacity was assessed. The best trade-off between cell recovery (89%) and protein clearance (67%) was achieved using an intermediate expansion bed rate (1.4). Furthermore, we also showed that EBA chromatography can be efficiently integrated on the already established process for the downstream processing (DSP) of hMSC, where it improved the washing efficiency more than 10-fold, recovering approximately 70% of cells after global processing. This strategy showed not to impact cell viability (>95%), neither hMSC's characteristics in terms of morphology, immunophenotype, proliferation, adhesion capacity and multipotent differentiation potential. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Optimizing autologous cell grafts to improve stem cell gene therapy.

    Science.gov (United States)

    Psatha, Nikoletta; Karponi, Garyfalia; Yannaki, Evangelia

    2016-07-01

    Over the past decade, stem cell gene therapy has achieved unprecedented curative outcomes for several genetic disorders. Despite the unequivocal success, clinical gene therapy still faces challenges. Genetically engineered hematopoietic stem cells are particularly vulnerable to attenuation of their repopulating capacity once exposed to culture conditions, ultimately leading to low engraftment levels posttransplant. This becomes of particular importance when transduction rates are low or/and competitive transplant conditions are generated by reduced-intensity conditioning in the absence of a selective advantage of the transduced over the unmodified cells. These limitations could partially be overcome by introducing megadoses of genetically modified CD34(+) cells into conditioned patients or by transplanting hematopoietic stem cells hematopoietic stem cells with high engrafting and repopulating potential. On the basis of the lessons gained from cord blood transplantation, we summarize the most promising approaches to date of increasing either the numbers of hematopoietic stem cells for transplantation or/and their engraftability, as a platform toward the optimization of engineered stem cell grafts. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

  7. Exogenous DNA internalisation by sperm cells is improved by combining lipofection and restriction enzyme mediated integration.

    Science.gov (United States)

    Churchil, R R; Gupta, J; Singh, A; Sharma, D

    2011-06-01

    1. Three types of exogenous DNA inserts, i.e. complete linearised pVIVO2-GFP/LacZ vector (9620 bp), the LacZ gene (5317 bp) and the GFP gene (2152 bp) were used to transfect chicken spermatozoa through simple incubation of sperm cells with insert. 2. PCR assay, Dot Blot hybridisation and Southern hybridisation showed the successful internalisation of exogenous DNA by chicken sperm cells. 3. Lipofection and Restriction Enzyme Mediated Integration (REMI) were used to improve the rate of internalisation of exogenous DNA by sperm cells. 4. Results from dot blot as well as Southern hybridisation were semi-quantified and improved exogenous DNA uptake by sperm cells through lipofection and REMI. Stronger signals were observed from hybridisation of LacZ as well as GFP specific probe with the DNA from lipofected exogenous DNA transfected sperm DNA in comparison with those transfected with nude exogenous DNA.

  8. Efficiency improvements by Metal Wrap Through technology for n-type Si solar cells and modules

    Energy Technology Data Exchange (ETDEWEB)

    Wenchao, Zhao; Jianming, Wang; Yanlong, Shen; Ziqian, Wang; Yingle, Chen; Shuquan, Tian; Zhiliang, Wan; Bo, Yu; Gaofei, Li; Zhiyan, Hu; Jingfeng, Xiong [Yingli Green Energy Holding Co., Ltd, 3399 North Chaoyang Avenue, Baoding (China); Guillevin, N.; Heurtault, B.; Aken, B.B. van; Bennett, I.J.; Geerligs, L.J.; Weeber, A.W.; Bultman, J.H. [ECN Solar Energy, Petten (Netherlands)

    2012-09-15

    N-type Metal Wrap Through (n-MWT) is presented as an industrially promising back-contact technology to reach high performance of silicon solar cells and modules. It can combine benefits from both n-type base and MWT metallization. In this paper, the efficiency improvements of commercial industrial n-type bifacial Si solar cells (239 cm{sup 2}) and modules (60 cells) by the integration of the MWT technique are described. For the cell, after the optimization of integration, over 0.3% absolute efficiency gain was achieved over the similar non-MWT technology, and Voc gain and Isc gain up to 0.9% and 3.5%, respectively. These gains are mainly attributed to reduced shading loss and surface recombination. Besides the front pattern optimization, a 0.1m{Omega} reduction of Rs in via part will induce further 0.06% absolute efficiency improvement. For the module part, a power output of n-MWT module up to 279W was achieved, corresponding to a module efficiency of about 17.7%.

  9. Amrubicin therapy improves patients with refractory small-cell lung cancer: A single-arm confirmatory Chinese clinical study

    Directory of Open Access Journals (Sweden)

    Mengli Zheng

    2016-09-01

    Full Text Available Our objective was to evaluate an open-label, multicenter, single-arm study to appraise whether amrubicin therapy improves patients with refractory small-cell lung cancer in Chinese clinical study. Patients (n=95 with refractory small-cell lung cancer received 3 consecutive days amrubicin therapy for 21 days. Overall response rate of response to amrubicin was 39%. Anemia, febrile neutropenia, thrombocytopenia, hyperglycemia, hyponatremia, infection, elevated serum transaminases levels were appeared, but the incidences of adverse events were very few. Our results suggest amrubicin therapy can improve patients with refractory small-cell lung cancer and may be an effective and safe treatment option.

  10. Can the outcomes of mesenchymal stem cell-based therapy for myocardial infarction be improved? Providing weapons and armour to cells.

    Science.gov (United States)

    Karpov, Andrey A; Udalova, Daria V; Pliss, Michael G; Galagudza, Michael M

    2017-04-01

    Use of mesenchymal stem cell (MSC) transplantation after myocardial infarction (MI) has been found to have infarct-limiting effects in numerous experimental and clinical studies. However, recent meta-analyses of randomized clinical trials on MSC-based MI therapy have highlighted the need for improving its efficacy. There are two principal approaches for increasing therapeutic effect of MSCs: (i) preventing massive MSC death in ischaemic tissue and (ii) increasing production of cardioreparative growth factors and cytokines with transplanted MSCs. In this review, we aim to integrate our current understanding of genetic approaches that are used for modification of MSCs to enable their improved survival, engraftment, integration, proliferation and differentiation in the ischaemic heart. Genetic modification of MSCs resulting in increased secretion of paracrine factors has also been discussed. In addition, data on MSC preconditioning with physical, chemical and pharmacological factors prior to transplantation are summarized. MSC seeding on three-dimensional polymeric scaffolds facilitates formation of both intercellular connections and contacts between cells and the extracellular matrix, thereby enhancing cell viability and function. Use of genetic and non-genetic approaches to modify MSC function holds great promise for regenerative therapy of myocardial ischaemic injury. © 2016 John Wiley & Sons Ltd.

  11. Cleaning the Air and Improving Health with Hydrogen Fuel-Cell Vehicles

    Science.gov (United States)

    Jacobson, M. Z.; Colella, W. G.; Golden, D. M.

    2005-06-01

    Converting all U.S. onroad vehicles to hydrogen fuel-cell vehicles (HFCVs) may improve air quality, health, and climate significantly, whether the hydrogen is produced by steam reforming of natural gas, wind electrolysis, or coal gasification. Most benefits would result from eliminating current vehicle exhaust. Wind and natural gas HFCVs offer the greatest potential health benefits and could save 3700 to 6400 U.S. lives annually. Wind HFCVs should benefit climate most. An all-HFCV fleet would hardly affect tropospheric water vapor concentrations. Conversion to coal HFCVs may improve health but would damage climate more than fossil/electric hybrids. The real cost of hydrogen from wind electrolysis may be below that of U.S. gasoline.

  12. Minimal RED Cell Pairs Markedly Improve Electrode Kinetics and Power Production in Microbial Reverse Electrodialysis Cells

    KAUST Repository

    Cusick, Roland D.

    2013-12-17

    Power production from microbial reverse electrodialysis cell (MRC) electrodes is substantially improved compared to microbial fuel cells (MFCs) by using ammonium bicarbonate (AmB) solutions in multiple RED cell pair stacks and the cathode chamber. Reducing the number of RED membranes pairs while maintaining enhanced electrode performance could help to reduce capital costs. We show here that using only a single RED cell pair (CP), created by operating the cathode in concentrated AmB, dramatically increased power production normalized to cathode area from both acetate (Acetate: from 0.9 to 3.1 W/m 2-cat) and wastewater (WW: 0.3 to 1.7 W/m2), by reducing solution and charge transfer resistances at the cathode. A second RED cell pair increased RED stack potential and reduced anode charge transfer resistance, further increasing power production (Acetate: 4.2 W/m2; WW: 1.9 W/m2). By maintaining near optimal electrode power production with fewer membranes, power densities normalized to total membrane area for the 1-CP (Acetate: 3.1 W/m2-mem; WW: 1.7 W/m2) and 2-CP (Acetate: 1.3 W/m2-mem; WW: 0.6 W/m2) reactors were much higher than previous MRCs (0.3-0.5 W/m2-mem with acetate). While operating at peak power, the rate of wastewater COD removal, normalized to reactor volume, was 30-50 times higher in 1-CP and 2-CP MRCs than that in a single chamber MFC. These findings show that even a single cell pair AmB RED stack can significantly enhance electrical power production and wastewater treatment. © 2013 American Chemical Society.

  13. Minimal RED Cell Pairs Markedly Improve Electrode Kinetics and Power Production in Microbial Reverse Electrodialysis Cells

    KAUST Repository

    Cusick, Roland D.; Hatzell, Marta; Zhang, Fang; Logan, Bruce E.

    2013-01-01

    Power production from microbial reverse electrodialysis cell (MRC) electrodes is substantially improved compared to microbial fuel cells (MFCs) by using ammonium bicarbonate (AmB) solutions in multiple RED cell pair stacks and the cathode chamber. Reducing the number of RED membranes pairs while maintaining enhanced electrode performance could help to reduce capital costs. We show here that using only a single RED cell pair (CP), created by operating the cathode in concentrated AmB, dramatically increased power production normalized to cathode area from both acetate (Acetate: from 0.9 to 3.1 W/m 2-cat) and wastewater (WW: 0.3 to 1.7 W/m2), by reducing solution and charge transfer resistances at the cathode. A second RED cell pair increased RED stack potential and reduced anode charge transfer resistance, further increasing power production (Acetate: 4.2 W/m2; WW: 1.9 W/m2). By maintaining near optimal electrode power production with fewer membranes, power densities normalized to total membrane area for the 1-CP (Acetate: 3.1 W/m2-mem; WW: 1.7 W/m2) and 2-CP (Acetate: 1.3 W/m2-mem; WW: 0.6 W/m2) reactors were much higher than previous MRCs (0.3-0.5 W/m2-mem with acetate). While operating at peak power, the rate of wastewater COD removal, normalized to reactor volume, was 30-50 times higher in 1-CP and 2-CP MRCs than that in a single chamber MFC. These findings show that even a single cell pair AmB RED stack can significantly enhance electrical power production and wastewater treatment. © 2013 American Chemical Society.

  14. Improved cell viability and hydroxyapatite growth on nitrogen ion-implanted surfaces

    Science.gov (United States)

    Shafique, Muhammad Ahsan; Murtaza, G.; Saadat, Shahzad; Uddin, Muhammad K. H.; Ahmad, Riaz

    2017-08-01

    Stainless steel 306 is implanted with various doses of nitrogen ions using a 2 MV pelletron accelerator for the improvement of its surface biomedical properties. Raman spectroscopy reveals incubation of hydroxyapatite (HA) on all the samples and it is found that the growth of incubated HA is greater in higher ion dose samples. SEM profiles depict uniform growth and greater spread of HA with higher ion implantation. Human oral fibroblast response is also found consistent with Raman spectroscopy and SEM results; the cell viability is found maximum in samples treated with the highest (more than 300%) dose. XRD profiles signified greater peak intensity of HA with ion implantation; a contact angle study revealed hydrophilic behavior of all the samples but the treated samples were found to be lesser hydrophilic compared to the control samples. Nitrogen implantation yields greater bioactivity, improved surface affinity for HA incubation and improved hardness of the surface.

  15. Mesenchymal stem cell and derived exosome as small RNA carrier and Immunomodulator to improve islet transplantation.

    Science.gov (United States)

    Wen, Di; Peng, Yang; Liu, Di; Weizmann, Yossi; Mahato, Ram I

    2016-09-28

    Human bone marrow mesenchymal stem cells (hBMSCs) and their exosomes can suppress immune reaction and deliver small RNAs. Thus, they may improve islet transplantation by delivering small RNAs for promoting islet function and inhibiting immune rejection. Here, we proposed an hBMSC and its exosome-based therapy to overcome immune rejection and poor islet function, both of which hinder the success of islet transplantation. We found overexpressed siFas and anti-miR-375 in plasmid encoding shFas and anti-miR-375 transfected hBMSC-derived exosomes, which silenced Fas and miR-375 of human islets and improved their viability and function against inflammatory cytokines. This plasmid transfected hBMSCs downregulated Fas and miR-375 of human islets in a humanized NOD scid gamma (NSG) mouse model, whose immune reaction was inhibited by injecting hBMSC and peripheral blood mononuclear cell (PBMC) co-cultured exosomes. These exosomes suppressed immune reaction by inhibiting PBMC proliferation and enhancing regulatory T cell (Treg) function. Collectively, our studies elucidated the mechanisms of RNA delivery from hBMSCs to human islets and the immunosuppressive effect of hBMSC and peripheral blood mononuclear cell co-cultured exosomes for improving islet transplantation. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Plexin A3 and turnout regulate motor axonal branch morphogenesis in zebrafish.

    Directory of Open Access Journals (Sweden)

    Rajiv Sainath

    Full Text Available During embryogenesis motor axons navigate to their target muscles, where individual motor axons develop complex branch morphologies. The mechanisms that control axonal branching morphogenesis have been studied intensively, yet it still remains unclear when branches begin to form or how branch locations are determined. Live cell imaging of individual zebrafish motor axons reveals that the first axonal branches are generated at the ventral extent of the myotome via bifurcation of the growth cone. Subsequent branches are generated by collateral branching restricted to their synaptic target field along the distal portion of the axon. This precisely timed and spatially restricted branching process is disrupted in turnout mutants we identified in a forward genetic screen. Molecular genetic mapping positioned the turnout mutation within a 300 kb region encompassing eight annotated genes, however sequence analysis of all eight open reading frames failed to unambiguously identify the turnout mutation. Chimeric analysis and single cell labeling reveal that turnout function is required cell non-autonomously for intraspinal motor axon guidance and peripheral branch formation. turnout mutant motor axons form the first branch on time via growth cone bifurcation, but unlike wild-type they form collateral branches precociously, when the growth cone is still navigating towards the ventral myotome. These precocious collateral branches emerge along the proximal region of the axon shaft typically devoid of branches, and they develop into stable, permanent branches. Furthermore, we find that null mutants of the guidance receptor plexin A3 display identical motor axon branching defects, and time lapse analysis reveals that precocious branch formation in turnout and plexin A3 mutants is due to increased stability of otherwise short-lived axonal protrusions. Thus, plexin A3 dependent intrinsic and turnout dependent extrinsic mechanisms suppress collateral branch

  17. Improved cell for water-vapor electrolysis

    Science.gov (United States)

    Aylward, J. R.

    1981-01-01

    Continuous-flow electrolytic cells decompose water vapor in steam and room air into hydrogen and oxygen. Sintered iridium oxide catalytic anode coating yields dissociation rates hundredfold greater than those obtained using platinum black. Cell consists of two mirror-image cells, with dual cathode sandwiched between two anodes. Gas traverses serpentine channels within cell and is dissociated at anode. Oxygen mingles with gas stream, while hydrogen migrates through porous matrix and is liberated as gas at cathode.

  18. Accelerated and Improved Differentiation of Retinal Organoids from Pluripotent Stem Cells in Rotating-Wall Vessel Bioreactors

    Directory of Open Access Journals (Sweden)

    Tyler DiStefano

    2018-01-01

    Full Text Available Pluripotent stem cells can be differentiated into 3D retinal organoids, with major cell types self-patterning into a polarized, laminated architecture. In static cultures, organoid development may be hindered by limitations in diffusion of oxygen and nutrients. Herein, we report a bioprocess using rotating-wall vessel (RWV bioreactors to culture retinal organoids derived from mouse pluripotent stem cells. Organoids in RWV demonstrate enhanced proliferation, with well-defined morphology and improved differentiation of neurons including ganglion cells and S-cone photoreceptors. Furthermore, RWV organoids at day 25 (D25 reveal similar maturation and transcriptome profile as those at D32 in static culture, closely recapitulating spatiotemporal development of postnatal day 6 mouse retina in vivo. Interestingly, however, retinal organoids do not differentiate further under any in vitro condition tested here, suggesting additional requirements for functional maturation. Our studies demonstrate that bioreactors can accelerate and improve organoid growth and differentiation for modeling retinal disease and evaluation of therapies.

  19. Alterations in regulatory T cells induced by specific oligosaccharides improve vaccine responsiveness in mice.

    Directory of Open Access Journals (Sweden)

    Marcel A Schijf

    Full Text Available Prophylactic vaccinations are generally performed to protect naïve individuals with or without suppressed immune responsiveness. In a mouse model for Influenza vaccinations the specific alterations of CD4(+CD25(+Foxp3(+ regulatory T-cells (Tregs in the immune modulation induced by orally supplied oligosaccharides containing scGOS/lcFOS/pAOS was assessed. This dietary intervention increased vaccine specific DTH responses. In addition, a significant increased percentage of T-bet(+ (Th1 activated CD69(+CD4(+ T cells (p<0.001 and reduced percentage of Gata-3(+ (Th2 activated CD69(+CD4(+T cells (p<0.001 was detected in the mesenteric lymph nodes (MLN of mice receiving scGOS/lcFOS/pAOS compared to control mice. Although no difference in the number or percentage of Tregs (CD4(+Foxp3(+ could be determined after scGOS/lcFOS/pAOS intervention, the percentage of CXCR3 (+ /T-bet(+ (Th1-Tregs was significantly reduced (p<0.05 in mice receiving scGOS/lcFOS/pAOS as compared to mice receiving placebo diets. Moreover, although no absolute difference in suppressive capacity could be detected, an alteration in cytokine profile suggests a regulatory T cell shift towards a reducing Th1 suppression profile, supporting an improved vaccination response.These data are indicative for improved vaccine responsiveness due to reduced Th1 suppressive capacity in the Treg population of mice fed the oligosaccharide specific diet, showing compartmentalization within the Treg population. The modulation of Tregs to control immune responses provides an additional arm of intervention using alternative strategies possibly leading to the development of improved vaccines.

  20. Embryonic eggshell thickness erosion: A literature survey re-assessing embryo-induced eggshell thinning in birds

    International Nuclear Information System (INIS)

    Orłowski, Grzegorz; Hałupka, Lucyna

    2015-01-01

    Although eggshell thinning has been described mainly in the context of environmental pollution, it can also be the effect of reproductive changes induced by a developing embryo. On the basis of a literature survey of 25 bird species (26 published papers) we reviewed data on embryo-induced eggshell thinning (EET) in three groups of birds: precocials, semi-precocials and altricials. The average EET at the equator of the eggs was 6.4% (median = 4.7%). Our review did not confirm a general prediction of elevated EET at the egg equator in precocial species: altricial birds exhibited the highest EET (average = 12.0%), followed by precocials (7.6%) and semi-precocials (4.2%). We make certain critical recommendations based on the results of this study. Studies aiming to assess variation in eggshell thickness should examine intrinsic factors affecting shell properties of avian eggs, like thickness, which are the result of anatomical or reproductive changes. - Highlights: • We reviewed literature data on embryo-induced eggshell thinning (EET) in birds. • The average EET at the equator of the eggs of 25 bird species was 6.4%. • Altricial birds exhibited the highest EET, followed by precocials and semi-precocials. • All studies on variation in eggshell thickness should take EET into consideration. - Our study emphasizes the need to consider embryo-induced eggshell thinning in studies aiming to assess variation in eggshell thickness

  1. Improving startup performance with carbon mesh anodes in separator electrode assembly microbial fuel cells

    KAUST Repository

    Zhang, Fang; Xia, Xue; Luo, Yong; Sun, Dan; Call, Douglas F.; Logan, Bruce E.

    2013-01-01

    In a separator electrode assembly microbial fuel cell, oxygen crossover from the cathode inhibits current generation by exoelectrogenic bacteria, resulting in poor reactor startup and performance. To determine the best approach for improving startup

  2. Improved Accelerated Stress Tests Based on Fuel Cell Vehicle Data

    Energy Technology Data Exchange (ETDEWEB)

    Patterson, Timothy [Research Engineer; Motupally, Sathya [Research Engineer

    2012-06-01

    UTC will led a top-tier team of industry and national laboratory participants to update and improve DOE’s Accelerated Stress Tests (AST’s) for hydrogen fuel cells. This in-depth investigation will focused on critical fuel cell components (e.g. membrane electrode assemblies - MEA) whose durability represented barriers for widespread commercialization of hydrogen fuel cell technology. UTC had access to MEA materials that had accrued significant load time under real-world conditions in PureMotion® 120 power plant used in transit buses. These materials are referred to as end-of-life (EOL) components in the rest of this document. Advanced characterization techniques were used to evaluate degradation mode progress using these critical cell components extracted from both bus power plants and corresponding materials tested using the DOE AST’s. These techniques were applied to samples at beginning-of-life (BOL) to serve as a baseline. These comparisons advised the progress of the various failure modes that these critical components were subjected to, such as membrane degradation, catalyst support corrosion, platinum group metal dissolution, and others. Gaps in the existing ASTs predicted the degradation observed in the field in terms of these modes were outlined. Using the gaps, new AST’s were recommended and tested to better reflect the degradation modes seen in field operation. Also, BOL components were degraded in a test vehicle at UTC designed to accelerate the bus field operation.

  3. Early metformin therapy (age 8-12 years) in girls with precocious pubarche to reduce hirsutism, androgen excess, and oligomenorrhea in adolescence.

    Science.gov (United States)

    Ibáñez, Lourdes; López-Bermejo, Abel; Díaz, Marta; Marcos, Maria Victoria; de Zegher, Francis

    2011-08-01

    Girls with a combined history of low(-normal) birth weight (LBW) and precocious pubarche (PP) are at high risk to develop polycystic ovary syndrome (PCOS). The objective of the study was to compare the capacity of early vs. late metformin treatment to prevent adolescent PCOS. This was a randomized, open-label study over 7 yr. The study was conducted at a university hospital. Thirty-eight LBW-PP girls were followed up from the mean age 8 until age 15 yr. Early metformin (study yr 1-4; age 8-12 yr) vs. late metformin (yr 6; age 13-14 yr). Measures included height; weight; hirsutism score; menstrual cycle; endocrine-metabolic screening (fasting; follicular phase); C-reactive protein; body composition (absorptiometry); abdominal fat partitioning (magnetic resonance imaging); ovarian morphology (ultrasound); PCOS (National Institutes of Health and Androgen Excess Society definitions) after yr 7 (all girls thus untreated for at least 1 yr). None of the girls dropped out of the study. At age 15 yr, early-metformin girls were taller (4 cm), were in a less proinflammatory state, and had less central fat due to reductions in visceral and hepatic fat. Hirsutism, androgen excess, oligomenorrhea, and PCOS were between 2- and 8-fold more prevalent in late- than early-treated girls. Abdominal adiposity was the first variable to diverge (at age 8-10 yr) between girls without vs. with PCOS at age 15 yr. In LBW-PP girls, early metformin therapy was found to prevent or delay the development of hirsutism, androgen excess, oligomenorrhea, and PCOS more effectively than late metformin. The time window of late childhood and early puberty may be more critical for the development, and thus for the prevention, of adolescent PCOS than the first years beyond menarche.

  4. Improving organic tandem solar cells based on water-processed nanoparticles by quantitative 3D nanoimaging

    DEFF Research Database (Denmark)

    Pedersen, Emil Bøje Lind; Angmo, Dechan; Dam, Henrik Friis

    2015-01-01

    particle active layer. We extract the layered morphology with structural and density information including the porosity present in the various layers and the silver electrode with high resolution in 3D. The Landfester particle layer is found to have an undesired morphology with negatively correlated top......Organic solar cells have great potential for upscaling due to roll-to-roll processing and a low energy payback time, making them an attractive sustainable energy source for the future. Active layers coated with water-dispersible Landfester particles enable greater control of the layer formation...... specifically reveals the need to improve the coatability and layer formation of Landfester nanoparticles, thus allowing improved solar cells to be produced....

  5. Improvement of the Chinese bean [Vigna Unguiculata (L.) Walp.], through radioinduced mutagenesis; Mejoramiento de Frijol Chino [Vigna Unguiculata (L.) Walp.], Mediante Mutagenesis Radioinducida

    Energy Technology Data Exchange (ETDEWEB)

    Salmeron E, J.; Bueno J, J.E.; Valencia E, F.; Solis M, M. [Colegio Superior Agropecuario del Estado de Guerrero, Iguala (Mexico); Cervantes S, T. [Instituto de Recursos Geneticos y Productividad (Mexico); Cruz T, E. de la [ININ, Carretera Mexico-La Marquesa S/N, La Marquesa Ocoyoacac, Mexico. C.P. 52750 (Mexico)]. e-mail: csaegro@prodigy.net.mx

    2006-07-01

    The advances in the process of genetic improvement of the Chinese bean (Vigna Unguiculata (L.) are presented, high nutritious value that it is evaluating as alternative for marginal areas producers of the State of Guerrero. The method of improvement applied it is recurrent radiation, continued by selection cycles applying the method of progeny by plant. The applied radiation doses were 200 and 250 Gray. The established selection approaches are: resistant plants or tolerant to the plagues attack and illnesses, vigorous, with more height to the first sheath, of compact and certain growth, with short internodes, bigger number of sheaths by plant and of grains by sheath, bigger number of grain size, among others. The obtained results show that the dose that induces bigger variability and that it has propitiated the biggest quantity in possible mutants it is 200Gy. Precocious plants with more height to the first sheath, with certain growth as well as with bigger number and sheaths size have been detected. The selected plants have incorporated to an increment process by means of the progeny method by plant. (Author)

  6. Yeast cell surface display: An efficient strategy for improvement of bioethanol fermentation performance.

    Science.gov (United States)

    Chen, Xianzhong

    2017-03-04

    The cell surface serves as a functional interface between the inside and the outside of the cell. Within the past 20 y the ability of yeast (Saccharomyces cerevisiae) to display heterologous proteins on the cell surface has been demonstrated. Furthermore, S. cerevisiae has been both developed and applied in expression of various proteins on the cell surface. Using this novel and useful strategy, proteins and peptides of various kinds can be displayed on the yeast cell surface by fusing the protein of interest with the glycosylphosphatidylinositol (GPI)-anchoring system. Consolidated bioprocessing (CBP) using S. cerevisiae represents a promising technology for bioethanol production. However, further work is needed to improve the fermentation performance. There is some excellent previous research regarding construction of yeast biocatalyst using the surface display system to decrease cost, increase efficiency of ethanol production and directly utilize starch or biomass for fuel production. In this commentary, we reviewed the yeast surface display system and highlighted recent work. Additionally, the strategy for decrease of phytate phosphate content in dried distillers grains with solubles (DDGS) by display of phytase on the yeast cell surface is discussed.

  7. Proteasomal targeting and minigene repetition improve cell-surface presentation of a transfected, modified melanoma tumour antigen

    DEFF Research Database (Denmark)

    Rasmussen, A B; Zocca, M-B; Bonefeld, C M

    2004-01-01

    Melanoma antigen recognized by T cell 1 (MART-1) is regarded as a candidate peptide for vaccination against malignant melanoma, and it is of importance to develop strategies to improve the vaccine-elicited T-cell activation towards MART-1. T-cell activation is, among other determinants, dependent...... on the density of specific major histocompatibility complex-peptide complexes on the surface of the antigen-presenting cell. In this study, we explored the cell-surface presentation of a substituted MART-1 peptide encoded by transfected minigenes. We investigated the potential of proteasomal targeting compared...... to non-proteasomal targeting of the epitope to increase its cell-surface presentation. Furthermore, we explored the potential of incorporating multiple minigenes instead of one to increase cell-surface presentation. We show that both proteasomal targeting and repetition of the minigene increase cell...

  8. Sustained IGF-1 Secretion by Adipose-Derived Stem Cells Improves Infarcted Heart Function.

    Science.gov (United States)

    Bagno, Luiza L; Carvalho, Deivid; Mesquita, Fernanda; Louzada, Ruy A; Andrade, Bruno; Kasai-Brunswick, Taís H; Lago, Vivian M; Suhet, Grazielle; Cipitelli, Debora; Werneck-de-Castro, João Pedro; Campos-de-Carvalho, Antonio C

    2016-01-01

    The mechanism by which stem cell-based therapy improves heart function is still unknown, but paracrine mechanisms seem to be involved. Adipose-derived stem cells (ADSCs) secrete several factors, including insulin-like growth factor-1 (IGF-1), which may contribute to myocardial regeneration. Our aim was to investigate whether the overexpression of IGF-1 in ADSCs (IGF-1-ADSCs) improves treatment of chronically infarcted rat hearts. ADSCs were transduced with a lentiviral vector to induce IGF-1 overexpression. IGF-1-ADSCs transcribe100- to 200-fold more IGF-1 mRNA levels compared to nontransduced ADSCs. IGF-1 transduction did not alter ADSC immunophenotypic characteristics even under hypoxic conditions. However, IGF-1-ADSCs proliferate at higher rates and release greater amounts of growth factors such as IGF-1, vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) under normoxic and hypoxic conditions. Importantly, IGF-1 secreted by IGF-1-ADSCs is functional given that Akt-1 phosphorylation was remarkably induced in neonatal cardiomyocytes cocultured with IGF-1-ADSCs, and this increase was prevented with phosphatidylinositol 3-kinase (PI3K) inhibitor treatment. Next, we tested IGF-1-ADSCs in a rat myocardial infarction (MI) model. MI was performed by coronary ligation, and 4 weeks after MI, animals received intramyocardial injections of either ADSCs (n = 7), IGF-1-ADSCs (n = 7), or vehicle (n = 7) into the infarcted border zone. Left ventricular function was evaluated by echocardiography before and after 6 weeks of treatment, and left ventricular hemodynamics were assessed 7 weeks after cell injection. Notably, IGF-1-ADSCs improved left ventricular ejection fraction and cardiac contractility index, but did not reduce scar size when compared to the ADSC-treated group. In summary, transplantation of ADSCs transduced with IGF-1 is a superior therapeutic approach to treat MI compared to nontransduced ADSCs, suggesting that gene and cell

  9. Improvement of Bioactive Compound Classification through Integration of Orthogonal Cell-Based Biosensing Methods

    Directory of Open Access Journals (Sweden)

    Goran N. Jovanovic

    2007-01-01

    Full Text Available Lack of specificity for different classes of chemical and biological agents, and false positives and negatives, can limit the range of applications for cell-based biosensors. This study suggests that the integration of results from algal cells (Mesotaenium caldariorum and fish chromatophores (Betta splendens improves classification efficiency and detection reliability. Cells were challenged with paraquat, mercuric chloride, sodium arsenite and clonidine. The two detection systems were independently investigated for classification of the toxin set by performing discriminant analysis. The algal system correctly classified 72% of the bioactive compounds, whereas the fish chromatophore system correctly classified 68%. The combined classification efficiency was 95%. The algal sensor readout is based on fluorescence measurements of changes in the energy producing pathways of photosynthetic cells, whereas the response from fish chromatophores was quantified using optical density. Change in optical density reflects interference with the functioning of cellular signal transduction networks. Thus, algal cells and fish chromatophores respond to the challenge agents through sufficiently different mechanisms of action to be considered orthogonal.

  10. Recovery Profiles of T-Cell Subsets Following Low-Dose Total Body Irradiation and Improvement With Cinnamon

    International Nuclear Information System (INIS)

    Zheng, Xiaodan; Guo, Yuqi; Wang, Lei; Zhang, Honghai; Wang, Shaobo; Wang, Li; An, Lei; Zhou, Xianbin; Li, Xia; Yao, Chengfang

    2015-01-01

    Purpose: Inefficient T-cell reconstitution from x-ray–induced immune damage reduces antitumor response. To understand the profile of T-cell reconstitution after irradiation will overcome the barrier of antitumor immunity. This study aimed to identify the recovery profile of T-cell subsets following x-ray irradiation and to highlight the role of cinnamon on efficient T-cell restoration postexposure in the antitumor response. Methods and Materials: CD3"+, CD8"+, and CD4"+ T cells and Th1, Th2, Th17, and regulatory T (Treg) cells were evaluated at different time points after single low-dose total body irradiation (SLTBI) with or without cinnamon treatments. T-bet, GATA3, RORγt, and Foxp3 signaling specific for Th1, Th2, Th17, and Treg were also analyzed by RT-PCR assay. The effects of cinnamon on efficient T-cell subset reconstitution was confirmed in a lung melanoma model in irradiated mice. Results: Reconstitution of CD4"+ T cells was delayed more than that of CD8"+ T cells in T-cell restoration after SLTBI. The production of IFNγ by Th1 or Tc1 cells was sharply decreased and was accompanied by reduced T-bet mRNA, even when total T-cell numbers had recovered; the frequencies of Th17 and Treg cells and their specific transcription factors (RORγt and Foxp3, respectively) were obviously increased. Irradiation-induced inefficient T-cell reconstitution impaired the antitumor capacities in the lung melanoma model. Pretreatment with cinnamon in irradiated mice accelerated the generation of Th1 and reduced the differentiation of Treg cells by activating T-bet and limiting transcriptions of Foxp3. Improvement resulting from cinnamon pretreatment on the efficient T-cell recovery profile from SLTBI promoted antitumor immunity in the lung melanoma model. Conclusions: T-cell reconstitution from SLTBI was characterized by impaired Th1 and elevated Th17 and Treg cells. Cinnamon effectively improved the imbalance of T-cell subsets by promoting the proliferation of Th1 and

  11. Recovery Profiles of T-Cell Subsets Following Low-Dose Total Body Irradiation and Improvement With Cinnamon

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Xiaodan [Key Laboratory for Tumor Immunology and Traditional Chinese Medicine Immunology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan (China); School of Medicine and Life Science, University of Jinan-Shandong Academy of Medical Science, Jinan (China); Guo, Yuqi [Key Laboratory for Tumor Immunology and Traditional Chinese Medicine Immunology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan (China); Wang, Lei [Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan (China); Zhang, Honghai [Key Laboratory for Tumor Immunology and Traditional Chinese Medicine Immunology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan (China); Wang, Shaobo [Shandong University, Jinan (China); Wang, Li [Key Laboratory for Tumor Immunology and Traditional Chinese Medicine Immunology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan (China); An, Lei [Key Laboratory for Tumor Immunology and Traditional Chinese Medicine Immunology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan (China); School of Medicine and Life Science, University of Jinan-Shandong Academy of Medical Science, Jinan (China); Zhou, Xianbin; Li, Xia [Key Laboratory for Tumor Immunology and Traditional Chinese Medicine Immunology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan (China); Yao, Chengfang, E-mail: yaocf9941@163.com [Key Laboratory for Tumor Immunology and Traditional Chinese Medicine Immunology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan (China)

    2015-12-01

    Purpose: Inefficient T-cell reconstitution from x-ray–induced immune damage reduces antitumor response. To understand the profile of T-cell reconstitution after irradiation will overcome the barrier of antitumor immunity. This study aimed to identify the recovery profile of T-cell subsets following x-ray irradiation and to highlight the role of cinnamon on efficient T-cell restoration postexposure in the antitumor response. Methods and Materials: CD3{sup +}, CD8{sup +}, and CD4{sup +} T cells and Th1, Th2, Th17, and regulatory T (Treg) cells were evaluated at different time points after single low-dose total body irradiation (SLTBI) with or without cinnamon treatments. T-bet, GATA3, RORγt, and Foxp3 signaling specific for Th1, Th2, Th17, and Treg were also analyzed by RT-PCR assay. The effects of cinnamon on efficient T-cell subset reconstitution was confirmed in a lung melanoma model in irradiated mice. Results: Reconstitution of CD4{sup +} T cells was delayed more than that of CD8{sup +} T cells in T-cell restoration after SLTBI. The production of IFNγ by Th1 or Tc1 cells was sharply decreased and was accompanied by reduced T-bet mRNA, even when total T-cell numbers had recovered; the frequencies of Th17 and Treg cells and their specific transcription factors (RORγt and Foxp3, respectively) were obviously increased. Irradiation-induced inefficient T-cell reconstitution impaired the antitumor capacities in the lung melanoma model. Pretreatment with cinnamon in irradiated mice accelerated the generation of Th1 and reduced the differentiation of Treg cells by activating T-bet and limiting transcriptions of Foxp3. Improvement resulting from cinnamon pretreatment on the efficient T-cell recovery profile from SLTBI promoted antitumor immunity in the lung melanoma model. Conclusions: T-cell reconstitution from SLTBI was characterized by impaired Th1 and elevated Th17 and Treg cells. Cinnamon effectively improved the imbalance of T-cell subsets by promoting the

  12. Mesenchymal stromal cells improve human islet function through released products and extracellular matrix.

    Science.gov (United States)

    Arzouni, Ahmed A; Vargas-Seymour, Andreia; Rackham, Chloe L; Dhadda, Paramjeet; Huang, Guo-Cai; Choudhary, Pratik; Nardi, Nance; King, Aileen J F; Jones, Peter M

    2017-12-01

    The aims of the present study were (i) to determine whether the reported beneficial effects of mesenchymal stromal cells (MSCs) on mouse islet function extend to clinically relevant human tissues (islets and MSCs), enabling translation into improved protocols for clinical human islet transplantation; and (ii) to identify possible mechanisms through which human MSCs influence human islet function. Human islets were co-cultured with human adipose tissue-derived MSCs (hASCs) or pre-treated with its products - extracellular matrix (ECM) and annexin A1 (ANXA1). Mouse islets were pre-treated with mouse MSC-derived ECM. Islet insulin secretory function was assessed in vitro by radioimmunoassay. Quantitative RT-PCR was used to screen human adipMSCs for potential ligands of human islet G-protein-coupled receptors. We show that co-culture with hASCs improves human islet secretory function in vitro , as measured by glucose-stimulated insulin secretion, confirming previous reports using rodent tissues. Furthermore, we demonstrate that these beneficial effects on islet function can be partly attributed to the MSC-derived products ECM and ANXA1. Our results suggest that hASCs have the potential to improve the quality of human islets isolated for transplantation therapy of Type 1 diabetes. Furthermore, it may be possible to achieve improvements in human islet quality in a cell-free culture system by using the MSC-derived products ANXA1 and ECM. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  13. Production of cloned mice and ES cells from adult somatic cells by nuclear transfer: how to improve cloning efficiency?

    Science.gov (United States)

    Wakayama, Teruhiko

    2007-02-01

    Although it has now been 10 years since the first cloned mammals were generated from somatic cells using nuclear transfer (NT), most cloned embryos usually undergo developmental arrest prior to or soon after implantation, and the success rate for producing live offspring by cloning remains below 5%. The low success rate is believed to be associated with epigenetic errors, including abnormal DNA hypermethylation, but the mechanism of "reprogramming" is unclear. We have been able to develop a stable NT method in the mouse in which donor nuclei are directly injected into the oocyte using a piezo-actuated micromanipulator. Especially in the mouse, only a few laboratories can make clones from adult somatic cells, and cloned mice are never successfully produced from most mouse strains. However, this technique promises to be an important tool for future research in basic biology. For example, NT can be used to generate embryonic stem (NT-ES) cell lines from a patient's own somatic cells. We have shown that NT-ES cells are equivalent to ES cells derived from fertilized embryos and that they can be generated relatively easily from a variety of mouse genotypes and cell types of both sexes, even though it may be more difficult to generate clones directly. In general, NT-ES cell techniques are expected to be applied to regenerative medicine; however, this technique can also be applied to the preservation of genetic resources of mouse strain instead of embryos, oocytes and spermatozoa. This review describes how to improve cloning efficiency and NT-ES cell establishment and further applications.

  14. Secondary chondrocyte-derived Ihh stimulates proliferation of periosteal cells during chick development.

    Science.gov (United States)

    Buxton, Paul G; Hall, Brian; Archer, Charles W; Francis-West, Philippa

    2003-10-01

    The development of the skull is characterised by its dependence upon epigenetic influences. One of the most important of these is secondary chondrogenesis, which occurs following ossification within certain membrane bone periostea, as a result of biomechanical articulation. We have studied the genesis, character and function of the secondary chondrocytes of the quadratojugal of the chick between embryonic days 11 and 14. Analysis of gene expression revealed that secondary chondrocytes formed coincident with Sox9 upregulation from a precursor population expressing Cbfa1/Runx2: a reversal of the normal sequence. Such secondary chondrocytes rapidly acquired a phenotype that is a compound of prehypertrophic and hypertrophic chondrocytes, exited from the cell cycle and upregulated Ihh. Pulse and pulse/chase experiments with BrdU confirmed the germinal region as the highly proliferative source of the secondary chondrocytes, which formed by division of chondrocyte-committed precursors. By blocking Hh signalling in explant cultures we show that the enhanced proliferation of the germinal region surrounding the secondary chondrocytes derives from this Ihh source. Additionally, in vitro studies on membrane bone periosteal cells (non-germinal region) demonstrated that these cells can also respond to Ihh, and do so both by enhanced proliferation and precocious osteogenesis. Despite the pro-osteogenic effects of Ihh on periosteal cell differentiation, mechanical articulation of the quadratojugal/quadrate joint in explant culture revealed a negative role for articulation in the regulation of osteocalcin by germinal region descendants. Thus, the mechanical stimulus that is the spur to secondary chondrocyte formation appears able to override the osteogenic influence of Ihh on the periosteum, but does not interfere with the cell cycle-promoting component of Hh signalling.

  15. Improving Cardiac Action Potential Measurements: 2D and 3D Cell Culture.

    Science.gov (United States)

    Daily, Neil J; Yin, Yue; Kemanli, Pinar; Ip, Brian; Wakatsuki, Tetsuro

    2015-11-01

    Progress in the development of assays for measuring cardiac action potential is crucial for the discovery of drugs for treating cardiac disease and assessing cardiotoxicity. Recently, high-throughput methods for assessing action potential using induced pluripotent stem cell (iPSC) derived cardiomyocytes in both two-dimensional monolayer cultures and three-dimensional tissues have been developed. We describe an improved method for assessing cardiac action potential using an ultra-fast cost-effective plate reader with commercially available dyes. Our methods improve dramatically the detection of the fluorescence signal from these dyes and make way for the development of more high-throughput methods for cardiac drug discovery and cardiotoxicity.

  16. Improvement in IBC-silicon solar cell performance by insertion of highly doped crystalline layer at heterojunction interfaces

    International Nuclear Information System (INIS)

    Bashiri, Hadi; Azim Karami, Mohammad; Mohammadnejad, Shahramm

    2017-01-01

    By inserting a thin highly doped crystalline silicon layer between the base region and amorphous silicon layer in an interdigitated back-contact (IBC) silicon solar cell, a new passivation layer is investigated. The passivation layer performance is characterized by numerical simulations. Moreover, the dependence of the output parameters of the solar cell on the additional layer parameters (doping concentration and thickness) is studied. By optimizing the additional passivation layer in terms of doping concentration and thickness, the power conversion efficiency could be improved by a factor of 2.5%, open circuit voltage is increased by 30 mV and the fill factor of the solar cell by 7.4%. The performance enhancement is achieved due to the decrease of recombination rate, a decrease in solar cell resistivity and improvement of field effect passivation at heterojunction interface. The above-mentioned results are compared with reported results of the same conventional interdigitated back-contact silicon solar cell structure. Furthermore, the effect of a-Si:H/c-Si interface defect density on IBC silicon solar cell parameters with a new passivation layer is studied. The additional passivation layer also reduces the sensitivity of output parameter of solar cell to interface defect density. (paper)

  17. Further Improvement and System Integration of High Temperature Polymer Electrolyte Membrane Fuel Cells

    DEFF Research Database (Denmark)

    Jensen, Jens Oluf; Li, Qingfeng

    Polymer electrolyte membrane fuel cell (PEMFC) technology based on Nafion membranes can operate at temperatures around 80°C. The new development in the field is high temperature PEMFC for operation above 100°C, which has been successfully demonstrated through the previous EC Joule III and the 5th......, and system integration of the high temperature PEMFC. The strategic developments of the FURIM are in three steps: (1) further improvement of the high temperature polymer membranes and related materials; (2) development of technological units including fuel cell stack, hydrocarbon reformer, afterburner...... and power management system, that are compatible with the HT-PEMFC; and (3) integration of the HT-PEMFC stack with these compatible subunits. The main goal of the project is a 2kWel HT-PEMFC stack operating in a temperature range of 120-220°C, with a single cell performance target of 0.7 A/cm² at a cell...

  18. Reducing macrophages to improve bone marrow stromal cell survival in the contused spinal cord.

    NARCIS (Netherlands)

    Ritfeld, G.J.; Nandoe Tewarie, R.D.S.; Rahiem, S.T.; Hurtado, A.; Roos, R.A.; Grotenhuis, A.; Oudega, M.

    2010-01-01

    We tested whether reducing macrophage infiltration would improve the survival of allogeneic bone marrow stromal cells (BMSC) transplanted in the contused adult rat thoracic spinal cord. Treatment with cyclosporine, minocycline, or methylprednisolone all resulted in a significant decrease in

  19. Synthesis and SAR of novel imidazoquinoxaline-based Lck inhibitors: improvement of cell potency.

    Science.gov (United States)

    Chen, Ping; Iwanowicz, Edwin J; Norris, Derek; Gu, Henry H; Lin, James; Moquin, Robert V; Das, Jagabandhu; Wityak, John; Spergel, Steven H; de Fex, Henry; Pang, Suhong; Pitt, Sydney; Shen, Ding Ren; Schieven, Gary L; Barrish, Joel C

    2002-11-04

    A series of anilino(imidazoquinoxaline) analogues bearing solubilizing side chains at the 6- and 7-positions of the fused phenyl ring has been prepared and evaluated for inhibition against Lck enzyme and of T-cell proliferation. Significant improvement of the cellular activity was achieved over the initial lead, compound 2.

  20. Regulation of germ cell development by intercellular signaling in the mammalian ovarian follicle.

    Science.gov (United States)

    Clarke, Hugh J

    2018-01-01

    Prior to ovulation, the mammalian oocyte undergoes a process of differentiation within the ovarian follicle that confers on it the ability to give rise to an embryo. Differentiation comprises two phases-growth, during which the oocyte increases more than 100-fold in volume as it accumulates macromolecules and organelles that will sustain early embryogenesis; and meiotic maturation, during which the oocyte executes the first meiotic division and prepares for the second division. Entry of an oocyte into the growth phase appears to be triggered when the adjacent granulosa cells produce specific growth factors. As the oocyte grows, it elaborates a thick extracellular coat termed the zona pellucida. Nonetheless, cytoplasmic extensions of the adjacent granulosa cells, termed transzonal projections (TZPs), enable them to maintain contact-dependent communication with the oocyte. Through gap junctions located where the TZP tips meet the oocyte membrane, they provide the oocyte with products that sustain its metabolic activity and signals that regulate its differentiation. Conversely, the oocyte secretes diffusible growth factors that regulate proliferation and differentiation of the granulosa cells. Gap junction-permeable products of the granulosa cells prevent precocious initiation of meiotic maturation, and the gap junctions also enable oocyte maturation to begin in response to hormonal signals received by the granulosa cells. Development of the oocyte or the somatic compartment may also be regulated by extracellular vesicles newly identified in follicular fluid and at TZP tips, which could mediate intercellular transfer of macromolecules. Oocyte differentiation thus depends on continuous signaling interactions with the somatic cells of the follicle. WIREs Dev Biol 2018, 7:e294. doi: 10.1002/wdev.294 This article is categorized under: Gene Expression and Transcriptional Hierarchies > Cellular Differentiation Signaling Pathways > Cell Fate Signaling Early Embryonic

  1. Integrated cell and process engineering for improved transient production of a "difficult-to-express" fusion protein by CHO cells.

    Science.gov (United States)

    Johari, Yusuf B; Estes, Scott D; Alves, Christina S; Sinacore, Marty S; James, David C

    2015-12-01

    Based on an optimized electroporation protocol, we designed a rapid, milliliter-scale diagnostic transient production assay to identify limitations in the ability of Chinese hamster ovary (CHO) cells to produce a model "difficult-to-express" homodimeric Fc-fusion protein, Sp35Fc, that exhibited very low volumetric titer and intracellular formation of disulfide-bonded oligomeric aggregates post-transfection. As expression of Sp35Fc induced an unfolded protein response in transfected host cells, we utilized the transient assay to compare, in parallel, multiple functionally diverse strategies to engineer intracellular processing of Sp35Fc in order to increase production and reduce aggregation as two discrete design objectives. Specifically, we compared the effect of (i) co-expression of ER-resident molecular chaperones (BiP, PDI, CypB) or active forms of UPR transactivators (ATF6c, XBP1s) at varying recombinant gene load, (ii) addition of small molecules known to act as chemical chaperones (PBA, DMSO, glycerol, betaine, TMAO) or modulate UPR signaling (PERK inhibitor GSK2606414) at varying concentration, (iii) a reduction in culture temperature to 32°C. Using this information, we designed a biphasic, Sp35Fc-specific transient manufacturing process mediated by lipofection that utilized CypB co-expression at an optimal Sp35Fc:CypB gene ratio of 5:1 to initially maximize transfected cell proliferation, followed by addition of a combination of PBA (0.5 mM) and glycerol (1% v/v) at the onset of stationary phase to maximize cell specific production and eliminate Sp35Fc aggregation. Using this optimal, engineered process transient Sp35Fc production was significantly increased sixfold over a 12 day production process with no evidence of disulfide-bonded aggregates. Finally, transient production in clonally derived sub-populations (derived from parental CHO host) screened for a heritably improved capability to produce Sp35Fc was also significantly improved by the optimized

  2. Membrane cholesterol regulates lysosome-plasma membrane fusion events and modulates Trypanosoma cruzi invasion of host cells.

    Directory of Open Access Journals (Sweden)

    Bárbara Hissa

    Full Text Available BACKGROUND: Trypomastigotes of Trypanosoma cruzi are able to invade several types of non-phagocytic cells through a lysosomal dependent mechanism. It has been shown that, during invasion, parasites trigger host cell lysosome exocytosis, which initially occurs at the parasite-host contact site. Acid sphingomyelinase released from lysosomes then induces endocytosis and parasite internalization. Lysosomes continue to fuse with the newly formed parasitophorous vacuole until the parasite is completely enclosed by lysosomal membrane, a process indispensable for a stable infection. Previous work has shown that host membrane cholesterol is also important for the T. cruzi invasion process in both professional (macrophages and non-professional (epithelial phagocytic cells. However, the mechanism by which cholesterol-enriched microdomains participate in this process has remained unclear. METHODOLOGY/PRINCIPAL FINDING: In the present work we show that cardiomyocytes treated with MβCD, a drug able to sequester cholesterol from cell membranes, leads to a 50% reduction in invasion by T. cruzi trypomastigotes, as well as a decrease in the number of recently internalized parasites co-localizing with lysosomal markers. Cholesterol depletion from host membranes was accompanied by a decrease in the labeling of host membrane lipid rafts, as well as excessive lysosome exocytic events during the earlier stages of treatment. Precocious lysosomal exocytosis in MβCD treated cells led to a change in lysosomal distribution, with a reduction in the number of these organelles at the cell periphery, and probably compromises the intracellular pool of lysosomes necessary for T. cruzi invasion. CONCLUSION/SIGNIFICANCE: Based on these results, we propose that cholesterol depletion leads to unregulated exocytic events, reducing lysosome availability at the cell cortex and consequently compromise T. cruzi entry into host cells. The results also suggest that two different pools of

  3. Does injection of metanephric mesenchymal cells improve renal function in rats?

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    Yu-qing Jiao

    2011-01-01

    Full Text Available Chronic kidney disease (CKD is a massive global health-care problem. Cell therapy offers a potential treatment for CKD. The aim of this study was to investigate whether the administration of a population of stem cells could be used to treat adriamycin (ADR-induced glomerulopathy in rats, a form of CKD. We intravenously transplanted metanephric mesenchymal cells (MMCs into rats treated with ADR. We also induced MMC differentiation in vitro using a medium derived from serum and homogenates of ADR-induced glomerulopathy rats. We detected the induction of an early epithelial phenotype (cytokeratin-18 expression and a proximal tubule phenotype (vitamin D receptor expression in vitro, and MMC-derived epithelial cells corresponding to the proximal tubule and glomeruli in vivo. Transplantation of MMCs after induction of glomerulopathy significantly increased the creatinine clearance rate (Ccr, a marker for glomerular filtration rate, but had no significant effect on other parameters (24-hour urinary protein excretion, serum albumin, total cholesterol. In addition, there was no significant difference in blood urea nitrogen or serum creatinine levels in rats with and without ADR administration. Our results indicate that MMCs might survive, engraft and differentiate into renal epithelia in vivo when transplanted into ADR-treated rats. However, further studies are needed to determine whether MMC transplantation improves renal function and causes renal repair in this model.

  4. Knocking out Ornithine Decarboxylase Antizyme 1 (OAZ1 Improves Recombinant Protein Expression in the HEK293 Cell Line

    Directory of Open Access Journals (Sweden)

    Laura Abaandou

    2018-06-01

    Full Text Available Creating efficient cell lines is a priority for the biopharmaceutical industry, which produces biologicals for various uses. A recent approach to achieving this goal is the use of non-coding RNAs, microRNA (miRNA and small interfering RNA (siRNA, to identify key genes that can potentially improve production or growth. The ornithine decarboxylase antizyme 1 (OAZ1 gene, a negative regulator of polyamine biosynthesis, was identified in a genome-wide siRNA screen as a potential engineering target, because its knock down by siRNA increased recombinant protein expression from human embryonic kidney 293 (HEK293 cells by two-fold. To investigate this further, the OAZ1 gene in HEK293 cells was knocked out using CRISPR genome editing. The OAZ1 knockout cell lines displayed up to four-fold higher expression of both stably and transiently expressed proteins, with comparable growth and metabolic activity to the parental cell line; and an approximately three-fold increase in intracellular polyamine content. The results indicate that genetic inactivation of OAZ1 in HEK293 cells is an effective strategy to improve recombinant protein expression in HEK293 cells.

  5. Improvement of inverted organic solar cells using acetic acid as an additive for ZnO layer processing

    Directory of Open Access Journals (Sweden)

    Yang Li

    2018-02-01

    Full Text Available In this work, we used acetic acid as an additive for the preparation of ZnO layers and improved the performance of poly{4,8-bis[(2-ethylhexyl-oxy]benzo[1,2-b:4,5-b’] dithiophene-2,6-diyl-alt-3-fluoro-2-[(2-ethylhexylcarbonyl]thieno[3,4-b]thiophene- 4,6-diyl} (PTB7-based inverted organic solar cells. The addition of acetic acid to the ZnO precursor solution improved the transparency and conductivity of the sol-gel-synthesized ZnO film, by increasing the grain size of the film. Accordingly, the power conversion efficiency (PCE of the organic solar cells was improved from 6.42% to 7.55%, which was mainly caused by the enhanced current density and fill factor. The best sample demonstrated a high PCE of 7.85% with negligible hysteresis and good stability. Our results indicate that using acetic acid as an additive for the preparation of ZnO is a simple and effective way of fabricating high-performance inverted organic solar cells.

  6. Improvement of inverted organic solar cells using acetic acid as an additive for ZnO layer processing

    Science.gov (United States)

    Li, Yang; Liu, Yawen; Liu, Zhihai; Xie, Xiaoyin; Lee, Eun-Cheol

    2018-02-01

    In this work, we used acetic acid as an additive for the preparation of ZnO layers and improved the performance of poly{4,8-bis[(2-ethylhexyl)-oxy]benzo[1,2-b:4,5-b'] dithiophene-2,6-diyl-alt-3-fluoro-2-[(2-ethylhexyl)carbonyl]thieno[3,4-b]thiophene- 4,6-diyl} (PTB7)-based inverted organic solar cells. The addition of acetic acid to the ZnO precursor solution improved the transparency and conductivity of the sol-gel-synthesized ZnO film, by increasing the grain size of the film. Accordingly, the power conversion efficiency (PCE) of the organic solar cells was improved from 6.42% to 7.55%, which was mainly caused by the enhanced current density and fill factor. The best sample demonstrated a high PCE of 7.85% with negligible hysteresis and good stability. Our results indicate that using acetic acid as an additive for the preparation of ZnO is a simple and effective way of fabricating high-performance inverted organic solar cells.

  7. Research on Analysis Method of Traffic Congestion Mechanism Based on Improved Cell Transmission Model

    Directory of Open Access Journals (Sweden)

    Hongzhao Dong

    2012-01-01

    Full Text Available To analyze the spreading regularity of the initial traffic congestion, the improved cell transmission model (CTM is proposed to describe the evolution mechanism of traffic congestion in regional road grid. Ordinary cells and oriented cells are applied to render the crowd roads and their adjacent roads. Therefore the traffic flow could be simulated by these cells. Resorting to the proposed model, the duration of the initial traffic congestion could be predicted and the subsequent secondary congestion could be located. Accordingly, the spatial diffusion of traffic congestion could be estimated. At last, taking a road network region of Hangzhou city as an example, the simulation experiment is implemented to verify the proposed method by PARAMICS software. The result shows that the method could predict the duration of the initial congestion and estimate its spatial diffusion accurately.

  8. Histone deacetylase inhibitor significantly improved the cloning efficiency of porcine somatic cell nuclear transfer embryos.

    Science.gov (United States)

    Huang, Yongye; Tang, Xiaochun; Xie, Wanhua; Zhou, Yan; Li, Dong; Yao, Chaogang; Zhou, Yang; Zhu, Jianguo; Lai, Liangxue; Ouyang, Hongsheng; Pang, Daxin

    2011-12-01

    Valproic acid (VPA), a histone deacetylase inbibitor, has been shown to generate inducible pluripotent stem (iPS) cells from mouse and human fibroblasts with a significant higher efficiency. Because successful cloning by somatic cell nuclear transfer (SCNT) undergoes a full reprogramming process in which the epigenetic state of a differentiated donor nuclear is converted into an embryonic totipotent state, we speculated that VPA would be useful in promoting cloning efficiency. Therefore, in the present study, we examined whether VPA can promote the developmental competence of SCNT embryos by improving the reprogramming state of donor nucleus. Here we report that 1 mM VPA for 14 to 16 h following activation significantly increased the rate of blastocyst formation of porcine SCNT embryos constructed from Landrace fetal fibroblast cells compared to the control (31.8 vs. 11.4%). However, we found that the acetylation level of Histone H3 lysine 14 and Histone H4 lysine 5 and expression level of Oct4, Sox2, and Klf4 was not significantly changed between VPA-treated and -untreated groups at the blastocyst stage. The SCNT embryos were transferred to 38 surrogates, and the cloning efficiency in the treated group was significantly improved compared with the control group. Taken together, we have demonstrated that VPA can improve both in vitro and in vivo development competence of porcine SCNT embryos.

  9. Improved hydroxyurea effect with the use of text messaging in children with sickle cell anemia.

    Science.gov (United States)

    Estepp, Jeremie H; Winter, Bryan; Johnson, Margery; Smeltzer, Matthew P; Howard, Scott C; Hankins, Jane S

    2014-11-01

    In children with sickle cell anemia (SCA), hydroxyurea reduces morbidity, but adherence is frequently suboptimal. Because most families of children with SCA have access to cellular telephone services, we assessed the impact of text messaged reminders as a tool to improve adherence to hydroxyurea. All patients hydroxyurea at a maximal tolerated dosage (MTD) at St. Jude Children's Research Hospital Comprehensive Pediatric Sickle Cell Program and who received automated text message reminders (SIMON®) were retrospectively identified. Laboratory parameters, hospitalizations, and medication possession ratios (MPR) prior to and after initiation of SIMON® were compared to assess the impact of SIMON®. Of the 97.3% of families with access to a cell phone, 91% elected to receive text message reminders. Among 55 children receiving hydroxyurea at MTD, laboratory parameters reflected waning medication compliance during the 12 months prior to SIMON®. Following initiation of SIMON®, children had higher mean corpuscular volumes, hemoglobin levels and fetal hemoglobin percentages and lower absolute reticulocyte counts and bilirubin levels, suggesting improved medication adherence. Hospitalizations were uncommon before and after SIMON®, and medication possession ratios (MPRs) were high before and after SIMON®, neither was significantly changed. SIMON® was feasible and improved hematologic parameters in children with SCA receiving hydroxyurea at a MTD. Future work will include extension of this technology to children with other chronic medical conditions who require daily use of medication. © 2014 Wiley Periodicals, Inc.

  10. Improvement of organic solar cells by flexible substrate and ITO surface treatments

    International Nuclear Information System (INIS)

    Cheng, Yuang-Tung; Ho, Jyh-Jier; Wang, Chien-Kun; Lee, William; Lu, Chih-Chiang; Yau, Bao-Shun; Nain, Jhen-Liang; Chang, Shun-Hsyung; Chang, Chiu-Cheng; Wang, Kang L.

    2010-01-01

    In this paper, surface treatments on polyethylene terephthalate with polymeric hard coating (PET-HC) substrates are described. The effect of the contact angle on the treatment is first investigated. It has been observed that detergent is quite effective in removing organic contamination on the flexible PET-HC substrates. Next, using a DC-reactive magnetron sputter, indium tin oxide (ITO) thin films of 90 nm are grown on a substrate treated by detergent. Then, various ITO surface treatments are made for improving the performance of the finally developed organic solar cells with structure Al/P3HT:PCBM/PEDOT:PSS/ITO/PET. It is found that the parameters of the ITO including resistivity, carrier concentration, transmittance, surface morphology, and work function depended on the surface treatments and significantly influence the solar cell performance. With the optimal conditions for detergent treatment on flexible PET substrates, the ITO film with a resistivity of 5.6 x 10 -4 Ω cm and average optical transmittance of 84.1% in the visible region are obtained. The optimal ITO surface treated by detergent for 5 min and then by UV ozone for 20 min exhibits the best WF value of 5.22 eV. This improves about 8.30% in the WF compared with that of the untreated ITO film. In the case of optimal treatment with the organic photovoltaic device, meanwhile, 36.6% enhancement in short circuit current density (J sc ) and 92.7% enhancement in conversion efficiency (η) over the untreated solar cell are obtained.

  11. Improved CORF model of simple cell combined with non-classical receptive field and its application on edge detection

    Science.gov (United States)

    Sun, Xiao; Chai, Guobei; Liu, Wei; Bao, Wenzhuo; Zhao, Xiaoning; Ming, Delie

    2018-02-01

    Simple cells in primary visual cortex are believed to extract local edge information from a visual scene. In this paper, inspired by different receptive field properties and visual information flow paths of neurons, an improved Combination of Receptive Fields (CORF) model combined with non-classical receptive fields was proposed to simulate the responses of simple cell's receptive fields. Compared to the classical model, the proposed model is able to better imitate simple cell's physiologic structure with consideration of facilitation and suppression of non-classical receptive fields. And on this base, an edge detection algorithm as an application of the improved CORF model was proposed. Experimental results validate the robustness of the proposed algorithm to noise and background interference.

  12. Improved Tumor Penetration and Single-Cell Targeting of Antibody-Drug Conjugates Increases Anticancer Efficacy and Host Survival.

    Science.gov (United States)

    Cilliers, Cornelius; Menezes, Bruna; Nessler, Ian; Linderman, Jennifer; Thurber, Greg M

    2018-02-01

    Current antibody-drug conjugates (ADC) have made advances in engineering the antibody, linker, conjugation site, small-molecule payload, and drug-to-antibody ratio (DAR). However, the relationship between heterogeneous intratumoral distribution and efficacy of ADCs is poorly understood. Here, we compared trastuzumab and ado-trastuzumab emtansine (T-DM1) to study the impact of ADC tumor distribution on efficacy. In a mouse xenograft model insensitive to trastuzumab, coadministration of trastuzumab with a fixed dose of T-DM1 at 3:1 and 8:1 ratios dramatically improved ADC tumor penetration and resulted in twice the improvement in median survival compared with T-DM1 alone. In this setting, the effective DAR was lowered, decreasing the amount of payload delivered to each targeted cell but increasing the number of cells that received payload. This result is counterintuitive because trastuzumab acts as an antagonist in vitro and has no single-agent efficacy in vivo , yet improves the effectiveness of T-DM1 in vivo Novel dual-channel fluorescence ratios quantified single-cell ADC uptake and metabolism and confirmed that the in vivo cellular dose of T-DM1 alone exceeded the minimum required for efficacy in this model. In addition, this technique characterized cellular pharmacokinetics with heterogeneous delivery after 1 day, degradation and payload release by 2 days, and in vitro cell killing and in vivo tumor shrinkage 2 to 3 days later. This work demonstrates that the intratumoral distribution of ADC, independent of payload dose or plasma clearance, plays a major role in ADC efficacy. Significance: This study shows how lowering the drug-to-antibody ratio during treatment can improve the intratumoral distribution of a antibody-drug conjugate, with implications for improving the efficacy of this class of cancer drugs. Cancer Res; 78(3); 758-68. ©2017 AACR . ©2017 American Association for Cancer Research.

  13. Improvements in low-cost label-free QPI microscope for live cell imaging

    Science.gov (United States)

    Seniya, C.; Towers, C. E.; Towers, D. P.

    2017-07-01

    This paper reports an improvement in the development of a low-cost QPI microscope offering new capabilities in term of phase measurement accuracy for label-free live samples in the longer term (i.e., hours to days). The spatially separated scattered and non-scattered image light fields are reshaped in the Fourier plane and modulated to form an interference image at a CCD camera. The apertures that enable these two beams to be generated have been optimised by means of laser-cut apertures placed on the mirrors of a Michelson interferometer and has improved the phase measuring and reconstruction capability of the QPI microscope. The microscope was tested with transparent onion cells as an object of interest.

  14. Improving immunological tumor microenvironment using electro-hyperthermia followed by dendritic cell immunotherapy.

    Science.gov (United States)

    Tsang, Yuk-Wah; Huang, Cheng-Chung; Yang, Kai-Lin; Chi, Mau-Shin; Chiang, Hsin-Chien; Wang, Yu-Shan; Andocs, Gabor; Szasz, Andras; Li, Wen-Tyng; Chi, Kwan-Hwa

    2015-10-15

    The treatment of intratumoral dentritic cells (DCs) commonly fails because it cannot evoke immunity in a poor tumor microenvironment (TME). Modulated electro-hyperthermia (mEHT, trade-name: oncothermia) represents a significant technological advancement in the hyperthermia field, allowing the autofocusing of electromagnetic power on a cell membrane to generate massive apoptosis. This approach turns local immunogenic cancer cell death (apoptosis) into a systemic anti-tumor immune response and may be implemented by treatment with intratumoral DCs. The CT26 murine colorectal cancer model was used in this investigation. The inhibition of growth of the tumor and the systemic anti-tumor immune response were measured. The tumor was heated to a core temperature of 42 °C for 30 min. The matured synergetic DCs were intratumorally injected 24 h following mEHT was applied. mEHT induced significant apoptosis and enhanced the release of heat shock protein70 (Hsp70) in CT26 tumors. Treatment with mEHT-DCs significantly inhibited CT26 tumor growth, relative to DCs alone or mEHT alone. The secondary tumor protection effect upon rechallenging was observed in mice that were treated with mEHT-DCs. Immunohistochemical staining of CD45 and F4/80 revealed that mEHT-DC treatment increased the number of leukocytes and macrophages. Most interestingly, mEHT also induced infiltrations of eosinophil, which has recently been reported to be an orchestrator of a specific T cell response. Cytotoxic T cell assay and ELISpot assay revealed a tumor-specific T cell activity. This study demonstrated that mEHT induces tumor cell apoptosis and enhances the release of Hsp70 from heated tumor cells, unlike conventional hyperthermia. mEHT can create a favorable tumor microenvironment for an immunological chain reaction that improves the success rate of intratumoral DC immunotherapy.

  15. Improving Labor Productivity and Labor Elasticity at Multiproduct Japanese Cuisine Restaurant Introducing Cell-Production System

    OpenAIRE

    Shimamura , Takeshi; Takenaka , Takeshi; Ohura , Syuichi

    2013-01-01

    Part III: Sustainable Services; International audience; This study examined improvement of labor productivity and elasticity of labor hour on sales of a multiproduct Japanese cuisine restaurant. Conventionally, multiproduct restaurant operations include a line production system in the kitchen. Japanese chefs are assumed to be low-skilled workers with staff members supported by someone. A cell production system is introduced into a Japanese Cuisine restaurant to improve it. Results show that t...

  16. GLP-1-RA Corrects Mitochondrial Labile Iron Accumulation and Improves β-Cell Function in Type 2 Wolfram Syndrome.

    Science.gov (United States)

    Danielpur, Liron; Sohn, Yang-Sung; Karmi, Ola; Fogel, Chen; Zinger, Adar; Abu-Libdeh, Abdulsalam; Israeli, Tal; Riahi, Yael; Pappo, Orit; Birk, Ruth; Zangen, David H; Mittler, Ron; Cabantchik, Zvi-Ioav; Cerasi, Erol; Nechushtai, Rachel; Leibowitz, Gil

    2016-10-01

    Type 2 Wolfram syndrome (T2-WFS) is a neuronal and β-cell degenerative disorder caused by mutations in the CISD2 gene. The mechanisms underlying β-cell dysfunction in T2-WFS are not known, and treatments that effectively improve diabetes in this context are lacking. Unraveling the mechanisms of β-cell dysfunction in T2-WFS and the effects of treatment with GLP-1 receptor agonist (GLP-1-RA). A case report and in vitro mechanistic studies. We treated an insulin-dependent T2-WFS patient with the GLP-1-RA exenatide for 9 weeks. An iv glucose/glucagon/arginine stimulation test was performed off-drug before and after intervention. We generated a cellular model of T2-WFS by shRNA knockdown of CISD2 (nutrient-deprivation autophagy factor-1 [NAF-1]) in rat insulinoma cells and studied the mechanisms of β-cell dysfunction and the effects of GLP-1-RA. Treatment with exenatide resulted in a 70% reduction in daily insulin dose with improved glycemic control, as well as an off-drug 7-fold increase in maximal insulin secretion. NAF-1 repression in INS-1 cells decreased insulin content and glucose-stimulated insulin secretion, while maintaining the response to cAMP, and enhanced the accumulation of labile iron and reactive oxygen species in mitochondria. Remarkably, treatment with GLP-1-RA and/or the iron chelator deferiprone reversed these defects. NAF-1 deficiency leads to mitochondrial labile iron accumulation and oxidative stress, which may contribute to β-cell dysfunction in T2-WFS. Treatment with GLP-1-RA and/or iron chelation improves mitochondrial function and restores β-cell function. Treatment with GLP-1-RA, probably aided by iron chelation, should be considered in WFS and other forms of diabetes associated with iron dysregulation.

  17. Improved methods for reprogramming human dermal fibroblasts using fluorescence activated cell sorting.

    Directory of Open Access Journals (Sweden)

    David J Kahler

    Full Text Available Current methods to derive induced pluripotent stem cell (iPSC lines from human dermal fibroblasts by viral infection rely on expensive and lengthy protocols. One major factor contributing to the time required to derive lines is the ability of researchers to identify fully reprogrammed unique candidate clones from a mixed cell population containing transformed or partially reprogrammed cells and fibroblasts at an early time point post infection. Failure to select high quality colonies early in the derivation process results in cell lines that require increased maintenance and unreliable experimental outcomes. Here, we describe an improved method for the derivation of iPSC lines using fluorescence activated cell sorting (FACS to isolate single cells expressing the cell surface marker signature CD13(NEGSSEA4(POSTra-1-60(POS on day 7-10 after infection. This technique prospectively isolates fully reprogrammed iPSCs, and depletes both parental and "contaminating" partially reprogrammed fibroblasts, thereby substantially reducing the time and reagents required to generate iPSC lines without the use of defined small molecule cocktails. FACS derived iPSC lines express common markers of pluripotency, and possess spontaneous differentiation potential in vitro and in vivo. To demonstrate the suitability of FACS for high-throughput iPSC generation, we derived 228 individual iPSC lines using either integrating (retroviral or non- integrating (Sendai virus reprogramming vectors and performed extensive characterization on a subset of those lines. The iPSC lines used in this study were derived from 76 unique samples from a variety of tissue sources, including fresh or frozen fibroblasts generated from biopsies harvested from healthy or disease patients.

  18. Novel back-reflector architecture with nanoparticle based buried light-scattering microstructures for improved solar cell performance

    Science.gov (United States)

    Desta, Derese; Ram, Sanjay K.; Rizzoli, Rita; Bellettato, Michele; Summonte, Caterina; Jeppesen, Bjarke R.; Jensen, Pia B.; Tsao, Yao-Chung; Wiggers, Hartmut; Pereira, Rui N.; Balling, Peter; Larsen, Arne Nylandsted

    2016-06-01

    A new back-reflector architecture for light-management in thin-film solar cells is proposed that includes a morphologically smooth top surface with light-scattering microstructures buried within. The microstructures are pyramid shaped, fabricated on a planar reflector using TiO2 nanoparticles and subsequently covered with a layer of Si nanoparticles to obtain a flattened top surface, thus enabling growth of good quality thin-film solar cells. The optical properties of this back-reflector show high broadband haze parameter and wide angular distribution of diffuse light-scattering. The n-i-p amorphous silicon thin-film solar cells grown on such a back-reflector show enhanced light absorption resulting in improved external quantum efficiency. The benefit of the light trapping in those solar cells is evidenced by the gains in short-circuit current density and efficiency up to 15.6% and 19.3% respectively, compared to the reference flat solar cells. This improvement in the current generation in the solar cells grown on the flat-topped (buried pyramid) back-reflector is observed even when the irradiation takes place at large oblique angles of incidence. Finite-difference-time-domain simulation results of optical absorption and ideal short-circuit current density values agree well with the experimental findings. The proposed approach uses a low cost and simple fabrication technique and allows effective light manipulation by utilizing the optical properties of micro-scale structures and nanoscale constituent particles.

  19. Differentiated cells derived from fetal neural stem cells improve motor deficits in a rat model of Parkinson’s disease

    Institute of Scientific and Technical Information of China (English)

    Wei Wang; Hao Song; Aifang Shen; Chao Chen; Yanming Liu; Yabing Dong; Fabin Han

    2015-01-01

    Objective: Parkinson’s disease(PD), which is one of the most common neuro‐degenerative disorders, is characterized by the loss of dopamine(DA) neurons in the substantia nigra in the midbrain. Experimental and clinical studies have shown that fetal neural stem cells(NSCs) have therapeutic effects in neurological disorders. The aim of this study was to examine whether cells that were differentiated from NSCs had therapeutic effects in a rat model of PD. Methods: NSCs were isolated from 14‐week‐old embryos and induced to differentiate into neurons, DA neurons, and glial cells, and these cells were characterized by their expression of the following markers: βⅢ‐tubulin and microtubule‐associated protein 2(neurons), tyrosine hydroxylase(DA neurons), and glial fibrillary acidic protein(glial cells). After a 6‐hydroxydopamine(6‐OHDA)‐lesioned rat model of PD was generated, the differentiated cells were transplanted into the striata of the 6‐OHDA‐lesioned PD rats. Results: The motor behaviors of the PD rats were assessed by the number of apomorphine‐induced rotation turns. The results showed that the NSCs differentiated in vitro into neurons and DA neurons with high efficiencies. After transplantation into the striata of the PD rats, the differentiated cells significantly improved the motor deficits of the transplanted PD rats compared to those of the control nontransplanted PD rats by decreasing the apomorphine‐induced turn cycles as early as 4 weeks after transplantation. Immunofluorescence analyses showed that the differentiated DA neurons survived more than 16 weeks. Conclusions: Our results showed that cells that were differentiated from NSCs had therapeutic effects in a rat PD model, which suggests that differentiated cells may be an effective treatment for patients with PD.

  20. Low concentrations of Rhodamine-6G selectively destroy tumor cells and improve survival of melanoma transplanted mice.

    Science.gov (United States)

    Kutushov, M; Gorelik, O

    2013-01-01

    Rhodamine-6G is a fluorescent dye binding to mitochondria, thus reducing the intact mitochondria number and inhibiting mitochondrial metabolic activity. Resultantly, the respiratory chain functioning becomes blocked, the cell "suffocated" and eventually destroyed. Unlike normal cells, malignant cells demonstrate a priori reduced mitochondrial numbers and aberrant metabolism. Therefore, a turning point might exist, when Rhodamine-induced loss of active mitochondria would selectively destroy malignant, but spare normal cells. Various malignant vs. non-malignant cell lines were cultured with Rhodamine-6G at different concentrations. In addition, C57Bl mice were implanted with B16-F10 melanoma and treated with Rhodamine-6G at different dosage/time regimens. Viability and proliferation of cultured tumor cells were time and dose-dependently inhibited, up to 90%, by Rhodamine-6G, with profound histological signs of cell death. By contrast, inhibition of normal control cell proliferation hardly exceeded 15-17%. Melanoma-transplanted mice receiving Rhodamine-6G demonstrated prolonged survival, improved clinical parameters, inhibited tumor growth and metastases count, compared to their untreated counterparts. Twice-a-week 10-6M Rhodamine-6G regimen yielded the most prominent results. We conclude that malignant, but not normal, cells are selectively destroyed by low doses of Rhodamine-6G. In vivo, such treatment selectively suppresses tumor progression and dissemination, thus improving prognosis. We suggest that selective anti-tumor properties of Rhodamine-6G are based on unique physiologic differences in energy metabolism between malignant and normal cells. If found clinically relevant, low concentrations of Rhodamine-6G might be useful for replacing, or backing up, more aggressive nonselective chemotherapeutic compounds.

  1. Antifibrotic Therapy in Simian Immunodeficiency Virus Infection Preserves CD4+ T-Cell Populations and Improves Immune Reconstitution With Antiretroviral Therapy

    Science.gov (United States)

    Estes, Jacob D.; Reilly, Cavan; Trubey, Charles M.; Fletcher, Courtney V.; Cory, Theodore J.; Piatak, Michael; Russ, Samuel; Anderson, Jodi; Reimann, Thomas G.; Star, Robert; Smith, Anthony; Tracy, Russell P.; Berglund, Anna; Schmidt, Thomas; Coalter, Vicky; Chertova, Elena; Smedley, Jeremy; Haase, Ashley T.; Lifson, Jeffrey D.; Schacker, Timothy W.

    2015-01-01

    Even with prolonged antiretroviral therapy (ART), many human immunodeficiency virus-infected individuals have <500 CD4+ T cells/µL, and CD4+ T cells in lymphoid tissues remain severely depleted, due in part to fibrosis of the paracortical T-cell zone (TZ) that impairs homeostatic mechanisms required for T-cell survival. We therefore used antifibrotic therapy in simian immunodeficiency virus-infected rhesus macaques to determine whether decreased TZ fibrosis would improve reconstitution of peripheral and lymphoid CD4+ T cells. Treatment with the antifibrotic drug pirfenidone preserved TZ architecture and was associated with significantly larger populations of CD4+ T cells in peripheral blood and lymphoid tissues. Combining pirfenidone with an ART regimen was associated with greater preservation of CD4+ T cells than ART alone and was also associated with higher pirfenidone concentrations. These data support a potential role for antifibrotic drug treatment as adjunctive therapy with ART to improve immune reconstitution. PMID:25246534

  2. Improved quality of optical coherence tomography imaging of basal cell carcinomas using speckle reduction

    DEFF Research Database (Denmark)

    Mogensen, Mette; Jørgensen, Thomas Martini; Thrane, Lars

    2010-01-01

    suggests a method for improving OCT image quality for skin cancer imaging. EXPERIMENTAL DESIGN: OCT is an optical imaging method analogous to ultrasound. Two basal cell carcinomas (BCC) were imaged using an OCT speckle reduction technique (SR-OCT) based on repeated scanning by altering the distance between...

  3. Improved Optics in Monolithic Perovskite/Silicon Tandem Solar Cells with a Nanocrystalline Silicon Recombination Junction

    KAUST Repository

    Sahli, Florent

    2017-10-09

    Perovskite/silicon tandem solar cells are increasingly recognized as promi­sing candidates for next-generation photovoltaics with performance beyond the single-junction limit at potentially low production costs. Current designs for monolithic tandems rely on transparent conductive oxides as an intermediate recombination layer, which lead to optical losses and reduced shunt resistance. An improved recombination junction based on nanocrystalline silicon layers to mitigate these losses is demonstrated. When employed in monolithic perovskite/silicon heterojunction tandem cells with a planar front side, this junction is found to increase the bottom cell photocurrent by more than 1 mA cm−2. In combination with a cesium-based perovskite top cell, this leads to tandem cell power-conversion efficiencies of up to 22.7% obtained from J–V measurements and steady-state efficiencies of up to 22.0% during maximum power point tracking. Thanks to its low lateral conductivity, the nanocrystalline silicon recombination junction enables upscaling of monolithic perovskite/silicon heterojunction tandem cells, resulting in a 12.96 cm2 monolithic tandem cell with a steady-state efficiency of 18%.

  4. Improved Optics in Monolithic Perovskite/Silicon Tandem Solar Cells with a Nanocrystalline Silicon Recombination Junction

    KAUST Repository

    Sahli, Florent; Kamino, Brett A.; Werner, Jé ré mie; Brä uninger, Matthias; Paviet-Salomon, Bertrand; Barraud, Loris; Monnard, Raphaë l; Seif, Johannes Peter; Tomasi, Andrea; Jeangros, Quentin; Hessler-Wyser, Aï cha; De Wolf, Stefaan; Despeisse, Matthieu; Nicolay, Sylvain; Niesen, Bjoern; Ballif, Christophe

    2017-01-01

    Perovskite/silicon tandem solar cells are increasingly recognized as promi­sing candidates for next-generation photovoltaics with performance beyond the single-junction limit at potentially low production costs. Current designs for monolithic tandems rely on transparent conductive oxides as an intermediate recombination layer, which lead to optical losses and reduced shunt resistance. An improved recombination junction based on nanocrystalline silicon layers to mitigate these losses is demonstrated. When employed in monolithic perovskite/silicon heterojunction tandem cells with a planar front side, this junction is found to increase the bottom cell photocurrent by more than 1 mA cm−2. In combination with a cesium-based perovskite top cell, this leads to tandem cell power-conversion efficiencies of up to 22.7% obtained from J–V measurements and steady-state efficiencies of up to 22.0% during maximum power point tracking. Thanks to its low lateral conductivity, the nanocrystalline silicon recombination junction enables upscaling of monolithic perovskite/silicon heterojunction tandem cells, resulting in a 12.96 cm2 monolithic tandem cell with a steady-state efficiency of 18%.

  5. Putative effects of endocrine disrupters on pubertal development in the human

    DEFF Research Database (Denmark)

    Teilmann, Grete; Juul, Anders; Skakkebaek, Niels E

    2002-01-01

    -called endocrine disrupters. Precocious puberty has been described in several case reports of accidental exposure to oestrogenic compounds in cosmetic products, food and pharmaceuticals. Local epidemics of premature thelarche have also been suggested to be linked to endocrine disrupters. Children adopted from...... developing countries to industrialized countries often develop precocious puberty. Not only precocious puberty, but also delayed puberty can, theoretically, be associated with exposure to endocrine disrupters. While it is very plausible that endocrine disrupters may disturb pubertal development...

  6. Novel T cells with improved in vivo anti-tumor activity generated by RNA electroporation

    Directory of Open Access Journals (Sweden)

    Xiaojun Liu

    2017-05-01

    Full Text Available ABSTRACT The generation of T cells with maximal anti-tumor activities will significantly impact the field of T-cell-based adoptive immunotherapy. In this report, we found that OKT3/IL-2-stimulated T cells were phenotypically more heterogeneous, with enhanced anti-tumor activity in vitro and when locally administered in a solid tumor mouse model. To further improve the OKT3/IL-2-based T cell manufacturing procedure, we developed a novel T cell stimulation and expansion method in which peripheral blood mononuclear cells were electroporated with mRNA encoding a chimeric membrane protein consisting of a single-chain variable fragment against CD3 and the intracellular domains of CD28 and 4-1BB (OKT3-28BB. The expanded T cells were phenotypically and functionally similar to T cells expanded by OKT3/IL-2. Moreover, co-electroporation of CD86 and 4-1BBL could further change the phenotype and enhance the in vivo anti-tumor activity. Although T cells expanded by the co-electroporation of OKT3-28BB with CD86 and 4-1BBL showed an increased central memory phenotype, the T cells still maintained tumor lytic activities as potent as those of OKT3/IL-2 or OKT3-28BB-stimulated T cells. In different tumor mouse models, T cells expanded by OKT3-28BB RNA electroporation showed anti-tumor activities superior to those of OKT3/IL-2 T cells. Hence, T cells with both a less differentiated phenotype and potent tumor killing ability can be generated by RNA electroporation, and this T cell manufacturing procedure can be further optimized by simply co-delivering other splices of RNA, thus providing a simple and cost-effective method for generating high-quality T cells for adoptive immunotherapy.

  7. Improving startup performance with carbon mesh anodes in separator electrode assembly microbial fuel cells

    KAUST Repository

    Zhang, Fang

    2013-04-01

    In a separator electrode assembly microbial fuel cell, oxygen crossover from the cathode inhibits current generation by exoelectrogenic bacteria, resulting in poor reactor startup and performance. To determine the best approach for improving startup performance, the effect of acclimation to a low set potential (-0.2V, versus standard hydrogen electrode) was compared to startup at a higher potential (+0.2V) or no set potential, and inoculation with wastewater or pre-acclimated cultures. Anodes acclimated to -0.2V produced the highest power of 1330±60mWm-2 for these different anode conditions, but unacclimated wastewater inocula produced inconsistent results despite the use of this set potential. By inoculating reactors with transferred cell suspensions, however, startup time was reduced and high power was consistently produced. These results show that pre-acclimation at -0.2V consistently improves power production compared to use of a more positive potential or the lack of a set potential. © 2013 Elsevier Ltd.

  8. Improving startup performance with carbon mesh anodes in separator electrode assembly microbial fuel cells.

    Science.gov (United States)

    Zhang, Fang; Xia, Xue; Luo, Yong; Sun, Dan; Call, Douglas F; Logan, Bruce E

    2013-04-01

    In a separator electrode assembly microbial fuel cell, oxygen crossover from the cathode inhibits current generation by exoelectrogenic bacteria, resulting in poor reactor startup and performance. To determine the best approach for improving startup performance, the effect of acclimation to a low set potential (-0.2V, versus standard hydrogen electrode) was compared to startup at a higher potential (+0.2 V) or no set potential, and inoculation with wastewater or pre-acclimated cultures. Anodes acclimated to -0.2 V produced the highest power of 1330±60 mW m(-2) for these different anode conditions, but unacclimated wastewater inocula produced inconsistent results despite the use of this set potential. By inoculating reactors with transferred cell suspensions, however, startup time was reduced and high power was consistently produced. These results show that pre-acclimation at -0.2 V consistently improves power production compared to use of a more positive potential or the lack of a set potential. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Pretransplant mobilization with granulocyte colony-stimulating factor improves B-cell reconstitution by lentiviral vector gene therapy in SCID-X1 mice.

    Science.gov (United States)

    Huston, Marshall W; Riegman, Adriaan R A; Yadak, Rana; van Helsdingen, Yvette; de Boer, Helen; van Til, Niek P; Wagemaker, Gerard

    2014-10-01

    Hematopoietic stem cell (HSC) gene therapy is a demonstrated effective treatment for X-linked severe combined immunodeficiency (SCID-X1), but B-cell reconstitution and function has been deficient in many of the gene therapy treated patients. Cytoreductive preconditioning is known to improve HSC engraftment, but in general it is not considered for SCID-X1 since the poor health of most of these patients at diagnosis and the risk of toxicity preclude the conditioning used in standard bone marrow stem cell transplantation. We hypothesized that mobilization of HSC by granulocyte colony-stimulating factor (G-CSF) should create temporary space in bone marrow niches to improve engraftment and thereby B-cell reconstitution. In the present pilot study supplementing our earlier preclinical evaluation (Huston et al., 2011), Il2rg(-/-) mice pretreated with G-CSF were transplanted with wild-type lineage negative (Lin(-)) cells or Il2rg(-/-) Lin(-) cells transduced with therapeutic IL2RG lentiviral vectors. Mice were monitored for reconstitution of lymphocyte populations, level of donor cell chimerism, and antibody responses as compared to 2 Gy total body irradiation (TBI), previously found effective in promoting B-cell reconstitution. The results demonstrate that G-CSF promotes B-cell reconstitution similar to low-dose TBI and provides proof of principle for an alternative approach to improve efficacy of gene therapy in SCID patients without adverse effects associated with cytoreductive conditioning.

  10. Combination growth hormone and gonadotropin releasing hormone analog therapy in 11beta-hydroxylase deficiency.

    Science.gov (United States)

    Bajpai, Anurag; Kabra, Madhulika; Menon, P S N

    2006-06-01

    Diagnosis of 11beta-hydroxylase deficiency was made in a boy at the age of 2 1/2 years on the basis of peripheral precocious puberty, growth acceleration (height standard deviation score +4.4) with advanced skeletal maturation (bone age 8.4 years) and elevated deoxycortisol levels. Glucocorticoid supplementation led to normalization of blood pressure but was associated with progression to central precocious puberty and increase in bone age resulting in decrease in predicted adult height to 133.7 cm (target height 163 cm). The child was started on GnRH analog (triptorelin 3.75 mg every 28 days), which led to improvement in predicted adult height by 3.1 cm over 15 months. Addition of growth hormone (0.1 IU/kg/day) resulted in improvement in predicted adult height (151 cm) and height deficit (12 cm) over the next 3.6 years. Final height (151 cm) exceeded predicted height at the initiation of GnRH analog treatment by 17.3 cm. This report suggests that combination GH and GnRH analog treatment may be useful in improving height outcome in children with 11beta-hydroxylase deficiency and compromised final height.

  11. Improved efficiency of NiOx-based p-i-n perovskite solar cells by using PTEG-1 as electron transport layer

    Science.gov (United States)

    Groeneveld, Bart G. H. M.; Najafi, Mehrdad; Steensma, Bauke; Adjokatse, Sampson; Fang, Hong-Hua; Jahani, Fatemeh; Qiu, Li; ten Brink, Gert H.; Hummelen, Jan C.; Loi, Maria Antonietta

    2017-07-01

    We present efficient p-i-n type perovskite solar cells using NiOx as the hole transport layer and a fulleropyrrolidine with a triethylene glycol monoethyl ether side chain (PTEG-1) as electron transport layer. This electron transport layer leads to higher power conversion efficiencies compared to perovskite solar cells with PCBM (phenyl-C61-butyric acid methyl ester). The improved performance of PTEG-1 devices is attributed to the reduced trap-assisted recombination and improved charge extraction in these solar cells, as determined by light intensity dependence and photoluminescence measurements. Through optimization of the hole and electron transport layers, the power conversion efficiency of the NiOx/perovskite/PTEG-1 solar cells was increased up to 16.1%.

  12. Functional high-intensity training improves pancreatic β-cell function in adults with type 2 diabetes.

    Science.gov (United States)

    Nieuwoudt, Stephan; Fealy, Ciarán E; Foucher, Julie A; Scelsi, Amanda R; Malin, Steven K; Pagadala, Mangesh; Rocco, Michael; Burguera, Bartolome; Kirwan, John P

    2017-09-01

    Type 2 diabetes (T2D) is characterized by reductions in β-cell function and insulin secretion on the background of elevated insulin resistance. Aerobic exercise has been shown to improve β-cell function, despite a subset of T2D patients displaying "exercise resistance." Further investigations into the effectiveness of alternate forms of exercise on β-cell function in the T2D patient population are needed. We examined the effect of a novel, 6-wk CrossFit functional high-intensity training (F-HIT) intervention on β-cell function in 12 sedentary adults with clinically diagnosed T2D (54 ± 2 yr, 166 ± 16 mg/dl fasting glucose). Supervised training was completed 3 days/wk, comprising functional movements performed at a high intensity in a variety of 10- to 20-min sessions. All subjects completed an oral glucose tolerance test and anthropometric measures at baseline and following the intervention. The mean disposition index, a validated measure of β-cell function, was significantly increased (PRE: 8.4 ± 3.1, POST: 11.5 ± 3.5, P = 0.02) after the intervention. Insulin processing inefficiency in the β-cell, expressed as the fasting proinsulin-to-insulin ratio, was also reduced (PRE: 2.40 ± 0.37, POST: 1.78 ± 0.30, P = 0.04). Increased β-cell function during the early-phase response to glucose correlated significantly with reductions in abdominal body fat ( R 2 = 0.56, P = 0.005) and fasting plasma alkaline phosphatase ( R 2 = 0.55, P = 0.006). Mean total body-fat percentage decreased significantly (Δ: -1.17 0.30%, P = 0.003), whereas lean body mass was preserved (Δ: +0.05 ± 0.68 kg, P = 0.94). We conclude that F-HIT is an effective exercise strategy for improving β-cell function in adults with T2D. Copyright © 2017 the American Physiological Society.

  13. Cell Adhesion Selectivity of Stent Material to improve Bio-functionality by Ion Beam Modification

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jaesang; Park, JUngchan; Jung, Myunghwan; Kim, Yongki [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Park, Junkyu [Bio alpha., Co. Ltd., Gimhae (Korea, Republic of)

    2014-05-15

    In this study, ion implantation into collagen coated Co-Cr alloy, which is a cheaper material of the artificial stent product comparing with Ti alloy, has been studied to develop small diameter artificial stent by the cell adhesion control. The size of stent was 1.6mm of the diameter and 18mm of the length. The life-time of artificial stent depends on adhesion property of endothelial-cells. We successfully controlled cell adhesion selectivity between endothelial cell and muscle cell by using collagen coated and He{sup +} ion beam irradiated Co-Cr-alloy to apply to artificial stent. But, we did not achieve the inhibition of platelet adhesion, yet by using collagen coating and He{sup +} ion beam irradiation. Based on this study, we have plan to research about separation between collagen coating effect and ion beam effect. Also, we will have more detail analysis of the mechanism of cell attachment. In recent years, ion implantation has been applied to the surface modification of prosthesis to improve blood compatibility and tissue compatibility in field of biomedical application. As well known, bio compatibility was concerned with the cell adhesion selectivity for bio-functionality. The biomedical application of ion beam technology would be used more widely in the future such as catheter and artificial graft.

  14. Cell Adhesion Selectivity of Stent Material to improve Bio-functionality by Ion Beam Modification

    International Nuclear Information System (INIS)

    Lee, Jaesang; Park, JUngchan; Jung, Myunghwan; Kim, Yongki; Park, Junkyu

    2014-01-01

    In this study, ion implantation into collagen coated Co-Cr alloy, which is a cheaper material of the artificial stent product comparing with Ti alloy, has been studied to develop small diameter artificial stent by the cell adhesion control. The size of stent was 1.6mm of the diameter and 18mm of the length. The life-time of artificial stent depends on adhesion property of endothelial-cells. We successfully controlled cell adhesion selectivity between endothelial cell and muscle cell by using collagen coated and He + ion beam irradiated Co-Cr-alloy to apply to artificial stent. But, we did not achieve the inhibition of platelet adhesion, yet by using collagen coating and He + ion beam irradiation. Based on this study, we have plan to research about separation between collagen coating effect and ion beam effect. Also, we will have more detail analysis of the mechanism of cell attachment. In recent years, ion implantation has been applied to the surface modification of prosthesis to improve blood compatibility and tissue compatibility in field of biomedical application. As well known, bio compatibility was concerned with the cell adhesion selectivity for bio-functionality. The biomedical application of ion beam technology would be used more widely in the future such as catheter and artificial graft

  15. Transplantation of motoneurons derived from MASH1-transfected mouse ES cells reconstitutes neural networks and improves motor function in hemiplegic mice.

    Science.gov (United States)

    Ikeda, Ritsuko; Kurokawa, Manae S; Chiba, Shunmei; Yoshikawa, Hideshi; Hashimoto, Takuo; Tadokoro, Mamoru; Suzuki, Noboru

    2004-10-01

    Mouse embryonic stem (ES) cells were transfected with a MASH1 expression vector and G418-resistant cells were selected. The MASH1-transfected cells became neuron-like appearance and expressed betaIIItubulin and panNCAM. Glial fibrillary acidic protein (GFAP) and galactocerebroside (GalC)-expressing cells were rarely detected. Half of the neural cells differentiated into the Islet1+ motoneuron lineage. Thus, we obtained motoneuron lineage-enriched neuronal cells by transfection of ES cells with MASH1. A hemiplegic model of mice was developed by cryogenic injury of the motor cortex, and motoneuron lineage-enriched neuronal cells were transplanted underneath the injured motor cortex neighboring the periventricular region. The motor function of the recipients was assessed by a beam walking and rotarod tests, whereby the results gradually improved, but little improvement was observed in vehicle injected control mice. We found that the grafted cells not only remained close to the implantation site, but also exhibited substantial migration, penetrating into the damaged lesion in a directed manner up to the cortical region. Grafted neuronal cells that had migrated into the cortex were elongated axon-positive for neurofilament middle chain (NFM). Synaptophysin immunostaining showed a positive staining pattern around the graft, suggesting that the transplanted neurons interacted with the recipient neurons to form a neural network. Our study suggests that the motoneuron lineage can be induced from ES cells, and grafted cells adapt to the host environment and can reconstitute a neural network to improve motor function of a paralyzed limb.

  16. Intracerebral neural stem cell transplantation improved the auditory of mice with presbycusis.

    Science.gov (United States)

    Ren, Hongmiao; Chen, Jichuan; Wang, Yinan; Zhang, Shichang; Zhang, Bo

    2013-01-01

    Stem cell-based regenerative therapy is a potential cellular therapeutic strategy for patients with incurable brain diseases. Embryonic neural stem cells (NSCs) represent an attractive cell source in regenerative medicine strategies in the treatment of diseased brains. Here, we assess the capability of intracerebral embryonic NSCs transplantation for C57BL/6J mice with presbycusis in vivo. Morphology analyses revealed that the neuronal rate of apoptosis was lower in the aged group (10 months of age) but not in the young group (2 months of age) after NSCs transplantation, while the electrophysiological data suggest that the Auditory Brain Stem Response (ABR) threshold was significantly decreased in the aged group at 2 weeks and 3 weeks after transplantation. By contrast, there was no difference in the aged group at 4 weeks post-transplantation or in the young group at any time post-transplantation. Furthermore, immunofluorescence experiments showed that NSCs differentiated into neurons that engrafted and migrated to the brain, even to sites of lesions. Together, our results demonstrate that NSCs transplantation improve the auditory of C57BL/6J mice with presbycusis.

  17. Human periodontal ligament stem cells cultured onto cortico-cancellous scaffold drive bone regenerative process

    Directory of Open Access Journals (Sweden)

    F Diomede

    2016-09-01

    Full Text Available The purpose of this work was to test, in vitro and in vivo, a new tissue-engineered construct constituted by porcine cortico-cancellous scaffold (Osteobiol Dual Block (DB and xeno-free ex vivo culture of human Periodontal Ligament Stem Cells (hPDLSCs. hPDLSCs cultured in xeno-free media formulation preserved the stem cells’ morphological features, the expression of stemness and pluripotency markers, and their ability to differentiate into mesenchymal lineage. Transmission electron microscopy analysis suggested that after one week of culture, both noninduced and osteogenic differentiation induced cells joined and grew on DB secreting extracellular matrix (ECM that in osteogenic induced samples was hierarchically assembled in fibrils. Quantitative RT-PCR (qRT-PCR showed the upregulation of key genes involved in the bone differentiation pathway in both differentiated and undifferentiated hPDLSCs cultured with DB (hPDLSCs/DB. Functional studies revealed a significant increased response of calcium transients in the presence of DB, both in undifferentiated and differentiated cells stimulated with calcitonin and parathormone, suggesting that the biomaterial could drive the osteogenic differentiation process of hPDLSCs. These data were confirmed by the increase of gene expression of L-type voltage-dependent Ca2+ (VDCCL, subunits α1C and α2D1 in undifferentiated cells in the presence of DB. In vivo implantation of the hPDLSCs/DB living construct in the mouse calvaria evidenced a precocious osteointegration and vascularisation process. Our results suggest consideration of DB as a biocompatible, osteoinductive and osteoconductive biomaterial, making it a promising tool to regulate cell activities in biological environments and for a potential use in the development of new custom-made tissue engineering.

  18. Ca2+ signalling in endothelial progenitor cells: a novel means to improve cell-based therapy and impair tumour vascularisation.

    Science.gov (United States)

    Moccia, Francesco; Lodola, Francesco; Dragoni, Silvia; Bonetti, Elisa; Bottino, Cinzia; Guerra, Germano; Laforenza, Umberto; Rosti, Vittorio; Tanzi, Franco

    2014-01-01

    Endothelial progenitor cells (EPCs) have recently been employed in cell-based therapy (CBT) to promote regeneration of ischemic organs, such as heart and limbs. Furthermore, EPCs may sustain tumour vascularisation and provide an additional target for anticancer therapies. CBT is limited by the paucity of cells harvested from peripheral blood and suffers from several pitfalls, including the low rate of engrafted EPCs, whereas classic antiangiogenic treatments manifest a number of side effects and may induce resistance into the patients. CBT will benefit of a better understanding of the signal transduction pathway(s) which drive(s) EPC proliferation, trafficking, and incorporation into injured tissues. At the same time, this information might outline alternative molecular targets to impair tumor neovascularisation and improve the therapeutic outcome of antiangiogenic strategies. An increase in intracellular Ca(2+) concentration is the key signal in the regulation of cellular replication, migration, and differentiation. In particular, Ca(2+) signalling may regulate cellcycle progression, due to the Ca(2+)-sensitivity of a number of cycline-dependent kinases, and gene expression, owing to the Ca(2+)-dependence of several transcription factors. Recent work has outlined the role of the so-called store-operated Ca(2+) entry in driving EPC proliferation and migration. Unravelling the mechanisms guiding EPC engraftment into neovessels might supply the biological bases required to improve CBT and anticancer treatments. For example, genetic manipulation of the Ca(2+) signalling machinery could provide a novel approach to increase the extent of limb regeneration or preventing tumour vascularisation by EPCs.

  19. Distributed generation system with PEM fuel cell for electrical power quality improvement

    Energy Technology Data Exchange (ETDEWEB)

    Ramirez, D.; Beites, L.F.; Blazquez, F. [Department of Electrical Engineering, ETSII, Escuela de Ingenieros Industriales, Universidad Politecnica de Madrid, C/ Jose Gutierrez Abascal 2, 28006 Madrid (Spain); Ballesteros, J.C. [Endesa Generacion, S.A. c/ Ribera de Loira 60, 28042 Madrid (Spain)

    2008-08-15

    In this paper, a physical model for a distributed generation (DG) system with power quality improvement capability is presented. The generating system consists of a 5 kW PEM fuel cell, a natural gas reformer, hydrogen storage bottles and a bank of ultra-capacitors. Additional power quality functions are implemented with a vector-controlled electronic converter for regulating the injected power. The capabilities of the system were experimentally tested on a scaled electrical network. It is composed of different lines, built with linear inductances and resistances, and taking into account both linear and non-linear loads. The ability to improve power quality was tested by means of different voltage and frequency perturbations produced on the physical model electrical network. (author)

  20. Percutaneous Mitral Valve Repair in Mitral Regurgitation Reduces Cell-Free Hemoglobin and Improves Endothelial Function.

    Directory of Open Access Journals (Sweden)

    Christos Rammos

    Full Text Available Endothelial dysfunction is predictive for cardiovascular events and may be caused by decreased bioavailability of nitric oxide (NO. NO is scavenged by cell-free hemoglobin with reduction of bioavailable NO up to 70% subsequently deteriorating vascular function. While patients with mitral regurgitation (MR suffer from an impaired prognosis, mechanisms relating to coexistent vascular dysfunctions have not been described yet. Therapy of MR using a percutaneous mitral valve repair (PMVR approach has been shown to lead to significant clinical benefits. We here sought to investigate the role of endothelial function in MR and the potential impact of PMVR.Twenty-seven patients with moderate-to-severe MR treated with the MitraClip® device were enrolled in an open-label single-center observational study. Patients underwent clinical assessment, conventional echocardiography, and determination of endothelial function by measuring flow-mediated dilation (FMD of the brachial artery using high-resolution ultrasound at baseline and at 3-month follow-up. Patients with MR demonstrated decompartmentalized hemoglobin and reduced endothelial function (cell-free plasma hemoglobin in heme 28.9±3.8 μM, FMD 3.9±0.9%. Three months post-procedure, PMVR improved ejection fraction (from 41±3% to 46±3%, p = 0.03 and NYHA functional class (from 3.0±0.1 to 1.9±1.7, p<0.001. PMVR was associated with a decrease in cell free plasma hemoglobin (22.3±2.4 μM, p = 0.02 and improved endothelial functions (FMD 4.8±1.0%, p<0.0001.We demonstrate here that plasma from patients with MR contains significant amounts of cell-free hemoglobin, which is accompanied by endothelial dysfunction. PMVR therapy is associated with an improved hemoglobin decompartmentalization and vascular function.

  1. Dynamic focus optical coherence tomography: feasibility for improved basal cell carcinoma investigation

    Science.gov (United States)

    Nasiri-Avanaki, M. R.; Aber, Ahmed; Hojjatoleslami, S. A.; Sira, Mano; Schofield, John B.; Jones, Carole; Podoleanu, A. Gh.

    2012-03-01

    Basal cell carcinoma (BCC) is the most common form of skin cancer. To improve the diagnostic accuracy, additional non-invasive methods of making a preliminary diagnosis have been sought. We have implemented an En-Face optical coherence tomography (OCT) for this study in which the dynamic focus was integrated into it. With the dynamic focus scheme, the coherence gate moves synchronously with the peak of confocal gate determined by the confocal interface optics. The transversal resolution is then conserved throughout the depth range and an enhanced signal is returned from all depths. The Basal Cell Carcinoma specimens were obtained from the eyelid a patient. The specimens under went analysis by DF-OCT imaging. We searched for remarkable features that were visualized by OCT and compared these findings with features presented in the histology slices.

  2. Endothelial Progenitor Cell Mobilization in Preterm Infants With Sepsis Is Associated With Improved Survival.

    Science.gov (United States)

    Siavashi, Vahid; Asadian, Simin; Taheri-Asl, Masoud; Keshavarz, Samaneh; Zamani-Ahmadmahmudi, Mohamad; Nassiri, Seyed Mahdi

    2017-10-01

    Microvascular dysfunction plays a key role in the pathology of sepsis, leading to multi-organ failure, and death. Circulating endothelial progenitor cells (cEPCs) are critically involved in the maintenance of the vascular homeostasis in both physiological and pathological contexts. In this study, concentration of cEPCs in preterm infants with sepsis was determined to recognize whether the EPC mobilization would affect the clinical outcome of infantile sepsis. One hundred and thirty-three preterm infants (81 with sepsis and 52 without sepsis) were enrolled in this study. The release of EPCs in circulation was first quantified. Thereafter, these cells were cultivated and biological features of these cells such as, proliferation and colony forming efficiency were analyzed. The levels of chemoattractant cytokines were also measured in infants. In mouse models of sepsis, effects of VEGF and SDF-1 as well as anti-VEGF and anti-SDF-1 were evaluated in order to shed light upon the role which the EPC mobilization plays in the overall survival of septic animals. Circulating EPCs were significantly higher in preterm infants with sepsis than in the non-sepsis group. Serum levels of VEGF, SDF-1, and Angiopoietin-2 were also higher in preterm infants with sepsis than in control non-sepsis. In the animal experiments, injection of VEGF and SDF-1 prompted the mobilization of EPCs, leading to an improvement in survival whereas injection of anti-VEGF and anti-SDF-1 was associated with significant deterioration of survival. Overall, our results demonstrated the beneficial effects of EPC release in preterm infants with sepsis, with increased mobilization of these cells was associated with improved survival. J. Cell. Biochem. 118: 3299-3307, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  3. Improved Direct Methanol Fuel Cell Stack

    Science.gov (United States)

    Wilson, Mahlon S.; Ramsey, John C.

    2005-03-08

    A stack of direct methanol fuel cells exhibiting a circular footprint. A cathode and anode manifold, tie-bolt penetrations and tie-bolts are located within the circular footprint. Each fuel cell uses two graphite-based plates. One plate includes a cathode active area that is defined by serpentine channels connecting the inlet and outlet cathode manifold. The other plate includes an anode active area defined by serpentine channels connecting the inlet and outlet of the anode manifold, where the serpentine channels of the anode are orthogonal to the serpentine channels of the cathode. Located between the two plates is the fuel cell active region.

  4. Total sensitivity and uncertainty analysis for LWR pin-cells with improved UNICORN code

    International Nuclear Information System (INIS)

    Wan, Chenghui; Cao, Liangzhi; Wu, Hongchun; Shen, Wei

    2017-01-01

    Highlights: • A new model is established for the total sensitivity and uncertainty analysis. • The NR approximation applied in S&U analysis can be avoided by the new model. • Sensitivity and uncertainty analysis is performed to PWR pin-cells by the new model. • The effects of the NR approximation for the PWR pin-cells are quantified. - Abstract: In this paper, improvements to the multigroup cross-section perturbation model have been proposed and applied in the self-developed UNICORN code, which is capable of performing the total sensitivity and total uncertainty analysis for the neutron-physics calculations by applying the direct numerical perturbation method and the statistical sampling method respectively. The narrow resonance (NR) approximation was applied in the multigroup cross-section perturbation model, implemented in UNICORN. As improvements to the NR approximation to refine the multigroup cross-section perturbation model, an ultrafine-group cross-section perturbation model has been established, in which the actual perturbations are applied to the ultrafine-group cross-section library and the reconstructions of the resonance cross sections are performed by solving the neutron slowing-down equation. The total sensitivity and total uncertainty analysis were then applied to the LWR pin-cells, using both the multigroup and the ultrafine-group cross-section perturbation models. The numerical results show that the NR approximation overestimates the relative sensitivity coefficients and the corresponding uncertainty results for the LWR pin-cells, and the effects of the NR approximation are significant for σ_(_n_,_γ_) and σ_(_n_,_e_l_a_s_) of "2"3"8U. Therefore, the effects of the NR approximation applied in the total sensitivity and total uncertainty analysis for the neutron-physics calculations of LWR should be taken into account.

  5. Improved fuel-cell-type hydrogen sensor

    Science.gov (United States)

    Rudek, F. P.; Rutkowski, M. D.

    1968-01-01

    Modified hydrogen sensor replaces oxygen cathode with a cathode consisting of a sealed paste of gold hydroxide and a pure gold current collector. The net reaction which occurs during cell operation is the reduction of the gold hydroxide to gold and water, with a half-cell potential of 1.4 volts.

  6. Improving power conversion efficiency of perovskite solar cells by cooperative LSPR of gold-silver dual nanoparticles

    Institute of Scientific and Technical Information of China (English)

    Peng Liu; Cong-hua Zhou; Bing-chu Yang; Gang Liu; Run-sheng Wu; Chu-jun Zhang; Fang Wan; Shui-gen Li; Jun-liang Yang; Yong-li Gao

    2017-01-01

    Enhancing optical and electrical performances is effective in improving power conversion efficiency of photovoltaic devices.Here,gold and silver dual nanoparticles were imported and embedded in the hole transport layer of perovskite solar cells.Due to the cooperative localized surface plasmon resonance of these two kinds of metal nanostructures,light harvest of perovskite material layer and the electrical performance of device were improved,which finally upgraded short circuit current density by 10.0%,and helped to increase power conversion efficiency from 10.4% to 11.6% under AM 1.5G illumination with intensity of 100 mW/cm2.In addition,we explored the influence of silver and gold nanoparticles on charge carrier generation,dissociation,recombination,and transportation inside perovskite solar cells.

  7. An optimized metal grid design to improve the solar cell performance under solar concentration using multiobjective computation

    International Nuclear Information System (INIS)

    Djeffal, F.; Bendib, T.; Arar, D.; Dibi, Z.

    2013-01-01

    Highlights: ► A new MOGA-based approach to design the solar cell metal grid is proposed. ► The cell parameters have been ascertained including the high illumination effects. ► An improved electrical behavior of the solar cell is found. ► The proposed optimized metal grid design is suitable for photovoltaic applications. -- Abstract: In this paper, a new multiobjective genetic algorithm (MOGA)-based approach is proposed to optimize the metal grid design in order to improve the electrical performance and the conversion efficiency behavior of the solar cells under high intensities of illumination. The proposed approach is applied to investigate the effect of two different metal grid patterns (one with 2 busbars outside the active area (linear grid) and another one with a circular busbar surrounding the active area (circular grid)) on the electrical performance of high efficiency c-Si solar cells under concentrated light (up to 150 suns). The dimensional and electrical parameters of the solar cell have been ascertained, and analytical expressions of the power losses and conversion efficiency, including high illumination effects, have been presented. The presented analytical models are used to formulate different objective functions, which are the prerequisite of the multiobjective optimization. The optimized design can also be incorporated into photovoltaic circuit simulator to study the impact of our approach on the photovoltaic circuit design

  8. Improved Efficiency and Stability of Perovskite Solar Cells Induced by CO Functionalized Hydrophobic Ammonium-Based Additives.

    Science.gov (United States)

    Wu, Zhifang; Raga, Sonia R; Juarez-Perez, Emilio J; Yao, Xuyang; Jiang, Yan; Ono, Luis K; Ning, Zhijun; Tian, He; Qi, Yabing

    2018-01-01

    Because of the rapid rise of the efficiency, perovskite solar cells are currently considered as the most promising next-generation photovoltaic technology. Much effort has been made to improve the efficiency and stability of perovskite solar cells. Here, it is demonstrated that the addition of a novel organic cation of 2-(6-bromo-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)ethan-1-ammonium iodide (2-NAM), which has strong Lewis acid and base interaction (between CO and Pb) with perovskite, can effectively increase crystalline grain size and reduce charge carrier recombination of the double cation FA 0.83 MA 0.17 PbI 2.51 Br 0.49 perovskite film, thus boosting the efficiency from 17.1 ± 0.8% to 18.6 ± 0.9% for the 0.1 cm 2 cell and from 15.5 ± 0.5% to 16.5 ± 0.6% for the 1.0 cm 2 cell. The champion cell shows efficiencies of 20.0% and 17.6% with active areas of 0.1 and 1.0 cm 2 , respectively. Moreover, the hysteresis behavior is suppressed and the stability is improved. The result provides a promising route to further elevate efficiency and stability of perovskite solar cells by the fine tuning of triple organic cations. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Improved Efficiency of Polymer Solar Cells by means of Coating Hole Transporting Layer as Double Layer Deposition

    Science.gov (United States)

    Chonsut, T.; Kayunkid, N.; Rahong, S.; Rangkasikorn, A.; Wirunchit, S.; Kaewprajak, A.; Kumnorkaew, P.; Nukeaw, J.

    2017-09-01

    Polymer solar cells is one of the promising technologies that gain tremendous attentions in the field of renewable energy. Optimization of thickness for each layer is an important factor determining the efficiency of the solar cells. In this work, the optimum thickness of Poly(3,4-ethylenedioxythione): poly(styrenesulfonate) (PEDOT:PSS), a famous polymer widely used as hole transporting layer in polymer solar cells, is determined through the analyzing of device’s photovoltaic parameters, e.g. short circuit current density (Jsc), open circuit voltage (Voc), fill factor (FF) as well as power conversion efficiency (PCE). The solar cells were prepared with multilayer of ITO/PEDOT:PSS/PCDTBT:PC70BM/TiOx/Al by rapid convective deposition. In such preparation technique, the thickness of the thin film is controlled by the deposition speed. The faster deposition speed is used, the thicker film is obtained. Furthermore, double layer deposition of PEDOT:PSS was introduced as an approach to improve solar cell efficiency. The results obviously reveal that, with the increase of PEDOT:PSS thickness, the increments of Jsc and FF play the important role to improve PCE from 3.21% to 4.03%. Interestingly, using double layer deposition of PEDOT:PSS shows the ability to enhance the performance of the solar cells to 6.12% under simulated AM 1.5G illumination of 100 mW/cm2.

  10. Cell Labeling for 19F MRI: New and Improved Approach to Perfluorocarbon Nanoemulsion Design

    Directory of Open Access Journals (Sweden)

    Jonathan Williams

    2013-09-01

    Full Text Available This report describes novel perfluorocarbon (PFC nanoemulsions designed to improve ex vivo cell labeling for 19F magnetic resonance imaging (MRI. 19F MRI is a powerful non-invasive technique for monitoring cells of the immune system in vivo, where cells are labeled ex vivo with PFC nanoemulsions in cell culture. The quality of 19F MRI is directly affected by the quality of ex vivo PFC cell labeling. When co-cultured with cells for longer periods of time, nanoemulsions tend to settle due to high specific weight of PFC oils (1.5–2.0 g/mL. This in turn can decrease efficacy of excess nanoemulsion removal and reliability of the cell labeling in vitro. To solve this problem, novel PFC nanoemulsions are reported which demonstrate lack of sedimentation and high stability under cell labeling conditions. They are monodisperse, have small droplet size (~130 nm and low polydispersity (<0.15, show a single peak in the 19F nuclear magnetic resonance spectrum at −71.4 ppm and possess high fluorine content. The droplet size and polydispersity remained unchanged after 160 days of follow up at three temperatures (4, 25 and 37 °C. Further, stressors such as elevated temperature in the presence of cells, and centrifugation, did not affect the nanoemulsion droplet size and polydispersity. Detailed synthetic methodology and in vitro testing for these new PFC nanoemulsions is presented.

  11. Loss of FliL alters Proteus mirabilis surface sensing and temperature-dependent swarming.

    Science.gov (United States)

    Lee, Yi-Ying; Belas, Robert

    2015-01-01

    Proteus mirabilis is a dimorphic motile bacterium well known for its flagellum-dependent swarming motility over surfaces. In liquid, P. mirabilis cells are 1.5- to 2.0-μm swimmer cells with 4 to 6 flagella. When P. mirabilis encounters a solid surface, where flagellar rotation is limited, swimmer cells differentiate into elongated (10- to 80-μm), highly flagellated swarmer cells. In order for P. mirabilis to swarm, it first needs to detect a surface. The ubiquitous but functionally enigmatic flagellar basal body protein FliL is involved in P. mirabilis surface sensing. Previous studies have suggested that FliL is essential for swarming through its involvement in viscosity-dependent monitoring of flagellar rotation. In this study, we constructed and characterized ΔfliL mutants of P. mirabilis and Escherichia coli. Unexpectedly and unlike other fliL mutants, both P. mirabilis and E. coli ΔfliL cells swarm (Swr(+)). Further analysis revealed that P. mirabilis ΔfliL cells also exhibit an alteration in their ability to sense a surface: e.g., ΔfliL P. mirabilis cells swarm precociously over surfaces with low viscosity that normally impede wild-type swarming. Precocious swarming is due to an increase in the number of elongated swarmer cells in the population. Loss of fliL also results in an inhibition of swarming at <30°C. E. coli ΔfliL cells also exhibit temperature-sensitive swarming. These results suggest an involvement of FliL in the energetics and function of the flagellar motor. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  12. An Improved Fruit Fly Optimization Algorithm Inspired from Cell Communication Mechanism

    Directory of Open Access Journals (Sweden)

    Chuncai Xiao

    2015-01-01

    Full Text Available Fruit fly optimization algorithm (FOA invented recently is a new swarm intelligence method based on fruit fly’s foraging behaviors and has been shown to be competitive with existing evolutionary algorithms, such as particle swarm optimization (PSO algorithm. However, there are still some disadvantages in the FOA, such as low convergence precision, easily trapped in a local optimum value at the later evolution stage. This paper presents an improved FOA based on the cell communication mechanism (CFOA, by considering the information of the global worst, mean, and best solutions into the search strategy to improve the exploitation. The results from a set of numerical benchmark functions show that the CFOA outperforms the FOA and the PSO in most of the experiments. Further, the CFOA is applied to optimize the controller for preoxidation furnaces in carbon fibers production. Simulation results demonstrate the effectiveness of the CFOA.

  13. Posttransplant Intramuscular Injection of PLX-R18 Mesenchymal-Like Adherent Stromal Cells Improves Human Hematopoietic Engraftment in A Murine Transplant Model

    Directory of Open Access Journals (Sweden)

    Leland Metheny

    2018-02-01

    Full Text Available Late-term complications of hematopoietic cell transplantation (HCT are numerous and include incomplete engraftment. One possible mechanism of incomplete engraftment after HCT is cytokine-mediated suppression or dysfunction of the bone marrow microenvironment. Mesenchymal stromal cells (MSCs elaborate cytokines that nurture or stimulate the marrow microenvironment by several mechanisms. We hypothesize that the administration of exogenous MSCs may modulate the bone marrow milieu and improve peripheral blood count recovery in the setting of incomplete engraftment. In the current study, we demonstrated that posttransplant intramuscular administration of human placental derived mesenchymal-like adherent stromal cells [PLacental eXpanded (PLX-R18] harvested from a three-dimensional in vitro culture system improved posttransplant engraftment of human immune compartment in an immune-deficient murine transplantation model. As measured by the percentage of CD45+ cell recovery, we observed improvement in the peripheral blood counts at weeks 6 (8.4 vs. 24.1%, p < 0.001 and 8 (7.3 vs. 13.1%, p < 0.05 and in the bone marrow at week 8 (28 vs. 40.0%, p < 0.01 in the PLX-R18 cohort. As measured by percentage of CD19+ cell recovery, there was improvement at weeks 6 (12.6 vs. 3.8% and 8 (10.1 vs. 4.1%. These results suggest that PLX-R18 may have a therapeutic role in improving incomplete engraftment after HCT.

  14. An improved haemolytic plaque assay for the detection of cells secreting antibody to bacterial antigens

    DEFF Research Database (Denmark)

    Barington, T; Heilmann, C

    1992-01-01

    Recent advances in the development of conjugate polysaccharide vaccines for human use have stimulated interest in the use of assays detecting antibody-secreting cells (AbSC) with specificity for bacterial antigens. Here we present improved haemolytic plaque-forming cell (PFC) assays detecting Ab......SC with specificity for tetanus and diphtheria toxoid as well as for Haemophilus influenzae type b and pneumococcal capsular polysaccharides. These assays were found to be less time consuming, more economical and yielded 1.9-3.4-fold higher plaque numbers than traditional Jerne-type PFC assays. In the case of anti......-polysaccharide antibodies aggregation of secreted monomeric antibody (IgG) is critical for plaque formation and increases the avidity of binding to target cells....

  15. Improved local and regional control with radiotherapy for Merkel cell carcinoma of the head and neck.

    Science.gov (United States)

    Strom, Tobin; Naghavi, Arash O; Messina, Jane L; Kim, Sungjune; Torres-Roca, Javier F; Russell, Jeffery; Sondak, Vernon K; Padhya, Tapan A; Trotti, Andy M; Caudell, Jimmy J; Harrison, Louis B

    2017-01-01

    We hypothesized that radiotherapy (RT) would improve both local and regional control with Merkel cell carcinoma of the head and neck. A single-institution institutional review board-approved study was performed including 113 patients with nonmetastatic Merkel cell carcinoma of the head and neck. Postoperative RT was delivered to the primary tumor bed (71.7% cases) ± draining lymphatics (33.3% RT cases). Postoperative local RT was associated with improved local control (3-year actuarial local control 89.4% vs 68.1%; p = .005; Cox hazard ratio [HR] 0.18; 95% confidence interval [CI] = 0.06-0.55; p = .002). Similarly, regional RT was associated with improved regional control (3-year actuarial regional control 95.0% vs 66.7%; p = .008; Cox HR = 0.09; 95% CI = 0.01-0.69; p = .02). Regional RT played an important role for both clinical node-negative patients (3-year regional control 100% vs 44.7%; p = .03) and clinical/pathological node-positive patients (3-year regional control 90.9% vs 55.6%; p = .047). Local RT was beneficial for all patients with Merkel cell carcinoma of the head and neck, whereas regional RT was beneficial for clinical node-negative and clinical/pathological node-positive patients. © 2016 Wiley Periodicals, Inc. Head Neck 39: 48-55, 2017. © 2016 Wiley Periodicals, Inc.

  16. Central precocious puberty following the diagnosis and treatment of paediatric cancer and central nervous system tumours: presentation and long-term outcomes.

    Science.gov (United States)

    Chemaitilly, Wassim; Merchant, Thomas E; Li, Zhenghong; Barnes, Nicole; Armstrong, Gregory T; Ness, Kirsten K; Pui, Ching-Hon; Kun, Larry E; Robison, Leslie L; Hudson, Melissa M; Sklar, Charles A; Gajjar, Amar

    2016-03-01

    To estimate the prevalence of central precocious puberty (CPP) after treatment for tumours and malignancies involving the central nervous system (CNS) and examine repercussions on growth and pubertal outcomes. Retrospective study of patients with tumours near and/or exposed to radiotherapy to the hypothalamus/pituitary axis (HPA). Patients with CPP were evaluated at puberty onset, completion of GnRH agonist treatment (GnRHa) and last follow-up. Multivariable analysis was used to test associations between tumour location, sex, age at CPP, GnRHa duration and a diagnosis of CPP with final height <-2SD score (SDS), gonadotropin deficiency (LH/FSHD) and obesity, respectively. Eighty patients (47 females) had CPP and were followed for 11·4 ± 5·0 years (mean ± SD). The prevalence of CPP was 15·2% overall, 29·2% following HPA tumours and 6·6% after radiotherapy for non-HPA tumours. Height <-2SDS was more common at the last follow-up than at the puberty onset (21·4% vs 2·4%, P = 0·005). Obesity was more prevalent at the last follow-up than at the completion of GnRHa or the puberty onset (37·7%, 22·6% and 20·8%, respectively, P = 0·03). Longer duration of GnRHa was associated with increased odds of final height <-2SDS (OR = 2·1, 95% CI 1·0-4·3) and longer follow-up with obesity (OR = 1·3, 95% CI 1·1-1·6). LH/FSHD was diagnosed in 32·6%. There was no independent association between CPP and final height <-2SDS, and LH/FSHD and obesity in the subset of patients with HPA low-grade gliomas. Patients with organic CPP experience an incomplete recovery of growth and a high prevalence of LH/FSHD and obesity. Early diagnosis and treatment of CPP may limit further deterioration of final height prospects. © 2015 John Wiley & Sons Ltd.

  17. Role of intermediate metallic sub-layers in improving the efficiency of kesterite solar cells: concept and optimization

    Science.gov (United States)

    Ferhati, H.; Djeffal, F.

    2018-03-01

    In this work, versatile CdS/Cu 2 ZnSnS 4 (CZTS) solar cell designs based on intermediate metallic sub-layers (Au, Ti, and Ag) engineering are proposed for enhancing light-scattering behavior and reducing recombination losses. The idea behind this work is to generate optical confinement regions in the CZTS absorber layer to achieve an improved absorption and appropriate antireflection effects. Moreover, the ultra-thin metal at the CZTS/Mo interface can be helpful for reducing the series resistance, where it behaves like a blocking layer for the Sulfur diffusion. We further combine the proposed designs with Particle Swarm Optimization (PSO)-based approach to achieve broadband absorption and boost the conversion efficiency. It is found that the optimized design with Ti sub-layer improves the CZTS solar cell properties, where it yields 31% improvement in short-circuit current and 60% in the power efficiency over the conventional one. Therefore, the optimized designs provide the opportunity for bridging the gap between improving the optical behavior and reducing the recombination losses.

  18. Change in body mass index and insulin resistance after 1-year treatment with gonadotropin-releasing hormone agonists in girls with central precocious puberty

    Directory of Open Access Journals (Sweden)

    Jina Park

    2017-03-01

    Full Text Available PurposeGonadotropin-releasing hormone agonist (GnRHa is used as a therapeutic agent for central precocious puberty (CPP; however, increased obesity may subsequently occur. This study compared body mass index (BMI and insulin resistance during the first year of GnRHa treatment for CPP.MethodsPatient group included 83 girls (aged 7.0–8.9 years with developed breasts and a peak luteinizing hormone level of ≥5 IU/L after GnRH stimulation. Control group included 48 prepubertal girls. BMI and insulin resistance-related indices (homeostasis model assessment of insulin resistance [HOMA-IR] and quantitative insulin sensitivity check index [QUICKI] were used to compare the groups before treatment, and among the patient group before and after GnRHa treatment.ResultsNo statistical difference in BMI z-score was detected between the 2 groups before treatment. Fasting insulin and HOMA-IR were increased in the patient group; fasting glucose-to-insulin ratio and QUICKI were increased in the control group (all P<0.001. In normal-weight subjects in the patient group, BMI z-score was significantly increased during GnRHa treatment (−0.1±0.7 vs. 0.1±0.8, P<0.001, whereas HOMA-IR and QUICKI exhibited no differences. In overweight subjects in the patient group; BMI z-score and HOMA-IR were not significantly different, whereas QUICKI was significantly decreased during GnRHa treatment (0.35±0.03 vs. 0.33±0.02, P=0.044.ConclusionGirls with CPP exhibited increased insulin resistance compared to the control group. During GnRHa treatment, normal-weight individuals showed increased BMI z-scores without increased insulin resistance; the overweight group demonstrated increased insulin resistance without significantly altered BMI z-scores. Long-term follow-up of BMI and insulin resistance changes in patients with CPP is required.

  19. Transgenic Expression of IL15 Improves Antiglioma Activity of IL13Rα2-CAR T Cells but Results in Antigen Loss Variants.

    Science.gov (United States)

    Krenciute, Giedre; Prinzing, Brooke L; Yi, Zhongzhen; Wu, Meng-Fen; Liu, Hao; Dotti, Gianpietro; Balyasnikova, Irina V; Gottschalk, Stephen

    2017-07-01

    Glioblastoma (GBM) is the most aggressive primary brain tumor in adults and is virtually incurable with conventional therapies. Immunotherapy with T cells expressing GBM-specific chimeric antigen receptors (CAR) is an attractive approach to improve outcomes. Although CAR T cells targeting GBM antigens, such as IL13 receptor subunit α2 (IL13Rα2), HER2, and EGFR variant III (EGFRvIII), have had antitumor activity in preclinical models, early-phase clinical testing has demonstrated limited antiglioma activity. Transgenic expression of IL15 is an appealing strategy to enhance CAR T-cell effector function. We tested this approach in our IL13Rα2-positive glioma model in which limited IL13Rα2-CAR T-cell persistence results in recurrence of antigen-positive gliomas. T cells were genetically modified with retroviral vectors encoding IL13Rα2-CARs or IL15 (IL13Rα2-CAR.IL15 T cells). IL13Rα2-CAR.IL15 T cells recognized glioma cells in an antigen-dependent fashion, had greater proliferative capacity, and produced more cytokines after repeated stimulations in comparison with IL13Rα2-CAR T cells. No autonomous IL13Rα2-CAR.IL15 T-cell proliferation was observed; however, IL15 expression increased IL13Rα2-CAR T-cell viability in the absence of exogenous cytokines or antigen. In vivo , IL13Rα2-CAR.IL15 T cells persisted longer and had greater antiglioma activity than IL13Rα2-CAR T cells, resulting in a survival advantage. Gliomas recurring after 40 days after T-cell injection had downregulated IL13Rα2 expression, indicating that antigen loss variants occur in the setting of improved T-cell persistence. Thus, CAR T cells for GBM should not only be genetically modified to improve their proliferation and persistence, but also to target multiple antigens. Summary: Glioblastoma responds imperfectly to immunotherapy. Transgenic expression of IL15 in T cells expressing CARs improved their proliferative capacity, persistence, and cytokine production. The emergence of antigen

  20. Human Primary Intestinal Epithelial Cells as an Improved In Vitro Model for Cryptosporidium parvum Infection

    Science.gov (United States)

    Cabada, Miguel M.; Nichols, Joan; Gomez, Guillermo; White, A. Clinton

    2013-01-01

    The study of human intestinal pathogens has been limited by the lack of methods for the long-term culture of primary human intestinal epithelial cells (PECs). The development of infection models with PECs would allow a better understanding of host-parasite interactions. The objective of this study was to develop a novel method for prolonged in vitro cultivation of PECs that can be used to study Cryptosporidium infection. We isolated intact crypts from human intestines removed during weight loss surgery. The fragments of intestinal layers were cultivated with culture medium supplemented with growth factors and antiapoptotic molecules. After 7 days, the PECs formed self-regenerating cell clusters, forming villi that resemble intestinal epithelium. The PECs proliferated and remained viable for at least 60 days. The cells expressed markers for intestinal stem cells, epithelial cells, and mature enterocytes. The PECs were infected with Cryptosporidium. In contrast to older models in which parasite numbers decay, the burden of parasites increased for >120 h. In summary, we describe here a novel method for the cultivation of self-regenerating human epithelial cells from small intestinal crypts, which contain both intestinal stem cells and mature villus cells. We present data that suggest these cells support Cryptosporidium better than existing cell lines. PECs should provide an improved tool for studying host-parasite interactions involving Cryptosporidium and other intestinal pathogens. PMID:23509153

  1. Improving immunological tumor microenvironment using electro-hyperthermia followed by dendritic cell immunotherapy

    International Nuclear Information System (INIS)

    Tsang, Yuk-Wah; Huang, Cheng-Chung; Yang, Kai-Lin; Chi, Mau-Shin; Chiang, Hsin-Chien; Wang, Yu-Shan; Andocs, Gabor; Szasz, Andras; Li, Wen-Tyng; Chi, Kwan-Hwa

    2015-01-01

    The treatment of intratumoral dentritic cells (DCs) commonly fails because it cannot evoke immunity in a poor tumor microenvironment (TME). Modulated electro-hyperthermia (mEHT, trade-name: oncothermia) represents a significant technological advancement in the hyperthermia field, allowing the autofocusing of electromagnetic power on a cell membrane to generate massive apoptosis. This approach turns local immunogenic cancer cell death (apoptosis) into a systemic anti-tumor immune response and may be implemented by treatment with intratumoral DCs. The CT26 murine colorectal cancer model was used in this investigation. The inhibition of growth of the tumor and the systemic anti-tumor immune response were measured. The tumor was heated to a core temperature of 42 °C for 30 min. The matured synergetic DCs were intratumorally injected 24 h following mEHT was applied. mEHT induced significant apoptosis and enhanced the release of heat shock protein70 (Hsp70) in CT26 tumors. Treatment with mEHT-DCs significantly inhibited CT26 tumor growth, relative to DCs alone or mEHT alone. The secondary tumor protection effect upon rechallenging was observed in mice that were treated with mEHT-DCs. Immunohistochemical staining of CD45 and F4/80 revealed that mEHT-DC treatment increased the number of leukocytes and macrophages. Most interestingly, mEHT also induced infiltrations of eosinophil, which has recently been reported to be an orchestrator of a specific T cell response. Cytotoxic T cell assay and ELISpot assay revealed a tumor-specific T cell activity. This study demonstrated that mEHT induces tumor cell apoptosis and enhances the release of Hsp70 from heated tumor cells, unlike conventional hyperthermia. mEHT can create a favorable tumor microenvironment for an immunological chain reaction that improves the success rate of intratumoral DC immunotherapy. The online version of this article (doi:10.1186/s12885-015-1690-2) contains supplementary material, which is available to

  2. Loss of Cln3 Function in the Social Amoeba Dictyostelium discoideum Causes Pleiotropic Effects That Are Rescued by Human CLN3

    Science.gov (United States)

    Huber, Robert J.

    2014-01-01

    The neuronal ceroid lipofuscinoses (NCL) are a group of inherited, severe neurodegenerative disorders also known as Batten disease. Juvenile NCL (JNCL) is caused by recessive loss-of-function mutations in CLN3, which encodes a transmembrane protein that regulates endocytic pathway trafficking, though its primary function is not yet known. The social amoeba Dictyostelium discoideum is increasingly utilized for neurological disease research and is particularly suited for investigation of protein function in trafficking. Therefore, here we establish new overexpression and knockout Dictyostelium cell lines for JNCL research. Dictyostelium Cln3 fused to GFP localized to the contractile vacuole system and to compartments of the endocytic pathway. cln3− cells displayed increased rates of proliferation and an associated reduction in the extracellular levels and cleavage of the autocrine proliferation repressor, AprA. Mid- and late development of cln3− cells was precocious and cln3− slugs displayed increased migration. Expression of either Dictyostelium Cln3 or human CLN3 in cln3− cells suppressed the precocious development and aberrant slug migration, which were also suppressed by calcium chelation. Taken together, our results show that Cln3 is a pleiotropic protein that negatively regulates proliferation and development in Dictyostelium. This new model system, which allows for the study of Cln3 function in both single cells and a multicellular organism, together with the observation that expression of human CLN3 restores abnormalities in Dictyostelium cln3− cells, strongly supports the use of this new model for JNCL research. PMID:25330233

  3. Loss of Cln3 function in the social amoeba Dictyostelium discoideum causes pleiotropic effects that are rescued by human CLN3.

    Directory of Open Access Journals (Sweden)

    Robert J Huber

    Full Text Available The neuronal ceroid lipofuscinoses (NCL are a group of inherited, severe neurodegenerative disorders also known as Batten disease. Juvenile NCL (JNCL is caused by recessive loss-of-function mutations in CLN3, which encodes a transmembrane protein that regulates endocytic pathway trafficking, though its primary function is not yet known. The social amoeba Dictyostelium discoideum is increasingly utilized for neurological disease research and is particularly suited for investigation of protein function in trafficking. Therefore, here we establish new overexpression and knockout Dictyostelium cell lines for JNCL research. Dictyostelium Cln3 fused to GFP localized to the contractile vacuole system and to compartments of the endocytic pathway. cln3- cells displayed increased rates of proliferation and an associated reduction in the extracellular levels and cleavage of the autocrine proliferation repressor, AprA. Mid- and late development of cln3- cells was precocious and cln3- slugs displayed increased migration. Expression of either Dictyostelium Cln3 or human CLN3 in cln3- cells suppressed the precocious development and aberrant slug migration, which were also suppressed by calcium chelation. Taken together, our results show that Cln3 is a pleiotropic protein that negatively regulates proliferation and development in Dictyostelium. This new model system, which allows for the study of Cln3 function in both single cells and a multicellular organism, together with the observation that expression of human CLN3 restores abnormalities in Dictyostelium cln3- cells, strongly supports the use of this new model for JNCL research.

  4. Ck2-Dependent Phosphorylation Is Required to Maintain Pax7 Protein Levels in Proliferating Muscle Progenitors.

    Directory of Open Access Journals (Sweden)

    Natalia González

    Full Text Available Skeletal muscle regeneration and long term maintenance is directly link to the balance between self-renewal and differentiation of resident adult stem cells known as satellite cells. In turn, satellite cell fate is influenced by a functional interaction between the transcription factor Pax7 and members of the MyoD family of muscle regulatory factors. Thus, changes in the Pax7-to-MyoD protein ratio may act as a molecular rheostat fine-tuning acquisition of lineage identity while preventing precocious terminal differentiation. Pax7 is expressed in quiescent and proliferating satellite cells, while its levels decrease sharply in differentiating progenitors Pax7 is maintained in cells (reacquiring quiescence. While the mechanisms regulating Pax7 levels based on differentiation status are not well understood, we have recently described that Pax7 levels are directly regulated by the ubiquitin-ligase Nedd4, thus promoting proteasome-dependent Pax7 degradation in differentiating satellite cells. Here we show that Pax7 levels are maintained in proliferating muscle progenitors by a mechanism involving casein kinase 2-dependent Pax7 phosphorylation at S201. Point mutations preventing S201 phosphorylation or casein kinase 2 inhibition result in decreased Pax7 protein in proliferating muscle progenitors. Accordingly, this correlates directly with increased Pax7 ubiquitination. Finally, Pax7 down regulation induced by casein kinase 2 inhibition results in precocious myogenic induction, indicating early commitment to terminal differentiation. These observations highlight the critical role of post translational regulation of Pax7 as a molecular switch controlling muscle progenitor fate.

  5. Putative effects of endocrine disrupters on pubertal development in the human

    DEFF Research Database (Denmark)

    Teilmann, Grete; Juul, Anders; Skakkebaek, Niels E

    2002-01-01

    developing countries to industrialized countries often develop precocious puberty. Not only precocious puberty, but also delayed puberty can, theoretically, be associated with exposure to endocrine disrupters. While it is very plausible that endocrine disrupters may disturb pubertal development...

  6. Drug Combination Synergy in Worm-like Polymeric Micelles Improves Treatment Outcome for Small Cell and Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Wan, Xiaomeng; Min, Yuanzeng; Bludau, Herdis; Keith, Andrew; Sheiko, Sergei S; Jordan, Rainer; Wang, Andrew Z; Sokolsky-Papkov, Marina; Kabanov, Alexander V

    2018-03-27

    Nanoparticle-based systems for concurrent delivery of multiple drugs can improve outcomes of cancer treatments, but face challenges because of differential solubility and fairly low threshold for incorporation of many drugs. Here we demonstrate that this approach can be used to greatly improve the treatment outcomes of etoposide (ETO) and platinum drug combination ("EP/PE") therapy that is the backbone for treatment of prevalent and deadly small cell lung cancer (SCLC). A polymeric micelle system based on amphiphilic block copolymer poly(2-oxazoline)s (POx) poly(2-methyl-2-oxazoline- block-2-butyl-2-oxazoline- block-2-methyl-2-oxazoline) (P(MeOx- b-BuOx- b-MeOx) is used along with an alkylated cisplatin prodrug to enable co-formulation of EP/PE in a single high-capacity vehicle. A broad range of drug mixing ratios and exceptionally high two-drug loading of over 50% wt. drug in dispersed phase is demonstrated. The highly loaded POx micelles have worm-like morphology, unprecedented for drug loaded polymeric micelles reported so far, which usually form spheres upon drug loading. The drugs co-loading in the micelles result in a slowed-down release, improved pharmacokinetics, and increased tumor distribution of both drugs. A superior antitumor activity of co-loaded EP/PE drug micelles compared to single drug micelles or their combination as well as free drug combination was demonstrated using several animal models of SCLC and non-small cell lung cancer.

  7. Improve T Cell Therapy in Neuroblastoma

    Science.gov (United States)

    2014-07-01

    relapsed lymphoma following genetic modi - fi cation of tumor-antigen presenting cells and T-lymphocyte transfer. Blood 110:2838–2845 4. Heslop HE et...CD4þCD25þFOXP3þ regulatory T cells of both healthy subjects and type 1 diabetic patients. J Immunol 2006;177:8338–47. 32. HeslopHE, SlobodKS,PuleMA

  8. Improvement of conversion efficiency of silicon solar cells using up-conversion molybdate La2Mo2O9:Yb,R (R=Er, Ho) phosphors

    Institute of Scientific and Technical Information of China (English)

    Yen-Chi Chen; Teng-Ming Chen

    2011-01-01

    The goal of this work was aimed to improve the power conversion efficiency of single crystalline silicon-based photovoltaic cells by using the solar spectral conversion principle,which employs an up-conversion phosphor to convert a low energy infrared photon to the more energetic visible photons to improve the spectral response.In this study,the surface of multicrystalline silicon solar cells was coated with an up-conversion molybdate phosphor to improve the spectral response of the solar cell in the ncar-infiared spectral range.The short circuit current (Isc),open circuit voltage (Voc),and conversion efficiency (η) of spectral conversion cells were measured.Preliminary experimental results revealed that the light conversion efficiency of a 1.5%-2.7% increase in Si-based cell was achieved.

  9. In pulmonary paracoccidioidomycosis IL-10 deficiency leads to increased immunity and regressive infection without enhancing tissue pathology.

    Directory of Open Access Journals (Sweden)

    Tânia A Costa

    Full Text Available BACKGROUND: Cellular immunity is the main defense mechanism in paracoccidioidomycosis (PCM, the most important systemic mycosis in Latin America. Th1 immunity and IFN-γ activated macrophages are fundamental to immunoprotection that is antagonized by IL-10, an anti-inflammatory cytokine. Both in human and experimental PCM, several evidences indicate that the suppressive effect of IL-10 causes detrimental effects to infected hosts. Because direct studies have not been performed, this study was aimed to characterize the function of IL-10 in pulmonary PCM. METHODOLOGY/PRINCIPAL FINDINGS: Wild type (WT and IL-10(-/- C57BL/6 mice were used to characterize the role of IL-10 in the innate and adaptive immunity against Paracoccidioides brasiliensis (Pb infection. We verified that Pb-infected peritoneal macrophages from IL-10(-/- mice presented higher phagocytic and fungicidal activities than WT macrophages, and these activities were associated with elevated production of IFN-γ, TNF-α, nitric oxide (NO and MCP-1. For in vivo studies, IL-10(-/- and WT mice were i.t. infected with 1×10(6 Pb yeasts and studied at several post-infection periods. Compared to WT mice, IL-10(-/- mice showed increased resistance to P. brasiliensis infection as determined by the progressive control of pulmonary fungal loads and total clearance of fungal cells from dissemination organs. This behavior was accompanied by enhanced delayed-type hypersensitivity reactions, precocious humoral immunity and controlled tissue pathology resulting in increased survival times. In addition, IL-10(-/- mice developed precocious T cell immunity mediated by increased numbers of lung infiltrating effector/memory CD4(+ and CD8(+ T cells. The inflammatory reactions and the production of Th1/Th2/Th17 cytokines were reduced at late phases of infection, paralleling the regressive infection of IL-10(-/- mice. CONCLUSIONS/SIGNIFICANCE: Our work demonstrates for the first time that IL-10 plays a

  10. The short circuit current improvement in P3HT:PCBM based polymer solar cell by introducing PSBTBT as additional electron donor.

    Science.gov (United States)

    Sun, Lu; Shen, Liang; Mengd, Fanxu; Xu, Peng; Guo, Wenbin; Ruan, Shengping

    2014-05-01

    Here we demonstrate the influence of electron-donating polymer addition on the performance of poly(3-hexylthiophene) (P3HT):1 -(3-methoxycarbonyl)-propyl-1-phenyl-(6,6) C61 (PCBM) solar cells. Poly[(4,42-bis(2-ethylhexyl) dithieno [3,2-b:22,32-d] silole)-2,6-diylalt-(2,1,3-benzothiadiazole)-4,7-diyl] (PSBTBT) was chosen as the electron-donating polymer to improve the short circuit current (J(sc)) due to its distinct absorption in the near-IR range and similar HOMO level with that of P3HT. In the study, we found that J(sc) was improved for ternary blend (P3HT:PSBTBT:PCBM) solar cells. The dependence of device performance was investigated. J(sc) got decreased with increasing the ratio of PSBTBT. Result showed that J(sc) of ternary blend solar cells was improved greatly after thermal annealing at 150 degrees C, close to that of the binary blend (PSBTBT:PCBM) solar cells.

  11. Cell culture medium improvement by rigorous shuffling of components using media blending.

    Science.gov (United States)

    Jordan, Martin; Voisard, Damien; Berthoud, Antoine; Tercier, Laetitia; Kleuser, Beate; Baer, Gianni; Broly, Hervé

    2013-01-01

    A novel high-throughput methodology for the simultaneous optimization of many cell culture media components is presented. The method is based on the media blending approach which has several advantages as it works with ready-to-use media. In particular it allows precise pH and osmolarity adjustments and eliminates the need of concentrated stock solutions, a frequent source of serious solubility issues. In addition, media blending easily generates a large number of new compositions providing a remarkable screening tool. However, media blending designs usually do not provide information on distinct factors or components that are causing the desired improvements. This paper addresses this last point by considering the concentration of individual medium components to fix the experimental design and for the interpretation of the results. The extended blending strategy was used to reshuffle the 20 amino acids in one round of experiments. A small set of 10 media was specifically designed to generate a large number of mixtures. 192 mixtures were then prepared by media blending and tested on a recombinant CHO cell line expressing a monoclonal antibody. A wide range of performances (titers and viable cell density) was achieved from the different mixtures with top titers significantly above our previous results seen with this cell line. In addition, information about major effects of key amino acids on cell densities and titers could be extracted from the experimental results. This demonstrates that the extended blending approach is a powerful experimental tool which allows systematic and simultaneous reshuffling of multiple medium components.

  12. Triiodothyronine improves the primary antibody response to sheep red blood cells in severely undernourished weanling mice

    International Nuclear Information System (INIS)

    Filteau, S.M.; Perry, K.J.; Woodward, B.

    1987-01-01

    Three experiments were conducted in which weanling mice were fed a nutritionally complete diet either ad libitum or in restricted quantities such that they lost about 30% of their initial weight over a 14-day period. In Experiments 1 and 2, half the animals from each group received dietary triiodothyronine (T 3 ) supplements. In Experiment 3, food-intake-restricted mice were fed graded levels of potassium iodide. Malnutrition reduced the number of nucleated cells per spleen, the number of splenic IgG plaque-forming cells (PFC) per 10 6 cells, and the serum antibody titers against sheep red blood cells as determined by radioimmunoassay. T 3 supplements increased antibody titers, the number of nucleated cells per spleen, and both IgM and IgG PFC per 10 6 spleen cells in malnourished mice, but had no effect on well-nourished mice. The beneficial effect of T 3 was not a result of improved protein, energy, or iodine status in the malnourished mice

  13. An Epigenetic Modifier Results in Improved In Vitro Blastocyst production after Somatic Cell Nuclear Transfer

    DEFF Research Database (Denmark)

    Zhang, Yunhai; Li, Juan; Villemoes, Klaus

    2007-01-01

    The present study was designed to examine the effect of trichostatin A (TSA), an inhibitor of histone deacetylase, on development of porcine cloned embryos. Our results showed that treatment of cloned embryos derived from sow oocytes with 50 nM TSA for up to 24 h after the onset of activation cou...... were tested, and for all cell lines an enhancement in blastocyst development compared to their corresponding control was observed. Our data demonstrate that TSA treatment after somatic cell nuclear transfer in the pig can significantly improve the in vitro blastocyst production...

  14. Improved Reliability of Small Molecule Organic Solar Cells by Double Anode Buffer Layers

    Directory of Open Access Journals (Sweden)

    Pao-Hsun Huang

    2014-01-01

    Full Text Available An optimized hybrid planar heterojunction (PHJ of small molecule organic solar cells (SM-OSCs based on copper phthalocyanine (CuPc as donor and fullerene (C60 as acceptor was fabricated, which obviously enhanced the performance of device by sequentially using both MoO3 and pentacene as double anode buffer layers (ABL, also known as hole extraction layer (HEL. A series of the vacuum-deposited ABL, acting as an electron and exciton blocking layer, were examined for their characteristics in SM-OSCs. The performance and reliability were compared between conventional ITO/ABL/CuPc/C60/BCP/Ag cells and the new ITO/double ABL/CuPc/C60/BCP/Ag cells. The effect on the electrical properties of these materials was also investigated to obtain the optimal thickness of ABL. The comparison shows that the modified cell has an enhanced reliability compared to traditional cells. The improvement of lifetime was attributed to the idea of double layers to prevent humidity and oxygen from diffusing into the active layer. We demonstrated that the interfacial extraction layers are necessary to avoid degradation of device. That is to say, in normal temperature and pressure, a new avenue for the device within double buffer layers has exhibited the highest values of open circuit voltage (Voc, fill factor (FF, and lifetime in this work compared to monolayer of ABL.

  15. Improving the characterization of endothelial progenitor cell subsets by an optimized FACS protocol.

    Directory of Open Access Journals (Sweden)

    Karin Huizer

    Full Text Available The characterization of circulating endothelial progenitor cells (EPCs is fundamental to any study related to angiogenesis. Unfortunately, current literature lacks consistency in the definition of EPC subsets due to variations in isolation strategies and inconsistencies in the use of lineage markers. Here we address critical points in the identification of hematopoietic progenitor cells (HPCs, circulating endothelial cells (CECs, and culture-generated outgrowth endothelial cells (OECs from blood samples of healthy adults (AB and umbilical cord (UCB. Peripheral blood mononuclear cells (PBMCs were enriched using a Ficoll-based gradient followed by an optimized staining and gating strategy to enrich for the target cells. Sorted EPC populations were subjected to RT-PCR for tracing the expression of markers beyond the limits of cell surface-based immunophenotyping. Using CD34, CD133 and c-kit staining, combined with FSC and SSC, we succeeded in the accurate and reproducible identification of four HPC subgroups and found significant differences in the respective populations in AB vs. UCB. Co-expression analysis of endothelial markers on HPCs revealed a complex pattern characterized by various subpopulations. CECs were identified by using CD34, KDR, CD45, and additional endothelial markers, and were subdivided according to their apoptotic state and expression of c-kit. Comparison of UCB-CECs vs. AB-CECs revealed significant differences in CD34 and KDR levels. OECs were grown from PBMC-fractions We found that viable c-kit+ CECs are a candidate circulating precursor for CECs. RT-PCR to angiogenic factors and receptors revealed that all EPC subsets expressed angiogenesis-related molecules. Taken together, the improvements in immunophenotyping and gating strategies resulted in accurate identification and comparison of better defined cell populations in a single procedure.

  16. Improvement of mouse cloning using nuclear transfer-derived embryonic stem cells and/or histone deacetylase inhibitor.

    Science.gov (United States)

    Wakayama, Sayaka; Wakayama, Teruhiko

    2010-01-01

    Nuclear transfer-derived ES (ntES) cell lines can be established from somatic cell nuclei with a relatively high success rate. Although ntES cells have been shown to be equivalent to ES cells, there are ethical objections concerning human cells, such as the use of fresh oocyte donation from young healthy woman. In contrast, the use of induced pluripotent stem (iPS) cells for cloning poses few ethical problems and is a relatively easy technique compared with nuclear transfer. Therefore, although there are several reports proposing the use of ntES cells as a model of regenerative medicine, the use of these cells in preliminary medical research is waning. However, in theory, 5 to 10 donor cells can establish one ntES cell line and, once established, these cells will propagate indefinitely. These cells can be used to generate cloned animals from ntES cell lines using a second round of NT. Even in infertile and "unclonable" strains of mice, we can generate offspring from somatic cells by combining cloning with ntES technology. Moreover, cloned offspring can be generated potentially even from the nuclei of dead bodies or freeze-dried cells via ntES cells, such as from an extinct frozen animal. Currently, only the ntES technology is available for this purpose, because all other techniques, including iPS cell derivation, require significant numbers of living donor cells. This review describes how to improve the efficiency of cloning, the establishment of clone-derived embryonic stem cells and further applications.

  17. Regulation of the number of cell division rounds by tissue-specific transcription factors and Cdk inhibitor during ascidian embryogenesis.

    Directory of Open Access Journals (Sweden)

    Mami Kuwajima

    Full Text Available Mechanisms that regulate the number of cell division rounds during embryogenesis have remained largely elusive. To investigate this issue, we used the ascidian, which develops into a tadpole larva with a small number of cells. The embryonic cells divide 11.45 times on average from fertilization to hatching. The number of cell division rounds varies depending on embryonic lineages. Notochord and muscle consist of large postmitotic cells and stop dividing early in developing embryos. Here we show that conversion of mesenchyme to muscle cell fates by inhibition of inductive FGF signaling or mis-expression of a muscle-specific key transcription factor for muscle differentiation, Tbx6, changed the number of cell divisions in accordance with the altered fate. Tbx6 likely activates a putative mechanism to halt cell division at a specific stage. However, precocious expression of Tbx6 has no effect on progression of the developmental clock itself. Zygotic expression of a cyclin-dependent kinase inhibitor, CKI-b, is initiated in muscle and then in notochord precursors. CKI-b is possibly downstream of tissue-specific key transcription factors of notochord and muscle. In the two distinct muscle lineages, postmitotic muscle cells are generated after 9 and 8 rounds of cell division depending on lineage, but the final cell divisions occur at a similar developmental stage. CKI-b gene expression starts simultaneously in both muscle lineages at the 110-cell stage, suggesting that CKI-b protein accumulation halts cell division at a similar stage. The difference in the number of cell divisions would be due to the cumulative difference in cell cycle length. These results suggest that muscle cells do not count the number of cell division rounds, and that accumulation of CKI-b protein triggered by tissue-specific key transcription factors after cell fate determination might act as a kind of timer that measures elapsed time before cell division termination.

  18. Ultrathin high band gap solar cells with improved efficiencies from the world's oldest photovoltaic material.

    Science.gov (United States)

    Todorov, Teodor K; Singh, Saurabh; Bishop, Douglas M; Gunawan, Oki; Lee, Yun Seog; Gershon, Talia S; Brew, Kevin W; Antunez, Priscilla D; Haight, Richard

    2017-09-25

    Selenium was used in the first solid state solar cell in 1883 and gave early insights into the photoelectric effect that inspired Einstein's Nobel Prize work; however, the latest efficiency milestone of 5.0% was more than 30 years ago. The recent surge of interest towards high-band gap absorbers for tandem applications led us to reconsider this attractive 1.95 eV material. Here, we show completely redesigned selenium devices with improved back and front interfaces optimized through combinatorial studies and demonstrate record open-circuit voltage (V OC ) of 970 mV and efficiency of 6.5% under 1 Sun. In addition, Se devices are air-stable, non-toxic, and extremely simple to fabricate. The absorber layer is only 100 nm thick, and can be processed at 200 ˚C, allowing temperature compatibility with most bottom substrates or sub-cells. We analyze device limitations and find significant potential for further improvement making selenium an attractive high-band-gap absorber for multi-junction device applications.Wide band gap semiconductors are important for the development of tandem photovoltaics. By introducing buffer layers at the front and rear side of solar cells based on selenium; Todorov et al., reduce interface recombination losses to achieve photoconversion efficiencies of 6.5%.

  19. An Improved Model of Nonuniform Coleochaete Cell Division.

    Science.gov (United States)

    Wang, Yuandi; Cong, Jinyu

    2016-08-01

    Cell division is a key biological process in which cells divide forming new daughter cells. In the present study, we investigate continuously how a Coleochaete cell divides by introducing a modified differential equation model in parametric equation form. We discuss both the influence of "dead" cells and the effects of various end-points on the formation of the new cells' boundaries. We find that the boundary condition on the free end-point is different from that on the fixed end-point; the former has a direction perpendicular to the surface. It is also shown that the outer boundaries of new cells are arc-shaped. The numerical experiments and theoretical analyses for this model to construct the outer boundary are given.

  20. Chronic treadmill exercise in rats delicately alters the Purkinje cell structure to improve motor performance and toxin resistance in the cerebellum.

    Science.gov (United States)

    Huang, Tung-Yi; Lin, Lung-Sheng; Cho, Keng-Chi; Chen, Shean-Jen; Kuo, Yu-Min; Yu, Lung; Wu, Fong-Sen; Chuang, Jih-Ing; Chen, Hsiun-Ing; Jen, Chauying J

    2012-09-01

    Although exercise usually improves motor performance, the underlying cellular changes in the cerebellum remain to be elucidated. This study aimed to investigate whether and how chronic treadmill exercise in young rats induced Purkinje cell changes to improve motor performance and rendered the cerebellum less vulnerable to toxin insults. After 1-wk familiarization of treadmill running, 6-wk-old male Wistar rats were divided into exercise and sedentary groups. The exercise group was then subjected to 8 wk of exercise training at moderate intensity. The rotarod test was carried out to evaluate motor performance. Purkinje cells in cerebellar slices were visualized by lucifer yellow labeling in single neurons and by calbindin immunostaining in groups of neurons. Compared with sedentary control rats, exercised rats not only performed better in the rotarod task, but also showed finer Purkinje cell structure (higher dendritic volume and spine density with the same dendritic field). The exercise-improved cerebellar functions were further evaluated by monitoring the long-lasting effects of intraventricular application of OX7-saporin. In the sedentary group, OX7-saporin treatment retarded the rotarod performance and induced ∼60% Purkinje cell loss in 3 wk. As a comparison, the exercise group showed much milder injuries in the cerebellum by the same toxin treatment. In conclusion, exercise training in young rats increased the dendritic density of Purkinje cells, which might play an important role in improving the motor performance. Furthermore, as Purkinje cells in the exercise group were relatively toxin resistant, the exercised rats showed good motor performance, even under toxin-treated conditions.

  1. Achieving 12.8% Efficiency by Simultaneously Improving Open-Circuit Voltage and Short-Circuit Current Density in Tandem Organic Solar Cells.

    Science.gov (United States)

    Qin, Yunpeng; Chen, Yu; Cui, Yong; Zhang, Shaoqing; Yao, Huifeng; Huang, Jiang; Li, Wanning; Zheng, Zhong; Hou, Jianhui

    2017-06-01

    Tandem organic solar cells (TOSCs), which integrate multiple organic photovoltaic layers with complementary absorption in series, have been proved to be a strong contender in organic photovoltaic depending on their advantages in harvesting a greater part of the solar spectrum and more efficient photon utilization than traditional single-junction organic solar cells. However, simultaneously improving open circuit voltage (V oc ) and short current density (J sc ) is a still particularly tricky issue for highly efficient TOSCs. In this work, by employing the low-bandgap nonfullerene acceptor, IEICO, into the rear cell to extend absorption, and meanwhile introducing PBDD4T-2F into the front cell for improving V oc , an impressive efficiency of 12.8% has been achieved in well-designed TOSC. This result is also one of the highest efficiencies reported in state-of-the-art organic solar cells. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Clinical Evaluation of Decellularized Nerve Allograft with Autologous Bone Marrow Stem Cells to Improve Peripheral Nerve Repair and Functional Outcomes

    Science.gov (United States)

    2017-07-01

    with autologous mesenchymal stem cells . Exp Neurol. 2007 Apr; 204(2):658-66. 19. Dezawa M., et al., Sciatic nerve regeneration in rats induced by...36 23. Mimura T., et al., Peripheral nerve regeneration by transplantation of bone marrow stromal cell -derived Schwann cells in adult rats. J...AWARD NUMBER: W81XWH-15-2-0026 TITLE: Clinical Evaluation of Decellularized Nerve Allograft with Autologous Bone Marrow Stem Cells to Improve

  3. Compact Flyeye concentrator with improved irradiance uniformity on solar cell

    Science.gov (United States)

    Zhuang, Zhenfeng; Yu, Feihong

    2013-08-01

    A Flyeye concentrator with improved irradiance distribution on the solar cell in a concentrator photovoltaic system is proposed. This Flyeye concentrator is composed of four surfaces: a refractive surface, mirror surface, freeform surface, and transmissive surface. Based on the principles of geometrical optics, the contours of the proposed Flyeye concentrator are calculated according to Fermat's principle, the edge-ray principle, and the ray reversibility principle without solving partial differential equations or using an optimization algorithm, therefore a slope angle control method is used to construct the freeform surface. The solid model is established by applying a symmetry of revolution around the optical axis. Additionally, the optical performance for the Flyeye concentrator is simulated and analyzed by Monte-Carlo method. Results show that the Flyeye concentrator optical efficiency of >96.2% is achievable with 1333× concentration ratio and ±1.3 deg acceptance angle, and 1.3 low aspect ratio (average thickness to entry aperture diameter ratio). Moreover, comparing the Flyeye concentrator specification to that of the Köhler concentrator and the traditional Fresnel-type concentrator, results indicate that this concentrator has the advantages of improved uniformity, reduced thickness, and increased tolerance to the incident sunlight.

  4. Early life stress accelerates behavioral and neural maturation of the hippocampus in male mice.

    Science.gov (United States)

    Bath, K; Manzano-Nieves, G; Goodwill, H

    2016-06-01

    Early life stress (ELS) increases the risk for later cognitive and emotional dysfunction. ELS is known to truncate neural development through effects on suppressing cell birth, increasing cell death, and altering neuronal morphology, effects that have been associated with behavioral profiles indicative of precocious maturation. However, how earlier silencing of growth drives accelerated behavioral maturation has remained puzzling. Here, we test the novel hypothesis that, ELS drives a switch from growth to maturation to accelerate neural and behavioral development. To test this, we used a mouse model of ELS, fragmented maternal care, and a cross-sectional dense sampling approach focusing on hippocampus and measured effects of ELS on the ontogeny of behavioral development and biomarkers of neural maturation. Consistent with previous work, ELS was associated with an earlier developmental decline in expression of markers of cell proliferation (Ki-67) and differentiation (doublecortin). However, ELS also led to a precocious arrival of Parvalbumin-positive cells, led to an earlier switch in NMDA receptor subunit expression (marker of synaptic maturity), and was associated with an earlier rise in myelin basic protein expression (key component of the myelin sheath). In addition, in a contextual fear-conditioning task, ELS accelerated the timed developmental suppression of contextual fear. Together, these data provide support for the hypothesis that ELS serves to switch neurodevelopment from processes of growth to maturation and promotes accelerated development of some forms of emotional learning. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Parasitic infection improves survival from septic peritonitis by enhancing mast cell responses to bacteria in mice.

    Directory of Open Access Journals (Sweden)

    Rachel E Sutherland

    Full Text Available Mammals are serially infected with a variety of microorganisms, including bacteria and parasites. Each infection reprograms the immune system's responses to re-exposure and potentially alters responses to first-time infection by different microorganisms. To examine whether infection with a metazoan parasite modulates host responses to subsequent bacterial infection, mice were infected with the hookworm-like intestinal nematode Nippostrongylus brasiliensis, followed in 2-4 weeks by peritoneal injection of the pathogenic bacterium Klebsiella pneumoniae. Survival from Klebsiella peritonitis two weeks after parasite infection was better in Nippostrongylus-infected animals than in unparasitized mice, with Nippostrongylus-infected mice having fewer peritoneal bacteria, more neutrophils, and higher levels of protective interleukin 6. The improved survival of Nippostrongylus-infected mice depends on IL-4 because the survival benefit is lost in mice lacking IL-4. Because mast cells protect mice from Klebsiella peritonitis, we examined responses in mast cell-deficient Kit(W-sh/Kit(W-sh mice, in which parasitosis failed to improve survival from Klebsiella peritonitis. However, adoptive transfer of cultured mast cells to Kit(W-sh/Kit(W-sh mice restored survival benefits of parasitosis. These results show that recent infection with Nippostrongylus brasiliensis protects mice from Klebsiella peritonitis by modulating mast cell contributions to host defense, and suggest more generally that parasitosis can yield survival advantages to a bacterially infected host.

  6. Improved differentiation of umbilical cord blood-derived mesenchymal stem cells into insulin-producing cells by PDX-1 mRNA transfection.

    Science.gov (United States)

    Van Pham, Phuc; Thi-My Nguyen, Phuoc; Thai-Quynh Nguyen, Anh; Minh Pham, Vuong; Nguyen-Tu Bui, Anh; Thi-Tung Dang, Loan; Gia Nguyen, Khue; Kim Phan, Ngoc

    2014-06-01

    Numerous studies have sought to identify diabetes mellitus treatment strategies with fewer side effects. Mesenchymal stem cell (MSC) therapy was previously considered as a promising therapy; however, it requires the cells to be trans-differentiated into cells of the pancreatic-endocrine lineage before transplantation. Previous studies have shown that PDX-1 expression can facilitate MSC differentiation into insulin-producing cells (IPCs), but the methods employed to date use viral or DNA-based tools to express PDX-1, with the associated risks of insertional mutation and immunogenicity. Thus, this study aimed to establish a new method to induce PDX-1 expression in MSCs by mRNA transfection. MSCs were isolated from human umbilical cord blood and expanded in vitro, with stemness confirmed by surface markers and multipotentiality. MSCs were transfected with PDX-1 mRNA by nucleofection and chemically induced to differentiate into IPCs (combinatorial group). This IPC differentiation was then compared with that of untransfected chemically induced cells (inducer group) and uninduced cells (control group). We found that PDX-1 mRNA transfection significantly improved the differentiation of MSCs into IPCs, with 8.3±2.5% IPCs in the combinatorial group, 3.21±2.11% in the inducer group and 0% in the control. Cells in the combinatorial group also strongly expressed several genes related to beta cells (Pdx-1, Ngn3, Nkx6.1 and insulin) and could produce C-peptide in the cytoplasm and insulin in the supernatant, which was dependent on the extracellular glucose concentration. These results indicate that PDX-1 mRNA may offer a promising approach to produce safe IPCs for clinical diabetes mellitus treatment. Copyright © 2014 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

  7. Reliable B cell epitope predictions: impacts of method development and improved benchmarking

    DEFF Research Database (Denmark)

    Kringelum, Jens Vindahl; Lundegaard, Claus; Lund, Ole

    2012-01-01

    biomedical applications such as; rational vaccine design, development of disease diagnostics and immunotherapeutics. However, experimental mapping of epitopes is resource intensive making in silico methods an appealing complementary approach. To date, the reported performance of methods for in silico mapping...... evaluation data set improved from 0.712 to 0.727. Our results thus demonstrate that given proper benchmark definitions, B-cell epitope prediction methods achieve highly significant predictive performances suggesting these tools to be a powerful asset in rational epitope discovery. The updated version...

  8. The effect of isolation and culture methods on epithelial stem cell populations and their progeny-toward an improved cell expansion protocol for clinical application.

    Science.gov (United States)

    Lenihan, Catherine; Rogers, Caroline; Metcalfe, Anthony D; Martin, Yella H

    2014-12-01

    The use of cultured epithelial keratinocytes in the treatment of burns and skin graft donor sites is well established in clinical practice. The most widely used culture method for clinical use was originally developed by Rheinwald and Green 40 years ago. This system uses irradiated mouse dermal fibroblasts as a feeder cell layer to promote keratinocyte growth, a process that is costly and labor-intensive for health care providers. The medium formulation contains several components of animal origin, which pose further safety risks for patients. Improvements and simplification in the culturing process would lead to clear advantages: improved safety through reduction of xenobiotic components and reduction in cost for health care providers by dispensing with feeder cells. We compared the Rheinwald and Green method to culture in three commercially available, feeder-free media systems with defined/absent components of animal origin. During the isolation process, short incubation times in high-strength trypsin resulted in increased numbers of liberated keratinocyte stem cells compared with longer incubation times. All three commercially available media tested in this study could support the expansion of keratinocytes, with phenotypes comparable to cells expanded using the established Rheinwald and Green method. Growth rates varied, with two of the media displaying comparable growth rates, whereas the third was significantly slower. Our study demonstrates the suitability of such feeder-free media systems in clinical use. It further outlines a range of techniques to evaluate keratinocyte phenotype when assessing the suitability of cells for clinical application. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  9. Subretinal Implantation of Retinal Pigment Epithelial Cells Derived From Human Embryonic Stem Cells: Improved Survival When Implanted as a Monolayer

    Science.gov (United States)

    Diniz, Bruno; Thomas, Padmaja; Thomas, Biju; Ribeiro, Ramiro; Hu, Yuntao; Brant, Rodrigo; Ahuja, Ashish; Zhu, Danhong; Liu, Laura; Koss, Michael; Maia, Mauricio; Chader, Gerald; Hinton, David R.; Humayun, Mark S.

    2013-01-01

    Purpose. To evaluate cell survival and tumorigenicity of human embryonic stem cell–derived retinal pigment epithelium (hESC-RPE) transplantation in immunocompromised nude rats. Cells were transplanted as a cell suspension (CS) or as a polarized monolayer plated on a parylene membrane (PM). Methods. Sixty-nine rats (38 male, 31 female) were surgically implanted with CS (n = 33) or PM (n = 36). Cohort subsets were killed at 1, 6, and 12 months after surgery. Both ocular tissues and systemic organs (brain, liver, kidneys, spleen, heart, and lungs) were fixed in 4% paraformaldehyde, embedded in paraffin, and sectioned. Every fifth section was stained with hematoxylin and eosin and analyzed histologically. Adjacent sections were processed for immunohistochemical analysis (as needed) using the following antibodies: anti-RPE65 (RPE-specific marker), anti-TRA-1-85 (human cell marker), anti-Ki67 (proliferation marker), anti-CD68 (macrophage), and anti-cytokeratin (epithelial marker). Results. The implanted cells were immunopositive for the RPE65 and TRA-1-85. Cell survival (P = 0.006) and the presence of a monolayer (P < 0.001) of hESC-RPE were significantly higher in eyes that received the PM. Gross morphological and histological analysis of the eye and the systemic organs after the surgery revealed no evidence of tumor or ectopic tissue formation in either group. Conclusions. hESC-RPE can survive for at least 12 months in an immunocompromised animal model. Polarized monolayers of hESC-RPE show improved survival compared to cell suspensions. The lack of teratoma or any ectopic tissue formation in the implanted rats bodes well for similar results with respect to safety in human subjects. PMID:23833067

  10. Improve T Cell Therapy in Neuroblastoma

    Science.gov (United States)

    2012-07-01

    Savoldo B, Vigouroux S et al. T lymphocytes redirected against the kappa light chain of human immunoglobulin efficiently kill mature B lymphocyte...Natl Acad Sci U S A. 2004;101(suppl 2):14622–14626. 8. Eghtesad S, Morel PA, Clemens PR. The companions : regulatory T cells and gene therapy...were euthanized and examined for NKT cell localiza- tion to the tumor tissues. Animals treated with anti-CCL2 or anti- CCL20 mAb had lower frequency

  11. Improve T Cell Therapy in Neuroblastoma

    Science.gov (United States)

    2015-09-01

    bioluminescence was then measured overtime. The graph is representative of one of 4 experiments using CMV-CTLs from 4 donors. Panel E. Kaplan-Meier...whole-cell vaccine expressing the iC9 gene and labeled with an enhanced firefly luciferase. Tumor growth was measured by in vivo imaging. Panel E...down regulation in LTE -T cells is not caused by specific culture conditions. T lymphocytes were activated with immobilized OKT3 (1 μg ml) and

  12. Si Hybrid Solar Cells with 13% Efficiency via Concurrent Improvement in Optical and Electrical Properties by Employing Graphene Quantum Dots

    KAUST Repository

    Tsai, Meng Lin

    2015-12-18

    By employing graphene quantum dots (GQDs) in PEDOT:PSS, we have achieved an efficiency of 13.22% in Si/PEDOT:PSS hybrid solar cells. The efficiency enhancement is based on concurrent improvement in optical and electrical properties by the photon downconversion process and the improved conductivity of PEDOT:PSS via appropriate incorporation of GQDs. After introducing GQDs into PEDOT:PSS, the short circuit current and the fill factor of rear-contact optimized hybrid cells are increased from 32.11 to 36.26 mA/cm and 62.85% to 63.87%, respectively. The organic-inorganic hybrid solar cell obtained herein holds the promise for developing photon-managing, low-cost, and highly efficient photovoltaic devices.

  13. Si Hybrid Solar Cells with 13% Efficiency via Concurrent Improvement in Optical and Electrical Properties by Employing Graphene Quantum Dots

    KAUST Repository

    Tsai, Meng Lin; Wei, Wan-Rou; Tang, Libin; Chang, Hung Chih; Tai, Shih Hsiang; Yang, Po Kang; Lau, Shu Ping; Chen, Lih Juann; He, Jr-Hau

    2015-01-01

    By employing graphene quantum dots (GQDs) in PEDOT:PSS, we have achieved an efficiency of 13.22% in Si/PEDOT:PSS hybrid solar cells. The efficiency enhancement is based on concurrent improvement in optical and electrical properties by the photon downconversion process and the improved conductivity of PEDOT:PSS via appropriate incorporation of GQDs. After introducing GQDs into PEDOT:PSS, the short circuit current and the fill factor of rear-contact optimized hybrid cells are increased from 32.11 to 36.26 mA/cm and 62.85% to 63.87%, respectively. The organic-inorganic hybrid solar cell obtained herein holds the promise for developing photon-managing, low-cost, and highly efficient photovoltaic devices.

  14. Puberdade precoce causada por tumores intracranianos: relato de 4 casos Pubertas praecox due to intracranial tumors: report of 4 cases

    Directory of Open Access Journals (Sweden)

    Reynaldo A. Brandt

    1974-12-01

    Full Text Available São relatados 4 casos de puberdade precoce conseqüentes a tumores intracranianos: um teratoma adulto do ventrículo lateral, um astrocitoma protoplasmático do terceiro ventrículo e diencéfalo, um astroblastoma do ter- ceiro ventrículo e diencéfalo e um hamartoma hipotalâmico. São apresentadas teorias que tentam explicar os mecanismos hormonais envolvidos e é salientada a importância do diagnóstico neuroradiológico preciso, pela possibilidade de cura em alguns casos e de tratamento satisfatório nos demais.Four cases of precocious puberty secondary to intracranial tumors are reported. A 3 year and 11 month old boy had a teratoma in the left lateral ventricle and total surgical excision was followed by recovery. An 8 year old girl with a protoplasmic astrocytoma of the third ventricle diagnosed by biopsy, followed by shunting and cobalt therapy was discharged improved. A five year old boy with an extensive astroblastoma of the diencephalon died following biopsy and shunting of cerebrospinal fluid. A posterior hypothalamic hamartoma totally excised from a 3 year old girl was followed by remission of the precocious puberty. The theories of hormonal mechanisms leading to precocious puberty are presented. It is stressed the importance of pneumoencephalography in the diagnosis of intracranial hamartomas, for they lack neurological signs.

  15. Novel Strategies for the Improvement of Stem Cells' Transplantation in Degenerative Retinal Diseases

    Science.gov (United States)

    Nicoară, Simona Delia; Șușman, Sergiu; Tudoran, Oana; Bărbos, Otilia; Cherecheș, Gabriela; Aștilean, Simion; Potara, Monica; Sorițău, Olga

    2016-01-01

    Currently, there is no cure for the permanent vision loss caused by degenerative retinal diseases. One of the novel therapeutic strategies aims at the development of stem cells (SCs) based neuroprotective and regenerative medicine. The main sources of SCs for the treatment of retinal diseases are the embryo, the bone marrow, the region of neuronal genesis, and the eye. The success of transplantation depends on the origin of cells, the route of administration, the local microenvironment, and the proper combinative formula of growth factors. The feasibility of SCs based therapies for degenerative retinal diseases was proved in the preclinical setting. However, their translation into the clinical realm is limited by various factors: the immunogenicity of the cells, the stability of the cell phenotype, the predilection of SCs to form tumors in situ, the abnormality of the microenvironment, and the association of a synaptic rewiring. To improve SCs based therapies, nanotechnology offers a smart delivery system for biomolecules, such as growth factors for SCs implantation and differentiation into retinal progenitors. This review explores the main advances in the field of retinal transplantology and applications of nanotechnology in the treatment of retinal diseases, discusses the challenges, and suggests new therapeutic approaches in retinal transplantation. PMID:27293444

  16. Long-Term Engraftment of Primary Bone Marrow Stromal Cells Repairs Niche Damage and Improves Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Abbuehl, Jean-Paul; Tatarova, Zuzana; Held, Werner; Huelsken, Joerg

    2017-08-03

    Hematopoietic stem cell (HSC) transplantation represents a curative treatment for various hematological disorders. However, delayed reconstitution of innate and adaptive immunity often causes fatal complications. HSC maintenance and lineage differentiation are supported by stromal niches, and we now find that bone marrow stroma cells (BMSCs) are severely and permanently damaged by the pre-conditioning irradiation required for efficient HSC transplantation. Using mouse models, we show that stromal insufficiency limits the number of donor-derived HSCs and B lymphopoiesis. Intra-bone transplantation of primary, but not cultured, BMSCs quantitatively reconstitutes stroma function in vivo, which is mediated by a multipotent NT5E + (CD73) + ENG - (CD105) - LY6A + (SCA1) + BMSC subpopulation. BMSC co-transplantation doubles the number of functional, donor-derived HSCs and significantly reduces clinically relevant side effects associated with HSC transplantation including neutropenia and humoral immunodeficiency. These data demonstrate the potential of stroma recovery to improve HSC transplantation. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Development and characterization of a spheroidal coculture model of endothelial cells and fibroblasts for improving angiogenesis in tissue engineering

    DEFF Research Database (Denmark)

    Wenger, Andreas; Kowalewski, Nadja; Stahl, Andreas

    2005-01-01

    Neovascularization is a critical step in tissue engineering applications since implantation of voluminous grafts without sufficient vascularity results in hypoxic cell death of central tissues. We have developed a three-dimensional spheroidal coculture system consisting of human umbilical vein...... endothelial cells (HUVECs) and human primary fibroblasts (hFBs) to improve angiogenesis in tissue engineering applications. Morphological analysis of cryosections from HUVEC/hFB cospheroids revealed a characteristic temporal and spatial organization with HUVECs located in the center of the cospheroid...... to the formation of heterogenic cell contacts between HUVECs and hFBs within the cospheroid. The model system introduced in this study is suitable for the development of a preformed lumenized capillary-like network ex vivo and may therefore be useful for improving angiogenesis in in vivo tissue engineering...

  18. Accelerated behavioural development changes fine-scale search behaviour and spatial memory in honey bees (Apis mellifera L.).

    Science.gov (United States)

    Ushitani, Tomokazu; Perry, Clint J; Cheng, Ken; Barron, Andrew B

    2016-02-01

    Normally, worker honey bees (Apis mellifera) begin foraging when more than 2 weeks old as adults, but if individual bees or the colony is stressed, bees often begin foraging precociously. Here, we examined whether bees that accelerated their behavioural development to begin foraging precociously differed from normal-aged foragers in cognitive performance. We used a social manipulation to generate precocious foragers from small experimental colonies and tested their performance in a free-flight visual reversal learning task, and a test of spatial memory. To assess spatial memory, bees were trained to learn the location of a small sucrose feeder within an array of three landmarks. In tests, the feeder and one landmark were removed and the search behaviour of the bees was recorded. Performance of precocious and normal-aged foragers did not differ in a visual reversal learning task, but the two groups showed a clear difference in spatial memory. Flight behaviour suggested normal-aged foragers were better able to infer the position of the removed landmark and feeder relative to the remaining landmarks than precocious foragers. Previous studies have documented the cognitive decline of old foragers, but this is the first suggestion of a cognitive deficit in young foragers. These data imply that worker honey bees continue their cognitive development during the adult stage. These findings may also help to explain why precocious foragers perform quite poorly as foragers and have a higher than normal loss rate. © 2016. Published by The Company of Biologists Ltd.

  19. Investigation of Micro- and Macro-Scale Transport Processes for Improved Fuel Cell Performance

    Energy Technology Data Exchange (ETDEWEB)

    Gu, Wenbin [General Motors LLC, Pontiac, MI (United States)

    2014-08-29

    This report documents the work performed by General Motors (GM) under the Cooperative agreement No. DE-EE0000470, “Investigation of Micro- and Macro-Scale Transport Processes for Improved Fuel Cell Performance,” in collaboration with the Penn State University (PSU), University of Tennessee Knoxville (UTK), Rochester Institute of Technology (RIT), and University of Rochester (UR) via subcontracts. The overall objectives of the project are to investigate and synthesize fundamental understanding of transport phenomena at both the macro- and micro-scales for the development of a down-the-channel model that accounts for all transport domains in a broad operating space. GM as a prime contractor focused on cell level experiments and modeling, and the Universities as subcontractors worked toward fundamental understanding of each component and associated interface.

  20. Quantify and improve PEM fuel cell durability. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Grahl-Madsen, L.; Odgaard, M.; Munksgaard Nielsen, R. (IRD Fuel Cell A/S, Svendborg (Denmark)); Li, Q.; Jensen, Jens Oluf (Technical Univ. of Denmark, Dept. of Chemistry, Kgs. Lyngby (Denmark)); Andersen, Shuang Ma; Speder, J.; Skou, E. (Syddansk Univ. (SDU), Odense (Denmark))

    2010-07-01

    approx 4,000 hours of operation correspond to a loss of catalytic active area of 58% for the anode and 69% for the cathode respectively, and the MEA can be expected to perform equivalent to MEAs with less than half the catalyst loating. DMFC durability tests were carried out on both Nafion and Hydrocarbon membrane based MEAs using different electrode designs. Several single DMFC cells and stacks have been tested up to 3,000 hours. The degradation rates found for both single cells and stacks were in the range between 10-90 muV/hours per cell, depending on the MEA configuration. Certain performance losses incurred by the cell during the steady-state operation were recovered, fully or in part, after the regular OCV hold. Regeneration of the Pt-catalyst particles include electro-reduction of the surface PtO that gradually forms over time, surface electro-oxidation of adsorbed poisons (namely CO formed from methanol crossover), and chemical reduction of PtO and/or PtOH via crossover methanol. The HT PEM FC results indicate that a degradation rate of approx 5 muV/h for HT PEM FC can be expected under continuous operation with hydrogen and air at 150-160 C, corresponding to a lifetime of 12,000 hours before 10% performance loss. This lifetime is somewhat shorter than aimed at in the national Danish HT PEM Road map (2009: 20,000 h), but it is in this context important to remember the limited knowledge on HT PEM lifetime at the time of the roadmap definition in 2008. The accelerated durability test with potential cycling showed significant catalyst degradation, primarily due to the corrosion of carbon supports, which triggers the platinum sintering/agglomeration. Modified catalyst supports in form of graphite or carbon nanotubes improve the catalyst and therefore the PBI cell durability. (LN)