WorldWideScience

Sample records for human endogenous cryogens

  1. Cryogenics and the Human Exploration of Mars

    Science.gov (United States)

    Salerno, Louis J.; Kittel, Peter; Rasky, Daniel J. (Technical Monitor)

    1997-01-01

    Current plans within NASA involve extending the human exploration of space from low earth orbit into the solar system, with the first human exploration of Mars presently planned in 2011. Integral to all hum Mars mission phases is cryogenic fluid management. Cryogenic fluids will be required both as propellant and for In-Situ Resource Utilization (ISRU). Without safe and efficient cryogen storage human Mars missions will not be possible. Effective control and handling of cryogenic fluids is the key to affordable Mars missions, and advancing active thermal control technology is synergistic with all of NASA's exploration initiatives and with existing and future instrument cooling programs, including MTPE and Origins. Present mission scenarios for human exploration require cryogenic propellant storage for up to 1700 days and for up to 60 metric tons. These requirements represent increases of an order of magnitude over previous storage masses and lifetimes. The key cryogenic terminology areas to be addressed in human Mars missions are long-term propellant storage, cryogenic refrigeration, cryogenic liquefaction, and zero gravity fluid management. Long-term storage for the thermal control of cryogenic propellants is best accomplished with a mix of passive and active technologies. Passive technologies such as advanced multilayer insulation (MLI) concepts will be combined with the development of active coolers (cryogenic refrigerators). Candidates for long-life active cooling applications include Reverse Turbo-Brayton, Stirling, and Pulse-Tube coolers. The integration of passive and active technologies will form a hybrid system optimized to minimize the launch mass while preserving the cryogenic propellants. Since cryogenic propellants are the largest mass that Mars missions must launch from earth, even a modest reduction in the percentage of propellant carried results in a significant weight saving. This paper will present a brief overview of cryogenic fluid management

  2. Cryogenic role of central endogenous hydrogen sulfide in the rat model of endotoxic shock.

    Science.gov (United States)

    Fernández, Rodrigo A R; Soriano, Renato N; Francescato, Heloísa D C; Sabino, João P; Coimbra, Terezila M; Branco, Luiz G S

    2016-11-01

    Thermoregulatory responses to lipopolysaccharide (LPS) are affected by modulators that increase (propyretic) or decrease (cryogenic) body temperature (Tb). We tested the hypothesis that central hydrogen sulfide (H2S) acts as a thermoregulatory modulator and that H2S production in the anteroventral preoptic region of the hypothalamus (AVPO) is increased during hypothermia and decreased during fever induced by bacterial lipopolysaccharide (LPS, 2.5mg/kg i.p.) in rats kept at an ambient temperature of 25°C. Deep Tb was recorded before and after pharmacological inhibition of the enzyme cystathionine β-synthase (CBS - responsible for H2S endogenous production in the brain) combined or not with LPS administration. To further investigate the mechanisms responsible for these thermoregulatory adjustments, we also measured prostaglandin D2 (PGD2) production in the AVPO. LPS caused typical hypothermia followed by fever. Levels of AVPO H2S were significantly increased during hypothermia when compared to both euthermic and febrile rats. Intracerebroventricular (icv) microinjection of aminooxyacetate (AOA, a CBS inhibitor; 100 pmol) neither affected Tb nor basal PGD2 production during euthermia. In LPS-treated rats, AOA caused increased Tb values during hypothermia, along with enhanced PGD2 production. We conclude that the gaseous messenger H2S modulates hypothermia during endotoxic shock, acting as a cryogenic molecule. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Optimal income taxation with endogenous human capital

    NARCIS (Netherlands)

    B. Jacobs

    2005-01-01

    This paper augments the theory of optimal linear income taxation by taking into account human capital accumulation as a dimension of labor supply. The distribution of earning potentials is endogenous because agents differ in the ability to learn. Taxation affects utilization rates of human capital t

  4. Endogenous retroviral promoter exaptation in human cancer

    Directory of Open Access Journals (Sweden)

    Artem Babaian

    2016-12-01

    Full Text Available Abstract Cancer arises from a series of genetic and epigenetic changes, which result in abnormal expression or mutational activation of oncogenes, as well as suppression/inactivation of tumor suppressor genes. Aberrant expression of coding genes or long non-coding RNAs (lncRNAs with oncogenic properties can be caused by translocations, gene amplifications, point mutations or other less characterized mechanisms. One such mechanism is the inappropriate usage of normally dormant, tissue-restricted or cryptic enhancers or promoters that serve to drive oncogenic gene expression. Dispersed across the human genome, endogenous retroviruses (ERVs provide an enormous reservoir of autonomous gene regulatory modules, some of which have been co-opted by the host during evolution to play important roles in normal regulation of genes and gene networks. This review focuses on the “dark side” of such ERV regulatory capacity. Specifically, we discuss a growing number of examples of normally dormant or epigenetically repressed ERVs that have been harnessed to drive oncogenes in human cancer, a process we term onco-exaptation, and we propose potential mechanisms that may underlie this phenomenon.

  5. K-type human endogenous retroviral elements in human melanoma

    Directory of Open Access Journals (Sweden)

    Rincon L

    2014-10-01

    Full Text Available Liliana Rincon,1 Michael P Sedrak,1 Huijian Sun,2 Gregorio Garza,3 Brent Kelly,4 Jianli Dong11Department of Pathology, 2School of Medicine, University of Texas Medical Branch, TX, USA; 3Ciencias de la Salud, Universidad de Monterrey, Nuevo León, Mexico; 4Department of Dermatology, University of Texas Medical Branch, TX, USAAbstract: Human endogenous retroviral elements (HERVs are thought to be germline-integrated genetic remnants of exogenous retroviral infections. HERVs comprise approximately 5%–8% of the human genome. Although all HERV genomes are highly defective, some, especially the K type (HERV-K, have the potential to be expressed and have biological activities. HERV-K expression has been detected in human melanomas. There are also reports on the regulation and potential activities of HERV-K in melanoma cells. Although a causal link between the activation of HERV-K and melanoma development has yet to be determined, existing data support the further research efforts in this area. In this review, we summarize the published studies on the expression, regulation, and activity of HERV-K in human melanoma.Keywords: HERV, HERV-K, melanoma development

  6. A revised nomenclature for transcribed human endogenous retroviral loci

    Directory of Open Access Journals (Sweden)

    Mayer Jens

    2011-05-01

    Full Text Available Abstract Background Endogenous retroviruses (ERVs and ERV-like sequences comprise 8% of the human genome. A hitherto unknown proportion of ERV loci are transcribed and thus contribute to the human transcriptome. A small proportion of these loci encode functional proteins. As the role of ERVs in normal and diseased biological processes is not yet established, transcribed ERV loci are of particular interest. As more transcribed ERV loci are likely to be identified in the near future, the development of a systematic nomenclature is important to ensure that all information on each locus can be easily retrieved. Results Here we present a revised nomenclature of transcribed human endogenous retroviral loci that sorts loci into groups based on Repbase classifications. Each symbol is of the format ERV + group symbol + unique number. Group symbols are based on a mixture of Repbase designations and well-supported symbols used in the literature. The presented guidelines will allow newly identified loci to be easily incorporated into the scheme. Conclusions The naming system will be employed by the HUGO Gene Nomenclature Committee for naming transcribed human ERV loci. We hope that the system will contribute to clarifying a certain aspect of a sometimes confusing nomenclature for human endogenous retroviruses. The presented system may also be employed for naming transcribed loci of human non-ERV repeat loci.

  7. Are human endogenous retroviruses triggers of autoimmune diseases?

    DEFF Research Database (Denmark)

    Nexø, Bjørn A; Villesen, Palle; Nissen, Kari K

    2016-01-01

    Autoimmune diseases encompass a plethora of conditions in which the immune system attacks its own tissue, identifying them as foreign. Multiple factors are thought to contribute to the development of immune response to self, including differences in genotypes, hormonal milieu, and environmental...... manner. In this study by means of genetic epidemiology, we have searched for the involvement of endogenous retroviruses in three selected autoimmune diseases: multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis. We found that at least one human endogenous retroviral locus...... was associated with each of the three diseases. Although there was a significant overlap, most loci only occurred in one of the studied disease. Remarkably, within each disease, there was a statistical interaction (synergy) between two loci. Additional synergy between retroviral loci and human lymphocyte...

  8. Inhibition of endogenous lactate turnover with lactate infusion in humans

    Energy Technology Data Exchange (ETDEWEB)

    Searle, G.L.; Feingold, K.R.; Hsu, F.S.; Clark, O.H.; Gertz, E.W.; Stanley, W.C. (Veterans Administration Medical Center, San Francisco, CA (USA))

    1989-11-01

    The extent to which lactate infusion may inhibit endogenous lactate production, though previously considered, has never been critically assessed. To examine this proposition, single injection tracer methodology (U-{sup 14}C Lactate) has been used for the estimation of lactate kinetics in 12 human subjects under basal conditions and with the infusion of sodium lactate. The basal rate of lactate turnover was measured on a day before the study with lactate infusion, and averaged 63.7 + 5.5 mg/kg/h. Six of these individuals received a stable lactate infusion at an approximate rate of 160 mg/kg/h, while the remaining six individuals were infused at the approximate rate of 100 mg/kg/h. It has been found that stable lactate infused at rates approximating 160 mg/kg/h consistently produced a complete inhibition of endogenous lactate production. Infusion of lactate at 100 mg/kg/h caused a lesser and more variable inhibition of endogenous lactate production (12% to 64%). In conclusion, lactate infusion significantly inhibits endogenous lactate production.

  9. Endogenous neurogenesis in the human brain following cerebral infarction.

    Science.gov (United States)

    Minger, Stephen L; Ekonomou, Antigoni; Carta, Eloisa M; Chinoy, Amish; Perry, Robert H; Ballard, Clive G

    2007-01-01

    Increased endogenous neurogenesis has a significant regenerative role in many experimental models of cerebrovascular diseases, but there have been very few studies in humans. We therefore examined whether there was evidence of altered endogenous neurogenesis in an 84-year-old patient who suffered a cerebrovascular accident 1 week prior to death. Using antibodies that specifically label neural stem/neural progenitor cells, we examined the presence of immunopositive cells around and distant from the infarcted area, and compared this with a control, age-matched individual. Interestingly, a large number of neural stem cells, vascular endothelial growth factor-immunopositive cells and new blood vessels were observed only around the region of infarction, and none in the corresponding brain areas of the healthy control. In addition, an increased number of neural stem cells was observed in the neurogenic region of the lateral ventricle wall. Our results suggest increased endogenous neurogenesis associated with neovascularization and migration of newly-formed cells towards a region of cerebrovascular damage in the adult human brain and highlight possible mechanisms underlying this process.

  10. Human Endogenous Retrovirus Group E and Its Involvement in Diseases

    Directory of Open Access Journals (Sweden)

    Christelle Le Dantec

    2015-03-01

    Full Text Available Human endogenous retrovirus group E (HERV-E elements are stably integrated into the human genome, transmitted vertically in a Mendelian manner, and are endowed with transcriptional activity as alternative promoters or enhancers. Such effects are under the control of the proviral long terminal repeats (LTR that are organized into three HERV-E phylogenetic subgroups, namely LTR2, LTR2B, and LTR2C. Moreover, HERV-E expression is tissue-specific, and silenced by epigenetic constraints that may be disrupted in cancer, autoimmunity, and human placentation. Interest in HERV-E with regard to these conditions has been stimulated further by concerns regarding the capacity of HERV-E elements to modify the expression of neighboring genes and/or to produce retroviral proteins, including immunosuppressive env peptides, which in turn may induce (auto-antibody (Ab production. Finally, better understanding of HERV-E elements may have clinical applications for prevention, diagnosis, prognosis, and therapy.

  11. Human Endogenous Retrovirus W Activity in Cartilage of Osteoarthritis Patients

    Directory of Open Access Journals (Sweden)

    Signy Bendiksen

    2014-01-01

    Full Text Available The etiology of viruses in osteoarthritis remains controversial because the prevalence of viral nucleic acid sequences in peripheral blood or synovial fluid from osteoarthritis patients and that in healthy control subjects are similar. Until now the presence of virus has not been analyzed in cartilage. We screened cartilage and chondrocytes from advanced and non-/early osteoarthritis patients for parvovirus B19, herpes simplex virus-1, Epstein Barr virus, cytomegalovirus, human herpes virus-6, hepatitis C virus, and human endogenous retroviruses transcripts. Endogenous retroviruses transcripts, but none of the other viruses, were detected in 15 out the 17 patients. Sequencing identified the virus as HERV-WE1 and E2. HERV-W activity was confirmed by high expression levels of syncytin, dsRNA, virus budding, and the presence of virus-like particles in all advanced osteoarthritis cartilages examined. Low levels of HERV-WE1, but not E2 envelope RNA, were observed in 3 out of 8 non-/early osteoarthritis patients, while only 3 out of 7 chondrocytes cultures displayed low levels of syncytin, and just one was positive for virus-like particles. This study demonstrates for the first time activation of HERV-W in cartilage of osteoarthritis patients; however, a causative role for HERV-W in development or deterioration of the disease remains to be proven.

  12. Molecular functions of human endogenous retroviruses in health and disease.

    Science.gov (United States)

    Suntsova, Maria; Garazha, Andrew; Ivanova, Alena; Kaminsky, Dmitry; Zhavoronkov, Alex; Buzdin, Anton

    2015-10-01

    Human endogenous retroviruses (HERVs) and related genetic elements form 504 distinct families and occupy ~8% of human genome. Recent success of high-throughput experimental technologies facilitated understanding functional impact of HERVs for molecular machinery of human cells. HERVs encode active retroviral proteins, which may exert important physiological functions in the body, but also may be involved in the progression of cancer and numerous human autoimmune, neurological and infectious diseases. The spectrum of related malignancies includes, but not limits to, multiple sclerosis, psoriasis, lupus, schizophrenia, multiple cancer types and HIV. In addition, HERVs regulate expression of the neighboring host genes and modify genomic regulatory landscape, e.g., by providing regulatory modules like transcription factor binding sites (TFBS). Indeed, recent bioinformatic profiling identified ~110,000 regulatory active HERV elements, which formed at least ~320,000 human TFBS. These and other peculiarities of HERVs might have played an important role in human evolution and speciation. In this paper, we focus on the current progress in understanding of normal and pathological molecular niches of HERVs, on their implications in human evolution, normal physiology and disease. We also review the available databases dealing with various aspects of HERV genetics.

  13. Inequality in Human Capital and Endogenous Credit Constraints.

    Science.gov (United States)

    Hai, Rong; Heckman, James J

    2017-04-01

    This paper investigates the determinants of inequality in human capital with an emphasis on the role of the credit constraints. We develop and estimate a model in which individuals face uninsured human capital risks and invest in education, acquire work experience, accumulate assets and smooth consumption. Agents can borrow from the private lending market and from government student loan programs. The private market credit limit is explicitly derived by extending the natural borrowing limit of Aiyagari (1994) to incorporate endogenous labor supply, human capital accumulation, psychic costs of working, and age. We quantify the effects of cognitive ability, noncognitive ability, parental education, and parental wealth on educational attainment, wages, and consumption. We conduct counterfactual experiments with respect to tuition subsidies and enhanced student loan limits and evaluate their effects on educational attainment and inequality. We compare the performance of our model with an influential ad hoc model in the literature with education-specific fixed loan limits. We find evidence of substantial life cycle credit constraints that affect human capital accumulation and inequality. The constrained fall into two groups: those who are permanently poor over their lifetimes and a group of well-endowed individuals with rising high levels of acquired skills who are constrained early in their life cycles. Equalizing cognitive and noncognitive ability has dramatic effects on inequality. Equalizing parental backgrounds has much weaker effects. Tuition costs have weak effects on inequality.

  14. New insight into transcription of human endogenous retroviral elements.

    Science.gov (United States)

    Pačes, Jan; Huang, Yao-Ting; Pačes, Václav; Rídl, Jakub; Chang, Chung-Ming

    2013-03-25

    It is generally assumed that human endogenous retroviral elements (HERVs) belong to the class of genomic repetitive nucleotide sequences often called 'junk DNA'. These elements were categorized to families, and members of some of these families (e.g. HERV-H, HERV-W and HERV-K) were shown to be transcribed. These transcriptions were associated with several severe diseases such as mental disorders, AIDS, autoimmune diseases and cancer. In this review we discuss several bioinformatics strategies for genome-wide scan of HERVs transcription using high-throughput RNA sequencing on several platforms. We show that many more HERVs than previously described are transcribed to various levels and we discuss possible implications of these transcriptions.

  15. Human endogenous retroviruses and cancer prevention: evidence and prospects

    Directory of Open Access Journals (Sweden)

    Cegolon Luca

    2013-01-01

    Full Text Available Abstract Background Cancer is a significant and growing problem worldwide. While this increase may, in part, be attributed to increasing longevity, improved case notifications and risk-enhancing lifestyle (such as smoking, diet and obesity, hygiene-related factors resulting in immuno-regulatory failure may also play a major role and call for a revision of vaccination strategies to protect against a range of cancers in addition to infections. Discussion Human endogenous retroviruses (HERVs are a significant component of a wider family of retroelements that constitutes part of the human genome. They were originated by the integration of exogenous retroviruses into the human genome millions of years ago. HERVs are estimated to comprise about 8% of human DNA and are ubiquitous in somatic and germinal tissues. Physiologic and pathologic processes are influenced by some biologically active HERV families. HERV antigens are only expressed at low levels by the host, but in circumstances of inappropriate control their genes may initiate or maintain pathological processes. Although the precise mechanism leading to abnormal HERVs gene expression has yet to be clearly elucidated, environmental factors seem to be involved by influencing the human immune system. HERV-K expression has been detected in different types of tumors. Among the various human endogenous retroviral families, the K series was the latest acquired by the human species. Probably because of its relatively recent origin, the HERV-K is the most complete and biologically active family. The abnormal expression of HERV-K seemingly triggers pathological processes leading to melanoma onset, but also contributes to the morphological and functional cellular modifications implicated in melanoma maintenance and progression. The HERV-K-MEL antigen is encoded by a pseudo-gene incorporated in the HERV-K env-gene. HERV-K-MEL is significantly expressed in the majority of dysplastic and normal naevi, as well

  16. Human endogenous retroviruses and cancer: Causality and therapeutic possibilities

    Institute of Scientific and Technical Information of China (English)

    Christina S Mullins; Michael Linnebacher

    2012-01-01

    A substantial part of the human genome is derived from transposable elements; remnants of ancient retroviral infections.Conservative estimates set the percentage of human endogenous retroviruses (HERVs)in the genome at 8%.For the most part,the interplay between mutations,epigenetic mechanisms and posttranscriptional regulations silence HERVs in somatic cells.We first highlight mechanisms by which activation of members of several HERV families may be associated with tumor development before discussing the arising chances for both diagnosis and therapy.It has been shown that at least in some cases,tumor cells expressing HERV open reading frames (ORFs) thus gain tumor-promoting functions.However,since these proteins are not expressed in healthy tissues,they become prime target structures.Of potential pharmacological interest are the prevention of HERV transposition,the inhibition of HERV-encoded protein expression and the interference with these proteins' activities.Evidence from recent studies unequivocally proves that HERV ORFs represent a very interesting source of novel tumor-specific antigens with even the potential to surpass entity boundaries.The development of new tumor (immune-) therapies is a very active field and true tumor-specific targets are of outstanding interest since they minimize the risk of autoimmunity and could reduce side effects.Finally,we postulate on main future research streams in order to stimulate discussion on this hot topic.

  17. Human endogenous retrovirus-K contributes to motor neuron disease.

    Science.gov (United States)

    Li, Wenxue; Lee, Myoung-Hwa; Henderson, Lisa; Tyagi, Richa; Bachani, Muzna; Steiner, Joseph; Campanac, Emilie; Hoffman, Dax A; von Geldern, Gloria; Johnson, Kory; Maric, Dragan; Morris, H Douglas; Lentz, Margaret; Pak, Katherine; Mammen, Andrew; Ostrow, Lyle; Rothstein, Jeffrey; Nath, Avindra

    2015-09-30

    The role of human endogenous retroviruses (HERVs) in disease pathogenesis is unclear. We show that HERV-K is activated in a subpopulation of patients with sporadic amyotrophic lateral sclerosis (ALS) and that its envelope (env) protein may contribute to neurodegeneration. The virus was expressed in cortical and spinal neurons of ALS patients, but not in neurons from control healthy individuals. Expression of HERV-K or its env protein in human neurons caused retraction and beading of neurites. Transgenic animals expressing the env gene developed progressive motor dysfunction accompanied by selective loss of volume of the motor cortex, decreased synaptic activity in pyramidal neurons, dendritic spine abnormalities, nucleolar dysfunction, and DNA damage. Injury to anterior horn cells in the spinal cord was manifested by muscle atrophy and pathological changes consistent with nerve fiber denervation and reinnervation. Expression of HERV-K was regulated by TAR (trans-activation responsive) DNA binding protein 43, which binds to the long terminal repeat region of the virus. Thus, HERV-K expression within neurons of patients with ALS may contribute to neurodegeneration and disease pathogenesis. Copyright © 2015, American Association for the Advancement of Science.

  18. Implication of Human Endogenous Retrovirus Envelope Proteins in Placental Functions

    Directory of Open Access Journals (Sweden)

    Adjimon Gatien Lokossou

    2014-11-01

    Full Text Available Human endogenous retroviruses (ERVs represent 8% of the total human genome. Although the majority of these ancient proviral sequences have only retained non-coding long terminal repeats (LTRs, a number of “endogenized” retroviral genes encode functional proteins. Previous studies have underlined the implication of these ERV-derived proteins in the development and the function of the placenta. In this review, we summarize recent findings showing that two ERV genes, termed Syncytin-1 and Syncytin-2, which encode former envelope (Env proteins, trigger fusion events between villous cytotrophoblasts and the peripheral multinucleated syncytiotrophoblast layer. Such fusion events maintain the stability of this latter cell structure, which plays an important role in fetal development by the active secretion of various soluble factors, gas exchange and regulation of fetomaternal immunotolerance. We also highlight new studies showing that these ERV proteins, in addition to their localization at the cell surface of cytotrophoblasts, are also incorporated on the surface of various extracellular microvesicles, including exosomes. Such exosome-associated proteins could be involved in the various functions attributed to these vesicles and could provide a form of tropism. Additionally, through their immunosuppressive domains, these ERV proteins could also contribute to fetomaternal immunotolerance in a local and more distal manner. These various aspects of the implication of Syncytin-1 and -2 in placental function are also addressed in the context of the placenta-related disorder, preeclampsia.

  19. Relative clock demonstrates the endogenous heterogeneity of human dynamics

    CERN Document Server

    Zhou, Tao; Yang, Zimo; Zhou, Changsong

    2011-01-01

    The heavy-tailed inter-event time distributions are widely observed in many human-activated systems, which may result from both endogenous mechanisms like the highest-priority-first protocol and exogenous factors like the varying global activity versus time. To distinguish the effects on temporal statistics from different mechanisms is this of theoretical significance. In this Letter, we propose a new timing method by using a relative clock, where the time length between two consecutive events of an individual is counted as the number of other individuals' events appeared during this interval. We propose a model, in which agents act either in a constant rate or with a power-law inter-event time distribution, and the global activity either keeps unchanged or varies periodically versus time. Our analysis shows that the heavy tails caused by the heterogeneity of global activity can be eliminated by setting the relative clock, yet the heterogeneity due to real individual behaviors still exists. We perform extensi...

  20. The role of human endogenous retroviruses in brain development and function.

    Science.gov (United States)

    Mortelmans, Kristien; Wang-Johanning, Feng; Johanning, Gary L

    2016-01-01

    Endogenous retroviral sequences are spread throughout the genome of all humans, and make up about 8% of the genome. Despite their prevalence, the function of human endogenous retroviruses (HERVs) in humans is largely unknown. In this review we focus on the brain, and evaluate studies in animal models that address mechanisms of endogenous retrovirus activation in the brain and central nervous system (CNS). One such study in mice found that TRIM28, a protein critical for mouse early development, regulates transcription and silencing of endogenous retroviruses in neural progenitor cells. Another intriguing finding in human brain cells and mouse models was that endogenous retrovirus HERV-K appears to be protective against neurotoxins. We also report on studies that associate HERVs with human diseases of the brain and CNS. There is little doubt of an association between HERVs and a number of CNS diseases. However, a cause and effect relationship between HERVs and these diseases has not yet been established.

  1. Detection and distribution of endogenous steroids in human stratum corneum

    Directory of Open Access Journals (Sweden)

    Shu-Ping Tseng

    2014-03-01

    Conclusion: The results demonstrate that, with the achievable sensitivity of current analytical technology, physiological concentrations of endogenous steroids, such as hydrocortisone and cortisone, can be found in the SC of some individuals.

  2. English walnuts (Juglans regia L.) protect endogenous antioxidants in humans

    Science.gov (United States)

    Ellagic acid monomers, polymeric tannins and related phenolic compounds isolated from English walnuts (Juglans regia L.) have been reported to inhibit LDL oxidation ex vivo and decrease biomarkers of oxidative stress in animal models. To determine whether dietary and endogenous antioxidants are pres...

  3. Improved methodology for the affinity isolation of human protein complexes expressed at near endogenous levels

    DEFF Research Database (Denmark)

    Domanski, Michal; Molloy, Kelly; Jiang, Hua;

    2012-01-01

    An efficient and reliable procedure for the capture of affinity-tagged proteins and associated complexes from human cell lines is reported. Through multiple optimizations, high yield and low background affinity-purifications are achieved from modest quantities of human cells expressing endogenous......-level tagged proteins. Isolations of triple-FLAG and GFP-tagged fusion proteins involved in RNA metabolism are presented.......An efficient and reliable procedure for the capture of affinity-tagged proteins and associated complexes from human cell lines is reported. Through multiple optimizations, high yield and low background affinity-purifications are achieved from modest quantities of human cells expressing endogenous...

  4. Involvement of human endogenous retroviral syncytin-1 in human osteoclast fusion

    DEFF Research Database (Denmark)

    Søe, Kent; Andersen, Thomas Lykke; Hobolt-Pedersen, Anne-Sofie

    2011-01-01

    fusion of the lipid bilayers of their cell membranes are still unknown. Syncytin-1 is a protein encoded by a human endogenous retroviral gene which was stably integrated into the human ancestor genome more than 24 million years ago. Upon activation, syncytin-1 is able to destabilize the lipid bilayer......Generation of osteoclasts through fusion of mono-nucleated precursors is a key event of bone physiology and bone resorption is inefficient without osteoclast fusion. Several factors playing a critical role in the fusion process have already been recognized, but the factors involved in the actual....... This was documented through Q-PCR, Western blot and immunofluorescence analyses. These in vitro findings were confirmed by immunohistochemical stainings in human iliac crest biopsies. A syncytin-1 inhibitory peptide reduced the number of nuclei per osteoclast by 30%, as well as TRACP activity. From a mechanistic...

  5. No association of polymorphisms in human endogenous retrovirus K18 and CD48 with schizophrenia

    DEFF Research Database (Denmark)

    Nyegaard, Mette; Demontis, Ditte; Thestrup, Britta Boserup;

    2012-01-01

    The human endogenous retrovirus HERV-K18 is located within intron 1 of CD48 on chromosome 1q and is still active in the human genome. Genetic variation in HERV-K18 single-nucleotide polymorphisms (SNPs) has previously been associated with an increased risk of schizophrenia (SZ) and with type 2...

  6. Endogenous APOBEC3B restricts LINE-1 retrotransposition in transformed cells and human embryonic stem cells.

    Science.gov (United States)

    Wissing, Silke; Montano, Mauricio; Garcia-Perez, Jose Luis; Moran, John V; Greene, Warner C

    2011-10-21

    Members of the APOBEC3 (A3) family of cytidine deaminase enzymes act as host defense mechanisms limiting both infections by exogenous retroviruses and mobilization of endogenous retrotransposons. Previous studies revealed that the overexpression of some A3 proteins could restrict engineered human Long INterspersed Element-1 (LINE-1 or L1) retrotransposition in HeLa cells. However, whether endogenous A3 proteins play a role in restricting L1 retrotransposition remains largely unexplored. Here, we show that HeLa cells express endogenous A3B and A3C, whereas human embryonic stem cells (hESCs) express A3B, A3C, A3DE, A3F, and A3G. To study the relative contribution of endogenous A3 proteins in restricting L1 retrotransposition, we first generated small hairpin RNAs (shRNAs) to suppress endogenous A3 mRNA expression, and then assessed L1 mobility using a cell-based L1 retrotransposition assay. We demonstrate that in both HeLa and hESCs, shRNA-based knockdown of A3B promotes a ∼2-3.7-fold increase in the retrotransposition efficiency of an engineered human L1. Knockdown of the other A3s produced no significant increase in L1 activity. Thus, A3B appears to restrict engineered L1 retrotransposition in a broad range of cell types, including pluripotent cells.

  7. Plasma adiponectin and endogenous glucose production in humans

    DEFF Research Database (Denmark)

    Stefan, Norbert; Stumvoll, Michael; Vozarova, Barbora

    2003-01-01

    High plasma adiponectin is associated with reduced risk of type 2 diabetes, probably a consequence of its insulin-sensitizing properties. In vivo data in rodents suggest that the insulin-sensitization responsible for improvement of glycemia occurs in muscle and liver. Whereas associations of plasma...... adiponectin with muscle insulin sensitivity in humans have been examined, this has not been done for the liver....

  8. Endogenous control of waking brain rhythms induces neuroplasticity in humans.

    NARCIS (Netherlands)

    Ros, T.; Munneke, M.; Ruge, D.; Gruzelier, J.H.; Rothwell, J.C.

    2010-01-01

    This study explores the possibility of noninvasively inducing long-term changes in human corticomotor excitability by means of a brain-computer interface, which enables users to exert internal control over the cortical rhythms recorded from the scalp. We demonstrate that self-regulation of electroen

  9. Endogenous collagen influences differentiation of human multipotent mesenchymal stromal cells

    NARCIS (Netherlands)

    Fernandes, H.; Mentink, A.; Bank, R.; Stoop, R.; Blitterswijk, C. van; Boer, J. de

    2010-01-01

    Human multipotent mesenchymal stromal cells (hMSCs) are multipotent cells that, in the presence of appropriate stimuli, can differentiate into different lineages such as the osteogenic, chondrogenic, and adipogenic lineages. In the presence of ascorbic acid, MSCs secrete an extracellular matrix main

  10. Monomethylarsonous acid inhibited endogenous cholesterol biosynthesis in human skin fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Lei [Environmental Toxicology Graduate Program, University of California, Riverside, CA 92521-0403 (United States); Xiao, Yongsheng [Department of Chemistry, University of California, Riverside, CA 92521-0403 (United States); Wang, Yinsheng, E-mail: yinsheng.wang@ucr.edu [Environmental Toxicology Graduate Program, University of California, Riverside, CA 92521-0403 (United States); Department of Chemistry, University of California, Riverside, CA 92521-0403 (United States)

    2014-05-15

    Human exposure to arsenic in drinking water is a widespread public health concern, and such exposure is known to be associated with many human diseases. The detailed molecular mechanisms about how arsenic species contribute to the adverse human health effects, however, remain incompletely understood. Monomethylarsonous acid [MMA(III)] is a highly toxic and stable metabolite of inorganic arsenic. To exploit the mechanisms through which MMA(III) exerts its cytotoxic effect, we adopted a quantitative proteomic approach, by coupling stable isotope labeling by amino acids in cell culture (SILAC) with LC-MS/MS analysis, to examine the variation in the entire proteome of GM00637 human skin fibroblasts following acute MMA(III) exposure. Among the ∼ 6500 unique proteins quantified, ∼ 300 displayed significant changes in expression after exposure with 2 μM MMA(III) for 24 h. Subsequent analysis revealed the perturbation of de novo cholesterol biosynthesis, selenoprotein synthesis and Nrf2 pathways evoked by MMA(III) exposure. Particularly, MMA(III) treatment resulted in considerable down-regulation of several enzymes involved in cholesterol biosynthesis. In addition, real-time PCR analysis showed reduced mRNA levels of select genes in this pathway. Furthermore, MMA(III) exposure contributed to a distinct decline in cellular cholesterol content and significant growth inhibition of multiple cell lines, both of which could be restored by supplementation of cholesterol to the culture media. Collectively, the present study demonstrated that the cytotoxicity of MMA(III) may arise, at least in part, from the down-regulation of cholesterol biosynthesis enzymes and the resultant decrease of cellular cholesterol content. - Highlights: • MMA(III)-induced perturbation of the entire proteome of GM00637 cells is studied. • Quantitative proteomic approach revealed alterations of multiple cellular pathways. • MMA(III) inhibits de novo cholesterol biosynthesis. • MMA

  11. Cell lineage analysis in human brain using endogenous retroelements.

    Science.gov (United States)

    Evrony, Gilad D; Lee, Eunjung; Mehta, Bhaven K; Benjamini, Yuval; Johnson, Robert M; Cai, Xuyu; Yang, Lixing; Haseley, Psalm; Lehmann, Hillel S; Park, Peter J; Walsh, Christopher A

    2015-01-07

    Somatic mutations occur during brain development and are increasingly implicated as a cause of neurogenetic disease. However, the patterns in which somatic mutations distribute in the human brain are unknown. We used high-coverage whole-genome sequencing of single neurons from a normal individual to identify spontaneous somatic mutations as clonal marks to track cell lineages in human brain. Somatic mutation analyses in >30 locations throughout the nervous system identified multiple lineages and sublineages of cells marked by different LINE-1 (L1) retrotransposition events and subsequent mutation of poly-A microsatellites within L1. One clone contained thousands of cells limited to the left middle frontal gyrus, whereas a second distinct clone contained millions of cells distributed over the entire left hemisphere. These patterns mirror known somatic mutation disorders of brain development and suggest that focally distributed mutations are also prevalent in normal brains. Single-cell analysis of somatic mutation enables tracing of cell lineage clones in human brain. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Transcriptional Activity of Human Endogenous Retroviruses in Human Peripheral Blood Mononuclear Cells

    Directory of Open Access Journals (Sweden)

    Emanuela Balestrieri

    2015-01-01

    Full Text Available Human endogenous retroviruses (HERVs have been implicated in human physiology and in human pathology. A better knowledge of the retroviral transcriptional activity in the general population and during the life span would greatly help the debate on its pathologic potential. The transcriptional activity of four HERV families (H, K, W, and E was assessed, by qualitative and quantitative PCR, in PBMCs from 261 individuals aged from 1 to 80 years. Our results show that HERV-H, HERV-K, and HERV-W, but not HERV-E, are transcriptionally active in the test population already in the early childhood. In addition, the transcriptional levels of HERV-H, HERV-K, and HERV-W change significantly during the life span, albeit with distinct patterns. Our results, reinforce the hypothesis of a physiological correlation between HERVs activity and the different stages of life in humans. Studies aiming at identifying the factors, which are responsible for these changes during the individual’s life, are still needed. Although the observed phenomena are presumably subjected to great variability, the basal transcriptional activity of each individual, also depending on the different ages of life, must be carefully considered in all the studies involving HERVs as causative agents of disease.

  13. Endogenous bile acid disposition in rat and human sandwich-cultured hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Marion, Tracy L., E-mail: tracylmarion@qualyst.com [Curriculum in Toxicology, UNC School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7270 (United States); Perry, Cassandra H., E-mail: cassandraperry@qualyst.com [Qualyst, Inc., Durham, NC 27713 (United States); St Claire, Robert L., E-mail: bobstclaire@qualyst.com [Qualyst, Inc., Durham, NC 27713 (United States); Brouwer, Kim L.R., E-mail: kbrouwer@unc.edu [Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, CB 7569 Kerr Hall, Chapel Hill, NC 27599-7569 (United States)

    2012-05-15

    Sandwich-cultured hepatocytes (SCH) are used commonly to investigate hepatic transport protein-mediated uptake and biliary excretion of substrates. However, little is known about the disposition of endogenous bile acids (BAs) in SCH. In this study, four endogenous conjugated BAs common to rats and humans [taurocholic acid (TCA), glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), and glycochenodeoxycholic acid (GCDCA)], as well as two BA species specific to rodents (α- and β-tauromuricholic acid; α/β TMCA), were profiled in primary rat and human SCH. Using B-CLEAR{sup ®} technology, BAs were measured in cells + bile canaliculi, cells, and medium of SCH by LC-MS/MS. Results indicated that, just as in vivo, taurine-conjugated BA species were predominant in rat SCH, while glycine-conjugated BAs were predominant in human SCH. Total intracellular BAs remained relatively constant over days in culture in rat SCH. Total BAs in control (CTL) cells + bile, cells, and medium were approximately 3.4, 2.9, and 8.3-fold greater in human than in rat. The estimated intracellular concentrations of the measured total BAs were 64.3 ± 5.9 μM in CTL rat and 183 ± 56 μM in CTL human SCH, while medium concentrations of the total BAs measured were 1.16 ± 0.21 μM in CTL rat SCH and 9.61 ± 6.36 μM in CTL human SCH. Treatment of cells for 24 h with 10 μM troglitazone (TRO), an inhibitor of the bile salt export pump (BSEP) and the Na{sup +}-taurocholate cotransporting polypeptide (NTCP), had no significant effect on endogenous BAs measured at the end of the 24-h culture period, potentially due to compensatory mechanisms that maintain BA homeostasis. These data demonstrate that BAs in SCH are similar to in vivo, and that SCH may be a useful in vitro model to study alterations in BA disposition if species differences are taken into account. -- Highlights: ► Bile acids (BAs) were measured in rat and human sandwich-cultured hepatocytes (SCH). ► Cell and medium BA

  14. Cryoprotectant-free ultra-rapid freezing of human spermatozoa in cryogenic vials.

    Science.gov (United States)

    Zhu, J; Jin, R-T; Wu, L-M; Johansson, L; Guo, T-H; Liu, Y-S; Tong, X-H

    2014-08-01

    The objective of this study was to investigate the effect of ultra-rapid freezing (direct immersion in liquid nitrogen) on human spermatozoa in cryogenic vials (≥0.5 ml) at different concentrations of sucrose. After swim-up, the sperm suspensions (N = 58) were diluted with sperm preparation medium and divided into six aliquots: swim-up (fresh), conventional freezing group (slow freezing) and four ultra-rapid freezing groups containing sucrose at different concentrations (0.15 m, 0.20 m, 0.25 m and 0.30 m). Sperm motility, progressive motility, plasma membrane integrity, DNA stability and acrosome integrity of fresh and cooled-warmed spermatozoa were analysed. The progressive motility, plasma membrane and acrosome integrity of spermatozoa in the 0.20 m sucrose group were significantly higher than those of the slow freezing group (47.5 ± 6.8% versus 36.4 ± 8.7%, 73.2 ± 6.9% versus 63.9 ± 6.3%, 53.7 ± 10.0% versus 35.9 ± 9.7% respectively, P 0.05 respectively) between the 0.20 m sucrose and the slow freezing group. No differences were found between the ultra-rapid and slow freezing group at the other concentrations of sucrose. Our findings suggest that the method of ultra-rapid freezing of human spermatozoa in cryogenic vials with a solution containing 0.20 m sucrose results in recovery of spermatozoon of superior qualities. In contrast to slow freezing, the ultra-rapid freezing technique of human spermatozoa seems to reduce cryoinjuries and maintain important physiological characteristics of the spermatozoa after warming. © 2013 Blackwell Verlag GmbH.

  15. Endogenous Hydrogen Sulfide Enhances Cell Proliferation of Human Gastric Cancer AGS Cells.

    Science.gov (United States)

    Sekiguchi, Fumiko; Sekimoto, Teruki; Ogura, Ayaka; Kawabata, Atsufumi

    2016-01-01

    Hydrogen sulfide (H2S), the third gasotransmitter, is endogenously generated by certain H2S synthesizing enzymes, including cystathionine-γ-lyase (CSE) and cystathionine-β-synthase (CBS) from L-cysteine in the mammalian body. Several studies have shown that endogenous and exogenous H2S affects the proliferation of cancer cells, although the effects of H2S appear to vary with cell type, being either promotive or suppressive. In the present study, we determined whether endogenously formed H2S regulates proliferation in human gastric cancer AGS cells. CSE, but not CBS, was expressed in AGS cells. CSE inhibitors, DL-propargylglycine (PPG) and β-cyano-L-alanine (BCA), significantly suppressed the proliferation of AGS cells in a concentration-dependent manner. CSE inhibitors did not increase lactate dehydrogenase (LDH) release in the same concentration range. The inhibitory effects of PPG and BCA on cell proliferation were reversed by repetitive application of NaHS, a donor of H2S. Interestingly, nuclear condensation and fragmentation were detected in AGS cells treated with PPG or BCA. These results suggest that endogenous H2S produced by CSE may contribute to the proliferation of gastric cancer AGS cells, most probably through anti-apoptotic actions.

  16. The Impact of Environmental and Endogenous Damage on Somatic Mutation Load in Human Skin Fibroblasts

    Science.gov (United States)

    Saini, Natalie; Chan, Kin; Grimm, Sara A.; Dai, Shuangshuang; Fargo, David C.; Kaufmann, William K.; Taylor, Jack A.; Lee, Eunjung; Cortes-Ciriano, Isidro; Park, Peter J.; Schurman, Shepherd H.; Malc, Ewa P.; Mieczkowski, Piotr A.

    2016-01-01

    Accumulation of somatic changes, due to environmental and endogenous lesions, in the human genome is associated with aging and cancer. Understanding the impacts of these processes on mutagenesis is fundamental to understanding the etiology, and improving the prognosis and prevention of cancers and other genetic diseases. Previous methods relying on either the generation of induced pluripotent stem cells, or sequencing of single-cell genomes were inherently error-prone and did not allow independent validation of the mutations. In the current study we eliminated these potential sources of error by high coverage genome sequencing of single-cell derived clonal fibroblast lineages, obtained after minimal propagation in culture, prepared from skin biopsies of two healthy adult humans. We report here accurate measurement of genome-wide magnitude and spectra of mutations accrued in skin fibroblasts of healthy adult humans. We found that every cell contains at least one chromosomal rearrangement and 600–13,000 base substitutions. The spectra and correlation of base substitutions with epigenomic features resemble many cancers. Moreover, because biopsies were taken from body parts differing by sun exposure, we can delineate the precise contributions of environmental and endogenous factors to the accrual of genetic changes within the same individual. We show here that UV-induced and endogenous DNA damage can have a comparable impact on the somatic mutation loads in skin fibroblasts. Trial Registration ClinicalTrials.gov NCT01087307 PMID:27788131

  17. The Impact of Environmental and Endogenous Damage on Somatic Mutation Load in Human Skin Fibroblasts.

    Directory of Open Access Journals (Sweden)

    Natalie Saini

    2016-10-01

    Full Text Available Accumulation of somatic changes, due to environmental and endogenous lesions, in the human genome is associated with aging and cancer. Understanding the impacts of these processes on mutagenesis is fundamental to understanding the etiology, and improving the prognosis and prevention of cancers and other genetic diseases. Previous methods relying on either the generation of induced pluripotent stem cells, or sequencing of single-cell genomes were inherently error-prone and did not allow independent validation of the mutations. In the current study we eliminated these potential sources of error by high coverage genome sequencing of single-cell derived clonal fibroblast lineages, obtained after minimal propagation in culture, prepared from skin biopsies of two healthy adult humans. We report here accurate measurement of genome-wide magnitude and spectra of mutations accrued in skin fibroblasts of healthy adult humans. We found that every cell contains at least one chromosomal rearrangement and 600–13,000 base substitutions. The spectra and correlation of base substitutions with epigenomic features resemble many cancers. Moreover, because biopsies were taken from body parts differing by sun exposure, we can delineate the precise contributions of environmental and endogenous factors to the accrual of genetic changes within the same individual. We show here that UV-induced and endogenous DNA damage can have a comparable impact on the somatic mutation loads in skin fibroblasts. Trial Registration: ClinicalTrials.gov NCT01087307.

  18. The Impact of Environmental and Endogenous Damage on Somatic Mutation Load in Human Skin Fibroblasts.

    Science.gov (United States)

    Saini, Natalie; Roberts, Steven A; Klimczak, Leszek J; Chan, Kin; Grimm, Sara A; Dai, Shuangshuang; Fargo, David C; Boyer, Jayne C; Kaufmann, William K; Taylor, Jack A; Lee, Eunjung; Cortes-Ciriano, Isidro; Park, Peter J; Schurman, Shepherd H; Malc, Ewa P; Mieczkowski, Piotr A; Gordenin, Dmitry A

    2016-10-01

    Accumulation of somatic changes, due to environmental and endogenous lesions, in the human genome is associated with aging and cancer. Understanding the impacts of these processes on mutagenesis is fundamental to understanding the etiology, and improving the prognosis and prevention of cancers and other genetic diseases. Previous methods relying on either the generation of induced pluripotent stem cells, or sequencing of single-cell genomes were inherently error-prone and did not allow independent validation of the mutations. In the current study we eliminated these potential sources of error by high coverage genome sequencing of single-cell derived clonal fibroblast lineages, obtained after minimal propagation in culture, prepared from skin biopsies of two healthy adult humans. We report here accurate measurement of genome-wide magnitude and spectra of mutations accrued in skin fibroblasts of healthy adult humans. We found that every cell contains at least one chromosomal rearrangement and 600–13,000 base substitutions. The spectra and correlation of base substitutions with epigenomic features resemble many cancers. Moreover, because biopsies were taken from body parts differing by sun exposure, we can delineate the precise contributions of environmental and endogenous factors to the accrual of genetic changes within the same individual. We show here that UV-induced and endogenous DNA damage can have a comparable impact on the somatic mutation loads in skin fibroblasts. Trial Registration: ClinicalTrials.gov NCT01087307.

  19. The Etiology of Multiple Sclerosis: Genetic Evidence for the Involvement of the Human Endogenous Retrovirus HERV-Fc1

    DEFF Research Database (Denmark)

    Nexø, Bjørn Andersen; Christensen, Tove; Frederiksen, Jette;

    2011-01-01

    We have investigated the role of human endogenous retroviruses in multiple sclerosis by analyzing the DNA of patients and controls in 4 cohorts for associations between multiple sclerosis and polymorphisms near viral restriction genes or near endogenous retroviral loci with one or more intact...

  20. A Two-Sector Growth Model with Endogenous Human Capital and Amenities

    Directory of Open Access Journals (Sweden)

    Wei-Bin Zhang

    2009-01-01

    Full Text Available This paper examines issues related to urbanization with labour migration. The main departures from the traditional approaches to dynamics of economic structures are that the paper uses an alternative approach to consumer behaviour and introduces human capital accumulation via learning by doing. The model describes dynamic interactions among agricultural and industrial production, rural and urban amenities, distribution of production factors and preferences with endogenous capital and human capital accumulation. We show that the dynamic system may have either a single or multiple equilibrium points, depending upon returns to scale in the two sectors. We also examined effects of changes in some parameters.

  1. Reprogramming triggers endogenous L1 and Alu retrotransposition in human induced pluripotent stem cells.

    Science.gov (United States)

    Klawitter, Sabine; Fuchs, Nina V; Upton, Kyle R; Muñoz-Lopez, Martin; Shukla, Ruchi; Wang, Jichang; Garcia-Cañadas, Marta; Lopez-Ruiz, Cesar; Gerhardt, Daniel J; Sebe, Attila; Grabundzija, Ivana; Merkert, Sylvia; Gerdes, Patricia; Pulgarin, J Andres; Bock, Anja; Held, Ulrike; Witthuhn, Anett; Haase, Alexandra; Sarkadi, Balázs; Löwer, Johannes; Wolvetang, Ernst J; Martin, Ulrich; Ivics, Zoltán; Izsvák, Zsuzsanna; Garcia-Perez, Jose L; Faulkner, Geoffrey J; Schumann, Gerald G

    2016-01-08

    Human induced pluripotent stem cells (hiPSCs) are capable of unlimited proliferation and can differentiate in vitro to generate derivatives of the three primary germ layers. Genetic and epigenetic abnormalities have been reported by Wissing and colleagues to occur during hiPSC derivation, including mobilization of engineered LINE-1 (L1) retrotransposons. However, incidence and functional impact of endogenous retrotransposition in hiPSCs are yet to be established. Here we apply retrotransposon capture sequencing to eight hiPSC lines and three human embryonic stem cell (hESC) lines, revealing endogenous L1, Alu and SINE-VNTR-Alu (SVA) mobilization during reprogramming and pluripotent stem cell cultivation. Surprisingly, 4/7 de novo L1 insertions are full length and 6/11 retrotransposition events occurred in protein-coding genes expressed in pluripotent stem cells. We further demonstrate that an intronic L1 insertion in the CADPS2 gene is acquired during hiPSC cultivation and disrupts CADPS2 expression. These experiments elucidate endogenous retrotransposition, and its potential consequences, in hiPSCs and hESCs.

  2. The human endogenous circadian system causes greatest platelet activation during the biological morning independent of behaviors.

    Directory of Open Access Journals (Sweden)

    Frank A J L Scheer

    Full Text Available BACKGROUND: Platelets are involved in the thromboses that are central to myocardial infarctions and ischemic strokes. Such adverse cardiovascular events have day/night patterns with peaks in the morning (~9 AM, potentially related to endogenous circadian clock control of platelet activation. The objective was to test if the human endogenous circadian system influences (1 platelet function and (2 platelet response to standardized behavioral stressors. We also aimed to compare the magnitude of any effects on platelet function caused by the circadian system with that caused by varied standardized behavioral stressors, including mental arithmetic, passive postural tilt and mild cycling exercise. METHODOLOGY/PRINCIPAL FINDINGS: We studied 12 healthy adults (6 female who lived in individual laboratory suites in dim light for 240 h, with all behaviors scheduled on a 20-h recurring cycle to permit assessment of endogenous circadian function independent from environmental and behavioral effects including the sleep/wake cycle. Circadian phase was assessed from core body temperature. There were highly significant endogenous circadian rhythms in platelet surface activated glycoprotein (GP IIb-IIIa, GPIb and P-selectin (6-17% peak-trough amplitudes; p ≤ 0.01. These circadian peaks occurred at a circadian phase corresponding to 8-9 AM. Platelet count, ATP release, aggregability, and plasma epinephrine also had significant circadian rhythms but with later peaks (corresponding to 3-8 PM. The circadian effects on the platelet activation markers were always larger than that of any of the three behavioral stressors. CONCLUSIONS/SIGNIFICANCE: These data demonstrate robust effects of the endogenous circadian system on platelet activation in humans--independent of the sleep/wake cycle, other behavioral influences and the environment. The 9 AM timing of the circadian peaks of the three platelet surface markers, including platelet surface activated GPIIb-IIIa, the

  3. Endogenous laminin is required for human airway smooth muscle cell maturation

    Directory of Open Access Journals (Sweden)

    Tran Thai

    2006-09-01

    Full Text Available Abstract Background Airway smooth muscle (ASM contraction underlies acute bronchospasm in asthma. ASM cells can switch between a synthetic-proliferative phenotype and a contractile phenotype. While the effects of extracellular matrix (ECM components on modulation of ASM cells to a synthetic phenotype have been reported, the role of ECM components on maturation of ASM cells to a contractile phenotype in adult lung is unclear. As both changes in ECM components and accumulation of contractile ASM are features of airway wall remodelling in asthma, we examined the role of the ECM protein, laminin, in the maturation of contractile phenotype in human ASM cells. Methods Human ASM cells were made senescence-resistant by stable expression of human telomerase reverse transcriptase. Maturation to a contractile phenotype was induced by 7-day serum deprivation, as assessed by immunoblotting for desmin and calponin. The role of laminin on ASM maturation was investigated by comparing the effects of exogenous laminin coated on culture plates, and of soluble laminin peptide competitors. Endogenous expression of laminin chains during ASM maturation was also measured. Results Myocyte binding to endogenously expressed laminin was required for ASM phenotype maturation, as laminin competing peptides (YIGSR or GRGDSP significantly reduced desmin and calponin protein accumulation that otherwise occurs with prolonged serum deprivation. Coating of plastic cell culture dishes with different purified laminin preparations was not sufficient to further promote accumulation of desmin or calponin during 7-day serum deprivation. Expression of α2, β1 and γ1 laminin chains by ASM cells was specifically up-regulated during myocyte maturation, suggesting a key role for laminin-2 in the development of the contractile phenotype. Conclusion While earlier reports suggest exogenously applied laminin slows the spontaneous modulation of ASM to a synthetic phenotype, we show for the

  4. In-Situ Cryogenic Propellant Liquefaction and Storage for a Precursor to a Human Mars Mission

    Science.gov (United States)

    Mueller, Paul; Durrant, Tom

    The current mission plan for the first human mission to Mars is based on an in-situ propellant production (ISPP) approach to reduce the amount of propellants needed to be taken to Mars and ultimately to reduce mission cost. Recent restructuring of the Mars Robotic Exploration Program has removed ISPP from the early sample return missions. A need still exists to demonstrate ISPP technologies on one or more robotic missions prior to the first human mission. This paper outlines a concept for an ISPP-based precursor mission as a technology demonstration prior to the first human mission. It will also return Martian soil samples to Earth for scientific analysis. The mission will primarily demonstrate cryogenic oxygen and fuel production, liquefaction, and storage for use as propellants for the return trip. Hydrogen will be brought from Earth as a feedstock to produce the hydrocarbon fuel (most likely methane). The analysis used to develop the mission concept includes several different thermal control and liquefaction options for the cryogens. Active cooling and liquefaction devices include Stirling, pulse tube, and Brayton-cycle cryocoolers. Insulation options include multilayer insulation, evacuated microspheres, aerogel blankets, and foam insulation. The cooling capacity and amount of insulation are traded off against each other for a minimum-mass system. In the case of hydrogen feedstock, the amount of hydrogen boiloff allowed during the trip to Mars is also included in the tradeoff. The spacecraft concept includes a Lander (including the propellant production plant) with a Mars Ascent Vehicle (MAV) mounted atop it. An option is explored where the engines on the MAV are also used for descent and landing on the Martian surface at the beginning of the mission. So the MAV propellant tanks would contain oxygen and methane during the trip from Earth. This propellant would be consumed in descent to the Martian surface, resulting in nearly-empty MAV tanks to be filled by the

  5. Profiling of endogenous peptides in human synovial fluid by NanoLC-MS : Method validation and peptide identification

    NARCIS (Netherlands)

    Kamphorst, J.J.; Heijden, R. van der; Groot, J. de; Lafeber, F.P.J.G.; Reijmers, T.H.; El, B. van; Tjaden, U.R.; Greef, J. van der; Hankemeier, T.

    2007-01-01

    Synovial fluid potentially contains markers for early diagnosis and disease progression in degenerative joint diseases such as osteoarthritis. Here, a method is described for profiling endogenous peptides in human synovial fluid, using ultrafiltration, solid-phase extraction, nanoscale liquid chroma

  6. Detection of the human endogenous retrovirus ERV3-encoded Env-protein in human tissues using antibody-based proteomics.

    Science.gov (United States)

    Fei, Chen; Atterby, Christina; Edqvist, Per-Henrik; Pontén, Fredrik; Zhang, Wei Wei; Larsson, Erik; Ryan, Frank P

    2014-01-01

    There is growing evidence to suggest that human endogenous retroviruses (HERVs) have contributed to human evolution, being expressed in development, normal physiology and disease. A key difficulty in the scientific evaluation of this potential viral contribution is the accurate demonstration of virally expressed protein in specific human cells and tissues. In this study, we have adopted the endogenous retrovirus, ERV3, as our test model in developing a reliable high-capacity methodology for the expression of such endogenous retrovirus-coded protein. Two affinity-purified polyclonal antibodies to ERV3 Env-encoded protein were generated to detect the corresponding protein expression pattern in specific human cells, tissues and organs. Sampling included normal tissues from 144 individuals ranging from childhood to old age. This included more than forty different tissues and organs and some 216 different cancer tissues representing the twenty commonest forms of human cancer. The Rudbeck Laboratory, Uppsala University and Uppsala University Hospital, Uppsala, Sweden. The potential expression at likely physiological level of the ERV3Env encoded protein in a wide range of human cells, tissues and organs. We found that ERV3 encoded Env protein is expressed at substantive levels in placenta, testis, adrenal gland, corpus luteum, Fallopian tubes, sebaceous glands, astrocytes, bronchial epithelium and the ducts of the salivary glands. Substantive expression was also seen in a variety of epithelial cells as well as cells known to undergo fusion in inflammation and in normal physiology, including fused macrophages, myocardium and striated muscle. This contrasted strongly with the low levels expressed in other tissues types. These findings suggest that this virus plays a significant role in human physiology and may also play a possible role in disease. This technique can now be extended to the study of other HERV genomes within the human chromosomes that may have contributed to

  7. Endogenous formaldehyde turnover in humans compared with exogenous contribution from food sources

    Directory of Open Access Journals (Sweden)

    European Food Safety Authority

    2014-02-01

    Full Text Available The FEEDAP Panel received a request to deliver a scientific opinion on the safety and efficacy of formaldehyde used in feed for all animal species based on dossiers submitted by applicants. In parallel, the ANS Panel evaluated the safety of formaldehyde formed from endogenous production and from dietary sources of methanol, including aspartame. In order to support both evaluations, assistance was requested to the SCER unit to evaluate the oral internal dose of formaldehyde in humans from endogenous production, food-derived from target animals exposed to formaldehyde-treated feed and formaldehyde generated from dietary sources of methanol, including from food additives such as aspartame. Endogenous turnover of formaldehyde was estimated to be approximately 0.61-0.91 mg/kg bw per minute and 878-1310 mg/kg bw per day assuming a half life of 1 1.5 min. Compared with formaldehyde turnover and the background levels of formaldehyde from food sources (1.7-1.4 mg/kg b. w per day for a 60-70 kg person, including from dietary methanol, the relative contribution of exogenous formaldehyde from consumption of animal products (milk, meat from target animals exposed to formaldehyde-treated feed was negligible (<0.001 %. Oral exposure to formaldehyde from aspartame involves metabolism to methanol and further oxidation to formaldehyde. At the current ADI of 40 mg/kg bw per day for aspartame, formaldehyde would be approximately 4 mg/kg bw per day and represent only 0.3-0.4 % of the endogenous turnover of formaldehyde.

  8. Suitability of endogenous reference genes for gene expression studies with human intraocular endothelial cells

    Directory of Open Access Journals (Sweden)

    Wei Ruoxin

    2013-02-01

    Full Text Available Abstract Background The use of quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR has become widely applied as a method to measure transcript abundance. In order to be reflective of biological processes during health and disease this method is dependent on normalisation of data against stable endogenous controls. However, these genes can vary in their stability in different cell types. The importance of reference gene validation for a particular cell type is now well recognised and is an important step in any gene expression study. Results Cultured primary human choroidal and retinal endothelial cells were treated with the immunostimulant polyinosinic: polycytidylic acid or untreated. qRT-PCR was used to quantify the expression levels of 10 commonly used endogenous control genes, TBP, HPRT1, GAPDH, GUSB, PPIA, RPLP0, B2M, 18S rRNA, PGK1 and ACTB. Three different mathematical algorithms, GeNorm, NormFinder, and BestKeeper were used to analyse gene stability to give the most representative validation. In choroidal endothelial cells the most stable genes were ranked as HPRT1 and GUSB by GeNorm and NormFinder and HPRT1 and PPIA by BestKeeper. In retinal endothelial cells the most stable genes ranked were TBP and PGK1 by GeNorm and NormFinder and HPRT1 by BestKeeper. The least stable gene for both cell types was 18S with all 3 algorithms. Conclusions We have identified the most stable endogenous control genes in intraocular endothelial cells. It is suggested future qRT-PCR studies using these cells would benefit from adopting the genes identified in this study as the most appropriate endogenous control genes.

  9. Orthologous endogenous retroviruses exhibit directional selection since the chimp-human split

    OpenAIRE

    Gemmell, Patrick; Hein, Jotun; Katzourakis, Aris

    2015-01-01

    Background Endogenous retroviruses (ERVs) are often viewed as selfish DNA that do not contribute to host phenotype. Yet ERVs have also been co-opted to play important roles in the maintenance of stem cell identity and placentation, amongst other things. This has led to debate over whether the typical ERV confers a cost or benefit upon the host. We studied the divergence of orthologous ERVs since the chimp-human split with the aim of assessing whether ERVs exert detectable fitness effects. Res...

  10. Antimicrobial activity and mechanism of PDC213, an endogenous peptide from human milk.

    Science.gov (United States)

    Sun, Yazhou; Zhou, Yahui; Liu, Xiao; Zhang, Fan; Yan, Linping; Chen, Ling; Wang, Xing; Ruan, Hongjie; Ji, Chenbo; Cui, Xianwei; Wang, Jiaqin

    2017-02-26

    Human milk has always been considered an ideal source of elemental nutrients to both preterm and full term infants in order to optimally develop the infant's tissues and organs. Recently, hundreds of endogenous milk peptides were identified in human milk. These peptides exhibited angiotensin-converting enzyme inhibition, immunomodulation, or antimicrobial activity. Here, we report the antimicrobial activity and mechanism of a novel type of human antimicrobial peptide (AMP), termed PDC213 (peptide derived from β-Casein 213-226 aa). PDC213 is an endogenous peptide and is present at higher levels in preterm milk than in full term milk. The inhibitory concentration curve and disk diffusion tests showed that PDC213 had obvious antimicrobial against S. aureus and Y. enterocolitica, the common nosocomial pathogens in neonatal intensive care units (NICUs). Fluorescent dye methods, electron microscopy experiments and DNA-binding activity assays further indicated that PDC213 can permeabilize bacterial membranes and cell walls rather than bind intracellular DNA to kill bacteria. Together, our results suggest that PDC213 is a novel type of AMP that warrants further investigation. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Design and Development of a Methane Cryogenic Propulsion Stage for Human Mars Exploration

    Science.gov (United States)

    Percy, Thomas K.; Polsgrove, Tara; Turpin, Jason; Alexander, Leslie

    2016-01-01

    NASA is currently working on the Evolvabe Mars Campaign (EMC) study to outline transportation and mission options for human exploration of Mars. One of the key aspects of the EMC is leveraging current and planned near-term technology investments to build an affordable and evolvable approach to Mars exploration. This leveraging of investments includes the use of high-power Solar Electric Propulsion (SEP) systems evolved from those currently under development in support of the Asteroid Redirect Mission to deliver payloads to Mars. The EMC is considering several transportation options that combine solar electric and chemical propulsion technologies to deliver crew and cargo to Mars. In one primary architecture option, the SEP propulsion system is used to pre-deploy mission elements to Mars while a high-thrust chemical propulsion system is used to send crew on faster ballistic transfers between Earth and Mars. This high-thrust chemical system uses liquid oxygen - liquid methane main propulsion and reaction control systems integrated into the Methane Cryogenic Propulsion Stage (MCPS). Over the past year, there have been several studies completed to provide critical design and development information related to the MCPS. This paper is intended to provide a summary of these efforts. A summary of the current point of departure design for the MCPS is provided as well as an overview of the mission architecture and concept of operations that the MCPS is intended to support. To leverage the capabilities of solar electric propulsion to the greatest extent possible, the EMC architecture pre-deploys the required stages for returning crew from Mars. While this changes the risk posture of the architecture, it provides mass savings by using higher-efficiency systems for interplanetary transfer. However, this does introduce significantly longer flight times to Mars which, in turn, increases the overall lifetime of the stages to as long as 3000 days. This unique aspect to the concept

  12. Design and Development of a Methane Cryogenic Propulsion Stage for Human Mars Exploration

    Science.gov (United States)

    Percy, Thomas K.; Polsgrove, Tara; Turpin, Jason; Alexander, Leslie

    2016-01-01

    NASA is currently working on the Evolvabe Mars Campaign (EMC) study to outline transportation and mission options for human exploration of Mars. One of the key aspects of the EMC is leveraging current and planned near-term technology investments to build an affordable and evolvable approach to Mars exploration. This leveraging of investments includes the use of high-power Solar Electric Propulsion (SEP) systems, evolved from those currently under development in support of the Asteroid Redirect Mission (ARM), to deliver payloads to Mars. The EMC is considering several transportation options that combine solar electric and chemical propulsion technologies to deliver crew and cargo to Mars. In one primary architecture option, the SEP propulsion system is used to pre-deploy mission elements to Mars while a high-thrust chemical propulsion system is used to send crew on faster ballistic transfers between Earth and Mars. This high-thrust chemical system uses liquid oxygen - liquid methane main propulsion and reaction control systems integrated into the Methane Cryogenic Propulsion Stage (MCPS). Over the past year, there have been several studies completed to provide critical design and development information related to the MCPS. This paper is intended to provide a summary of these efforts. A summary of the current point of departure design for the MCPS is provided as well as an overview of the mission architecture and concept of operations that the MCPS is intended to support. To leverage the capabilities of solar electric propulsion to the greatest extent possible, the EMC architecture pre-deploys to Mars orbit the stages required for returning crew from Mars. While this changes the risk posture of the architecture, it can provide some mass savings by using higher-efficiency systems for interplanetary transfer. However, this does introduce significantly longer flight times to Mars which, in turn, increases the overall lifetime of the stages to as long as 2500 days. This

  13. An endogenous aryl hydrocarbon receptor ligand inhibits proliferation and migration of human ovarian cancer cells.

    Science.gov (United States)

    Wang, Kai; Li, Yan; Jiang, Yi-Zhou; Dai, Cai-Feng; Patankar, Manish S; Song, Jia-Sheng; Zheng, Jing

    2013-10-28

    The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor mediates many biological processes. Herein, we investigated if 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE, an endogenous AhR ligand) regulated proliferation and migration of human ovarian cancer cells via AhR. We found that AhR was widely present in many histotypes of ovarian cancer tissues. ITE suppressed OVCAR-3 cell proliferation and SKOV-3 cell migration in vitro, which were blocked by AhR knockdown. ITE also suppressed OVCAR-3 cell growth in mice. These data suggest that the ITE might potentially be used for therapeutic intervention for at least a subset of human ovarian cancer.

  14. Helium cryogenics

    CERN Document Server

    Van Sciver, Steven W

    2012-01-01

    Twenty five years have elapsed since the original publication of Helium Cryogenics. During this time, a considerable amount of research and development involving helium fluids has been carried out culminating in several large-scale projects. Furthermore, the field has matured through these efforts so that there is now a broad engineering base to assist the development of future projects. Helium Cryogenics, 2nd edition brings these advances in helium cryogenics together in an updated form. As in the original edition, the author's approach is to survey the field of cryogenics with emphasis on helium fluids. This approach is more specialized and fundamental than that contained in other cryogenics books, which treat the associated range of cryogenic fluids. As a result, the level of treatment is more advanced and assumes a certain knowledge of fundamental engineering and physics principles, including some quantum mechanics. The goal throughout the work is to bridge the gap between the physics and engineering aspe...

  15. Transcripts from a novel human KRAB zinc finger gene contain spliced Alu and endogenous retroviral segments

    Energy Technology Data Exchange (ETDEWEB)

    Baban, S.; Freeman, J.D.; Mager, D.L. [Univ. of British Columbia, Vancouver, British Columbia (Canada)

    1996-05-01

    During the course of an investigation into the potential effects of endogenous retroviruses on adjacent gene expression, we isolated two cDNA clones containing a small sequence segment belonging to the human endogenous retrovirus family, HERV-H. Characterization of the clones revealed that they represent transcripts from a novel KRAB zinc finger gene termed ZNF177. The two cDNA clones differ at their 5{prime} termini and in the presence of a 559-bp internal exon. The clone containing this internal exon has six imperfect zinc finger motifs followed by seven perfect copies of the C{sub 2}H{sub 2} type but has a frame shift between the KRAB domain and the downstream zinc finger region. The smaller clone lacks the six imperfect motifs and has an intact ORF. The 5{prime} putative untranslated regions of both cDNAs contain an 86-bp HERV-H env segment and a segment of an Alu repeat, both in the antisense orientation, that have been incorporated by splicing. RT-PCR experiments show evidence of alternative splicing but the majority of transcripts appear to contain the Alu and env segments. Genomic PCR and hybridization experiments suggest that a partial HERV-H element is integrated within the ZNF177 locus, which Southern analysis has shown to be a single-copy gene. Northern and RT-PCR analyses suggest that ZNF177 is transcribed at a low level in a variety of cell types. 41 refs., 8 figs.

  16. Expression and pharmacology of endogenous Cav channels in SH-SY5Y human neuroblastoma cells.

    Directory of Open Access Journals (Sweden)

    Silmara R Sousa

    Full Text Available SH-SY5Y human neuroblastoma cells provide a useful in vitro model to study the mechanisms underlying neurotransmission and nociception. These cells are derived from human sympathetic neuronal tissue and thus, express a number of the Cav channel subtypes essential for regulation of important physiological functions, such as heart contraction and nociception, including the clinically validated pain target Cav2.2. We have detected mRNA transcripts for a range of endogenous expressed subtypes Cav1.3, Cav2.2 (including two Cav1.3, and three Cav2.2 splice variant isoforms and Cav3.1 in SH-SY5Y cells; as well as Cav auxiliary subunits α2δ1-3, β1, β3, β4, γ1, γ4-5, and γ7. Both high- and low-voltage activated Cav channels generated calcium signals in SH-SY5Y cells. Pharmacological characterisation using ω-conotoxins CVID and MVIIA revealed significantly (∼ 10-fold higher affinity at human versus rat Cav2.2, while GVIA, which interacts with Cav2.2 through a distinct pharmacophore had similar affinity for both species. CVID, GVIA and MVIIA affinity was higher for SH-SY5Y membranes vs whole cells in the binding assays and functional assays, suggesting auxiliary subunits expressed endogenously in native systems can strongly influence Cav2.2 channels pharmacology. These results may have implications for strategies used to identify therapeutic leads at Cav2.2 channels.

  17. Cryogenic exciter

    Science.gov (United States)

    Bray, James William [Niskayuna, NY; Garces, Luis Jose [Niskayuna, NY

    2012-03-13

    The disclosed technology is a cryogenic static exciter. The cryogenic static exciter is connected to a synchronous electric machine that has a field winding. The synchronous electric machine is cooled via a refrigerator or cryogen like liquid nitrogen. The static exciter is in communication with the field winding and is operating at ambient temperature. The static exciter receives cooling from a refrigerator or cryogen source, which may also service the synchronous machine, to selected areas of the static exciter and the cooling selectively reduces the operating temperature of the selected areas of the static exciter.

  18. Analysis of endogenous aldehydes in human urine by static headspace gas chromatography-mass spectrometry.

    Science.gov (United States)

    Serrano, María; Gallego, Mercedes; Silva, Manuel

    2016-03-11

    Endogenous aldehydes (EAs) generated during oxidative stress and cell processes are associated with many pathogenic and toxicogenic processes. The aim of this research was to develop a solvent-free and automated analytical method for the determination of EAs in human urine using a static headspace generator sampler coupled with gas chromatography-mass spectrometry (HS-GC-MS). Twelve significant EAs used as markers of different biochemical and physiological processes, namely short- and medium-chain alkanals, α,β-unsaturated aldehydes and dicarbonyl aldehydes have been selected as target analytes. Human urine samples (no dilution is required) were derivatized with O-2,3,4,5,6-pentafluorobenzylhydroxylamine in alkaline medium (hydrogen carbonate-carbonate buffer, pH 10.3). The HS-GC-MS method developed renders an efficient tool for the sensitive and precise determination of EAs in human urine with limits of detection from 1 to 15ng/L and relative standard deviations, (RSDs) from 6.0 to 7.9%. Average recoveries by enriching urine samples ranged between 92 and 95%. Aldehydes were readily determined at 0.005-50μg/L levels in human urine from healthy subjects, smokers and diabetic adults.

  19. New bioinformatic tool for quick identification of functionally relevant endogenous retroviral inserts in human genome.

    Science.gov (United States)

    Garazha, Andrew; Ivanova, Alena; Suntsova, Maria; Malakhova, Galina; Roumiantsev, Sergey; Zhavoronkov, Alex; Buzdin, Anton

    2015-01-01

    Endogenous retroviruses (ERVs) and LTR retrotransposons (LRs) occupy ∼8% of human genome. Deep sequencing technologies provide clues to understanding of functional relevance of individual ERVs/LRs by enabling direct identification of transcription factor binding sites (TFBS) and other landmarks of functional genomic elements. Here, we performed the genome-wide identification of human ERVs/LRs containing TFBS according to the ENCODE project. We created the first interactive ERV/LRs database that groups the individual inserts according to their familial nomenclature, number of mapped TFBS and divergence from their consensus sequence. Information on any particular element can be easily extracted by the user. We also created a genome browser tool, which enables quick mapping of any ERV/LR insert according to genomic coordinates, known human genes and TFBS. These tools can be used to easily explore functionally relevant individual ERV/LRs, and for studying their impact on the regulation of human genes. Overall, we identified ∼110,000 ERV/LR genomic elements having TFBS. We propose a hypothesis of "domestication" of ERV/LR TFBS by the genome milieu including subsequent stages of initial epigenetic repression, partial functional release, and further mutation-driven reshaping of TFBS in tight coevolution with the enclosing genomic loci.

  20. Lipid-Conjugation of Endogenous Neuropeptides: Improved Biotherapy against Human Pancreatic Cancer.

    Science.gov (United States)

    Gopalakrishnan, Gopakumar; Lepetre, Sinda; Maksimenko, Andrei; Mura, Simona; Desmaële, Didier; Couvreur, Patrick

    2015-05-01

    Neuropeptides are small neuronal signaling molecules that act as neuromodulators for a variety of neural functions including analgesia, reproduction, social behavior, learning, and memory. One of the endogenous neuropeptides-Met-Enkephalin (Met-Enk), has been shown to display an inhibitory effect on cell proliferation and differentiation. Here, a novel lipid-modification approach is shown to create a small library of neuropeptides that will allow increased bioavailability and plasma stability after systemic administration. It is demonstrated, on an experimental model of human pancreatic adenocarcinoma, that lipid conjugation of Met-Enk enhances its tumor suppression efficacy compared to its nonlipidated counterparts, both in vitro and in vivo. More strikingly, the in vivo studies show that a combination therapy with a reduced concentration of Gemcitabine has suppressed the tumor growth considerably even three weeks after the last treatment.

  1. (Some) cellular mechanisms influencing the transcription of human endogenous retrovirus, HERV-Fc1

    DEFF Research Database (Denmark)

    Laska, Magdalena Janina; Nissen, Kari Konstantin; Nexø, Bjørn Andersen

    2013-01-01

    DNA methylation and histone acetylation are epigenetic modifications that act as regulators of gene expression. DNA methylation is considered an important mechanism for silencing of retroelements in the mammalian genome. However, the methylation of human endogenous retroviruses (HERVs) is not well...... investigated. The aim of this study was to investigate the transcriptional potential of HERV-Fc1 proviral 5'LTR in more detail, and examined the specific influence of CpG methylation on this LTR in number of cell lines. Specifically, the role of demethylating chemicals e.g. 5-aza-2' deoxycytidine...... and Trichostatin-A, in inducing or reactivating expression of HERV-Fc1 specific sequences and the mechanisms were investigated. In our present study, 5-aza-dC is shown to be a powerful inducer of HERV-Fc1, and at the same time it strongly inhibits methylation of DNA. Treatment with this demethylating agent 5-aza...

  2. Endogenous attention signals evoked by threshold contrast detection in human superior colliculus.

    Science.gov (United States)

    Katyal, Sucharit; Ress, David

    2014-01-15

    Human superior colliculus (SC) responds in a retinotopically selective manner when attention is deployed on a high-contrast visual stimulus using a discrimination task. To further elucidate the role of SC in endogenous visual attention, high-resolution fMRI was used to demonstrate that SC also exhibits a retinotopically selective response for covert attention in the absence of significant visual stimulation using a threshold-contrast detection task. SC neurons have a laminar organization according to their function, with visually responsive neurons present in the superficial layers and visuomotor neurons in the intermediate layers. The results show that the response evoked by the threshold-contrast detection task is significantly deeper than the response evoked by the high-contrast speed discrimination task, reflecting a functional dissociation of the attentional enhancement of visuomotor and visual neurons, respectively. Such a functional dissociation of attention within SC laminae provides a subcortical basis for the oculomotor theory of attention.

  3. Insertional polymorphisms: a new lease of life for endogenous retroviruses in human disease.

    Science.gov (United States)

    Moyes, David; Griffiths, David J; Venables, Patrick J

    2007-07-01

    Human endogenous retroviruses (HERVs) result from ancestral infection by infectious viruses over millions of years of primate evolution. Some are transcriptionally active, express proteins and therefore have the potential to cause disease. Here we review the controversial attempts to link them with cancer and autoimmunity. The main difficulty is that most HERVs investigated to date are present at the same locus in 100% of the population. However, a new class of insertionally polymorphic HERV-K family members, present in a minority of individuals, has recently been described. We propose that insertionally polymorphic HERVs could be novel genetic risk factors and hence provide a new lease of life for research into HERVs and disease.

  4. Purification of proteins specifically binding human endogenous retrovirus K long terminal repeat by affinity elution chromatography.

    Science.gov (United States)

    Trubetskoy, D O; Zavalova, L L; Akopov, S B; Nikolaev, L G

    2002-11-01

    A novel affinity elution procedure for purification of DNA-binding proteins was developed and employed to purify to near homogeneity the proteins recognizing a 21 base pair sequence within the long terminal repeat of human endogenous retroviruses K. The approach involves loading the initial protein mixture on a heparin-agarose column and elution of protein(s) of interest with a solution of double-stranded oligonucleotide containing binding sites of the protein(s). The affinity elution has several advantages over conventional DNA-affinity chromatography: (i) it is easier and faster, permitting to isolate proteins in a 1 day-one stage procedure; (ii) yield of a target protein is severalfold higher than that in DNA-affinity chromatography; (iii) it is not necessary to prepare a special affinity support for each factor to be isolated. Theaffinity elution could be a useful alternative to conventional DNA-affinity chromatography.

  5. Regulation of endogenous human gene expression by ligand-inducible TALE transcription factors.

    Science.gov (United States)

    Mercer, Andrew C; Gaj, Thomas; Sirk, Shannon J; Lamb, Brian M; Barbas, Carlos F

    2014-10-17

    The construction of increasingly sophisticated synthetic biological circuits is dependent on the development of extensible tools capable of providing specific control of gene expression in eukaryotic cells. Here, we describe a new class of synthetic transcription factors that activate gene expression in response to extracellular chemical stimuli. These inducible activators consist of customizable transcription activator-like effector (TALE) proteins combined with steroid hormone receptor ligand-binding domains. We demonstrate that these ligand-responsive TALE transcription factors allow for tunable and conditional control of gene activation and can be used to regulate the expression of endogenous genes in human cells. Since TALEs can be designed to recognize any contiguous DNA sequence, the conditional gene regulatory system described herein will enable the design of advanced synthetic gene networks.

  6. Deep sequencing reveals low incidence of endogenous LINE-1 retrotransposition in human induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Hubert Arokium

    Full Text Available Long interspersed element-1 (LINE-1 or L1 retrotransposition induces insertional mutations that can result in diseases. It was recently shown that the copy number of L1 and other retroelements is stable in induced pluripotent stem cells (iPSCs. However, by using an engineered reporter construct over-expressing L1, another study suggests that reprogramming activates L1 mobility in iPSCs. Given the potential of human iPSCs in therapeutic applications, it is important to clarify whether these cells harbor somatic insertions resulting from endogenous L1 retrotransposition. Here, we verified L1 expression during and after reprogramming as well as potential somatic insertions driven by the most active human endogenous L1 subfamily (L1Hs. Our results indicate that L1 over-expression is initiated during the reprogramming process and is subsequently sustained in isolated clones. To detect potential somatic insertions in iPSCs caused by L1Hs retotransposition, we used a novel sequencing strategy. As opposed to conventional sequencing direction, we sequenced from the 3' end of L1Hs to the genomic DNA, thus enabling the direct detection of the polyA tail signature of retrotransposition for verification of true insertions. Deep coverage sequencing thus allowed us to detect seven potential somatic insertions with low read counts from two iPSC clones. Negative PCR amplification in parental cells, presence of a polyA tail and absence from seven L1 germline insertion databases highly suggested true somatic insertions in iPSCs. Furthermore, these insertions could not be detected in iPSCs by PCR, likely due to low abundance. We conclude that L1Hs retrotransposes at low levels in iPSCs and therefore warrants careful analyses for genotoxic effects.

  7. The association between human endogenous retroviruses and multiple sclerosis: A systematic review and meta-analysis

    Science.gov (United States)

    Morandi, Elena; Tanasescu, Radu; Tarlinton, Rachael E.; Constantinescu, Cris S.; Zhang, Weiya; Tench, Christopher

    2017-01-01

    Background The interaction between genetic and environmental factors is crucial to multiple sclerosis (MS) pathogenesis. Human Endogenous Retroviruses (HERVs) are endogenous viral elements of the human genome whose expression is associated with MS. Objective To perform a systematic review and meta-analysis and to assess qualitative and quantitative evidence on the expression of HERV families in MS patients. Methods Medline, Embase and the Cochrane Library were searched for published studies on the association of HERVs and MS. Meta-analysis was performed on the HERV-W family. Odds Ratio (OR) and 95% confidence interval (CI) were calculated for association. Results 43 reports were extracted (25 related to HERV-W, 13 to HERV-H, 9 to HERV-K, 5 to HRES-1 and 1 to HER-15 family). The analysis showed an association between expression of all HERV families and MS. For HERV-W, adequate data was available for meta-analysis. Results from meta-analyses of HERV-W were OR = 22.66 (95%CI 6.32 to 81.20) from 4 studies investigating MSRV/HERV-W (MS-associated retrovirus) envelope mRNA in peripheral blood mononuclear cells, OR = 44.11 (95%CI 12.95 to 150.30) from 6 studies of MSRV/HERV-W polymerase mRNA in serum/plasma and OR = 6.00 (95%CI 3.35 to 10.74) from 4 studies of MSRV/HERV-W polymerase mRNA in CSF. Conclusions This systematic review and meta-analysis shows an association between expression of HERVs, and in particular the HERV-W family, and MS. PMID:28207850

  8. Deep sequencing reveals low incidence of endogenous LINE-1 retrotransposition in human induced pluripotent stem cells.

    Science.gov (United States)

    Arokium, Hubert; Kamata, Masakazu; Kim, Sanggu; Kim, Namshin; Liang, Min; Presson, Angela P; Chen, Irvin S

    2014-01-01

    Long interspersed element-1 (LINE-1 or L1) retrotransposition induces insertional mutations that can result in diseases. It was recently shown that the copy number of L1 and other retroelements is stable in induced pluripotent stem cells (iPSCs). However, by using an engineered reporter construct over-expressing L1, another study suggests that reprogramming activates L1 mobility in iPSCs. Given the potential of human iPSCs in therapeutic applications, it is important to clarify whether these cells harbor somatic insertions resulting from endogenous L1 retrotransposition. Here, we verified L1 expression during and after reprogramming as well as potential somatic insertions driven by the most active human endogenous L1 subfamily (L1Hs). Our results indicate that L1 over-expression is initiated during the reprogramming process and is subsequently sustained in isolated clones. To detect potential somatic insertions in iPSCs caused by L1Hs retotransposition, we used a novel sequencing strategy. As opposed to conventional sequencing direction, we sequenced from the 3' end of L1Hs to the genomic DNA, thus enabling the direct detection of the polyA tail signature of retrotransposition for verification of true insertions. Deep coverage sequencing thus allowed us to detect seven potential somatic insertions with low read counts from two iPSC clones. Negative PCR amplification in parental cells, presence of a polyA tail and absence from seven L1 germline insertion databases highly suggested true somatic insertions in iPSCs. Furthermore, these insertions could not be detected in iPSCs by PCR, likely due to low abundance. We conclude that L1Hs retrotransposes at low levels in iPSCs and therefore warrants careful analyses for genotoxic effects.

  9. Acute Consumption of Flavan-3-ol-Enriched Dark Chocolate Affects Human Endogenous Metabolism.

    Science.gov (United States)

    Ostertag, Luisa M; Philo, Mark; Colquhoun, Ian J; Tapp, Henri S; Saha, Shikha; Duthie, Garry G; Kemsley, E Kate; de Roos, Baukje; Kroon, Paul A; Le Gall, Gwénaëlle

    2017-07-07

    Flavan-3-ols and methylxanthines have potential beneficial effects on human health including reducing cardiovascular risk. We performed a randomized controlled crossover intervention trial to assess the acute effects of consumption of flavan-3-ol-enriched dark chocolate, compared with standard dark chocolate and white chocolate, on the human metabolome. We assessed the metabolome in urine and blood plasma samples collected before and at 2 and 6 h after consumption of chocolates in 42 healthy volunteers using a nontargeted metabolomics approach. Plasma samples were assessed and showed differentiation between time points with no further separation among the three chocolate treatments. Multivariate statistics applied to urine samples could readily separate the postprandial time points and distinguish between the treatments. Most of the markers responsible for the multivariate discrimination between the chocolates were of dietary origin. Interestingly, small but significant level changes were also observed for a subset of endogenous metabolites. (1)H NMR revealed that flavan-3-ol-enriched dark chocolate and standard dark chocolate reduced urinary levels of creatinine, lactate, some amino acids, and related degradation products and increased the levels of pyruvate and 4-hydroxyphenylacetate, a phenolic compound of bacterial origin. This study demonstrates that an acute chocolate intervention can significantly affect human metabolism.

  10. Colocalization of endogenous TNF with a functional intracellular splice form of human TNF receptor type 2

    Directory of Open Access Journals (Sweden)

    Schütze Stephan

    2005-07-01

    Full Text Available Abstract Background Tumor necrosis factor (TNF is a pleiotropic cytokine involved in a broad spectrum of inflammatory and immune responses including proliferation, differentiation, and cell death. The biological effects of TNF are mediated via two cell surface TNF receptors: p55TNFR (TNFR1; CD120a and p75TNFR (TNFR2; CD120b. Soluble forms of these two receptors consisting of the extracellular domains are proteolytically cleaved from the membrane and act as inhibitors. A novel p75TNFR isoform generated by the use of an additional transcriptional start site has been described and was termed hicp75TNFR. We focused on the characterization of this new isoform as this protein may be involved in chronic inflammatory processes. Methods Cell lines were retroviraly transduced with hp75TNFR isoforms. Subcellular localization and colocalization studies with TNF were performed using fluorescence microscopy including exhaustive photon reassignment software, flow cytometry, and receptosome isolation by magnetic means. Biochemical properties of the hicp75TNFR were determined by affinity chromatography, ELISA, and western blot techniques. Results We describe the localization and activation of a differentially spliced and mainly intracellularly expressed isoform of human p75TNFR, termed hicp75TNFR. Expression studies with hicp75TNFR cDNA in different cell types showed the resulting protein mostly retained in the trans-Golgi network and in endosomes and colocalizes with endogenous TNF. Surface expressed hicp75TNFR behaves like hp75TNFR demonstrating susceptibility for TACE-induced shedding and NFκB activation after TNF binding. Conclusion Our data demonstrate that intracellular hicp75TNFR is not accessible for exogenously provided TNF but colocalizes with endogenously produced TNF. These findings suggest a possible intracellular activation mechanism of hicp75TNFR by endogenous TNF. Subsequent NFκB activation might induce anti-apoptotic mechanisms to protect TNF

  11. Endogenous Protein Interactome of Human UDP-Glucuronosyltransferases Exposed by Untargeted Proteomics

    Science.gov (United States)

    Rouleau, Michèle; Audet-Delage, Yannick; Desjardins, Sylvie; Rouleau, Mélanie; Girard-Bock, Camille; Guillemette, Chantal

    2017-01-01

    The conjugative metabolism mediated by UDP-glucuronosyltransferase enzymes (UGTs) significantly influences the bioavailability and biological responses of endogenous molecule substrates and xenobiotics including drugs. UGTs participate in the regulation of cellular homeostasis by limiting stress induced by toxic molecules, and by controlling hormonal signaling networks. Glucuronidation is highly regulated at genomic, transcriptional, post-transcriptional and post-translational levels. However, the UGT protein interaction network, which is likely to influence glucuronidation, has received little attention. We investigated the endogenous protein interactome of human UGT1A enzymes in main drug metabolizing non-malignant tissues where UGT expression is most prevalent, using an unbiased proteomics approach. Mass spectrometry analysis of affinity-purified UGT1A enzymes and associated protein complexes in liver, kidney and intestine tissues revealed an intricate interactome linking UGT1A enzymes to multiple metabolic pathways. Several proteins of pharmacological importance such as transferases (including UGT2 enzymes), transporters and dehydrogenases were identified, upholding a potential coordinated cellular response to small lipophilic molecules and drugs. Furthermore, a significant cluster of functionally related enzymes involved in fatty acid β-oxidation, as well as in the glycolysis and glycogenolysis pathways were enriched in UGT1A enzymes complexes. Several partnerships were confirmed by co-immunoprecipitations and co-localization by confocal microscopy. An enhanced accumulation of lipid droplets in a kidney cell model overexpressing the UGT1A9 enzyme supported the presence of a functional interplay. Our work provides unprecedented evidence for a functional interaction between glucuronidation and bioenergetic metabolism. PMID:28217095

  12. Prevalence of human endogenous retroviral element associates with Hodgkin's lymphoma incidence rates

    Directory of Open Access Journals (Sweden)

    Wee Hong Woo

    2014-01-01

    Full Text Available Human endogenous retrovirus-H (HERV-H is implicated in leukaemias and lymphomas, but the precise molecular mechanism underlying HERV-mediated carcinogenesis remains unknown. We determined the prevalence of HERV-H in a cross-section of the Singapore population and explored the relationship between HERV-H positivity and incidence rates for Hodgkin's lymphoma in three major ethnic groups of Singapore. We observed that Malays were 1.11 times likely (95% CI=1.05–1.17; P<0.01, and Indians 1.12 times likely (95% CI=1.07–1.18; P<0.01 to be HERV-H positive when compared to Chinese. Interestingly, the incidence rates of Hodgkin's lymphoma for the three races positively correlated to the respective prevalence rate for HERV-H positivity (r=0.9921 for male; r=0.9801 for female, suggesting that viral inheritance in human may predispose certain racial origin unfavourably to malignancy.

  13. Age-related reduction of antibody response against the human endogenous retrovirus K envelope in women.

    Science.gov (United States)

    Kim, Hyoung Jin; Moon, Byung-In; Lee, Jun Woo; Kim, Seung Cheol; Kim, Hong-Jin

    2016-04-05

    In the present study, the correlation between the antibody response against human endogenous retrovirus K (HERV-K) envelope and human age was investigated. Antibody levels were compared in groups in their 20s (n = 25), 30s (n = 39), 40s (n = 68), 50s (n = 32), and 60s and over (n = 25), which included healthy individuals and breast cancer and/or cervical cancer patients. It appeared that both IgM and IgG responses against the HERV-K envelope fell with increasing age. There were no differences in anti-HERV-K envelope antibody levels between healthy individuals and cancer patients. Therefore, our results indicated that the anti-HERV-K antibody levels cannot be considered as cancer-specific marker. Also, IgG1 appeared to be the predominant subtype in the reduction of the IgG response by age. Receiver operating characteristic curves of anti-HERV-K envelope IgM levels indicated that the groups of people in their 20s or 30s could be distinguished from those in their 40s, 50s or 60s and over with satisfactory sensitivity and specificity. These findings indicate that the serum antibody level of HERV-K envelope is a critical parameter reflecting person's age.

  14. (Some cellular mechanisms influencing the transcription of human endogenous retrovirus, HERV-Fc1.

    Directory of Open Access Journals (Sweden)

    Magdalena Janina Laska

    Full Text Available DNA methylation and histone acetylation are epigenetic modifications that act as regulators of gene expression. DNA methylation is considered an important mechanism for silencing of retroelements in the mammalian genome. However, the methylation of human endogenous retroviruses (HERVs is not well investigated. The aim of this study was to investigate the transcriptional potential of HERV-Fc1 proviral 5'LTR in more detail, and examined the specific influence of CpG methylation on this LTR in number of cell lines. Specifically, the role of demethylating chemicals e.g. 5-aza-2' deoxycytidine and Trichostatin-A, in inducing or reactivating expression of HERV-Fc1 specific sequences and the mechanisms were investigated. In our present study, 5-aza-dC is shown to be a powerful inducer of HERV-Fc1, and at the same time it strongly inhibits methylation of DNA. Treatment with this demethylating agent 5-aza-dC, results in significantly increased levels of HERV-Fc1 expression in cells previously not expressing HERV-Fc1, or with a very low expression level. The extent of expression of HERV-Fc1 RNAs precisely correlates with the apparent extent of demethylation of the related DNA sequences. In conclusion, the results suggest that inhibition of DNA methylation/histone deacetylase can interfere with gene silencing mechanisms affecting HERV-Fc1 expression in human cells.

  15. [Study of human leucine-rich amelogenin peptide and its regulation of mineralization by cryogenic transmission electron microscopy].

    Science.gov (United States)

    Kun, Tian; Xiaoyun, Feng; Qin, Du; Chuhang, Liao; Xiaohua, Ren

    2017-02-01

    Recombinant human leucine-rich amelogenin peptide (LRAP) was studied by cryogenic transmission electron microscopy (TEM); evaluation focused on its self-assembly and crystal growth in vitro. Human LRAP was recombined through prokaryotic expression vector pCold-SUMO and transformed into Escherichia coli BL21plys to acquire purified proteins. Cryogen TEM recorded assembly and self-assembling of LRAP from pH 3.5 to pH 8.0, and the hydroxyapatite crystal growth in the mixture of LRAP protein solution and artificial saliva was observed using TEM and selected area electron diffraction. More than 90% purity LRAP was expressed, purified and identified as described in methods. LRAP linked into oligomers, nanospheres, nanochains, and microribbons, whereas pH value increased from 3.5 to 8.0. Mature hydroxyapatite crystal growth was guided in artificial saliva filled with calcium phosphate. LRAP is simplified amelogenin functional domain and conserved the basic characters of amelogenin such as self-assembling and inducing crystallization along c axis. In the area of acellular synthesis of hydroxyapatite using extracellular enamel matrix protein, LRAP is one of candidate repair materials for irregular hard tissue defection.
.

  16. Adsorbing/dissolving Lyoprotectant Matrix Technology for Non-cryogenic Storage of Archival Human Sera.

    Science.gov (United States)

    Solivio, Morwena J; Less, Rebekah; Rynes, Mathew L; Kramer, Marcus; Aksan, Alptekin

    2016-04-12

    Despite abundant research conducted on cancer biomarker discovery and validation, to date, less than two-dozen biomarkers have been approved by the FDA for clinical use. One main reason is attributed to inadvertent use of low quality biospecimens in biomarker research. Most proteinaceous biomarkers are extremely susceptible to pre-analytical factors such as collection, processing, and storage. For example, cryogenic storage imposes very harsh chemical, physical, and mechanical stresses on biospecimens, significantly compromising sample quality. In this communication, we report the development of an electrospun lyoprotectant matrix and isothermal vitrification methodology for non-cryogenic stabilization and storage of liquid biospecimens. The lyoprotectant matrix was mainly composed of trehalose and dextran (and various low concentration excipients targeting different mechanisms of damage), and it was engineered to minimize heterogeneity during vitrification. The technology was validated using five biomarkers; LDH, CRP, PSA, MMP-7, and C3a. Complete recovery of LDH, CRP, and PSA levels was achieved post-rehydration while more than 90% recovery was accomplished for MMP-7 and C3a, showing promise for isothermal vitrification as a safe, efficient, and low-cost alternative to cryogenic storage.

  17. Hepatic-intestinal disposal of endogenous human alpha atrial natriuretic factor99-126 in patients with cirrhosis

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Bendtsen, Flemming; Schütten, H J

    1990-01-01

    Hepatic-intestinal disposal of endogenous human alpha atrial natriuretic factor99-126 (ANF) was assessed in 13 patients with cirrhosis (six Child-Turcotte class A, five class B, and two class C) and eight control subjects. The Fick principle was applied during hepatic vein catheterization. Arterial...

  18. Hepatic-intestinal disposal of endogenous human alpha atrial natriuretic factor99-126 in patients with cirrhosis

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Bendtsen, F; Schütten, H J

    1990-01-01

    Hepatic-intestinal disposal of endogenous human alpha atrial natriuretic factor99-126 (ANF) was assessed in 13 patients with cirrhosis (six Child-Turcotte class A, five class B, and two class C) and eight control subjects. The Fick principle was applied during hepatic vein catheterization. Arterial...

  19. Synergistic effect of exogeneous and endogeneous electrostimulation on osteogenic differentiation of human mesenchymal stem cells seeded on silk scaffolds.

    Science.gov (United States)

    Çakmak, Anıl S; Çakmak, Soner; White, James D; Raja, Waseem K; Kim, Kyungsook; Yiğit, Sezin; Kaplan, David L; Gümüşderelioğlu, Menemşe

    2016-04-01

    Bioelectrical regulation of bone fracture healing is important for many cellular events such as proliferation, migration, and differentiation. The aim of this study was to investigate the osteogenic differentiation potential of human mesenchymal stem cells (hMSCs) cultivated on silk scaffolds in response to different modes of electrostimulation (e.g., exogeneous and/or endogeneous). Endogeneous electrophysiology was altered through the use of monensin (10 nM) and glibenclamide (10 μM), along with external electrostimulation (60 kHz; 100-500 mV). Monensin enhanced the expression of early osteogenic markers such as alkaline phosphatase (ALP) and runt-related transcription factor 2 (RUNX-2). When exogeneous electrostimulation was combined with glibenclamide, more mature osteogenic marker upregulation based on bone sialoprotein expression (BSP) and mineralization was found. These results suggest the potential to exploit both exogeneous and endogeneous biophysical control of cell functions towards tissue-specific goals.

  20. Endogenous oils derived from human adipocytes are potent adjuvants that promote IL-1α-dependent inflammation.

    Science.gov (United States)

    Tynan, Graham A; Hearnden, Claire H; Oleszycka, Ewa; Lyons, Claire L; Coutts, Graham; O'Connell, Jean; Corrigan, Michelle A; Lynch, Lydia; Campbell, Matthew; Callanan, John J; Mok, Kenneth H; Geoghegan, Justin; O'Farrelly, Cliona; Allan, Stuart M; Roche, Helen M; O'Shea, Donal B; Lavelle, Ed C

    2014-06-01

    Obesity is characterized by chronic inflammation associated with neutrophil and M1 macrophage infiltration into white adipose tissue. However, the mechanisms underlying this process remain largely unknown. Based on the ability of oil-based adjuvants to induce immune responses, we hypothesized that endogenous oils derived from necrotic adipocytes may function as an immunological "danger signal." Here we show that endogenous oils of human origin are potent adjuvants, enhancing antibody responses to a level comparable to Freund's incomplete adjuvant. The endogenous oils were capable of promoting interleukin (IL)-1α-dependent recruitment of neutrophils and M1-like macrophages, while simultaneously diminishing M2-like macrophages. We found that endogenous oils from subcutaneous and omental adipocytes, and from healthy and unhealthy obese individuals, promoted comparable inflammatory responses. Furthermore, we also confirmed that white adipocytes in visceral fat of metabolically unhealthy obese (MUO) individuals are significantly larger than those in metabolically healthy obese individuals. Since adipocyte size is positively correlated with adipocyte death, we propose that endogenous oils have a higher propensity to be released from hypertrophied visceral fat in MUO individuals and that this is the key factor in driving inflammation. In summary, this study shows that adipocytes contain a potent oil adjuvant which drives IL-1α-dependent proinflammatory responses in vivo.

  1. Estimating the effect of endogenous dopamine on baseline [(11) C]-(+)-PHNO binding in the human brain.

    Science.gov (United States)

    Caravaggio, Fernando; Kegeles, Lawrence S; Wilson, Alan A; Remington, Gary; Borlido, Carol; Mamo, David C; Graff-Guerrero, Ariel

    2016-11-01

    Endogenous dopamine (DA) levels at dopamine D2/3 receptors (D2/3 R) have been quantified in the living human brain using the agonist radiotracer [(11) C]-(+)-PHNO. As an agonist radiotracer, [(11) C]-(+)-PHNO is more sensitive to endogenous DA levels than antagonist radiotracers. We sought to determine the proportion of the variance in baseline [(11) C]-(+)-PHNO binding to D2/3 Rs which can be accounted for by variation in endogenous DA levels. This was done by computing the Pearson's coefficient for the correlation between baseline binding potential (BPND ) and the change in BPND after acute DA depletion, using previously published data. All correlations were inverse, and the proportion of the variance in baseline [(11) C]-(+)-PHNO BPND that can be accounted for by variation in endogenous DA levels across the striatal subregions ranged from 42-59%. These results indicate that lower baseline values of [(11) C]-(+)-PHNO BPND reflect greater stimulation by endogenous DA. To further validate this interpretation, we sought to examine whether these data could be used to estimate the dissociation constant (Kd) of DA at D2/3 R. In line with previous in vitro work, we estimated the in vivo Kd of DA to be around 20 nM. In summary, the agonist radiotracer [(11) C]-(+)-PHNO can detect the impact of endogenous DA levels at D2/3 R in the living human brain from a single baseline scan, and may be more sensitive to this impact than other commonly employed radiotracers.

  2. CRISPR-on system for the activation of the endogenous human INS gene.

    Science.gov (United States)

    Giménez, C A; Ielpi, M; Mutto, A; Grosembacher, L; Argibay, P; Pereyra-Bonnet, F

    2016-06-01

    Advances in the field of epigenetics have allowed the design of new therapeutic strategies to address complex diseases such as type 1 diabetes (T1D). Clustered regularly interspaced short palindromic repeats (CRISPR)-on is a novel and powerful RNA-guided transcriptional activator system that can turn on specific gene expression; however, it remains unclear whether this system can be widely used or whether its use will be restricted depending on cell types, methylation promoter statuses or the capacity to modulate chromatin state. Our results revealed that the CRISPR-on system fused with transcriptional activators (dCas9-VP160) activated endogenous human INS, which is a silenced gene with a fully methylated promoter. Similarly, we observed a synergistic effect on gene activation when multiple single guide RNAs were used, and the transcriptional activation was maintained until day 21. Regarding the epigenetic profile, the targeted promoter gene did not exhibit alteration in its methylation status but rather exhibited altered levels of H3K9ac following treatment. Importantly, we showed that dCas9-VP160 acts on patients' cells in vitro, particularly the fibroblasts of patients with T1D.

  3. Endogenous retroviral LTRs as promoters for human genes: a critical assessment.

    Science.gov (United States)

    Cohen, Carla J; Lock, Wynne M; Mager, Dixie L

    2009-12-15

    Gene regulatory changes are thought to be major factors driving species evolution, with creation of new regulatory regions likely being instrumental in contributing to diversity among vertebrates. There is growing appreciation for the role of transposable elements (TEs) in gene regulation and, indeed, laboratory investigations have confirmed many specific examples of mammalian genes regulated by promoters donated by endogenous retroviruses (ERVs) or other TEs. Bioinformatics studies have revealed hundreds of additional instances where this is likely to be the case. Since the long terminal repeats (LTRs) of retroviruses naturally contain abundant transcriptional regulatory signals, roles for ERV LTRs in regulating mammalian genes are eminently plausible. Moreover, it seems reasonable that exaptation of an LTR regulatory module provides opportunities for evolution of new gene regulatory patterns. In this Review we summarize known examples of LTRs that function as human gene alternative promoters, as well as the evidence that LTR exaptation has resulted in a pattern of novel gene expression significantly different from the pattern before LTR insertion or from that of gene orthologs lacking the LTR. Available data suggest that, while new expression patterns can arise as a result of LTR usage, this situation is relatively rare and is largely restricted to the placenta. In many cases, the LTR appears to be a minor, alternative promoter with an expression pattern similar to that of the native promoter(s) and hence likely exerts a subtle overall effect on gene expression. We discuss these findings and offer evolutionary models to explain these trends.

  4. Design and Applications of Biodegradable Polyester Tissue Scaffolds Based on Endogenous Monomers Found in Human Metabolism

    Directory of Open Access Journals (Sweden)

    Devin G. Barrett

    2009-10-01

    Full Text Available Synthetic polyesters have deeply impacted various biomedical and engineering fields, such as tissue scaffolding and therapeutic delivery. Currently, many applications involving polyesters are being explored with polymers derived from monomers that are endogenous to the human metabolism. Examples of these monomers include glycerol, xylitol, sorbitol, and lactic, sebacic, citric, succinic, α-ketoglutaric, and fumaric acids. In terms of mechanical versatility, crystallinity, hydrophobicity, and biocompatibility, polyesters synthesized partially or completely from these monomers can display a wide range of properties. The flexibility in these macromolecular properties allows for materials to be tailored according to the needs of a particular application. Along with the presence of natural monomers that allows for a high probability of biocompatibility, there is also an added benefit that this class of polyesters is more environmentally friendly than many other materials used in biomedical engineering. While the selection of monomers may be limited by nature, these polymers have produced or have the potential to produce an enormous number of successes in vitro and in vivo.

  5. Validation of endogenous control genes for gene expression studies on human ocular surface epithelium.

    Directory of Open Access Journals (Sweden)

    Bina Kulkarni

    Full Text Available PURPOSE: To evaluate a panel of ten known endogenous control genes (ECG with quantitative reverse transcription PCR (qPCR, for identification of stably expressed endogenous control genes in the ocular surface (OS epithelial regions including cornea, limbus, limbal epithelial crypt and conjunctiva to normalise the quantitative reverse transcription PCR data of genes of interest expressed in above-mentioned regions. METHOD: The lasermicrodissected (LMD OS epithelial regions of cryosectioned corneoscleral buttons from the cadaver eyes were processed for RNA extraction and cDNA synthesis to detect genes of interest with qPCR. Gene expression of 10 known ECG--glyceraldehyde-3-phosphate dehydrogenase (GAPDH, beta actin (ACTB, peptidylprolyl isomerase (PPIA, TATA-box binding protein (TBP1, hypoxanthine guanine phosphoribosyl transferase (HPRT1, beta glucuronidase (GUSB, Eucaryotic 18S ribosomal RNA (18S, phosphoglycerate kinase (PGK1, beta-2-microglobulin (B2M, ribosomal protein, large, P0 (RPLP0--was measured in the OS epithelial regions by qPCR method and the data collected was further analysed using geNorm software. RESULTS: The expression stability of ecgs in the os epithelial regions in increasing order as determined with genorm software is as follows: ACTB<18Shuman OS epithelium and provide evidence for the use

  6. Cryogenic Systems

    Science.gov (United States)

    Hosoyama, Kenji

    2002-02-01

    In this lecture we discuss the principle of method of cooling to a very low temperature, i.e. cryogenic. The "gas molecular model" will be introduced to explain the mechanism cooling by the expansion engine and the Joule-Thomson expansion valve. These two expansion processes are normally used in helium refrigeration systems to cool the process gas to cryogenic temperature. The reverse Carnot cycle will be discussed in detail as an ideal refrigeration cycle. First the fundamental process of liquefaction and refrigeration cycles will be discussed, and then the practical helium refrigeration system. The process flow of the system and the key components; -compressor, expander, and heat exchanger- will be discussed. As an example of an actual refrigeration system, we will use the cryogenic system for the KEKB superconducting RF cavity. We will also discuss the liquid helium distribution system, which is very important, especially for the cryogenic systems used in accelerator applications. 1 Principles of Cooling and Fundamental Cooling Cycle 2 Expansion engine, Joule-Thomson expansion, kinetic molecular theory, and enthalpy 3 Liquefaction Systems 4 Refrigeration Systems 5 Practical helium liquefier/refrigeration system 6 Cryogenic System for TRISTAN Superconducting RF Cavity

  7. Human Endogenous Retrovirus HERV-Fc1 Association with Multiple Sclerosis Susceptibility: A Meta-Analysis

    Science.gov (United States)

    García-Montojo, Marta; Alcina, Antonio; Fedetz, María; Alloza, Iraide; Astobiza, Ianire; Leyva, Laura; Fernández, Oscar; Izquierdo, Guillermo; Antigüedad, Alfredo; Arroyo, Rafael; Álvarez-Lafuente, Roberto; Vandenbroeck, Koen; Matesanz, Fuencisla; Urcelay, Elena

    2014-01-01

    Background Human endogenous retroviruses (HERVs) are repetitive sequences derived from ancestral germ-line infections by exogenous retroviruses and different HERV families have been integrated in the genome. HERV-Fc1 in chromosome X has been previously associated with multiple sclerosis (MS) in Northern European populations. Additionally, HERV-Fc1 RNA levels of expression have been found increased in plasma of MS patients with active disease. Considering the North-South latitude gradient in MS prevalence, we aimed to evaluate the role of HERV-Fc1on MS risk in three independent Spanish cohorts. Methods A single nucleotide polymorphism near HERV-Fc1, rs391745, was genotyped by Taqman chemistry in a total of 2473 MS patients and 3031 ethnically matched controls, consecutively recruited from: Northern (569 patients and 980 controls), Central (883 patients and 692 controls) and Southern (1021 patients and 1359 controls) Spain. Our results were pooled in a meta-analysis with previously published data. Results Significant associations of the HERV-Fc1 polymorphism with MS were observed in two Spanish cohorts and the combined meta-analysis with previous data yielded a significant association [rs391745 C-allele carriers: pM-H = 0.0005; ORM-H (95% CI) = 1.27 (1.11–1.45)]. Concordantly to previous findings, when the analysis was restricted to relapsing remitting and secondary progressive MS samples, a slight enhancement in the strength of the association was observed [pM-H = 0.0003, ORM-H (95% CI) = 1.32 (1.14–1.53)]. Conclusion Association of the HERV-Fc1 polymorphism rs391745 with bout-onset MS susceptibility was confirmed in Southern European cohorts. PMID:24594754

  8. Human endogenous retrovirus HERV-Fc1 association with multiple sclerosis susceptibility: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Belén de la Hera

    Full Text Available BACKGROUND: Human endogenous retroviruses (HERVs are repetitive sequences derived from ancestral germ-line infections by exogenous retroviruses and different HERV families have been integrated in the genome. HERV-Fc1 in chromosome X has been previously associated with multiple sclerosis (MS in Northern European populations. Additionally, HERV-Fc1 RNA levels of expression have been found increased in plasma of MS patients with active disease. Considering the North-South latitude gradient in MS prevalence, we aimed to evaluate the role of HERV-Fc1on MS risk in three independent Spanish cohorts. METHODS: A single nucleotide polymorphism near HERV-Fc1, rs391745, was genotyped by Taqman chemistry in a total of 2473 MS patients and 3031 ethnically matched controls, consecutively recruited from: Northern (569 patients and 980 controls, Central (883 patients and 692 controls and Southern (1021 patients and 1359 controls Spain. Our results were pooled in a meta-analysis with previously published data. RESULTS: Significant associations of the HERV-Fc1 polymorphism with MS were observed in two Spanish cohorts and the combined meta-analysis with previous data yielded a significant association [rs391745 C-allele carriers: pM-H = 0.0005; ORM-H (95% CI = 1.27 (1.11-1.45]. Concordantly to previous findings, when the analysis was restricted to relapsing remitting and secondary progressive MS samples, a slight enhancement in the strength of the association was observed [pM-H = 0.0003, ORM-H (95% CI = 1.32 (1.14-1.53]. CONCLUSION: Association of the HERV-Fc1 polymorphism rs391745 with bout-onset MS susceptibility was confirmed in Southern European cohorts.

  9. Fragmentation of contaminant and endogenous DNA in ancient samples determined by shotgun sequencing; prospects for human palaeogenomics.

    Directory of Open Access Journals (Sweden)

    Marc García-Garcerà

    Full Text Available BACKGROUND: Despite the successful retrieval of genomes from past remains, the prospects for human palaeogenomics remain unclear because of the difficulty of distinguishing contaminant from endogenous DNA sequences. Previous sequence data generated on high-throughput sequencing platforms indicate that fragmentation of ancient DNA sequences is a characteristic trait primarily arising due to depurination processes that create abasic sites leading to DNA breaks. METHODOLOGY/PRINCIPALS FINDINGS: To investigate whether this pattern is present in ancient remains from a temperate environment, we have 454-FLX pyrosequenced different samples dated between 5,500 and 49,000 years ago: a bone from an extinct goat (Myotragus balearicus that was treated with a depurinating agent (bleach, an Iberian lynx bone not subjected to any treatment, a human Neolithic sample from Barcelona (Spain, and a Neandertal sample from the El Sidrón site (Asturias, Spain. The efficiency of retrieval of endogenous sequences is below 1% in all cases. We have used the non-human samples to identify human sequences (0.35 and 1.4%, respectively, that we positively know are contaminants. CONCLUSIONS: We observed that bleach treatment appears to create a depurination-associated fragmentation pattern in resulting contaminant sequences that is indistinguishable from previously described endogenous sequences. Furthermore, the nucleotide composition pattern observed in 5' and 3' ends of contaminant sequences is much more complex than the flat pattern previously described in some Neandertal contaminants. Although much research on samples with known contaminant histories is needed, our results suggest that endogenous and contaminant sequences cannot be distinguished by the fragmentation pattern alone.

  10. CRISPR/Cas9-mediated endogenous protein tagging for RESOLFT super-resolution microscopy of living human cells.

    Science.gov (United States)

    Ratz, Michael; Testa, Ilaria; Hell, Stefan W; Jakobs, Stefan

    2015-04-20

    Overexpression is a notorious concern in conventional and especially in super-resolution fluorescence light microscopy studies because it may cause numerous artifacts including ectopic sub-cellular localizations, erroneous formation of protein complexes, and others. Nonetheless, current live cell super-resolution microscopy studies generally rely on the overexpression of a host protein fused to a fluorescent protein. Here, we establish CRISPR/Cas9-mediated generation of heterozygous and homozygous human knockin cell lines expressing fluorescently tagged proteins from their respective native genomic loci at close to endogenous levels. We tagged three different proteins, exhibiting various localizations and expression levels, with the reversibly switchable fluorescent protein rsEGFP2. We demonstrate the benefit of endogenous expression levels compared to overexpression and show that typical overexpression-induced artefacts were avoided in genome-edited cells. Fluorescence activated cell sorting analysis revealed a narrow distribution of fusion protein expression levels in genome-edited cells, compared to a pronounced variability in transiently transfected cells. Using low light intensity RESOLFT (reversible saturable optical fluorescence transitions) nanoscopy we show sub-diffraction resolution imaging of living human knockin cells. Our strategy to generate human cell lines expressing fluorescent fusion proteins at endogenous levels for RESOLFT nanoscopy can be extended to other fluorescent tags and super-resolution approaches.

  11. Identification and characterization of endogenous viral elements for the three key schistosomes of humans.

    Science.gov (United States)

    Li, Na; Li, Quhuan

    2015-01-01

    Endogenous viral elements (EVEs) are widely distributed throughout eukaryotic genomes, and their evolution and potential function have attracted a lot of interest. Draft genome sequences for Schistosoma mansoni, Schistosoma japonicum and Schistosoma haematobium are now available; however, information about EVEs in blood flukes of the genus schistosoma is scanty. Here, genome-wide survey into the putative EVE sequences of the three key schistosome genomes were present. Totally 4, 117 gene sequences were identified, including retrovirus-like gypsy elements, RNA viruses and dsDNA viruses. Compared with S. japonicum and S. haematobium, S. mansoni appeared to greatly out numbered by gypsy members. Phylogenetic analysis revealed one novel endogenous retrovirus element in S. mansoni. This initial characterization of schistosomes showed that schistosomes harbour distinct EVEs that may have played an important evolutionary role. Studies of schistosomes' endogenous viruses helped us to glance at an earlier viral event in the class Trematoda, greatly broadening the field of palaeovirology.

  12. Molecular characteristics of Human Endogenous Retrovirus type-W in schizophrenia and bipolar disorder.

    Science.gov (United States)

    Perron, H; Hamdani, N; Faucard, R; Lajnef, M; Jamain, S; Daban-Huard, C; Sarrazin, S; LeGuen, E; Houenou, J; Delavest, M; Moins-Teisserenc, H; Moins-Teiserenc, H; Bengoufa, D; Yolken, R; Madeira, A; Garcia-Montojo, M; Gehin, N; Burgelin, I; Ollagnier, G; Bernard, C; Dumaine, A; Henrion, A; Gombert, A; Le Dudal, K; Charron, D; Krishnamoorthy, R; Tamouza, R; Leboyer, M

    2012-12-04

    Epidemiological and genome-wide association studies of severe psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BD), suggest complex interactions between multiple genetic elements and environmental factors. The involvement of genetic elements such as Human Endogenous Retroviruses type 'W' family (HERV-W) has consistently been associated with SZ. HERV-W envelope gene (env) is activated by environmental factors and encodes a protein displaying inflammation and neurotoxicity. The present study addressed the molecular characteristics of HERV-W env in SZ and BD. Hundred and thirty-six patients, 91 with BD, 45 with SZ and 73 healthy controls (HC) were included. HERV-W env transcription was found to be elevated in BD (P<10-4) and in SZ (P=0.012) as compared with HC, but with higher values in BD than in SZ group (P<0.01). The corresponding DNA copy number was paradoxically lower in the genome of patients with BD (P=0.0016) or SZ (P<0.0003) than in HC. Differences in nucleotide sequence of HERV-W env were found between patients with SZ and BD as compared with HC, as well as between SZ and BD. The molecular characteristics of HERV-W env also differ from what was observed in Multiple Sclerosis (MS) and may represent distinct features of the genome of patients with BD and SZ. The seroprevalence for Toxoplasma gondii yielded low but significant association with HERV-W transcriptional level in a subgroup of BD and SZ, suggesting a potential role in particular patients. A global hypothesis of mechanisms inducing such major psychoses is discussed, placing HERV-W at the crossroads between environmental, genetic and immunological factors. Thus, particular infections would act as activators of HERV-W elements in earliest life, resulting in the production of an HERV-W envelope protein, which then stimulates pro-inflammatory and neurotoxic cascades. This hypothesis needs to be further explored as it may yield major changes in our understanding and treatment of

  13. Systematic identification and characterization of regulatory elements derived from human endogenous retroviruses.

    Directory of Open Access Journals (Sweden)

    Jumpei Ito

    2017-07-01

    Full Text Available Human endogenous retroviruses (HERVs and other long terminal repeat (LTR-type retrotransposons (HERV/LTRs have regulatory elements that possibly influence the transcription of host genes. We systematically identified and characterized these regulatory elements based on publicly available datasets of ChIP-Seq of 97 transcription factors (TFs provided by ENCODE and Roadmap Epigenomics projects. We determined transcription factor-binding sites (TFBSs using the ChIP-Seq datasets and identified TFBSs observed on HERV/LTR sequences (HERV-TFBSs. Overall, 794,972 HERV-TFBSs were identified. Subsequently, we identified "HERV/LTR-shared regulatory element (HSRE," defined as a TF-binding motif in HERV-TFBSs, shared within a substantial fraction of a HERV/LTR type. HSREs could be an indication that the regulatory elements of HERV/LTRs are present before their insertions. We identified 2,201 HSREs, comprising specific associations of 354 HERV/LTRs and 84 TFs. Clustering analysis showed that HERV/LTRs can be grouped according to the TF binding patterns; HERV/LTR groups bounded to pluripotent TFs (e.g., SOX2, POU5F1, and NANOG, embryonic endoderm/mesendoderm TFs (e.g., GATA4/6, SOX17, and FOXA1/2, hematopoietic TFs (e.g., SPI1 (PU1, GATA1/2, and TAL1, and CTCF were identified. Regulatory elements of HERV/LTRs tended to locate nearby and/or interact three-dimensionally with the genes involved in immune responses, indicating that the regulatory elements play an important role in controlling the immune regulatory network. Further, we demonstrated subgroup-specific TF binding within LTR7, LTR5B, and LTR5_Hs, indicating that gains or losses of the regulatory elements occurred during genomic invasions of the HERV/LTRs. Finally, we constructed dbHERV-REs, an interactive database of HERV/LTR regulatory elements (http://herv-tfbs.com/. This study provides fundamental information in understanding the impact of HERV/LTRs on host transcription, and offers insights into

  14. Endogenous and exogenous components in the circadian variation of core body temperature in humans

    NARCIS (Netherlands)

    Hiddinga, AE; Beersma, DGM; VandenHoofdakker, RH

    1997-01-01

    Core body temperature is predominantly modulated by endogenous and exogenous components. In the present study we tested whether these two components can be reliably assessed in a protocol which lasts for only 120 h. In this so-called forced desynchrony protocol, 12 healthy male subjects (age 23.7 +/

  15. Native human interferon-α is a strong inductor of endogenous cytokines involved in the suppression of procollagen type I.

    Science.gov (United States)

    Santak, G; Santak, M; Forčić, D

    2013-09-01

    Native human interferon-α (nHuIFN-α) has a stronger reductive effect on procollagen type I mRNA expression than recombinant human interferon-α (rHuIFN-α). It is partially due to the additive activity of interleukin-1β (IL-1β), which is present in small concentrations in nHuIFN-α. Here, we show that the reductive effect is also the result of the endogenous cytokines induced by the activity of nHuIFN-α. In the culture of MRC5 fibroblasts, we have further found that nHuIFN-α induces endogenous interferons in higher amounts than rHuIFN-α, measured with PCR. That is more pronounced when interferon-γ (IFN-γ) is measured. This result puts a new light on IFN-γ activity in the nHuIFN-α treatment because its role was neglected due to the loss of its activity during the nHuIFN-α preparation process. The findings lead to the conclusion that endogenous cytokines play a significant role in the nHuIFN-α -mediated reduction of procollagen type I mRNA and are therefore an important factor in potential therapeutic usage. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  16. A New Nanobody-Based Biosensor to Study Endogenous PARP1 In Vitro and in Live Human Cells

    Science.gov (United States)

    Nüske, Stefan; Scholz, Armin M.; Bogner, Jacqueline; Ruf, Benjamin; Zolghadr, Kourosh; Drexler, Sophie E.; Drexler, Guido A.; Girst, Stefanie; Greubel, Christoph; Reindl, Judith; Siebenwirth, Christian; Romer, Tina; Friedl, Anna A.; Rothbauer, Ulrich

    2016-01-01

    Poly(ADP-ribose) polymerase 1 (PARP1) is a key player in DNA repair, genomic stability and cell survival and it emerges as a highly relevant target for cancer therapies. To deepen our understanding of PARP biology and mechanisms of action of PARP1-targeting anti-cancer compounds, we generated a novel PARP1-affinity reagent, active both in vitro and in live cells. This PARP1-biosensor is based on a PARP1-specific single-domain antibody fragment (~ 15 kDa), termed nanobody, which recognizes the N-terminus of human PARP1 with nanomolar affinity. In proteomic approaches, immobilized PARP1 nanobody facilitates quantitative immunoprecipitation of functional, endogenous PARP1 from cellular lysates. For cellular studies, we engineered an intracellularly functional PARP1 chromobody by combining the nanobody coding sequence with a fluorescent protein sequence. By following the chromobody signal, we were for the first time able to monitor the recruitment of endogenous PARP1 to DNA damage sites in live cells. Moreover, tracing of the sub-nuclear translocation of the chromobody signal upon treatment of human cells with chemical substances enables real-time profiling of active compounds in high content imaging. Due to its ability to perform as a biosensor at the endogenous level of the PARP1 enzyme, the novel PARP1 nanobody is a unique and versatile tool for basic and applied studies of PARP1 biology and DNA repair. PMID:26950694

  17. A New Nanobody-Based Biosensor to Study Endogenous PARP1 In Vitro and in Live Human Cells.

    Science.gov (United States)

    Buchfellner, Andrea; Yurlova, Larisa; Nüske, Stefan; Scholz, Armin M; Bogner, Jacqueline; Ruf, Benjamin; Zolghadr, Kourosh; Drexler, Sophie E; Drexler, Guido A; Girst, Stefanie; Greubel, Christoph; Reindl, Judith; Siebenwirth, Christian; Romer, Tina; Friedl, Anna A; Rothbauer, Ulrich

    2016-01-01

    Poly(ADP-ribose) polymerase 1 (PARP1) is a key player in DNA repair, genomic stability and cell survival and it emerges as a highly relevant target for cancer therapies. To deepen our understanding of PARP biology and mechanisms of action of PARP1-targeting anti-cancer compounds, we generated a novel PARP1-affinity reagent, active both in vitro and in live cells. This PARP1-biosensor is based on a PARP1-specific single-domain antibody fragment (~ 15 kDa), termed nanobody, which recognizes the N-terminus of human PARP1 with nanomolar affinity. In proteomic approaches, immobilized PARP1 nanobody facilitates quantitative immunoprecipitation of functional, endogenous PARP1 from cellular lysates. For cellular studies, we engineered an intracellularly functional PARP1 chromobody by combining the nanobody coding sequence with a fluorescent protein sequence. By following the chromobody signal, we were for the first time able to monitor the recruitment of endogenous PARP1 to DNA damage sites in live cells. Moreover, tracing of the sub-nuclear translocation of the chromobody signal upon treatment of human cells with chemical substances enables real-time profiling of active compounds in high content imaging. Due to its ability to perform as a biosensor at the endogenous level of the PARP1 enzyme, the novel PARP1 nanobody is a unique and versatile tool for basic and applied studies of PARP1 biology and DNA repair.

  18. A New Nanobody-Based Biosensor to Study Endogenous PARP1 In Vitro and in Live Human Cells.

    Directory of Open Access Journals (Sweden)

    Andrea Buchfellner

    Full Text Available Poly(ADP-ribose polymerase 1 (PARP1 is a key player in DNA repair, genomic stability and cell survival and it emerges as a highly relevant target for cancer therapies. To deepen our understanding of PARP biology and mechanisms of action of PARP1-targeting anti-cancer compounds, we generated a novel PARP1-affinity reagent, active both in vitro and in live cells. This PARP1-biosensor is based on a PARP1-specific single-domain antibody fragment (~ 15 kDa, termed nanobody, which recognizes the N-terminus of human PARP1 with nanomolar affinity. In proteomic approaches, immobilized PARP1 nanobody facilitates quantitative immunoprecipitation of functional, endogenous PARP1 from cellular lysates. For cellular studies, we engineered an intracellularly functional PARP1 chromobody by combining the nanobody coding sequence with a fluorescent protein sequence. By following the chromobody signal, we were for the first time able to monitor the recruitment of endogenous PARP1 to DNA damage sites in live cells. Moreover, tracing of the sub-nuclear translocation of the chromobody signal upon treatment of human cells with chemical substances enables real-time profiling of active compounds in high content imaging. Due to its ability to perform as a biosensor at the endogenous level of the PARP1 enzyme, the novel PARP1 nanobody is a unique and versatile tool for basic and applied studies of PARP1 biology and DNA repair.

  19. Safety implications of high-field MRI: actuation of endogenous magnetic iron oxides in the human body.

    Directory of Open Access Journals (Sweden)

    Jon Dobson

    Full Text Available BACKGROUND: Magnetic Resonance Imaging scanners have become ubiquitous in hospitals and high-field systems (greater than 3 Tesla are becoming increasingly common. In light of recent European Union moves to limit high-field exposure for those working with MRI scanners, we have evaluated the potential for detrimental cellular effects via nanomagnetic actuation of endogenous iron oxides in the body. METHODOLOGY: Theoretical models and experimental data on the composition and magnetic properties of endogenous iron oxides in human tissue were used to analyze the forces on iron oxide particles. PRINCIPAL FINDING AND CONCLUSIONS: Results show that, even at 9.4 Tesla, forces on these particles are unlikely to disrupt normal cellular function via nanomagnetic actuation.

  20. An endogenous inhibitor of angiogenesis inversely correlates with side population phenotype and function in human lung cancer cells.

    Science.gov (United States)

    Han, H; Bourboulia, D; Jensen-Taubman, S; Isaac, B; Wei, B; Stetler-Stevenson, W G

    2014-02-27

    The side population (SP) in human lung cancer cell lines and tumors is enriched with cancer stem cells. An endogenous inhibitor of angiogenesis known as tissue inhibitor of matrix metalloproteinase-2 (TIMP-2), characterized for its ability to inhibit matrix metalloproteinases (MMPs), has been shown by several laboratories to impede tumor progression through MMP-dependent or -independent mechanisms. We recently reported that forced expression of TIMP-2, as well as the modified form Ala+TIMP-2 (that lacks MMP inhibitory activity) significantly blocks growth of A549 human lung cancer cells in vivo. However, the mechanisms underlying TIMP-2 antitumor effects are not fully characterized. Here, we examine the hypothesis that the TIMP-2 antitumor activity may involve regulation of the SP in human lung cancer cells. Indeed, using Hoechst dye efflux assay and flow cytometry, as well as quantitative reverse transcriptase-PCR analysis, we found that endogenous TIMP-2 mRNA levels showed a significant inverse correlation with SP fraction size in six non-small cell lung cancer cell lines. In A549 cells expressing increased levels of TIMP-2, a significant decrease in SP was observed, and this decrease was associated with lowered gene expression of ABCG2, ABCB1 and AKR1C1. Functional analysis of A549 cells showed that TIMP-2 overexpression increased chemosensitivity to cytotoxic drugs. The SP isolated from TIMP-2-overexpressing A549 cells also demonstrated impaired migratory capacity compared with the SP from empty vector control. More importantly, our data provide strong evidence that these TIMP-2 functions occur independent of MMP inhibition, as A549 cells overexpressing Ala+TIMP-2 exhibited identical behavior to those overexpressing TIMP-2 alone. Our findings provide the first indication that TIMP-2 modulates SP phenotype and function, and suggests that TIMP-2 may act as an endogenous suppressor of the SP in human lung cancer cells.

  1. CRYOGENIC MAGNETS

    Science.gov (United States)

    Post, R.F.; Taylor, C.E.

    1963-05-21

    A cryogenic magnet coil is described for generating magnetic fields of the order of 100,000 gauss with a minimum expenditure of energy lost in resistive heating of the coil inductors and energy lost irreversibly in running the coil refrigeration plant. The cryogenic coil comprises a coil conductor for generating a magnetic field upon energization with electrical current, and refrigeration means disposed in heat conductive relation to the coil conductor for cooling to a low temperature. A substantial reduction in the power requirements for generating these magnetic fields is attained by scaling the field generating coil to large size and particular dimensions for a particular conductor, and operating the coil at a particular optimum temperature commensurate with minimum overall power requirements. (AEC)

  2. Cryogenics; Criogenia

    Energy Technology Data Exchange (ETDEWEB)

    Gutierrez R, C.; Jimenez D, J.; Cejudo A, J.; Hernandez M, V. [Instituto Nacional de Investigaciones Nucleares, A.P. 18-1027, 11801 Mexico D.F. (Mexico)

    1997-07-01

    Cryogenics is one of these technologies which contributes to scientific research that supports to the industry in the following benefits: 1. Storage ability and a great quantity of dense gases with cryogenic liquid which is found at high pressure. 2. Production ability at low cost with high purity gases through distillation or condensation. 3. Ability to use low temperatures in the refrigerating materials or alteration of the physical properties. This technology is used for reprocessing of those short and long half life radioactive wastes which always have been required that to be separated with classical methods. In this text we report the radioactive wastes separation by more sophisticated methods but more quickly and reliable. (Author)

  3. Endogenous circadian regulation of pro-inflammatory cytokines and chemokines in the presence of bacterial lipopolysaccharide in humans.

    Science.gov (United States)

    Rahman, Shadab A; Castanon-Cervantes, Oscar; Scheer, Frank A J L; Shea, Steven A; Czeisler, Charles A; Davidson, Alec J; Lockley, Steven W

    2015-07-01

    Various aspects of immune response exhibit 24-h variations suggesting that infection susceptibility and treatment efficacy may vary by time of day. Whether these 24-h variations are endogenous or evoked by changes in environmental or behavioral conditions is not known. We assessed the endogenous circadian control and environmental and behavioral influences on ex-vivo lipopolysaccharide stimulation of whole blood in thirteen healthy participants under 48h of baseline conditions with standard sleep-wake schedules and 40-50h of constant environmental and behavioral (constant routine; CR) conditions. Significant 24-h rhythms were observed under baseline conditions in Monocyte Chemotactic Protein, Granulocyte-Macrophage Colony-Stimulating Factor and Interleukin 8 but not Tumor Necrosis Factor alpha whereas significant 24-h rhythms were observed in all four immune factors under CR conditions. The rhythm amplitudes, expressed as a percentage of mean, were comparable between immune factors and across conditions. In contrast, the acrophase time (time of the fitted peak) was different between immune factors, and included daytime and nighttime peaks and changes across behavioral conditions. These results suggest that the endogenous circadian system underpins the temporal organization of immune responses in humans with additional effects of external environmental and behavioral cycles. These findings have implications for understanding the adverse effects of recurrent circadian disruption and sleep curtailment on immune function. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. LLL12 inhibits endogenous and exogenous interleukin-6-induced STAT3 phosphorylation in human pancreatic cancer cells.

    Science.gov (United States)

    Liu, Aiguo; Liu, Yan; Li, Pui-Kai; Li, Chenglong; Lin, Jiayuh

    2011-06-01

    Pancreatic cancer is one of the most serious types of cancer, with a five-year survival rate at only 6%. There is a critical need to develop more effective treatments for pancreatic cancer. Growing evidence shows that chronic inflammation plays a crucial role in tumor initiation and progression. Here we demonstrated that the endogenous expression of the inflammatory cytokine interleukin-6 (IL-6) correlates with signal transducer and activator of transcription 3 (STAT3) phosphorylation in human pancreatic cancer cells. Inhibition of the endogenous IL-6/STAT3 pathway reduces cell viability. Exogenous IL-6 induces STAT3 phosphorylation, but differently induces phosphorylation of STAT3 upstream kinases, Janus kinase 1(JAK1), JAK2, and tyrosine kinase 2 (TYK2). Interestingly, LLL12, a nonpeptide, cell-permeable small molecule, selectively blocked exogenous IL-6-induced STAT3 phosphorylation and nuclear translocation in both PANC-1 and ASPC-1 pancreatic cancer cell lines independently of the phosphorylation of JAK1, JAK2, and TYK2. These results suggest that the inhibition of endogenous and exogenous IL-6-mediated STAT3 signaling may be a potential therapeutic approach for pancreatic cancer.

  5. The Effects of Reducing the Structural Mass of the Transit Habitat on the Cryogenic Propellant Required for a Human Phobos Mission

    Science.gov (United States)

    Zipay, John J.

    2016-01-01

    A technique for rapidly determining the relationship between the pressurized volume, structural mass and the cryogenic propellant required to be delivered to Earth orbit for a Mars Transit Habitat is provided. This technique is based on assumptions for the required delta-V's, the Exploration Upper Stage performance and the historical structural masses for human spacecraft from Mercury Program through the International Space Station. If the Mars Transit Habitat is constructed from aluminum, structural mass estimates based on the habitat pressurized volume are accurate to within 15 percent. Other structural material options for the Mars Transit Habitat are also evaluated. The results show that small, achievable reductions in the structural mass of the Transit Habitat can save tens of thousands of pounds of cryogenic propellant that need to be delivered to Earth orbit for a human Phobos Mission.

  6. Two-photon excited spectroscopies of ex vivo human skin endogenous species irradiated by femtosecond laser pulses

    Institute of Scientific and Technical Information of China (English)

    Jianxin Chen; Shuangmu Zhuo; Tianshu Luo; Jingjun Zhao

    2006-01-01

    Two-photon excited spectroscopies from ex vivo human skin are investigated by using a femtosecond laser and a confocal microscope (Zeiss LSM 510 META). In the dermis, collagen is responsible for second harmonic generation (SHG); elastin, nicotinamide adenine dinucleotide (NADH), melanin and porphyrin are the primary endogenous sources of two-photon excited autofluorescence. In the epidermis, keratin,NADH, melanin and porphyrins contribute to autofluorescence signals. The results also show that the SHG spectra have the ability to shift with the excitation wavelength and the autofluorescence spectra display a red shift of the spectral peaks when increasing the excitation wavelength. These results may have practical implications for diagnosis of skin diseases.

  7. Two-photon excited spectroscopies of ex vivo human skin endogenous species irradiated by femtosecond laser pulses

    Science.gov (United States)

    Chen, Jianxin; Zhuo, Shuangmu; Luo, Tianshu; Zhao, Jingjun

    2006-10-01

    Two-photon excited spectroscopies from ex vivo human skin are investigated by using a femtosecond laser and a confocal microscope (Zeiss LSM 510 META). In the dermis, collagen is responsible for second harmonic generation (SHG); elastin, nicotinamide adenine dinucleotide (NADH), melanin and porphyrin are the primary endogenous sources of two-photon excited autofluorescence. In the epidermis, keratin, NADH, melanin and porphyrins contribute to autofluorescence signals. The results also show that the SHG spectra have the ability to shift with the excitation wavelength and the autofluorescence spectra display a red shift of the spectral peaks when increasing the excitation wavelength. These results may have practical implications for diagnosis of skin diseases.

  8. Multiple Localization of Endogenous MARK4L Protein in Human Glioma

    Directory of Open Access Journals (Sweden)

    Ivana Magnani

    2009-01-01

    Full Text Available Background: We have previously shown that the sustained expression of MARK4L transcripts in glioma and neural progenitors (NHNPs declines after exposure to antisense MARK4L oligonucleotides in glioblastoma cell lines. Array-CGH confirmed the genomic duplication of MARK4L identified by FISH in a glioblastoma cell line. This background together with literature data on the exogenous association of MARK4 with interphase centrosome prompted us to investigate the sub-cellular localization of the endogenous MARK4L protein aiming at achieving insights on its possible role in the pathomechanisms of glioma.

  9. Endogenous retrovirus drives hitherto unknown proapoptotic p63 isoforms in the male germ line of humans and great apes.

    Science.gov (United States)

    Beyer, Ulrike; Moll-Rocek, Julian; Moll, Ute M; Dobbelstein, Matthias

    2011-03-01

    TAp63, but not its homolog p53, eliminates oocytes that suffered DNA damage. An equivalent gene for guarding the male germ line is currently not known. Here we identify hitherto unknown human p63 transcripts with unique 5'-ends derived from incorporated exons upstream of the currently mapped TP63 gene. These unique p63 transcripts are highly and specifically expressed in testis. Their most upstream region corresponds to a LTR of the human endogenous retrovirus 9 (ERV9). The insertion of this LTR upstream of the TP63 locus occurred only recently in evolution and is unique to humans and great apes (Hominidae). A corresponding p63 protein is the sole p63 species in healthy human testis, and is strongly expressed in spermatogenic precursors but not in mature spermatozoa. In response to DNA damage, this human male germ-cell-encoded TAp63 protein (designated GTAp63) is activated by caspase cleavage near its carboxyterminal domain and induces apoptosis. Human testicular cancer tissues and cell lines largely lost p63 expression. However, pharmacological inhibition of histone deacetylases completely restores p63 expression in testicular cancer cells (>3,000-fold increase). Our data support a model whereby testis-specific GTAp63 protects the genomic integrity of the male germ line and acts as a tumor suppressor. In Hominidae, this guardian function was greatly enhanced by integration of an endogenous retrovirus upstream of the TP63 locus that occurred 15 million years ago. By providing increased germ-line stability, this event may have contributed to the evolution of hominids and enabled their long reproductive periods.

  10. Differential capacity of chaperone-rich lysates in cross-presenting human endogenous and exogenous melanoma differentiation antigens.

    Science.gov (United States)

    Bleifuss, Elke; Bendz, Henriette; Sirch, Birgit; Thompson, Sylvia; Brandl, Anna; Milani, Valeria; Graner, Michael W; Drexler, Ingo; Kuppner, Maria; Katsanis, Emmanuel; Noessner, Elfriede; Issels, Rolf-Dieter

    2008-12-01

    The goal of immune-based tumor therapies is the activation of immune cells reactive against a broad spectrum of tumor-expressed antigens. Vaccines based on chaperone proteins appear promising as these proteins naturally exist as complexes with various protein fragments including those derived from tumor-associated antigens. Multi-chaperone systems are expected to have highest polyvalency as different chaperones can carry distinct sets of antigenic fragments. A free-solution isoelectric focusing (FS-IEF) technique was established to generate chaperone-rich cell lysates (CRCL). Results from murine systems support the contention that CRCL induce superior anti-tumor responses than single chaperone vaccines. We established an in vitro model for human melanoma to evaluate the capacity of CRCL to transfer endogenously expressed tumor antigens to the cross-presentation pathway of dendritic cells (DC) for antigen-specific T cell stimulation. CRCL prepared from human melanoma lines contained the four major chaperone proteins Hsp/Hsc70, Hsp90, Grp94/gp96 and calreticulin. The chaperones within the melanoma cell-derived CRCL were functionally active in that they enhanced cross-presentation of exogenous peptides mixed into the CRCL preparation. Superior activity was observed for Hsp70-rich CRCL obtained from heat-stressed melanoma cells. Despite the presence of active chaperones, melanoma cell-derived CRCL failed to transfer endogenously expressed melanoma-associated antigens to DC for cross-presentation and cytotoxic T cell (CTL) recognition, even after increasing intracellular protein levels of tumor antigen or chaperones. These findings reveal limitations of the CRCL approach regarding cross-presentation of endogenously expressed melanoma-associated antigens. Yet, CRCL may be utilized as vehicles to enhance the delivery of exogenous antigens for DC-mediated cross-presentation and T cell stimulation.

  11. [Endogenous hypertriglyceridemia].

    Science.gov (United States)

    Tsukamoto, Kazuhisa

    2013-09-01

    Endogenous hypertriglyceridemia, which includes familial hypertriglyceridemia and idiopathic hypertriglyceridemia, is characterized by the increased level of VLDL-triglycerides in the blood. Increased production of VLDL from the liver and the decreased catabolism of VLDL-TG in the vessel, which are also the main metabolic features of insulin resistance, have been proposed to be the causes of endogenous hypertriglyceridemia. Genetic factors responsible for endogenous hypertriglyceridemia have been elucidated in several studies, however, these factors have so far not been clearly identified yet; thus the causes of endogenous hypertriglyceridemia would be polygenic. Recent advances in the genetic analytical methods like genome-wide association study would hopefully unveil the whole pictures of endogenous hypertriglyceridemia.

  12. Identification, characterization, and comparative genomic distribution of the HERV-K (HML-2 group of human endogenous retroviruses

    Directory of Open Access Journals (Sweden)

    Subramanian Ravi P

    2011-11-01

    Full Text Available Abstract Background Integration of retroviral DNA into a germ cell may lead to a provirus that is transmitted vertically to that host's offspring as an endogenous retrovirus (ERV. In humans, ERVs (HERVs comprise about 8% of the genome, the vast majority of which are truncated and/or highly mutated and no longer encode functional genes. The most recently active retroviruses that integrated into the human germ line are members of the Betaretrovirus-like HERV-K (HML-2 group, many of which contain intact open reading frames (ORFs in some or all genes, sometimes encoding functional proteins that are expressed in various tissues. Interestingly, this expression is upregulated in many tumors ranging from breast and ovarian tissues to lymphomas and melanomas, as well as schizophrenia, rheumatoid arthritis, and other disorders. Results No study to date has characterized all HML-2 elements in the genome, an essential step towards determining a possible functional role of HML-2 expression in disease. We present here the most comprehensive and accurate catalog of all full-length and partial HML-2 proviruses, as well as solo LTR elements, within the published human genome to date. Furthermore, we provide evidence for preferential maintenance of proviruses and solo LTR elements on gene-rich chromosomes of the human genome and in proximity to gene regions. Conclusions Our analysis has found and corrected several errors in the annotation of HML-2 elements in the human genome, including mislabeling of a newly identified group called HML-11. HML-elements have been implicated in a wide array of diseases, and characterization of these elements will play a fundamental role to understand the relationship between endogenous retrovirus expression and disease.

  13. A critical review of reports of endogenous psychedelic N, N-dimethyltryptamines in humans: 1955-2010.

    Science.gov (United States)

    Barker, Steven A; McIlhenny, Ethan H; Strassman, Rick

    2012-01-01

    Three indole alkaloids that possess differing degrees of psychotropic/psychedelic activity have been reported as endogenous substances in humans; N,N-dimethyltryptamine (DMT), 5-hydroxy-DMT (bufotenine, HDMT), and 5-methoxy-DMT (MDMT). We have undertaken a critical review of 69 published studies reporting the detection or detection and quantitation of these compounds in human body fluids. In reviewing this literature, we address the methods applied and the criteria used in the determination of the presence of DMT, MDMT, and HDMT. The review provides a historical perspective of the research conducted from 1955 to 2010, summarizing the findings for the individual compounds in blood, urine, and/or cerebrospinal fluid. A critique of the data is offered that addresses the strengths and weaknesses of the methods and approaches to date. The review also discusses the shortcomings of the existing data in light of more recent findings and how these may be overcome. Suggestions for the future directions of endogenous psychedelics research are offered. Copyright © 2012 John Wiley & Sons, Ltd.

  14. The human endogenous retrovirus link between genes and environment in multiple sclerosis and in multifactorial diseases associating neuroinflammation.

    Science.gov (United States)

    Perron, Hervé; Lang, Alois

    2010-08-01

    Endogenous retroviruses represent about 8% of the human genome and belong to the superfamily of transposable and retrotransposable genetic elements. Altogether, these mobile genetic elements and their numerous inactivated "junk" sequences represent nearly one half of the human DNA. Nonetheless, a significant part of this "non-conventional" genome has retained potential activity. Epigenetic control is notably involved in silencing most of these genetic elements but certain environmental factors such as viruses are known to dysregulate their expression in susceptible cells. More particularly, embryonal cells with limited gene methylation are most susceptible to uncontrolled activation of these mobile genetic elements by, e.g., viral infections. In particular, certain viruses transactivate promoters from endogenous retroviral family type W (HERV-W). HERV-W RNA was first isolated in circulating viral particles (Multiple Sclerosis-associated RetroViral element, MSRV) that have been associated with the evolution and prognosis of multiple sclerosis. HERV-W elements encode a powerful immunopathogenic envelope protein (ENV) that activates a pro-inflammatory and autoimmune cascade through interaction with Toll-like receptor 4 on immune cells. This ENV protein has repeatedly been detected in MS brain lesions and may be involved in other diseases. Epigenetic factors controlling HERV-W ENV protein expression then reveal critical. This review addresses the gene-environment epigenetic interface of such HERV-W elements and its potential involvement in disease.

  15. A potential role for endogenous proteins as sacrificial sunscreens and antioxidants in human tissues.

    Science.gov (United States)

    Hibbert, Sarah A; Watson, Rachel E B; Gibbs, Neil K; Costello, Patrick; Baldock, Clair; Weiss, Anthony S; Griffiths, Christopher E M; Sherratt, Michael J

    2015-08-01

    Excessive ultraviolet radiation (UVR) exposure of the skin is associated with adverse clinical outcomes. Although both exogenous sunscreens and endogenous tissue components (including melanins and tryptophan-derived compounds) reduce UVR penetration, the role of endogenous proteins in absorbing environmental UV wavelengths is poorly defined. Having previously demonstrated that proteins which are rich in UVR-absorbing amino acid residues are readily degraded by broadband UVB-radiation (containing UVA, UVB and UVC wavelengths) here we hypothesised that UV chromophore (Cys, Trp and Tyr) content can predict the susceptibility of structural proteins in skin and the eye to damage by physiologically relevant doses (up to 15.4 J/cm(2)) of solar UVR (95% UVA, 5% UVB). We show that: i) purified suspensions of UV-chromophore-rich fibronectin dimers, fibrillin microfibrils and β- and γ-lens crystallins undergo solar simulated radiation (SSR)-induced aggregation and/or decomposition and ii) exposure to identical doses of SSR has minimal effect on the size or ultrastructure of UV chromophore-poor tropoelastin, collagen I, collagen VI microfibrils and α-crystallin. If UV chromophore content is a factor in determining protein stability in vivo, we would expect that the tissue distribution of Cys, Trp and Tyr-rich proteins would correlate with regional UVR exposure. From bioinformatic analysis of 244 key structural proteins we identified several biochemically distinct, yet UV chromophore-rich, protein families. The majority of these putative UV-absorbing proteins (including the late cornified envelope proteins, keratin associated proteins, elastic fibre-associated components and β- and γ-crystallins) are localised and/or particularly abundant in tissues that are exposed to the highest doses of environmental UVR, specifically the stratum corneum, hair, papillary dermis and lens. We therefore propose that UV chromophore-rich proteins are localised in regions of high UVR exposure

  16. Activation of the Long Terminal Repeat of Human Endogenous Retrovirus K by Melanoma-Specific Transcription Factor MITF-M

    Directory of Open Access Journals (Sweden)

    Iyoko Katoh

    2011-11-01

    Full Text Available The human and Old World primate genomes possess conserved endogenous retrovirus sequences that have been implicated in evolution, reproduction, and carcinogenesis. Human endogenous retrovirus (HERV-K with 5′LTR-gag-pro-pol-env-rec/np9-3′LTR sequences represents the newest retrovirus family that integrated into the human genome 1 to 5 million years ago. Although a high-level expression of HERV-K in melanomas, breast cancers, and terato-carcinomas has been demonstrated, the mechanism of the lineage-specific activation of the long terminal repeat (LTR remains obscure. We studied chromosomal HERV-K expression in MeWo melanoma cells in comparison with the basal expression in human embryonic kidney 293 (HEK293 cells. Cloned LTR of HERV-K (HML-2.HOM was also characterized by mutation and transactivation experiments. We detected multiple transcriptional initiator (Inr sites in the LTR by rapid amplification of complementary DNA ends (5′ RACE. HEK293 and MeWo showed different Inr usage. The most potent Inr was associated with a TATA box and three binding motifs of microphthalmia-associated transcription factor (MITF. Both chromosomal HERV-K expression and the cloned LTR function were strongly activated in HEK293 by transfection with MITF-M, a melanocyte/melanoma–specific isoform of MITF. Coexpression of MITF and the HERV-K core antigen was detected in retinal pigmented epithelium by an immunofluorescence analysis. Although malignant melanoma lines MeWo, G361, and SK-MEL-28 showed enhanced HERV-K transcription compared with normal melanocytes, the level of MITF-M messenger RNA persisted from normal to transformed melanocytes. Thus, MITF-M may be a prerequisite for the pigmented cell lineage–specific function of HERV-K LTR, leading to the high-level expression in malignant melanomas.

  17. Selectable one-step PCR-mediated integration of a degron for rapid depletion of endogenous human proteins.

    Science.gov (United States)

    Sheridan, Ryan M; Bentley, David L

    2016-02-01

    Manipulation of protein stability with ligand-regulated degron fusions is a powerful method for investigating gene function. We developed a selectable cassette for easy C-terminal tagging of endogenous human proteins with the E. coli dihydrofolate reductase (eDHFR) degron using CRISPR/Cas9 genome editing. This cassette permits high-efficiency recovery of correct integration events using an in-frame self-cleaving 2A peptide and the puromycin resistance gene. PCR amplified donor eDHFR cassette fragments with 100 bases of homology on each end are integrated by homology-directed repair (HDR) of guide RNA (gRNA)-targeted double-stranded DNA breaks at the 3' ends of open reading frames (ORFs). As proof of principle, we generated cell lines in which three endogenous proteins were tagged with the eDHFR degron. When the antibiotic trimethoprim is removed from the media, each of the eDHFR-tagged proteins was depleted by >90% within 2-4 h, and this depletion was reversed by re-addition of trimethoprim. Since puromycin selection permits recovery of in-frame degron fusions with high efficiency using only 100-bp long regions of homology, this method should be applicable on a genome-wide scale for generating libraries of conditional mutant cell lines.

  18. A potential role for endogenous proteins as sacrificial sunscreens and antioxidants in human tissues

    Directory of Open Access Journals (Sweden)

    Sarah A. Hibbert

    2015-08-01

    Full Text Available Excessive ultraviolet radiation (UVR exposure of the skin is associated with adverse clinical outcomes. Although both exogenous sunscreens and endogenous tissue components (including melanins and tryptophan-derived compounds reduce UVR penetration, the role of endogenous proteins in absorbing environmental UV wavelengths is poorly defined. Having previously demonstrated that proteins which are rich in UVR-absorbing amino acid residues are readily degraded by broadband UVB-radiation (containing UVA, UVB and UVC wavelengths here we hypothesised that UV chromophore (Cys, Trp and Tyr content can predict the susceptibility of structural proteins in skin and the eye to damage by physiologically relevant doses (up to 15.4 J/cm2 of solar UVR (95% UVA, 5% UVB. We show that: i purified suspensions of UV-chromophore-rich fibronectin dimers, fibrillin microfibrils and β- and γ-lens crystallins undergo solar simulated radiation (SSR-induced aggregation and/or decomposition and ii exposure to identical doses of SSR has minimal effect on the size or ultrastructure of UV chromophore-poor tropoelastin, collagen I, collagen VI microfibrils and α-crystallin. If UV chromophore content is a factor in determining protein stability in vivo, we would expect that the tissue distribution of Cys, Trp and Tyr-rich proteins would correlate with regional UVR exposure. From bioinformatic analysis of 244 key structural proteins we identified several biochemically distinct, yet UV chromophore-rich, protein families. The majority of these putative UV-absorbing proteins (including the late cornified envelope proteins, keratin associated proteins, elastic fibre-associated components and β- and γ-crystallins are localised and/or particularly abundant in tissues that are exposed to the highest doses of environmental UVR, specifically the stratum corneum, hair, papillary dermis and lens. We therefore propose that UV chromophore-rich proteins are localised in regions of high UVR

  19. Protective effects of endomorphins, endogenous opioid peptides in the brain, on human low density lipoprotein oxidation.

    Science.gov (United States)

    Lin, Xin; Xue, Li-Ying; Wang, Rui; Zhao, Qian-Yu; Chen, Qiang

    2006-03-01

    Neurodegenerative disorders are associated with oxidative stress. Low density lipoprotein (LDL) exists in the brain and is especially sensitive to oxidative damage. Oxidative modification of LDL has been implicated in the pathogenesis of neurodegenerative diseases. Therefore, protecting LDL from oxidation may be essential in the brain. The antioxidative effects of endomorphin 1 (EM1) and endomorphin 2 (EM2), endogenous opioid peptides in the brain, on LDL oxidation has been investigated in vitro. The peroxidation was initiated by either copper ions or a water-soluble initiator 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH). Oxidation of the LDL lipid moiety was monitored by measuring conjugated dienes, thiobarbituric acid reactive substances, and the relative electrophoretic mobility. Low density lipoprotein oxidative modifications were assessed by evaluating apoB carbonylation and fragmentation. Endomorphins markedly and in a concentration-dependent manner inhibited Cu2+ and AAPH induced the oxidation of LDL, due to the free radical scavenging effects of endomorphins. In all assay systems, EM1 was more potent than EM2 and l-glutathione, a major intracellular water-soluble antioxidant. We propose that endomorphins provide protection against free radical-induced neurodegenerative disorders.

  20. Endomorphins, endogenous opioid peptides, induce apoptosis in human leukemia HL-60 cells.

    Science.gov (United States)

    Lin, Xin; Chen, Qiang; Xue, Li-Ying; Ma, Xiao-Jun; Wang, Rui

    2004-11-01

    Opioids play a role in the apoptosis machinery. We studied the induction of apoptosis in endomorphin 1 (EM1) and endomorphin 2 (EM2), 2 newly isolated endogenous mu-opioid receptor agonists. These endomorphins were able to reduce the viability of cultured HL-60 cells. The antiproliferative properties of endomorphins appeared to be attributable to their induction of apoptotic cell death as determined by ultrastructural change, internucleosomal DNA fragmentation, and increased proportion of the subdiploid cell population. To elucidate molecular events in the apoptosis, protein expressions of Bcl-2, Bax, Fas, and FasL were measured by western blotting using specific antibodies in HL-60 cells. The level of Bcl-2 indicated down-regulation, but the Bax, Fas, and FasL expression showed up-regulation as compared with the untreated control cells. These data support the idea that endomorphins induce apoptosis in HL-60 cells through the activation of the Bcl-2-Bax and the Fas-FasL pathway. We suggest that endomorphins may play an important role in the regulation of tumor cell death.

  1. CRYOGENIC DEWAR

    Science.gov (United States)

    Chamberlain, W.H.; Maseck, H.E.

    1964-01-28

    This patent relates to a dewar for storing cryogenic gase and is of the type having aii inner flask surrounded by a vacuum jacket and having a vent spout through which evaporating gas escapes. Heretofore substantial gas loss has resulted from the radiation of heat towards the flask from the warmer outer elements of the dewar. In this invention, the mask is surrounded by a thermally conducting shield which is disposed in the vacuum space between the flask and the outer elements of the dewar. The shield contacts only the vent spout, which is cooled by the evaporating gas, and thus is maintained at a temperature very close to that of the flask itself. Accordingly, heat radiated toward the flask is intercepted and conducted to the evaporating gas rather than being re-radiated towards the hask. In a liquid helium dewar of typical configniration the mention reduces the boil-off rate by approximately one-half.(AEC)

  2. Minimized human telomerase maintains telomeres and resolves endogenous roles of H/ACA proteins, TCAB1, and Cajal bodies.

    Science.gov (United States)

    Vogan, Jacob M; Zhang, Xiaozhu; Youmans, Daniel T; Regalado, Samuel G; Johnson, Joshua Z; Hockemeyer, Dirk; Collins, Kathleen

    2016-08-15

    We dissected the importance of human telomerase biogenesis and trafficking pathways for telomere maintenance. Biological stability of human telomerase RNA (hTR) relies on H/ACA proteins, but other eukaryotes use other RNP assembly pathways. To investigate additional rationale for human telomerase assembly as H/ACA RNP, we developed a minimized cellular hTR. Remarkably, with only binding sites for telomerase reverse transcriptase (TERT), minimized hTR assembled biologically active enzyme. TERT overexpression was required for cellular interaction with minimized hTR, indicating that H/ACA RNP assembly enhances endogenous hTR-TERT interaction. Telomere maintenance by minimized telomerase was unaffected by the elimination of the telomerase holoenzyme Cajal body chaperone TCAB1 or the Cajal body scaffold protein Coilin. Surprisingly, wild-type hTR also maintained and elongated telomeres in TCAB1 or Coilin knockout cells, with distinct changes in telomerase action. Overall, we elucidate trafficking requirements for telomerase biogenesis and function and expand mechanisms by which altered telomere maintenance engenders human disease.

  3. Activation of endogenous human stem cell-associated retroviruses (SCARs) and therapy-resistant phenotypes of malignant tumors.

    Science.gov (United States)

    Glinsky, Gennadi V

    2016-07-01

    Recent reports revealed consistent activation of specific endogenous retroviral elements in human preimplantation embryos and embryonic stem cells. Activity of stem cell associated retroviruses (SCARs) has been implicated in seeding thousands of human-specific regulatory sequences in the hESC genome. Activation of specific SCARs has been demonstrated in patients diagnosed with multiple types of cancer, autoimmune diseases, and neurodegenerative disorders, and appears associated with clinically lethal therapy resistant death-from-cancer phenotypes in a sub-set of cancer patients diagnosed with different types of malignant tumors. A hallmark feature of human-specific SCAR integration sites is deletions of ancestral DNA. Analysis of human-specific genetic loci of SCARs' stemness networks in tumor samples of TCGA cohorts representing 29 cancer types suggests that this approach may facilitate identification of pan-cancer genomic signatures of clinically-lethal disease defined by the presence of somatic non-silent mutations, gene-level copy number changes, and transcripts and proteins' expression of SCAR-regulated host genes. Present analyses indicate that multiple lines of strong circumstantial evidence support the hypothesis that activation of SCARs' networks may play an important role in cancer progression and metastasis, perhaps contributing to the emergence of clinically-lethal therapy-resistant death-from-cancer phenotypes.

  4. A novel function of RNAs arising from the long terminal repeat of human endogenous retrovirus 9 in cell cycle arrest.

    Science.gov (United States)

    Xu, Lai; Elkahloun, Abdel G; Candotti, Fabio; Grajkowski, Andrzej; Beaucage, Serge L; Petricoin, Emanuel F; Calvert, Valerie; Juhl, Hartmut; Mills, Frederick; Mason, Karen; Shastri, Neal; Chik, Josh; Xu, Cynthia; Rosenberg, Amy S

    2013-01-01

    The human genome contains approximately 50 copies of the replication-defective human endogenous retrovirus 9 (ERV-9) and thousands of copies of its solitary long term repeat (sLTR) element. While some sLTRs are located upstream of critical genes and have enhancer activity, other sLTRs are located within introns and may be transcribed as RNAs. We found that intronic RNAs arising from U3 sLTRs of ERV-9 were expressed as both sense (S) and antisense (AS) transcripts in all human cells tested but that expression levels differed in malignant versus nonmalignant cells. In nonmalignant cells, AS was expressed at higher levels than S and at higher levels than in malignant cells; in malignant cells, AS was expressed at amounts equivalent to those of S RNA. Critically, U3 AS RNA was found to physically bind to key transcription factors for cellular proliferation, including NF-Y, p53, and sp1, indicating that such RNA transcripts may function as decoy targets or traps for NF-Y and thus inhibit the growth of human cancer cells. Indeed, short U3 oligodeoxynucleotides (ODNs) based on these RNA sequences ably inhibited proliferation of cancer cell lines driven by cyclins B1/B2, the gene targets of NF-Y.

  5. Human motor neuron progenitor transplantation leads to endogenous neuronal sparing in 3 models of motor neuron loss.

    Science.gov (United States)

    Wyatt, Tanya J; Rossi, Sharyn L; Siegenthaler, Monica M; Frame, Jennifer; Robles, Rockelle; Nistor, Gabriel; Keirstead, Hans S

    2011-01-01

    Motor neuron loss is characteristic of many neurodegenerative disorders and results in rapid loss of muscle control, paralysis, and eventual death in severe cases. In order to investigate the neurotrophic effects of a motor neuron lineage graft, we transplanted human embryonic stem cell-derived motor neuron progenitors (hMNPs) and examined their histopathological effect in three animal models of motor neuron loss. Specifically, we transplanted hMNPs into rodent models of SMA (Δ7SMN), ALS (SOD1 G93A), and spinal cord injury (SCI). The transplanted cells survived and differentiated in all models. In addition, we have also found that hMNPs secrete physiologically active growth factors in vivo, including NGF and NT-3, which significantly enhanced the number of spared endogenous neurons in all three animal models. The ability to maintain dying motor neurons by delivering motor neuron-specific neurotrophic support represents a powerful treatment strategy for diseases characterized by motor neuron loss.

  6. Endogenous glucose production increases in response to metformin treatment in the glycogen-depleted state in humans

    DEFF Research Database (Denmark)

    Christensen, Mette Marie H; Højlund, Kurt; Hother-Nielsen, Ole

    2015-01-01

    had two reduced-function alleles in OCT1). Three were excluded from the analysis because of early dropout. Metformin significantly stimulated glucose disposal rates and non-oxidative glucose metabolism with no effect on glucose oxidation. This increase in glucose utilisation was explained...... of metformin on glucose metabolism in humans after a glycogen-depleting fast and the role of reduced-function alleles in OCT1 (also known as SLC22A1). METHODS: In a randomised, crossover trial, healthy individuals with or without reduced-function alleles in OCT1 were fasted for 42 h twice, either...... metabolism were assessed using [3-(3)H]glucose, indirect calorimetry and measurement of substrates and counter-regulatory hormones. The primary outcome was endogenous glucose production (EGP). RESULTS: Thirty-seven individuals were randomised. Thirty-four completed the study (12 had none, 13 had one and nine...

  7. Serologic analysis of anti-porcine endogenous retroviruses immune responses in humans after ex vivo transgenic pig liver perfusion.

    Science.gov (United States)

    Xu, Hui; Sharma, Ajay; Okabe, Jeannine; Cui, Cunqi; Huang, Liping; Wei, Yuan Yuan; Wan, Hua; Lei, Ying; Logan, John S; Levy, Marlon F; Byrne, Guerard W

    2003-01-01

    Improvements in xenotransplantation may significantly increase the availability of organs for human transplantation. The use of porcine organs, however, has raised concern about possible transmission of porcine endogenous retroviruses (PERV) to the recipients. The authors developed monoclonal antibodies specific to the PERV Gag viral product and show that these antibodies can detect PERV antigen under a variety of assay conditions, including enzyme linked immunosorbent assay (ELISA), Western blot, and immunofluorescence staining methods. Two patients in fulminant hepatic failure were treated by extracorporeal perfusion using transgenic porcine livers before receiving orthotopic liver transplants. Despite the use of immune suppression that allowed survival of the allograft, these patients both showed a strong immune response to the xenograft suggesting a largely intact capability to mount a humoral immune response. However, analysis of patient serum samples over a 3 to 4 year period has showed no evidence of an immune response to PERV antigens, suggesting a lack of PERV infection.

  8. Methodologic basis for the radioimmunoassay of endogenous LH-like activity in human prostatic tissue

    Energy Technology Data Exchange (ETDEWEB)

    Dorobek, W.; Misiorowski, W.; Niewiadomska, A.; Baranowska, B.; Zgliczynski, S.; Kuzaka, B.; Krzeski, T.

    1983-12-01

    The aim of this study was to develop a technique for the radioimmunological determination of the activity of LH-like substances in the human prostate. The material comprised 19 specimens of prostatic tissue obtained during transbladder extirpation in patients with benign prostatic hyperplasia. Tissues of human testes and human skeletal muscle were used as controls. The method adopted for LH extraction from the membrane fraction of human prostatic tissue appeared to be sufficiently specific, accurate and sensitive for routine laboratory investigations. The concentrations of the LH-like immunoreactivity in human testicular tissue was found to be 57, 46 and 70 mU per g of the membrane fraction while those of the prostatic gland tissues ranged from 34 to 155 mU per g of the membrane fraction. However such LH-like substance was not found in human skeletal muscle tissue. It seems that the LH-type activity is an indirect proof for the existence of LH receptors in the human prostate.

  9. Human μ-opioid receptor overexpressed in Sf9 insect cells functionally coupled to endogenous Gi/o proteins

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Human μ-opioid receptor (HμOR) with a tag of six consecutive histidines at its carboxyl terminus had been expressed in recombinant baculovirus infected Sf9 insect cells.The maximal binding capacity for the [3H] diprenorphine and [3H]ohmefentanyl (Ohm) were 9.1 ± 0.7 and 6.52 ±0.23 nmol/g protein, respectively. The [3H] diprenorphine or [3H] Ohm binding to the receptor expressed in Sf9 cells was strongly inhibited by μ-selective agonists [D-Ala2, N-methyl-Phe4, glyol5]enkephalin (DAGO), Ohm, and morphine, but neither by δ nor by κ selective agonist. Na+ (100 mM) and GTP (50μM) could reduce HμOR agonists etorphine and Ohm affinity binding to the overexpressed HμOR.μ-selective agonists DAGO and Ohm effectively stimulated [35S]GTPγS binding (EC50 = 2.7nM and 6.9 nM) and inhibited forskolin- stimulated cAMP accumulation (IC50 = 0.9 nM and 0.3 nM). The agonist-dependent effects could be blocked by opioid antagonist naloxone or by pretreatment of cells with pertussis toxin (PTX). These results demonstrated that HμOR overexpressed in Sf9 insect cells functionally coupled to endogenous Gi/o proteins.Key words: Human μ-opioid receptor (Hμ OR), Sf9 insect cells, pertussis toxin (PTX), endogenous Gi/o proteins.

  10. A sensitive RNase protection assay to detect transcripts from potentially functional human endogenous L1 retrotransposons

    DEFF Research Database (Denmark)

    Woodcock, D M; Williamson, M R; Doherty, J P

    1996-01-01

    A high background of read-through transcripts from degenerate human L1 retrotransposons is present in almost all human cell types. This prevents the detection of RNA transcripts from potentially functional elements. To overcome this, we have developed an RNase protection assay based on the recons...... transcripts from divergent L1 families but are either discrete shorter transcripts or specifically processed products from longer initial transcripts....

  11. Molecular basis of engineered meganuclease targeting of the endogenous human RAG1 locus.

    Science.gov (United States)

    Muñoz, Inés G; Prieto, Jesús; Subramanian, Sunita; Coloma, Javier; Redondo, Pilar; Villate, Maider; Merino, Nekane; Marenchino, Marco; D'Abramo, Marco; Gervasio, Francesco L; Grizot, Sylvestre; Daboussi, Fayza; Smith, Julianne; Chion-Sotinel, Isabelle; Pâques, Frédéric; Duchateau, Philippe; Alibés, Andreu; Stricher, François; Serrano, Luis; Blanco, Francisco J; Montoya, Guillermo

    2011-01-01

    Homing endonucleases recognize long target DNA sequences generating an accurate double-strand break that promotes gene targeting through homologous recombination. We have modified the homodimeric I-CreI endonuclease through protein engineering to target a specific DNA sequence within the human RAG1 gene. Mutations in RAG1 produce severe combined immunodeficiency (SCID), a monogenic disease leading to defective immune response in the individuals, leaving them vulnerable to infectious diseases. The structures of two engineered heterodimeric variants and one single-chain variant of I-CreI, in complex with a 24-bp oligonucleotide of the human RAG1 gene sequence, show how the DNA binding is achieved through interactions in the major groove. In addition, the introduction of the G19S mutation in the neighborhood of the catalytic site lowers the reaction energy barrier for DNA cleavage without compromising DNA recognition. Gene-targeting experiments in human cell lines show that the designed single-chain molecule preserves its in vivo activity with higher specificity, further enhanced by the G19S mutation. This is the first time that an engineered meganuclease variant targets the human RAG1 locus by stimulating homologous recombination in human cell lines up to 265 bp away from the cleavage site. Our analysis illustrates the key features for à la carte procedure in protein-DNA recognition design, opening new possibilities for SCID patients whose illness can be treated ex vivo.

  12. Molecular cloning and long terminal repeat sequences of human endogenous retrovirus genes related to types A and B retrovirus genes

    Energy Technology Data Exchange (ETDEWEB)

    Ono, M.

    1986-06-01

    By using a DNA fragment primarily encoding the reverse transcriptase (pol) region of the Syrian hamster intracisternal A particle (IAP; type A retrovirus) gene as a probe, human endogenous retrovirus genes, tentatively termed HERV-K genes, were cloned from a fetal human liver gene library. Typical HERV-K genes were 9.1 or 9.4 kilobases in length, having long terminal repeats (LTRs) of ca. 970 base pairs. Many structural features commonly observed on the retrovirus LTRs, such as the TATAA box, polyadenylation signal, and terminal inverted repeats, were present on each LTR, and a lysine (K) tRNA having a CUU anticodon was identified as a presumed primer tRNA. The HERV-K LTR, however, had little sequence homology to either the IAP LTR or other typical oncovirus LTRs. By filter hybridization, the number of HERV-K genes was estimated to be ca. 50 copies per haploid human genome. The cloned mouse mammary tumor virus (type B) gene was found to hybridize with both the HERV-K and IAP genes to essentially the same extent.

  13. Estimating Endogenous Dopamine Levels at D2 and D3 Receptors in Humans using the Agonist Radiotracer [11C]-(+)-PHNO

    Science.gov (United States)

    Caravaggio, Fernando; Nakajima, Shinichiro; Borlido, Carol; Remington, Gary; Gerretsen, Philip; Wilson, Alan; Houle, Sylvain; Menon, Mahesh; Mamo, David; Graff-Guerrero, Ariel

    2014-01-01

    Using positron emission tomography (PET) and an acute dopamine depletion challenge it is possible to estimate endogenous dopamine levels occupying dopamine D2/3 receptors (D2/3R) in humans in vivo. Our group has developed [11C]-(+)-PHNO, the first agonist radiotracer with preferential in vivo affinity for D3R. Thus, the use of [11C]-(+)-PHNO offers the novel possibility of (i) estimating in vivo endogenous dopamine levels at D2/3R using an agonist radiotracer, and (ii) estimating endogenous dopamine levels at D3R in extrastriatal regions such as the substantia nigra, hypothalamus, and ventral pallidum. Ten healthy participants underwent a [11C]-(+)-PHNO PET scan under baseline conditions and another under acute endogenous dopamine depletion achieved via oral administration of alpha-methyl-para-tyrosine (64 mg/kg). [11C]-(+)-PHNO binding was sensitive to acute dopamine depletion, allowing in vivo estimates of endogenous dopamine in D2R-rich regions (caudate and putamen), mixed D2/3R-rich regions (ventral striatum and globus pallidus), and extrastriatal D3R-rich regions (hypothalamus and ventral pallidum). Dopamine depletion decreased self-reported vigor, which was correlated with the reduction in dopamine levels in the globus pallidus. [11C]-(+)-PHNO is a suitable radiotracer for use in estimating endogenous dopamine levels at D2R and D3R in neuropsychiatric populations. PMID:24874713

  14. Estimating endogenous dopamine levels at D2 and D3 receptors in humans using the agonist radiotracer [(11)C]-(+)-PHNO.

    Science.gov (United States)

    Caravaggio, Fernando; Nakajima, Shinichiro; Borlido, Carol; Remington, Gary; Gerretsen, Philip; Wilson, Alan; Houle, Sylvain; Menon, Mahesh; Mamo, David; Graff-Guerrero, Ariel

    2014-11-01

    Using positron emission tomography (PET) and an acute dopamine depletion challenge it is possible to estimate endogenous dopamine levels occupying dopamine D2/3 receptors (D2/3R) in humans in vivo. Our group has developed [(11)C]-(+)-PHNO, the first agonist radiotracer with preferential in vivo affinity for D3R. Thus, the use of [(11)C]-(+)-PHNO offers the novel possibility of (i) estimating in vivo endogenous dopamine levels at D2/3R using an agonist radiotracer, and (ii) estimating endogenous dopamine levels at D3R in extrastriatal regions such as the substantia nigra, hypothalamus, and ventral pallidum. Ten healthy participants underwent a [(11)C]-(+)-PHNO PET scan under baseline conditions and another under acute endogenous dopamine depletion achieved via oral administration of alpha-methyl-para-tyrosine (64 mg/kg). [(11)C]-(+)-PHNO binding was sensitive to acute dopamine depletion, allowing in vivo estimates of endogenous dopamine in D2R-rich regions (caudate and putamen), mixed D2/3R-rich regions (ventral striatum and globus pallidus), and extrastriatal D3R-rich regions (hypothalamus and ventral pallidum). Dopamine depletion decreased self-reported vigor, which was correlated with the reduction in dopamine levels in the globus pallidus. [(11)C]-(+)-PHNO is a suitable radiotracer for use in estimating endogenous dopamine levels at D2R and D3R in neuropsychiatric populations.

  15. Endogenous Opioid-Masked Latent Pain Sensitization: Studies from Mouse to Human.

    Directory of Open Access Journals (Sweden)

    Manuel P Pereira

    Full Text Available Following the resolution of a severe inflammatory injury in rodents, administration of mu-opioid receptor inverse agonists leads to reinstatement of pain hypersensitivity. The mechanisms underlying this form of latent pain sensitization (LS likely contribute to the development of chronic pain, but LS has not yet been demonstrated in humans. Using a C57BL/6 mouse model of cutaneous mild heat injury (MHI we demonstrated a dose-dependent reinstatement of pain sensitization, assessed as primary (P < 0.001 and secondary hyperalgesia (P < 0.001 by naloxone (0.3–10 mg/kg, 168 hrs after the induction of MHI. Forward-translating the dose data to a human MHI model (n = 12 we could show that LS does indeed occur after naloxone 2 mg/kg, 168 hrs after a MHI. Our previous unsuccessful efforts to demonstrate unmasking of LS in humans are thus likely explained by an insufficient naloxone dose (0.021 mg/kg. However, while LS was consistently demonstrated in 21/24 mice, LS was only seen in 4/12 subjects. This difference is likely due to selection bias since the C57BL/6 mouse strain exhibits markedly enhanced pain sensitivity in assays of acute thermal nociception. Future exploratory studies in humans should prioritize inclusion of “high-sensitizers” prone to develop LS and use post-surgical models to elucidate markers of vulnerability to chronic postsurgical pain.EudraCT 2012-005663-27.

  16. Endogenous human milk Peptide release is greater after preterm birth than term birth

    NARCIS (Netherlands)

    Dallas, D.C.; Smink, C.J.; Robinson, R.C.; Tian, T.; Guerrero, A.; Parker, E.A.; Smilowitz, J.T.; Hettinga, K.A.; Underwood, M.A.; Lebrilla, C.B.; German, J.B.; Barile, D.

    2015-01-01

    Background: Hundreds of naturally occurring milk peptides are present in term human milk. Preterm milk is produced before complete maturation of the mammary gland, which could change milk synthesis and secretion processes within the mammary gland, leading to differences in protein expression and enz

  17. Identification and validation of suitable endogenous reference genes for gene expression studies in human peripheral blood

    Directory of Open Access Journals (Sweden)

    Turner Renee J

    2009-08-01

    Full Text Available Abstract Background Gene expression studies require appropriate normalization methods. One such method uses stably expressed reference genes. Since suitable reference genes appear to be unique for each tissue, we have identified an optimal set of the most stably expressed genes in human blood that can be used for normalization. Methods Whole-genome Affymetrix Human 2.0 Plus arrays were examined from 526 samples of males and females ages 2 to 78, including control subjects and patients with Tourette syndrome, stroke, migraine, muscular dystrophy, and autism. The top 100 most stably expressed genes with a broad range of expression levels were identified. To validate the best candidate genes, we performed quantitative RT-PCR on a subset of 10 genes (TRAP1, DECR1, FPGS, FARP1, MAPRE2, PEX16, GINS2, CRY2, CSNK1G2 and A4GALT, 4 commonly employed reference genes (GAPDH, ACTB, B2M and HMBS and PPIB, previously reported to be stably expressed in blood. Expression stability and ranking analysis were performed using GeNorm and NormFinder algorithms. Results Reference genes were ranked based on their expression stability and the minimum number of genes needed for nomalization as calculated using GeNorm showed that the fewest, most stably expressed genes needed for acurate normalization in RNA expression studies of human whole blood is a combination of TRAP1, FPGS, DECR1 and PPIB. We confirmed the ranking of the best candidate control genes by using an alternative algorithm (NormFinder. Conclusion The reference genes identified in this study are stably expressed in whole blood of humans of both genders with multiple disease conditions and ages 2 to 78. Importantly, they also have different functions within cells and thus should be expressed independently of each other. These genes should be useful as normalization genes for microarray and RT-PCR whole blood studies of human physiology, metabolism and disease.

  18. Health and endogenous growth.

    Science.gov (United States)

    van Zon, A; Muysken, J

    2001-03-01

    The focus of endogenous growth theory on human capital formation and the physical embodiment of knowledge in people, suggests the integration of the growth supporting character of health production and the growth generating services of human capital accumulation in an endogenous growth framework. We show that a slow down in growth may be explained by a preference for health that is positively influenced by a growing income per head, or by an ageing population. Growth may virtually disappear for countries with high rates of decay of health, low productivity of the health-sector, or high rates of discount.

  19. Endogenous microRNAs in human microvascular endothelial cells regulate mRNAs encoded by hypertension-related genes.

    Science.gov (United States)

    Kriegel, Alison J; Baker, Maria Angeles; Liu, Yong; Liu, Pengyuan; Cowley, Allen W; Liang, Mingyu

    2015-10-01

    The goal of this study was to systematically identify endogenous microRNAs (miRNAs) in endothelial cells that regulate mRNAs encoded by genes relevant to hypertension. Small RNA deep sequencing was performed in cultured human microvascular endothelial cells. Of the 50 most abundant miRNAs identified, 30 had predicted target mRNAs encoded by genes with known involvement in hypertension or blood pressure regulation. The cells were transfected with anti-miR oligonucleotides to inhibit each of the 30 miRNAs and the mRNA abundance of predicted targets was examined. Of 95 miRNA-target pairs examined, the target mRNAs were significantly upregulated in 35 pairs and paradoxically downregulated in 8 pairs. The result indicated significant suppression of the abundance of mRNA encoded by ADM by endogenous miR-181a-5p, ATP2B1 by the miR-27 family, FURIN by miR-125a-5p, FGF5 by the let-7 family, GOSR2 by miR-27a-3p, JAG1 by miR-21-5p, SH2B3 by miR-30a-5p, miR-98, miR-181a-5p, and the miR-125 family, TBX3 by the miR-92 family, ADRA1B by miR-22-3p, ADRA2A by miR-30a-5p and miR-30e-5p, ADRA2B by miR-30e-5p, ADRB1 by the let-7 family and miR-98, EDNRB by the miR-92 family, and NOX4 by the miR-92 family, miR-100-5p, and miR-99b-5p (n=3-9; Phypertension.

  20. Human amniotic epithelial cell feeder layers maintain human iPS cell pluripotency via inhibited endogenous microRNA-145 and increased Sox2 expression

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Te, E-mail: liute79@yahoo.com [School of Environmental Science and Engineering, Donghua University, Shanghai 201620 (China); Shanghai Geriatric Institute of Chinese Medicine, Shanghai 200031 (China); Cheng, Weiwei [International Peace Maternity and Child Health Hospital, Shanghai Jiaotong University, Shanghai 200030 (China); Huang, Yongyi [Laboratoire PROTEE, Batiment R, Universite du Sud Toulon-Var, 83957 LA GARDE Cedex (France); Huang, Qin; Jiang, Lizhen [Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Guo, Lihe, E-mail: liute79@yahoo.com [Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China)

    2012-02-15

    Currently, human induced pluripotent stem (iPS) cells were generated from patient or disease-specific sources and share the same key properties as embryonic stem cells. This makes them attractive for personalized medicine, drug screens or cellular therapy. Long-term cultivation and maintenance of normal iPS cells in an undifferentiated self-renewing state are a major challenge. Our previous studies have shown that human amniotic epithelial cells (HuAECs) could provide a good source of feeder cells for mouse and human embryonic stem cells, or spermatogonial stem cells, but the mechanism for this is unknown. Here, we examined the effect of endogenous microRNA-145 regulation on Sox2 expression in human iPS cells by HuAECs feeder cells regulation, and in turn on human iPS cells pluripotency. We found that human IPS cells transfected with a microRNA-145 mutant expressed Sox2 at high levels, allowing iPS to maintain a high level of AP activity in long-term culture and form teratomas in SCID mice. Expression of stem cell markers was increased in iPS transfected with the microRNA-145 mutant, compared with iPS was transfected with microRNA-145. Besides, the expression of Drosha proteins of the microRNA-processor complex, required for the generation of precursor pre-miRNA, was significantly increased in human iPS cells cultured on MEF but not on HuAECs. Taken together, these results suggest that endogenous Sox2 expression may be regulated by microRNA-145 in human iPS cells with HuAECs feeder cells, and Sox2 is a crucial component required for maintenance of them in an undifferentiated, proliferative state capable of self-renewal. Highlights: Black-Right-Pointing-Pointer microRNA-145 inhibits Sox2 expression in human iPS cells. Black-Right-Pointing-Pointer microRNA-145 suppresses the self-renewal and pluripotency of human iPS cells. Black-Right-Pointing-Pointer HuAECs regulate expression of microRNA-145 and Sox2 in human iPS cells. Black-Right-Pointing-Pointer HuAECs feeder

  1. OSCILLATIONS IN THE WALRASIAN GENERAL EQUILIBRIUM THEORY WITH ENDOGENOUS WEALTH AND HUMAN CAPITAL ACCUMULATION

    Directory of Open Access Journals (Sweden)

    Wei Bin ZHANG

    2016-02-01

    Full Text Available This paper generalizes the dynamic growth model with wealth accumulation and human capital accumulation proposed by Zhang (2013 by making all the parameters as time-dependent parameters. The original model is an extension of the Uzawa-Lucas model to a heterogeneous household economy with multiple ways of human capital accumulation. It synthesizes the basic ideas of the Walrasian general equilibrium theory, Arrow’s learning by producing, Zhang’s learning by consuming (creative learning, the neoclassical growth theory, and the Uzawa-Lucas two-sector model. The behavior of the household is described with an alternative approach to household behavior. The economic system consists of one production sector and one education sector. Households are different in propensities to save, to obtain education and to consume, and in learning abilities. We simulate the model to demonstrate existence of equilibrium points, motion of the dynamic system, and oscillations due to different exogenous shocks. 

  2. Endogenous production of infectious Inoue-Melnick virus in a human meningioma cell line.

    Science.gov (United States)

    Nishibe, Y; Inoue, Y K; Hollinshead, A C

    1987-11-01

    We investigated continuous production of Inoue-Melnick virus (IMV) in the MG-1 cell line, established from human meningioma. The infectious virus, identified as a type 1 virus, was mostly recovered extracellularly. Assay of MG-1 cells as infective centers indicated that most of the cells were capable of producing infectious virus. By immunofluorescence, more than 90% of the cells were found to have IMV-associated cytoplasmic antigen(s) (IMCA).

  3. Activation and inhibition of the endogenous opioid system in human heart failure.

    OpenAIRE

    Oldroyd, K. G.; Gray, C E; Carter, R.; Harvey, K.; Borland, W; BEASTALL, G; Cobbe, S M

    1995-01-01

    BACKGROUND--In a canine model of congestive heart failure beta endorphin concentrations were high and opioid receptor antagonists exerted beneficial haemodynamic effects. In humans previous studies have suggested that opioid peptides may modify the perception of breathlessness and fatigue in heart failure. METHODS--Plasma concentrations of beta endorphin were measured in patients with acute and chronic heart failure and cardiogenic shock. A subgroup of eight patients with New York Heart Assoc...

  4. Expression of human endogenous retrovirus-K is strongly associated with the basal-like breast cancer phenotype

    Science.gov (United States)

    Johanning, Gary L.; Malouf, Gabriel G.; Zheng, Xiaofeng; Esteva, Francisco J.; Weinstein, John N.; Wang-Johanning, Feng; Su, Xiaoping

    2017-01-01

    Human endogenous retroviruses (HERVs), which make up approximately 8% of the human genome, are overexpressed in some breast cancer cells and tissues but without regard to cancer subtype. We, therefore, analyzed TCGA RNA-Seq data to evaluate differences in expression of the HERV-K family in breast cancers of the various subtypes. Four HERV-K loci on different chromosomes were analyzed in basal, Her2E, LumA, and LumB breast cancer subtypes of 512 breast cancer patients with invasive ductal carcinoma (IDC). The results for all four loci showed higher HERV-K expression in the basal subtype, suggesting similar mechanisms of regulation regardless of locus. Expression of the HERV-K envelope gene (env) was highly significantly increased in basal tumors in comparison with the also-upregulated expression of other HERV-K genes. Analysis of reverse-phase protein array data indicated that increased expression of HERV-K is associated with decreased mutation of H-Ras (wild-type). Our results show elevation of HERV-K expression exclusively in the basal subtype of IDC breast cancer (as opposed to the other subtypes) and suggest HERV-K as a possible target for cancer vaccines or immunotherapy against this highly aggressive form of breast cancer. PMID:28165048

  5. Resveratrol mobilizes endogenous copper in human peripheral lymphocytes leading to oxidative DNA breakage: a putative mechanism for chemoprevention of cancer.

    Science.gov (United States)

    Hadi, S M; Ullah, M F; Azmi, A S; Ahmad, A; Shamim, U; Zubair, H; Khan, H Y

    2010-06-01

    Plant polyphenols are important components of human diet, and a number of them are considered to possess chemopreventive and therapeutic properties against cancer. They are recognized as naturally occurring anti-oxidants but also act as pro-oxidants catalyzing DNA degradation in the presence of metal ions such as copper. The plant polyphenol resveratrol confers resistance to plants against fungal agents and has been implicated as a cancer chemopreventive agent. Of particular interest is the observation that resveratrol has been found to induce apoptosis in cancer cell lines but not in normal cells. Over the last few years, we have shown that resveratrol is capable of causing DNA breakage in cells such as human lymphocytes. Such cellular DNA breakage is inhibited by copper specific chelators but not by iron and zinc chelating agents. Similar results are obtained by using permeabilized cells or with isolated nuclei, indicating that chromatin-bound copper is mobilized in this reaction. It is well established that tissue, cellular and serum copper levels are considerably elevated in various malignancies. Therefore, cancer cells may be more subject to electron transfer between copper ions and resveratrol to generate reactive oxygen species responsible for DNA cleavage. The results are in support of our hypothesis that anti-cancer mechanism of plant polyphenols involves mobilization of endogenous copper and the consequent pro-oxidant action. Such a mechanism better explains the anti-cancer effects of resveratrol, as it accounts for the preferential cytotoxicity towards cancer cells.

  6. Validation of endogenous normalizing genes for expression analyses in adult human testis and germ cell neoplasms

    DEFF Research Database (Denmark)

    Svingen, T; Jørgensen, Anne; Rajpert-De Meyts, E

    2014-01-01

    expressed across the samples analysed: a so-called normalizing or housekeeping gene. Although this is a valid strategy, the identification of stable normalizing genes has proved challenging and a gene showing stable expression across all cells or tissues is unlikely to exist. Therefore, it is necessary...... to define suitable normalizing genes for specific cells and tissues. Here, we report on the performance of a panel of nine commonly employed normalizing genes in adult human testis and testicular pathologies. Our analyses revealed significant variability in transcript abundance for commonly used normalizers...

  7. Knock-Down of Endogenous Bornavirus-Like Nucleoprotein 1 Inhibits Cell Growth and Induces Apoptosis in Human Oligodendroglia Cells

    Directory of Open Access Journals (Sweden)

    Peng He

    2016-03-01

    Full Text Available Endogenous bornavirus-like nucleoprotein elements (EBLNs have been discovered in the genomes of various animals including humans, whose functions have been seldom studied. To explore the biological functions of human EBLNs, we constructed a lentiviral vector expressing a short-hairpin RNA against human EBLN1, which successfully inhibited EBLN1 expression by above 80% in infected human oligodendroglia cells (OL cells. We found that EBLN1 silencing suppressed cell proliferation, induced G2/M phase arrest, and promoted apoptosis in OL cells. Gene expression profiling demonstrated that 1067 genes were up-regulated, and 2004 were down-regulated after EBLN1 silencing. The top 10 most upregulated genes were PI3, RND3, BLZF1, SOD2, EPGN, SBSN, INSIG1, OSMR, CREB3L2, and MSMO1, and the top 10 most-downregulated genes were KRTAP2-4, FLRT2, DIDO1, FAT4, ESCO2, ZNF804A, SUV420H1, ZC3H4, YAE1D1, and NCOA5. Pathway analysis revealed that these differentially expressed genes were mainly involved in pathways related to the cell cycle, the mitogen-activated protein kinase pathway, p53 signaling, and apoptosis. The gene expression profiles were validated by using quantitative reverse transcription polymerase chain reaction (RT-PCR for detecting these 20 most-changed genes. Three genes closely related to glioma, RND3, OSMR, and CREB3L2, were significantly upregulated and might be the key factors in EBLN1 regulating the proliferation and apoptosis of OL cells. This study provides evidence that EBLN1 plays a key role in regulating cell life and death, thereby opening several avenues of investigation regarding EBLN1 in the future.

  8. Endogenous biosynthesis of arachidonic acid epoxides in humans: Increased formation in pregnancy-induced hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Catella, F.; Lawson, J.A.; Fitzgerald, D.J.; FitzGerald, G.A. (Vanderbilt Univ., Nashville, TN (USA))

    1990-08-01

    Arachidonic acid is metabolized by means of P450 isoenzyme(s) to form epoxyeicosatrienoic acids (EETs) and their corresponding dihydroxy derivatives (DHETs). In the present study, we established the presence in human urine of 8,9-, 11,12-, and 14,15-EETs and their corresponding DHETs by developing quantitative assays and using negative ion, chemical ionization GC/MS and octadeuterated internal standards. Urinary excretion of 8,9- and 11,12-DHET increased in healthy pregnant women compared with nonpregnant female volunteers. By contrast, excretion of 11,12-DHET and 14,15-DHET, but not the 8,9-DHET regioisomer, increased even further in patients with pregnancy-induced hypertension. Intravenous administration of (3H)14,15-EET to three dogs markedly increased its DHET in plasma. The terminal half-life ranged from 7.9-12.3 min and the volume of distribution (3.5-5.3 liters) suggested limited distribution outside the plasma compartment. Negligible radioactivity was detected in urine; this fact infers that under physiological circumstances, urinary DHETs largely derive from the kidney. That P450 metabolites of arachidonic acid are formed in humans supports the hypothesis that these metabolites contribute to the physiological response to normal pregnancy and the pathophysiology of pregnancy-induced hypertension.

  9. Human Gut Bacteria Are Sensitive to Melatonin and Express Endogenous Circadian Rhythmicity.

    Directory of Open Access Journals (Sweden)

    Jiffin K Paulose

    Full Text Available Circadian rhythms are fundamental properties of most eukaryotes, but evidence of biological clocks that drive these rhythms in prokaryotes has been restricted to Cyanobacteria. In vertebrates, the gastrointestinal system expresses circadian patterns of gene expression, motility and secretion in vivo and in vitro, and recent studies suggest that the enteric microbiome is regulated by the host's circadian clock. However, it is not clear how the host's clock regulates the microbiome. Here, we demonstrate at least one species of commensal bacterium from the human gastrointestinal system, Enterobacter aerogenes, is sensitive to the neurohormone melatonin, which is secreted into the gastrointestinal lumen, and expresses circadian patterns of swarming and motility. Melatonin specifically increases the magnitude of swarming in cultures of E. aerogenes, but not in Escherichia coli or Klebsiella pneumoniae. The swarming appears to occur daily, and transformation of E. aerogenes with a flagellar motor-protein driven lux plasmid confirms a temperature-compensated circadian rhythm of luciferase activity, which is synchronized in the presence of melatonin. Altogether, these data demonstrate a circadian clock in a non-cyanobacterial prokaryote and suggest the human circadian system may regulate its microbiome through the entrainment of bacterial clocks.

  10. Cryogenic Propulsion Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The storage of cryogenic propellants is challenging because heat leaks into the cryogenic storage tanks no matter how good the insulation, resulting in a necessity...

  11. Cryogenics a textbook

    CERN Document Server

    Thipse, S S

    2013-01-01

    A Textbook covers lucidly various cryogenic applications including cryogenic engines and space and electronic applications. Importance of cryogenic engines in space propulsion, complete thermodynamic analysis of cryogenic systems with special emphasis on cryogenic cycles, Dewar vessels used to store cryogenic fluids and their applications in various industries have also been discussed in detail. Explanation of Superconductivity and its applications with a description of various Cryocoolers used in industry has also been provided with extensive details. Further technical information on cryogens has been specified alongwith the vacuum technology which has been sufficiently described with examples. Science of Cryonics has been elaborated and all aspects of technology related to functioning of cryogenic plants and their construction including valves, pipes has been incorporated in this book.

  12. Energy Efficient Cryogenics

    Science.gov (United States)

    Meneghelli, Barry J.; Notardonato, William; Fesmire, James E.

    2016-01-01

    The Cryogenics Test Laboratory, NASA Kennedy Space Center, works to provide practical solutions to low-temperature problems while focusing on long-term technology targets for the energy-efficient use of cryogenics on Earth and in space.

  13. Endogenous HLA-DR-restricted presentation of the cartilage antigens human cartilage gp-39 and melanoma inhibitory activity in the inflamed rheumatoid joint

    NARCIS (Netherlands)

    van Lierop, M. J. C.; den Hoed, L.; Houbiers, J.; Vencovsky, J.; Ruzickova, S.; Krystufkova, O.; van Schaardenburg, M.; van den Hoogen, F.; Vandooren, B.; Baeten, D.; De Keyser, F.; Sonderstrup, G.; Bos, E.; Boots, A. M.

    2007-01-01

    Objective. The cartilage proteins melanoma inhibitory activity (MIA) and human cartilage gp-39 (HC gp-39) are candidate autoantigens in rheumatoid arthritis (RA). The present study was undertaken to investigate the endogenous HLA-DR4-restricted presentation of these self proteins, in order to seek i

  14. Cryogenic immersion microscope

    Science.gov (United States)

    Le Gros, Mark; Larabell, Carolyn A.

    2010-12-14

    A cryogenic immersion microscope whose objective lens is at least partially in contact with a liquid reservoir of a cryogenic liquid, in which reservoir a sample of interest is immersed is disclosed. When the cryogenic liquid has an index of refraction that reduces refraction at interfaces between the lens and the sample, overall resolution and image quality are improved. A combination of an immersion microscope and x-ray microscope, suitable for imaging at cryogenic temperatures is also disclosed.

  15. Characterization and quantification of endogenous fatty acid nitroalkene metabolites in human urine.

    Science.gov (United States)

    Salvatore, Sonia R; Vitturi, Dario A; Baker, Paul R S; Bonacci, Gustavo; Koenitzer, Jeffrey R; Woodcock, Steven R; Freeman, Bruce A; Schopfer, Francisco J

    2013-07-01

    The oxidation and nitration of unsaturated fatty acids transforms cell membrane and lipoprotein constituents into mediators that regulate signal transduction. The formation of 9-NO2-octadeca-9,11-dienoic acid and 12-NO2-octadeca-9,11-dienoic acid stems from peroxynitrite- and myeloperoxidase-derived nitrogen dioxide reactions as well as secondary to nitrite disproportionation under the acidic conditions of digestion. Broad anti-inflammatory and tissue-protective responses are mediated by nitro-fatty acids. It is now shown that electrophilic fatty acid nitroalkenes are present in the urine of healthy human volunteers (9.9 ± 4.0 pmol/mg creatinine); along with electrophilic 16- and 14-carbon nitroalkenyl β-oxidation metabolites. High resolution mass determinations and coelution with isotopically-labeled metabolites support renal excretion of cysteine-nitroalkene conjugates. These products of Michael addition are in equilibrium with the free nitroalkene pool in urine and are displaced by thiol reaction with mercury chloride. This reaction increases the level of free nitroalkene fraction >10-fold and displays a K(D) of 7.5 × 10(-6) M. In aggregate, the data indicates that formation of Michael adducts by electrophilic fatty acids is favored under biological conditions and that reversal of these addition reactions is critical for detecting both parent nitroalkenes and their metabolites. The measurement of this class of mediators can constitute a sensitive noninvasive index of metabolic and inflammatory status.

  16. Modulation of endogenous antioxidant system by wine polyphenols in human disease.

    Science.gov (United States)

    Rodrigo, Ramón; Miranda, Andrés; Vergara, Leonardo

    2011-02-20

    Numerous studies indicate that moderate red wine consumption is associated with a protective effect against all-cause mortality. Since oxidative stress constitutes a unifying mechanism of injury of many types of disease processes, it should be expected that polyphenolic antioxidants account for this beneficial effect. Nevertheless, beyond the well-known antioxidant properties of these compounds, they may exert several other protective mechanisms. Indeed, the overall protective effect of polyphenols is due to their large array of biological actions, such as free radical-scavenging, metal chelation, enzyme modulation, cell signalling pathways modulation and gene expression effects, among others. Wine possesses a variety of polyphenols, being resveratrol its most outstanding representative, due to its pleiotropic biological properties. The presence of ethanol in wine aids to polyphenol absorption, thereby contributing to their bioavailability. Before absorption, polyphenols must be hydrolyzed by intestinal enzymes or by colonic microflora. Then, they undergo intestinal and liver metabolism. There have been no reported polyphenol adverse effects derived from intakes currently associated with the normal diet. However, supplements for health-protection should be cautiously used as no level definition has been given to make sure the dose is safe. The role of oxidative stress and the beneficial effects of wine polyphenols against cardiovascular, cancer, diabetes, microbial, inflammatory, neurodegenerative and kidney diseases and ageing are reviewed. Future large scale randomized clinical trials should be conducted to fully establish the therapeutic use of each individual wine polyphenol against human disease.

  17. The increase in human plasma antioxidant capacity after acute coffee intake is not associated with endogenous non-enzymatic antioxidant components.

    Science.gov (United States)

    Moura-Nunes, Nathália; Perrone, Daniel; Farah, Adriana; Donangelo, Carmen M

    2009-01-01

    This study evaluated the association between the main plasma endogenous non-enzymatic antioxidant components and the increase in human antioxidant capacity (AC) after acute coffee intake. Ten adults were tested before and 90 min after consumption of coffee or water, in a crossover design, with a 7-day interval between tests. AC (FRAP and TRAP), ascorbic acid, α-tocopherol and γ-tocopherol, albumin, bilirubin and uric acid were analyzed in plasma/serum. After coffee consumption FRAP and TRAP increased 2.6% and 7.6% (P0.75; P coffee intake did not correlate with endogenous components, which remained unchanged. These results suggest that coffee components spare endogenous antioxidants or are themselves the main contributors to plasma AC increase after coffee intake.

  18. Human gut endogenous proteins as a potential source of angiotensin-I-converting enzyme (ACE-I)-, renin inhibitory and antioxidant peptides.

    Science.gov (United States)

    Dave, Lakshmi A; Hayes, Maria; Montoya, Carlos A; Rutherfurd, Shane M; Moughan, Paul J

    2016-02-01

    It is well known that endogenous bioactive proteins and peptides play a substantial role in the body's first line of immunological defence, immune-regulation and normal body functioning. Further, the peptides derived from the luminal digestion of proteins are also important for body function. For example, within the peptide database BIOPEP (http://www.uwm.edu.pl/biochemia/index.php/en/biopep) 12 endogenous antimicrobial and 64 angiotensin-I-converting enzyme (ACE-I) inhibitory peptides derived from human milk and plasma proteins are listed. The antimicrobial peptide database (http://aps.unmc.edu/AP/main.php) lists over 111 human host-defence peptides. Several endogenous proteins are secreted in the gut and are subject to the same gastrointestinal digestion processes as food proteins derived from the diet. The human gut endogenous proteins (GEP) include mucins, serum albumin, digestive enzymes, hormones, and proteins from sloughed off epithelial cells and gut microbiota, and numerous other secreted proteins. To date, much work has been carried out regarding the health altering effects of food-derived bioactive peptides but little attention has been paid to the possibility that GEP may also be a source of bioactive peptides. In this review, we discuss the potential of GEP to constitute a gut cryptome from which bioactive peptides such as ACE-I inhibitory, renin inhibitory and antioxidant peptides may be derived.

  19. Expression of endogenic lectins and their glycoligands in the tear fluid, human corneal and conjunctival epithelium under physiological and disease conditions

    OpenAIRE

    Hrdličková, Enkela

    2016-01-01

    Purpose: Lectins play an important role in many biological processes. The aim of this work was to analyse mainly the expression of endogenic lectins, such as galectins and plant lectin, e.g. Dolichos biflorus agglutinin (DBA), and their glycoligands in the tear fluid, human corneal and conjunctival epithelium in physiological and disease conditions. Further, we studied the human natural antibody against Galα1,3Gal-R, which is mainly responsible for hyperacute rejection of xenografts transplan...

  20. Correlation between endogenous polyamines in human cardiac tissues and clinical parameters in patients with heart failure.

    Science.gov (United States)

    Meana, Clara; Rubín, José Manuel; Bordallo, Carmen; Suárez, Lorena; Bordallo, Javier; Sánchez, Manuel

    2016-02-01

    Polyamines contribute to several physiological and pathological processes, including cardiac hypertrophy in experimental animals. This involves an increase in ornithine decarboxylase (ODC) activity and intracellular polyamines associated with cyclic adenosine monophosphate (cAMP) increases. The aim of the study was to establish the role of these in the human heart in living patients. For this, polyamines (by high performance liquid chromatography) and the activity of ODC and N(1)-acetylpolyamine oxidases (APAO) were determined in the right atrial appendage of 17 patients undergoing extracorporeal circulation to correlate with clinical parameters. There existed enzymatic activity associated with the homeostasis of polyamines. Left atria size was positively associated with ODC (r = 0.661, P = 0.027) and negatively with APAO-N(1) -acetylspermine (r = -0.769, P = 0.026), suggesting that increased levels of polyamines are associated with left atrial hemodynamic overload. Left ventricular ejection fraction (LVEF) and heart rate were positively associated with spermidine (r = 0.690, P = 0.003; r = 0.590, P = 0.021) and negatively with N(1)-acetylspermidine (r = -0.554, P = 0.032; r = -0.644, P = 0.018). LVEF was negatively correlated with cAMP levels (r = -0.835, P = 0.001) and with cAMP/ODC (r = -0.794, P = 0.011), cAMP/spermidine (r = -0.813, P = 0.001) and cAMP/spermine (r = -0.747, P = 0.003) ratios. Abnormal LVEF patients showed decreased ODC activity and spermidine, and increased N(1) -acetylspermidine, and cAMP. Spermine decreased in congestive heart failure patients. The trace amine isoamylamine negatively correlated with septal wall thickness (r = -0.634, P = 0.008) and was increased in cardiac heart failure. The results indicated that modifications in polyamine homeostasis might be associated with cardiac function and remodelling. Increased cAMP might have a deleterious effect on function. Further studies should confirm these findings and the involvement of

  1. Human μ—opioid receptor overexpressed in Sf9 insect cells functionally coupled to endogenous Gi/0 proteins

    Institute of Scientific and Technical Information of China (English)

    WEIQIANG; QINGXIANGSHEN; 等

    2000-01-01

    Human μ-opioid receptor(HμOR) with a tag of six consecutive histidines at its carboxyl terminus has been expressed in recombinant baculovirus infected Sf9 insect cells.The maximal binding capacity for the [3H] diprenorphine and [3H] ohmefentanyl (Ohm) were 9.1±0.7 and 6.52±0.23 nmol/g protein,respectively.The [3H] diprenorphine or [3H] Ohm binding to the receptor expressed in Sf9 cells was strongly inhibited by μ-selective agonists [D-Ala2,N-methyl-Phe4,glyol5] enkephalin(DAGO),Ohm,and morphine,but neither by δ nor by κ selective agonist.Na+ (100mM) and GTP(50μM) could reduce HμOR agonists etorphine and Ohm affinity binding to the overexpressed HμOR.μ-selective agonists DAGO and Ohm effectively stimulated [35S]GTP γS binding (EC50=2.7nM and 6.9 nM)and inhibited forskolin-stimulated cAMP accumulation(IC50=0.9 nM and 0.3 nM).The agonist-dependent effects could be blocked by opioid antagonist naloxone or by pretreatment of cells with pertussis toxin (PTX).These results demonstrated that HμOR overexpressed in Sf9 insect cells functionally coupled to endogenous Ci/o proteins.

  2. Human Motor Neuron Progenitor Transplantation Leads to Endogenous Neuronal Sparing in 3 Models of Motor Neuron Loss

    Directory of Open Access Journals (Sweden)

    Tanya J. Wyatt

    2011-01-01

    Full Text Available Motor neuron loss is characteristic of many neurodegenerative disorders and results in rapid loss of muscle control, paralysis, and eventual death in severe cases. In order to investigate the neurotrophic effects of a motor neuron lineage graft, we transplanted human embryonic stem cell-derived motor neuron progenitors (hMNPs and examined their histopathological effect in three animal models of motor neuron loss. Specifically, we transplanted hMNPs into rodent models of SMA (Δ7SMN, ALS (SOD1 G93A, and spinal cord injury (SCI. The transplanted cells survived and differentiated in all models. In addition, we have also found that hMNPs secrete physiologically active growth factors in vivo, including NGF and NT-3, which significantly enhanced the number of spared endogenous neurons in all three animal models. The ability to maintain dying motor neurons by delivering motor neuron-specific neurotrophic support represents a powerful treatment strategy for diseases characterized by motor neuron loss.

  3. Identification and detection of a novel human endogenous retrovirus-related gene, and structural characterization of its related elements

    Directory of Open Access Journals (Sweden)

    Qiaoyi Liang

    2009-01-01

    Full Text Available Up-regulation of human endogenous retroviruses (HERVs is associated with many diseases, including cancer. In this study, an H family HERV (HERV-H-related gene was identified and characterized. Its spliced transcript lacks protein-coding capacity and may belong to the emerging class of noncoding RNAs (ncRNAs. The 1.3-kb RNA consisting of four exons is transcribed from an Alu element upstream of a 5.0-kb structurally incomplete HERV-H element. RT-PCR and quantitative RT-PCR results indicated that expression of this HERV-related transcript was negatively associated with colon, stomach, and kidney cancers. Its expression was induced upon treatment with DNA methylation and histone deacetylation inhibitors. A BLAT search using long terminal repeats (LTRs identified 50 other LTR homogenous HERV-H elements. Further analysis of these elements revealed that all are structurally incomplete and only five exert transcriptional activity. The results presented here recommend further investigation into a potentially functional HERV-H-related ncRNA.

  4. Cryogenic heat transfer

    CERN Document Server

    Barron, Randall F

    2016-01-01

    Cryogenic Heat Transfer, Second Edition continues to address specific heat transfer problems that occur in the cryogenic temperature range where there are distinct differences from conventional heat transfer problems. This updated version examines the use of computer-aided design in cryogenic engineering and emphasizes commonly used computer programs to address modern cryogenic heat transfer problems. It introduces additional topics in cryogenic heat transfer that include latent heat expressions; lumped-capacity transient heat transfer; thermal stresses; Laplace transform solutions; oscillating flow heat transfer, and computer-aided heat exchanger design. It also includes new examples and homework problems throughout the book, and provides ample references for further study.

  5. Cryogen Safety Course 8876

    Energy Technology Data Exchange (ETDEWEB)

    Glass, George [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-06-13

    Cryogenics (from the Greek word κρvoζ, meaning frost or icy cold) is the study of the behavior of matter at very cold temperatures. The purpose of this course is to provide trainees with an introduction to cryogen use, the hazards and potential accidents related to cryogen systems, cryogen safety components, and the requirements that govern the design and use of cryogen systems at Los Alamos National Laboratory (LANL). The knowledge you gain will help you keep your workplace safe for yourself and your coworkers.

  6. Exogenous and Endogeneous Disialosyl Ganglioside GD1b Induces Apoptosis of MCF-7 Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Sun-Hyung Ha

    2016-04-01

    Full Text Available Gangliosides have been known to play a role in the regulation of apoptosis in cancer cells. This study has employed disialyl-ganglioside GD1b to apoptosis in human breast cancer MCF-7 cells using exogenous treatment of the cells with GD1b and endogenous expression of GD1b in MCF-7 cells. First, apoptosis in MCF-7 cells was observed after treatment of GD1b. Treatment of MCF-7 cells with GD1b reduced cell growth rates in a dose and time dependent manner during GD1b treatment, as determined by XTT assay. Among the various gangliosides, GD1b specifically induced apoptosis of the MCF-7 cells. Flow cytometry and immunofluorescence assays showed that GD1b specifically induces apoptosis in the MCF-7 cells with Annexin V binding for apoptotic actions in early stage and propidium iodide (PI staining the nucleus of the MCF-7 cells. Treatment of MCF-7 cells with GD1b activated apoptotic molecules such as processed forms of caspase-8, -7 and PARP (Poly(ADP-ribose polymerase, without any change in the expression of mitochondria-mediated apoptosis molecules such as Bax and Bcl-2. Second, to investigate the effect of endogenously produced GD1b on the regulation of cell function, UDP-gal: β1,3-galactosyltransferase-2 (GD1b synthase, Gal-T2 gene has been transfected into the MCF-7 cells. Using the GD1b synthase-transfectants, apoptosis-related signal proteins linked to phenotype changes were examined. Similar to the exogenous GD1b treatment, the cell growth of the GD1b synthase gene-transfectants was significantly suppressed compared with the vector-transfectant cell lines and transfection activated the apoptotic molecules such as processed forms of caspase-8, -7 and PARP, but not the levels of expression of Bax and Bcl-2. GD1b-induced apoptosis was blocked by caspase inhibitor, Z-VAD. Therefore, taken together, it was concluded that GD1b could play an important role in the regulation of breast cancer apoptosis.

  7. LLL12 inhibits endogenous and exogenous interleukin-6-induced STAT3 phosphorylation in human pancreatic cancer cells

    National Research Council Canada - National Science Library

    Liu, Aiguo; Liu, Yan; Li, Pui-Kai; Li, Chenglong; Lin, Jiayuh

    2011-01-01

    .... Inhibition of the endogenous IL-6/STAT3 pathway reduces cell viability. Exogenous IL-6 induces STAT3 phosphorylation, but differently induces phosphorylation of STAT3 upstream kinases, Janus kinase 1(JAK1...

  8. Anti-inflammatory and vasoprotective activity of a retroviral-derived peptide, homologous to human endogenous retroviruses: endothelial cell effects.

    Directory of Open Access Journals (Sweden)

    George J Cianciolo

    Full Text Available Malignant and inflammatory tissues sometimes express endogenous retroviruses or their proteins. A highly-conserved sequence from retroviral transmembrane (TM proteins, termed the "immunosuppressive domain (ID", is associated with inhibition of immune and inflammatory functions. An octadecapeptide (MN10021 from the ID of retroviral TM protein p15E inhibits in vitro release of pro-inflammatory cytokines and increases synthesis of anti-inflammatory IL-10. We sought to determine if MN10021 has significant in vivo effects. MN10021, prepared by solid-phase synthesis, was dimerized through a naturally-occurring, carboxy-terminal cysteine. In vivo anti-inflammatory activity was determined using a murine model of sodium periodate (NaIO(4-induced peritonitis. In vivo vasoprotective effects were determined using: (1 a carrageenan-induced model of disseminated intravascular coagulation (DIC in mice; (2 a reverse passive Arthus model in guinea pigs; and (3 vasoregulatory effects in spontaneously hypertensive rats (SHR. In vitro studies included: (1 binding/uptake of MN10021 using human monocytes, cultured fibroblasts, and vascular endothelial cells (VEC; (2 gene expression by RT-PCR of MN10021-treated VEC; and (3 apoptosis of MN10021-treated VEC exposed to staurosporine or TNF-α. One-tenth nmol MN10021 inhibits 50 percent of the inflammatory response in the mouse peritonitis model. Furthermore, 73 nmol MN10021 completely protects mice in a lethal model of carrageenan-induced DIC and inhibits vascular leak in both the mouse DIC model and a guinea pig reverse passive Arthus reaction. MN10021 binds to and is taken up in a specific manner by both human monocytes and VEC but not by cultured human fibroblasts. Surprisingly, orally-administered MN10021 lowers blood pressure in SHR rats by 10-15% within 1 h suggesting a direct or indirect effect on the vascular endothelium. MN10021 and derived octapeptides induce iNOS (inducible nitric oxide synthase mRNA in VEC

  9. Association between endogenous gene expression and growth regulation induced by TGF-β1 in human gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    Xue Li; Yun-Yan Zhang; Qi Wang; Song-Bin Fu

    2005-01-01

    AIM: To investigate the association between endogenous gene expression and growth regulation including proliferation and apoptosis induced by transforming growth factor-β1(TGF-β1) in human gastric cancer (GC) cells.METHODS: Reverse transcription polymerase chain reaction (RT-PCR) was performed to detect the main components of the TGF-β1/Smads signal pathway in human poorly differentiated GC cell line BGC-823. Localization of Smad proteins was also determined using immunofluorescence.Then, the BGC-823 cells were cultured in the presence or absence of TGF-β1 (10 ng/mL) for 24 and 48 h, and the effects of TGF-β1 on proliferation and apoptosis were measured by cell growth curve and flow cytometry (FCM)analysis. The ultrastructural features of BGC-823 cells with or without TGF-β1 treatment were observed under transmission electron microscope. The apoptotic cells were visualized by means of the terminal deoxynucleotidyl transferase (TdT)-mediated dTUPin situ nick end-labeling (TUNEL) method. Meanwhile, the expression levels of endogenous p15, p21 and Smad7 mRNA and the corresponding proteins in the cells were detected at 1, 2and 3 h after culture in the presence or absence of TGF-β1(10 ng/mL) by semi-quantitative RT-PCR and Western blot,respectively.RESULTS: The TGF-β1/Smad signaling was found to be intact and functional in BGC-823 cells. The growth curve revealed the most evident inhibition of cell proliferation by TGF-β1 at 48 h, and FCM assay showed G1 arrest accompanied with apoptosis induced by TGF-β1. The typical morphological changes of apoptosis were observed in cells exposed to TGF-β1. The apoptosis index (AI) in TGF-β1-treated cells was significantly higher than that in the untreated controls (10.7±1.3% vs 0.32±0.06%, P<0.01).The levels of p15, p21 and Smad7mRNA and corresponding proteins in cells were significantly up-regulated at 1 h, but gradually returned to basal levels at 3 h following TGF-β1(10 ng/mL) treatment.CONCLUSION: TGF-β1

  10. Transcriptional and functional studies of Human Endogenous Retrovirus envelope EnvP(b) and EnvV genes in human trophoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Vargas, Amandine, E-mail: amandine.vargas@voila.fr; Thiery, Maxime, E-mail: thiery.maxime@courrier.uqam.ca; Lafond, Julie, E-mail: lafond.julie@uqam.ca; Barbeau, Benoit, E-mail: barbeau.benoit@uqam.ca

    2012-03-30

    HERV (Human Endogenous Retrovirus)-encoded envelope proteins are implicated in the development of the placenta. Indeed, Syncytin-1 and -2 play a crucial role in the fusion of human trophoblasts, a key step in placentation. Other studies have identified two other HERV env proteins, namely EnvP(b) and EnvV, both expressed in the placenta. In this study, we have fully characterized both env transcripts and their expression pattern and have assessed their implication in trophoblast fusion. Through RACE analyses, standard spliced transcripts were detected, while EnvV transcripts demonstrated alternative splicing at its 3 Prime end. Promoter activity and expression of both genes were induced in forskolin-stimulated BeWo cells and in primary trophoblasts. Although we have confirmed the fusogenic activity of EnvP(b), overexpression or silencing experiments revealed no impact of this protein on trophoblast fusion. Our results demonstrate that both env genes are expressed in human trophoblasts but are not required for syncytialization.

  11. A cryogenic test facility

    Science.gov (United States)

    Veenendaal, Ian

    The next generation, space-borne instruments for far infrared spectroscopy will utilize large diameter, cryogenically cooled telescopes in order to achieve unprecedented sensitivities. Low background, ground-based cryogenic facilities are required for the cryogenic testing of materials, components and subsystems. The Test Facility Cryostat (TFC) at the University of Lethbridge is a large volume, closed cycle, 4K cryogenic facility, developed for this purpose. This thesis discusses the design and performance of the facility and associated external instrumentation. An apparatus for measuring the thermal properties of materials is presented, and measurements of the thermal expansion and conductivity of carbon fibre reinforced polymers (CFRPs) at cryogenic temperatures are reported. Finally, I discuss the progress towards the design and fabrication of a demonstrator cryogenic, far infrared Fourier transform spectrometer.

  12. Introduction to cryogenic engineering

    CERN Document Server

    CERN. Geneva; Vandoni, Giovanna; Niinikoski, Tapio O

    2005-01-01

    Cryogenic engineering is one of the key technologies at CERN. It is widely used in research and has many applications in industry and last but not least in medicine. In research cryogenic engineering and its applications are omnipresent from the smallest laboratories to fusion reactors, hughe detectors and accelerators. With the termination of the LHC, CERN will in fact become the world's largest cryogenic installation. This series of talks intends to introduce the non-cryogenist to the basic principles and challenges of cryogenic engineering and its applications. The course will also provide a basis for practical application as well as for further learning.

  13. Human embryonic stem cells and metastatic colorectal cancer cells shared the common endogenous human microRNA-26b.

    Science.gov (United States)

    Ma, Yan-Lei; Zhang, Peng; Wang, Feng; Moyer, Mary Pat; Yang, Jian-Jun; Liu, Zhi-Hua; Peng, Jia-Yuan; Chen, Hong-Qi; Zhou, Yu-Kun; Liu, Wei-Jie; Qin, Huan-Long

    2011-09-01

    The increase in proliferation and the lack of differentiation of cancer cells resemble what occur in the embryonic stem cells during physiological process of embryogenesis. There are also striking similarities in the behaviour between the invasive placental cells and invasive cancer cells. In the present study, microarrays were used to analyse the global expression of microRNAs in a human embryonic stem cell line (i.e. HUES-17) and four colorectal cancer (CRC) cell lines (i.e. LoVo, SW480, HT29 and Caco-2) with different metastatic potentialities. Only the expression of miR-26b was significant decreased in HUES-17s and LoVo cells, compared with other three cell lines (P cell growth and the induction of apoptosis in LoVo cells in vitro, and the inhibition of tumour growth in vivo. Moreover, the potential targets of miR-26b was predicted by using bioinformatics, and then the predicted target genes were further validated by comparing gene expression profiles between LoVo and NCM460 cell lines. Four genes (TAF12, PTP4A1, CHFR and ALS2CR2) with intersection were found to be the targets of miR-26b. MetaCore network analysis further showed that the regulatory pathways of miR-26b were significantly associated with the invasiveness and metastasis of CRC cells. These data suggest that miR-26b might serve as a novel prognostic factor and a potential therapeutic target for CRC.

  14. The cryogenic control system of BEPCⅡ

    Institute of Scientific and Technical Information of China (English)

    LI Gang; WANG Ke-Xiang; ZHAO Ji-Jiu; YUE Ke-Juan; DAI Ming-Sui; HUANG Yi-Ling; JIANG Bo

    2008-01-01

    A superconducting cryogenic system has been designed and deployed in the Beijing Electron-Positron Collider Upgrade Project(BEPCⅡ).The system consists of a Siemens PLC(ST-PLC,Programmable Logic Controller)for the compressor control,an Allen Bradley(AB)PLC for the cryogenic equipments,and the Experimental Physics and Industrial Control System(EPICS)that integrates the PLCs.The system fully automates the superconducting cryogenic control with process control,PID(Proportional-Integral-Differential)control loops,real-time data access and data storage,alarm handler and human machine interface.It is capable of automatic recovery as well.This paper describes the BEPCⅡ cryogenic control system,data communication between ST-PLC and EPICS Input/Output Controllers(IOCs),and the integration of the flow control,the low level interlock,the AB-PLC,and EPICS.

  15. The cryogenic control system of BEPCII

    Science.gov (United States)

    Li, Gang; Wang, Ke-Xiang; Zhao, Ji-Jiu; Yue, Ke-Juan; Dai, Ming-Hui; Huang, Yi-Ling; Jiang, Bo

    2008-04-01

    A superconducting cryogenic system has been designed and deployed in the Beijing Electron- Positron Collider Upgrade Project (BEPCII). The system consists of a Siemens PLC (S7-PLC, Programmable Logic Controller) for the compressor control, an Allen Bradley (AB) PLC for the cryogenic equipments, and the Experimental Physics and Industrial Control System (EPICS) that integrates the PLCs. The system fully automates the superconducting cryogenic control with process control, PID (Proportional-Integral-Differential) control loops, real-time data access and data storage, alarm handler and human machine interface. It is capable of automatic recovery as well. This paper describes the BEPCII cryogenic control system, data communication between S7-PLC and EPICS Input/Output Controllers (IOCs), and the integration of the flow control, the low level interlock, the AB-PLC, and EPICS.

  16. Human endogenous retrovirus W family envelope gene activates the small conductance Ca2+-activated K+ channel in human neuroblastoma cells through CREB.

    Science.gov (United States)

    Li, S; Liu, Z C; Yin, S J; Chen, Y T; Yu, H L; Zeng, J; Zhang, Q; Zhu, F

    2013-09-05

    Numerous studies have shown that human endogenous retrovirus W family (HERV-W) envelope gene (env) is related to various diseases but the underlying mechanism has remained poorly understood. Our previous study showed that there was abnormal expression of HERV-W env in sera of patients with schizophrenia. In this paper, we reported that overexpression of the HERV-W env elevated the levels of small conductance Ca(2+)-activated K(+) channel protein 3 (SK3) in human neuroblastoma cells. Using a luciferase reporter system and RNA interference method, we found that functional cAMP response element site was required for the expression of SK3 triggered by HERV-W env. In addition, it was also found that the SK3 channel was activated by HERV-W env. Further study indicated that cAMP response element-binding protein (CREB) was required for the activation of the SK3 channel. Thus, a novel signaling mechanism of how HERV-W env influences neuronal activity and contributes to mental illnesses such as schizophrenia was proposed.

  17. A Cryogenic Flow Sensor Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Advanced Technologies Group, Inc. proposes the development of a Cryogenic Flow Sensor (CFS) for determining mass flow of cryogens in spacecraft propellant...

  18. Effects of Endogenous Formaldehyde in Nasal Tissues on Inhaled Formmaldehyde Dosimetry Predictions in the Rat, Monkey, and Human Nasal Passages

    Science.gov (United States)

    ABSTRACT Formaldehyde, a nasal carcinogen, is also an endogenous compound that is present in all living cells. Due to its high solubility and reactivity, quantitative risk estimates for inhaled formaldehyde rely on internal dose calculations in the upper respiratory tract which ...

  19. A breath of fresh air for cryogenics training

    CERN Multimedia

    HSE Unit

    2014-01-01

    Whether you work full-time in a cryogenic installation or are required to handle cryogenic substances temporarily, you need to have followed the appropriate safety training.   Photo: Christoph Balle. Two new training courses are now available in English and French at CERN: “Cryogenic Safety – Fundamentals” (at the Prévessin Training Centre) and “Cryogenic Safety – Helium Transfer” (at the Cryolab). The first covers the content of levels 1 and 2 of the old “Cryogenic Safety” course. The second is a completely new course for CERN: it covers specific aspects of the transfer of liquid helium, such as the evaporation process of helium and the associated risks to human health (asphyxia due to displacement of oxygen), the colour code for gas bottles, etc. These training modules have been rewritten in response to the increase in the number of projects involving cryogenics and following various related incident...

  20. Short-Lived Human Umbilical Cord-Blood-Derived Neural Stem Cells Influence the Endogenous Secretome and Increase the Number of Endogenous Neural Progenitors in a Rat Model of Lacunar Stroke.

    Science.gov (United States)

    Jablonska, Anna; Drela, Katarzyna; Wojcik-Stanaszek, Luiza; Janowski, Miroslaw; Zalewska, Teresa; Lukomska, Barbara

    2016-11-01

    Stroke is the leading cause of severe disability, and lacunar stroke is related to cognitive decline and hemiparesis. There is no effective treatment for the majority of patients with stroke. Thus, stem cell-based regenerative medicine has drawn a growing body of attention due to the capabilities for trophic factor expression and neurogenesis enhancement. Moreover, it was shown in an experimental autoimmune encephalomyelitis (EAE) model that even short-lived stem cells can be therapeutic, and we have previously observed that phenomenon indirectly. Here, in a rat model of lacunar stroke, we investigated the molecular mechanisms underlying the positive therapeutic effects of short-lived human umbilical cord-blood-derived neural stem cells (HUCB-NSCs) through the distinct measurement of exogenous human and endogenous rat trophic factors. We have also evaluated neurogenesis and metalloproteinase activity as cellular components of therapeutic activity. As expected, we observed an increased proliferation and migration of progenitors, as well as metalloproteinase activity up to 14 days post transplantation. These changes were most prominent at the 7-day time point when we observed 30 % increases in the number of bromodeoxyuridine (BrdU)-positive cells in HUCB-NSC transplanted animals. The expression of human trophic factors was present until 7 days post transplantation, which correlated well with the survival of the human graft. For these 7 days, the level of messenger RNA (mRNA) in the analyzed trophic factors was from 300-fold for CNTF to 10,000-fold for IGF, much higher compared to constitutive expression in HUCB-NSCs in vitro. What is interesting is that there was no increase in the expression of rat trophic factors during the human graft survival, compared to that in non-transplanted animals. However, there was a prolongation of a period of increased trophic expression until 14 days post transplantation, while, in non-transplanted animals, there was a

  1. Polymers at cryogenic temperatures

    CERN Document Server

    Fu, Shao-Yun

    2013-01-01

    Kalia and Fu's novel monograph covers cryogenic treatment, properties and applications of cryo-treated polymer materials. Written by numerous international experts, the twelve chapters in this book offer the reader a comprehensive picture of the latest findings and developments, as well as an outlook on the field. Cryogenic technology has seen remarkable progress in the past few years and especially cryogenic properties of polymers are attracting attention through new breakthroughs in space, superconducting, magnetic and electronic techniques. This book is a valuable resource for researchers, educators, engineers and graduate students in the field and at technical institutions.

  2. SNS Cryogenic Systems Commissioning

    Science.gov (United States)

    Hatfield, D.; Casagrande, F.; Campisi, I.; Gurd, P.; Howell, M.; Stout, D.; Strong, H.; Arenius, D.; Creel, J.; Dixon, K.; Ganni, V.; Knudsen, P.

    2006-04-01

    The Spallation Neutron Source (SNS) is under construction at Oak Ridge National Laboratory. The cold section of the Linac consists of 81 superconducting radio frequency cavities cooled to 2.1K by a 2400 watt cryogenic refrigeration system. The major cryogenic system components include warm helium compressors with associated oil removal and gas management, 4.5K cold box, 7000L liquid helium dewar, 2.1K cold box (consisting of 4 stages of cold compressors), gaseous helium storage, helium purification and gas impurity monitoring system, liquid nitrogen storage and the cryogenic distribution transfer line system. The overall system commissioning and future plans will be presented.

  3. FRIB Cryogenic Plant Status

    Energy Technology Data Exchange (ETDEWEB)

    Dixon, Kelly D. [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); Ganni, Venkatarao [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); Knudsen, Peter N. [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); Casagranda, Fabio [Michigan State Univ., East Lansing, MI (United States)

    2015-12-01

    After practical changes were approved to the initial conceptual design of the cryogenic system for MSU FRIB and an agreement was made with JLab in 2012 to lead the design effort of the cryogenic plant, many activities are in place leading toward a cool-down of the linacs prior to 2018. This is mostly due to using similar equipment used at CHLII for the 12 GeV upgrade at JLab and an aggressive schedule maintained by the MSU Conventional Facilities department. Reported here is an updated status of the cryogenic plant, including the equipment procurement status, plant layout, facility equipment and project schedule.

  4. SNS Cryogenic Systems Commissioning

    Energy Technology Data Exchange (ETDEWEB)

    D. Hatfield; F. Casagrande; I. Campisi; P. Gurd; M. Howell; D. Stout; H. Strong; D. Arenius; J. Creel; K. Dixon; V. Ganni; and P. Knudsen

    2005-08-29

    The Spallation Neutron Source (SNS) is under construction at Oak Ridge National Laboratory. The cold section of the Linac consists of 81 superconducting radio frequency cavities cooled to 2.1K by a 2400 watt cryogenic refrigeration system. The major cryogenic system components include warm helium compressors with associated oil removal and gas management, 4.5K cold box, 7000L liquid helium dewar, 2.1K cold box (consisting of 4 stages of cold compressors), gaseous helium storage, helium purification and gas impurity monitoring system, liquid nitrogen storage and the cryogenic distribution transfer line system. The overall system commissioning and future plans will be presented.

  5. Fundamentals of cryogenic engineering

    CERN Document Server

    Mukhopadhyay, Mamata

    2014-01-01

    The author, with her vast and varied experience in teaching and allied fields, clearly enunciates the behaviour and various properties of common cryogenic fluids, methods of liquefaction, and separation and applications of cryogens with thermodynamic analysis for process selection. This profusely illustrated study with clear-cut diagrams and process charts, should serve not only as a textbook for students but also as an excellent reference for researchers and practising engineers on design of cryogenic refrigeration, and liquefaction and separation process plants for various applications.

  6. The multiple sclerosis-associated retrovirus and its HERV-W endogenous family: a biological interface between virology, genetics, and immunology in human physiology and disease.

    Science.gov (United States)

    Dolei, Antonina; Perron, Hervé

    2009-01-01

    This mini-review summarizes current knowledge of MSRV (multiple sclerosis-associated retrovirus), founder member of the type W family of human endogenous retroviruses (HERVs), its pathogenic potential and association with diseases. As retrotransposable elements, HERVs behave differently from stable genes, and cannot be studied with "Mendelian genetics" concepts only. They also display complex interactions with other HERV families, and with classical viruses. These concepts may contribute to unravelling the etiopathogenesis of complex diseases such as multiple sclerosis, schizophrenia, and other chronic multifactorial diseases.

  7. Characterisation of Population Pharmacokinetics and Endogenous Follicle Stimulating Hormone (FSH) Levels after Multiple Dosing of a Recombinant Human FSH, FE 999049, in Healthy Women

    DEFF Research Database (Denmark)

    Rose, Trine Høyer; Roshammer, Daniel; Erichsen, Lars

    2016-01-01

    Objective: The aim of this study was to characterise the population pharmacokinetics of FE 999049, a novel recombinant human follicle-stimulating hormone (FSH), after multiple dosing in healthy women, taking into account endogenous FSH levels and the reproductive hormone dynamics. Methods......: Longitudinal measurements of FSH, luteinising hormone, progesterone, estradiol, and inhibin B levels were collected after repeated subcutaneous dosing with 225 IU of FE 999049 in 24 gonadotropin downregulated healthy women. The FSH data were described using nonlinear mixed-effects modelling. Results...

  8. Recurrent 8q13.2-13.3 microdeletions associated with branchio-oto-renal syndrome are mediated by human endogenous retroviral (HERV) sequence blocks.

    Science.gov (United States)

    Chen, Xiaoli; Wang, Jun; Mitchell, Elyse; Guo, Jin; Wang, Liwen; Zhang, Yu; Hodge, Jennelle C; Shen, Yiping

    2014-08-19

    Human endogenous retroviral (HERV) sequences are the remnants of ancient retroviral infection and comprise approximately 8% of the human genome. The high abundance and interspersed nature of homologous HERV sequences make them ideal substrates for genomic rearrangements. A role for HERV sequences in mediating human disease-associated rearrangement has been reported but is likely currently underappreciated. In the present study, two independent de novo 8q13.2-13.3 microdeletion events were identified in patients with clinical features of Branchio-Oto-Renal (BOR) syndrome. Nucleotide-level mapping demonstrated the identical breakpoints, suggesting a recurrent microdeletion including multiple genes such as EYA1, SULF1, and SLCO5A1, which is mediated by HERV1 homologous sequences. These findings raise the potential that HERV sequences may more commonly underlie recombination of dosage sensitive regions associated with recurrent syndromes.

  9. Cryogenics for LHC experiments

    CERN Multimedia

    2001-01-01

    Cryogenic systems will be used by LHC experiments to maximize their performance. Institutes around the world are collaborating with CERN in the construction of these very low temperature systems. The cryogenic test facility in hall 180 for ATLAS magnets. High Energy Physics experiments have frequently adopted cryogenic versions of their apparatus to achieve optimal performance, and those for the LHC will be no exception. The two largest experiments for CERN's new flagship accelerator, ATLAS and CMS, will both use large superconducting magnets operated at 4.5 Kelvin - almost 270 degrees below the freezing point of water. ATLAS also includes calorimeters filled with liquid argon at 87 Kelvin. For the magnets, the choice of a cryogenic version was dictated by a combination economy and transparency to emerging particles. For the calorimeters, liquid argon was selected as the fluid best suited to the experiment's physics requirements. High Energy Physics experiments are the result of worldwide collaborations and...

  10. Advances in Cryogenic Principles

    Science.gov (United States)

    Barron, R. F.

    During the past 50 years, the use of digital computers has significantly influenced the design and analysis of cryogenic systems. At the time when the first Cryogenic Engineering Conference was held, thermodynamic data were presented in graphical or tabular form (the "steam table" format), whereas thermodynamic data for cryogenic system design is computer generated today. The thermal analysis of cryogenic systems in the 1950s involved analytical solutions, graphical solutions, and relatively simple finite-difference approaches. These approaches have been supplanted by finite-element numerical programs which readily solve complicated thermal problems that could not be solved easily using the methods of the 1950s. In distillation column design, the use of the McCabe-Thiele graphical method for determination of the number of theoretical plates has been replaced by numerical methods that allow consideration of several different components in the feed and product streams.

  11. Introduction of exogenous T-cell receptors into human hematopoietic progenitors results in exclusion of endogenous T-cell receptor expression.

    Science.gov (United States)

    Vatakis, Dimitrios N; Arumugam, Balamurugan; Kim, Sohn G; Bristol, Gregory; Yang, Otto; Zack, Jerome A

    2013-05-01

    Current tumor immunotherapy approaches include the genetic modification of peripheral T cells to express tumor antigen-specific T-cell receptors (TCRs). The approach, tested in melanoma, has led to some limited success of tumor regression in patients. Yet, the introduction of exogenous TCRs into mature T cells entails an underlying risk; the generation of autoreactive clones due to potential TCR mispairing, and the lack of effective negative selection, as these peripheral cells do not undergo thymic selection following introduction of the exogenous TCR. We have successfully generated MART-1-specific CD8 T cells from genetically modified human hematopoietic stem cells (hHSC) in a humanized mouse model. The advantages of this approach include a long-term source of antigen specific T cells and proper T-cell selection due to thymopoiesis following expression of the TCR. In this report, we examine the molecular processes occurring on endogenous TCR expression and demonstrate that this approach results in exclusive cell surface expression of the newly introduced TCR, and the exclusion of endogenous TCR cell surface expression. This suggests that this stem cell based approach can provide a potentially safer approach for anticancer immunotherapy due to the involvement of thymic selection.

  12. An optimized single chain TCR scaffold relying on the assembly with the native CD3-complex prevents residual mispairing with endogenous TCRs in human T-cells.

    Science.gov (United States)

    Knies, Diana; Klobuch, Sebastian; Xue, Shao-An; Birtel, Matthias; Echchannaoui, Hakim; Yildiz, Oezlem; Omokoko, Tana; Guillaume, Philippe; Romero, Pedro; Stauss, Hans; Sahin, Ugur; Herr, Wolfgang; Theobald, Matthias; Thomas, Simone; Voss, Ralf-Holger

    2016-04-19

    Immunotherapy of cancer envisions the adoptive transfer of T-cells genetically engineered with tumor-specific heterodimeric α/β T-cell receptors (TCRα/β). However, potential mispairing of introduced TCRα/β-chains with endogenous β/α-ones may evoke unpredictable autoimmune reactivities. A novel single chain (sc)TCR format relies on the fusion of the Vα-Linker-Vβ-fragment to the TCR Cβ-domain and coexpression of the TCR Cα-domain capable of recruiting the natural CD3-complex for full and hence, native T-cell signaling. Here, we tested whether such a gp100(280-288)- or p53(264-272) tumor antigen-specific scTCR is still prone to mispairing with TCRα. In a human Jurkat-76 T-cell line lacking endogenous TCRs, surface expression and function of a scTCR could be reconstituted by any cointroduced TCRα-chain indicating mispairing to take place on a molecular basis. In contrast, transduction into human TCRα/β-positive T-cells revealed that mispairing is largely reduced. Competition experiments in Jurkat-76 confirmed the preference of dcTCR to selfpair and to spare scTCR. This also allowed for the generation of dc/scTCR-modified cytomegalovirus/tumor antigen-bispecific T-cells to augment T-cell activation in CMV-infected tumor patients. Residual mispairing was prevented by strenghtening the Vα-Li-Vβ-fragment through the design of a novel disulfide bond between a Vα- and a linker-resident residue close to Vβ. Multimer-stainings, and cytotoxicity-, IFNγ-secretion-, and CFSE-proliferation-assays, the latter towards dendritic cells endogenously processing RNA-electroporated gp100 antigen proved the absence of hybrid scTCR/TCRα-formation without impairing avidity of scTCR/Cα in T-cells. Moreover, a fragile cytomegalovirus pp65(495-503)-specific scTCR modified this way acquired enhanced cytotoxicity. Thus, optimized scTCR/Cα inhibits residual TCR mispairing to accomplish safe adoptive immunotherapy for bulk endogenous TCRα/β-positive T-cells.

  13. Multimodal optical imaging database from tumour brain human tissue: endogenous fluorescence from glioma, metastasis and control tissues

    Science.gov (United States)

    Poulon, Fanny; Ibrahim, Ali; Zanello, Marc; Pallud, Johan; Varlet, Pascale; Malouki, Fatima; Abi Lahoud, Georges; Devaux, Bertrand; Abi Haidar, Darine

    2017-02-01

    Eliminating time-consuming process of conventional biopsy is a practical improvement, as well as increasing the accuracy of tissue diagnoses and patient comfort. We addressed these needs by developing a multimodal nonlinear endomicroscope that allows real-time optical biopsies during surgical procedure. It will provide immediate information for diagnostic use without removal of tissue and will assist the choice of the optimal surgical strategy. This instrument will combine several means of contrast: non-linear fluorescence, second harmonic generation signal, reflectance, fluorescence lifetime and spectral analysis. Multimodality is crucial for reliable and comprehensive analysis of tissue. Parallel to the instrumental development, we currently improve our understanding of the endogeneous fluorescence signal with the different modalities that will be implemented in the stated. This endeavor will allow to create a database on the optical signature of the diseased and control brain tissues. This proceeding will present the preliminary results of this database on three types of tissues: cortex, metastasis and glioblastoma.

  14. Structural analysis of the endogenous glycoallergen Hev b 2 (endo-β-1,3-glucanase) from Hevea brasiliensis and its recognition by human basophils

    Energy Technology Data Exchange (ETDEWEB)

    Rodríguez-Romero, Adela, E-mail: adela@unam.mx; Hernández-Santoyo, Alejandra; Fuentes-Silva, Deyanira [Universidad Nacional Autónoma de México, Circuito Exterior, CU, 04310 Coyoacán, DF (Mexico); Palomares, Laura A. [Universidad Nacional Autónoma de México, Apartado Postal 510-3, 62250 Cuernavaca, MOR (Mexico); Muñoz-Cruz, Samira; Yépez-Mulia, Lilian [Centro Médico Nacional Siglo XXI, IMSS, Avenida Cuauhtémoc 330, Colonia Doctores, Mexico, DF (Mexico); Orozco-Martínez, Socorro [Instituto Nacional de Pediatría, Insurgentes Sur 3700C, 04530 Cuicuilco, DF (Mexico); Universidad Nacional Autónoma de México, Circuito Exterior, CU, 04310 Coyoacán, DF (Mexico)

    2014-02-01

    This study describes the three-dimensional structure of the endogenous glycosylated allergen Hev b 2 (endo-β-1,3-glucanase), which exhibits three post-translational modifications that form a patch on the surface of the molecule that is proposed to be an allergenic IgE epitope. Endogenous glycosylated Hev b 2 (endo-β-1,3-glucanase) from Hevea brasiliensis is an important latex allergen that is recognized by IgE antibodies from patients who suffer from latex allergy. The carbohydrate moieties of Hev b 2 constitute a potentially important IgE-binding epitope that could be responsible for its cross-reactivity. Here, the structure of the endogenous isoform II of Hev b 2 that exhibits three post-translational modifications, including an N-terminal pyroglutamate and two glycosylation sites at Asn27 and at Asn314, is reported from two crystal polymorphs. These modifications form a patch on the surface of the molecule that is proposed to be one of the binding sites for IgE. A structure is also proposed for the most important N-glycan present in this protein as determined by digestion with specific enzymes. To analyze the role of the carbohydrate moieties in IgE antibody binding and in human basophil activation, the glycoallergen was enzymatically deglycosylated and evaluated. Time-lapse automated video microscopy of basophils stimulated with glycosylated Hev b 2 revealed basophil activation and degranulation. Immunological studies suggested that carbohydrates on Hev b 2 represent an allergenic IgE epitope. In addition, a dimer was found in each asymmetric unit that may reflect a regulatory mechanism of this plant defence protein.

  15. Analytical approach for the determination of steroid profile of humans by gas chromatography isotope ratio mass spectrometry aimed at distinguishing between endogenous and exogenous steroids.

    Science.gov (United States)

    Bulska, Ewa; Gorczyca, Damian; Zalewska, Izabela; Pokrywka, Andrzej; Kwiatkowska, Dorota

    2015-03-15

    The contamination of commonly used supplements by unknown steroids as well as their metabolites (parent compounds) become a challenge for the analytical laboratories. Although the determination of steroids profile is not trivial because of the complex matrix and low concentration of single compound, one of the most difficult current problem is to distinguish, during analytical procedure, endogenous androgens such as testosterone, dehydrotestosterone or dehydroepiandrosterone from their synthetic equivalents. The aim of this work was to develop and validate an analytical procedure for determination of the steroid profile in human urine by gas chromatography-combustion-isotope ratio mass spectrometry (GC/C/IRMS) toward distinguishing between endogenous and exogenous steroids. Beside the optimization of the experimental parameters for gas chromatography separation and mass spectrometry, attention was focused on urine sample preparation. Using an optimized sample preparation protocol it was possible to achieve better chromatographic resolutions and better sensitivity enabling the determination of 5 steroids, androsterone, etiocholanolone, testosterone, 5-androstandiol, 11-hydroxyandrdostane, pregnandiol, with the expanded uncertainty (k=2) below 1‰. This enable to evaluate the significant shift of the δ(13)C/(12)C [‰] values for each of examined steroids (excluding ERC). The analytical protocol described in this work was successfully used for the confirmation of positive founding urine by evaluation T/E ratio after GC/C/IRMS analysis.

  16. Structural analysis of the endogenous glycoallergen Hev b 2 (endo-β-1,3-glucanase) from Hevea brasiliensis and its recognition by human basophils.

    Science.gov (United States)

    Rodríguez-Romero, Adela; Hernández-Santoyo, Alejandra; Fuentes-Silva, Deyanira; Palomares, Laura A; Muñoz-Cruz, Samira; Yépez-Mulia, Lilian; Orozco-Martínez, Socorro

    2014-02-01

    Endogenous glycosylated Hev b 2 (endo-β-1,3-glucanase) from Hevea brasiliensis is an important latex allergen that is recognized by IgE antibodies from patients who suffer from latex allergy. The carbohydrate moieties of Hev b 2 constitute a potentially important IgE-binding epitope that could be responsible for its cross-reactivity. Here, the structure of the endogenous isoform II of Hev b 2 that exhibits three post-translational modifications, including an N-terminal pyroglutamate and two glycosylation sites at Asn27 and at Asn314, is reported from two crystal polymorphs. These modifications form a patch on the surface of the molecule that is proposed to be one of the binding sites for IgE. A structure is also proposed for the most important N-glycan present in this protein as determined by digestion with specific enzymes. To analyze the role of the carbohydrate moieties in IgE antibody binding and in human basophil activation, the glycoallergen was enzymatically deglycosylated and evaluated. Time-lapse automated video microscopy of basophils stimulated with glycosylated Hev b 2 revealed basophil activation and degranulation. Immunological studies suggested that carbohydrates on Hev b 2 represent an allergenic IgE epitope. In addition, a dimer was found in each asymmetric unit that may reflect a regulatory mechanism of this plant defence protein.

  17. ENDOGENOUS EXPRESSION AND HLA STABILIZATION ASSAY OF PLASMODIUM FALCIPARUM CTL EPITOPE MINIGENE IN HUMAN HLA-A2.1 AND HLA-B51 CELLS

    Institute of Scientific and Technical Information of China (English)

    唐玉阳; 王恒

    2001-01-01

    Objective. To evaluate the Plasmodium falciparum CTL epitope vaccines in HLA class I allele specific human cell lines that have high frequency among Chinese population. Methods. Synthesized oligonucleotides encoding for P.f. CTL epitope genes, constructed eukaryotic expression plasmids, transfected the minigenes into HLA class I allele specific human cell lines and identified endogenous expressing of the minigenes by RT-PCR and HLA stabilization assay. Results. Two mini-genes encoding Plasmodium falciparum CTL epitopes were designed and cloned, respectively, into an eukaryotic expressing vector to form TR26 which was restricted to HLA-B51, SH6 which was restricted to HLA-A2.1, and TS, which had the two aforementioned mini-genes fused in tandem. All of these CTL epitope genes were transfected and endogenously expressed in respective cell lines containing appropriate HLA molecules. The obviously increased expressions of HLA class I molecules were detected in the transfected cell lines. It was demonstrated that the two discrete Plasmodium falciparum epitope genes were effectively processed and presented, and the close proximity of the two epitope genes in one chain as in mini-gene TS did not interfere with the processing and presenting of each epitope gene in corresponding cell line. Conclusion. A successful expression and presentation of multiple CTL epitope mini-gene in MHC class I allele specific human cell lines were demonstrated by an in vitro assay, which could be corresponding to the vaccination of CTL vaccines in people with different MHC I molecules. This work also suggested the possibility of constructing a multiple CTL epitope plasmodium falciparum DNA vaccine that could cover most of Chinese population.

  18. Human endogenous retrovirus type W (HERV-W) in schizophrenia: a new avenue of research at the gene-environment interface.

    Science.gov (United States)

    Leboyer, Marion; Tamouza, Ryad; Charron, Dominique; Faucard, Raphaél; Perron, Hervé

    2013-03-01

    Provide a synthetic review of recent studies evidencing an association between human endogenous retrovirus-W (HERV-W) and schizophrenia. Bibliography analysis and contextual synthesis. Epidemiological studies suggest that the aetiology of schizophrenia is complex and involves a complex interplay of genetic and environmental factors such as infections. Eight percentof the human genome consists of human endogenous retroviruses (HERV), and this part of the genome was previously thought to be without importance, but new research has refuted this. HERVs share similarities with viruses and it is assumed that HERVs are present in the genome as a result of retroviruses infecting germ line cells many million years ago. A specific type of HERVs, called HERV-W, has through several recent studies been associated with schizophrenia. Elevated transcription of HERV-W elements has been documented, and antigens of HERV-W envelope and capsid proteins have been found in blood samples from patients. Viruses that have been implicated in pathology of schizophrenia, such as herpes and influenza, have been shown to activate HERV-W elements, and such activation has been associated with elevated biomarkers of systemic inflammation. New research indicates that HERV-W may be an important genetic factor interplaying with the environmental risk factor of infections and that, through this, HERV-W may be important for disease pathogenesis. A lifelong scenario of a detrimental interaction between infectious agents and HERV-W genes may decipher the actual development and course of schizophrenia. Further research is needed to find out if specific treatment strategies could reduce the expression of HERV-W and if this will be associated with remission.

  19. Development of transgenic rats producing human β-amyloid precursor protein as a model for Alzheimer's disease: Transgene and endogenous APP genes are regulated tissue-specifically

    Directory of Open Access Journals (Sweden)

    Chan Anthony WS

    2008-02-01

    Full Text Available Abstract Background Alzheimer's disease (AD is a devastating neurodegenerative disorder that affects a large and growing number of elderly individuals. In addition to idiopathic disease, AD is also associated with autosomal dominant inheritance, which causes a familial form of AD (FAD. Some instances of FAD have been linked to mutations in the β-amyloid protein precursor (APP. Although there are numerous mouse AD models available, few rat AD models, which have several advantages over mice, have been generated. Results Fischer 344 rats expressing human APP driven by the ubiquitin-C promoter were generated via lentiviral vector infection of Fischer 344 zygotes. We generated two separate APP-transgenic rat lines, APP21 and APP31. Serum levels of human amyloid-beta (Aβ40 were 298 pg/ml for hemizygous and 486 pg/ml for homozygous APP21 animals. Serum Aβ42 levels in APP21 homozygous rats were 135 pg/ml. Immunohistochemistry in brain showed that the human APP transgene was expressed in neurons, but not in glial cells. These findings were consistent with independent examination of enhanced green fluorescent protein (eGFP in the brains of eGFP-transgenic rats. APP21 and APP31 rats expressed 7.5- and 3-times more APP mRNA, respectively, than did wild-type rats. Northern blots showed that the human APP transgene, driven by the ubiquitin-C promoter, is expressed significantly more in brain, kidney and lung compared to heart and liver. A similar expression pattern was also seen for the endogenous rat APP. The unexpected similarity in the tissue-specific expression patterns of endogenous rat APP and transgenic human APP mRNAs suggests regulatory elements within the cDNA sequence of APP. Conclusion This manuscript describes the generation of APP-transgenic inbred Fischer 344 rats. These are the first human AD model rat lines generated by lentiviral infection. The APP21 rat line expresses high levels of human APP and could be a useful model for AD. Tissue

  20. Matrix Metalloproteinase-3 (MMP-3) Is an Endogenous Activator of the MMP-9 Secreted by Placental Leukocytes: Implication in Human Labor.

    Science.gov (United States)

    Flores-Pliego, Arturo; Espejel-Nuñez, Aurora; Castillo-Castrejon, Marisol; Meraz-Cruz, Noemi; Beltran-Montoya, Jorge; Zaga-Clavellina, Veronica; Nava-Salazar, Sonia; Sanchez-Martinez, Maribel; Vadillo-Ortega, Felipe; Estrada-Gutierrez, Guadalupe

    2015-01-01

    The activity of matrix degrading enzymes plays a leading role in the rupture of the fetal membranes under normal and pathological human labor, and matrix metalloproteinase-9 (MMP-9) it is considered a biomarker of this event. To gain further insight into local MMP-9 origin and activation, in this study we analyzed the contribution of human placental leukocytes to MMP-9 secretion and explored the local mechanisms of the pro-enzyme activation. Placental blood leukocytes were obtained from women at term gestation without labor and maintained in culture up to 72 h. MMP-9 activity in the culture supernatants was determined by zymography and using a specific substrate. The presence of a potential pro-MMP-9 activator in the culture supernatants was monitored using a recombinant biotin-labeled human pro-MMP-9. To characterize the endogenous pro-MMP-9 activator, MMP-1, -3, -7 and -9 were measured by multiplex assay in the supernatants, and an inhibition assay of MMP-9 activation was performed using an anti-human MMP-3 and a specific MMP-3 inhibitor. Finally, production of MMP-9 and MMP-3 in placental leukocytes obtained from term pregnancies with and without labor was assessed by immunofluorescence. Placental leukocytes spontaneously secreted pro-MMP-9 after 24 h of culture, increasing significantly at 48 h (P≤0.05), when the active form of MMP-9 was detected. Culture supernatants activated the recombinant pro-MMP-9 showing that placental leukocytes secrete the activator. A significant increase in MMP-3 secretion by placental leukocytes was observed since 48 h in culture (P≤0.05) and up to 72 h (P≤0.001), when concentration reached its maximum value. Specific activity of MMP-9 decreased significantly (P≤0.005) when an anti-MMP-3 antibody or a specific MMP-3 inhibitor were added to the culture media. Placental leukocytes from term labor produced more MMP-9 and MMP-3 compared to term non-labor cells. In this work we confirm that placental leukocytes from human term

  1. Matrix Metalloproteinase-3 (MMP-3 Is an Endogenous Activator of the MMP-9 Secreted by Placental Leukocytes: Implication in Human Labor.

    Directory of Open Access Journals (Sweden)

    Arturo Flores-Pliego

    Full Text Available The activity of matrix degrading enzymes plays a leading role in the rupture of the fetal membranes under normal and pathological human labor, and matrix metalloproteinase-9 (MMP-9 it is considered a biomarker of this event. To gain further insight into local MMP-9 origin and activation, in this study we analyzed the contribution of human placental leukocytes to MMP-9 secretion and explored the local mechanisms of the pro-enzyme activation.Placental blood leukocytes were obtained from women at term gestation without labor and maintained in culture up to 72 h. MMP-9 activity in the culture supernatants was determined by zymography and using a specific substrate. The presence of a potential pro-MMP-9 activator in the culture supernatants was monitored using a recombinant biotin-labeled human pro-MMP-9. To characterize the endogenous pro-MMP-9 activator, MMP-1, -3, -7 and -9 were measured by multiplex assay in the supernatants, and an inhibition assay of MMP-9 activation was performed using an anti-human MMP-3 and a specific MMP-3 inhibitor. Finally, production of MMP-9 and MMP-3 in placental leukocytes obtained from term pregnancies with and without labor was assessed by immunofluorescence.Placental leukocytes spontaneously secreted pro-MMP-9 after 24 h of culture, increasing significantly at 48 h (P≤0.05, when the active form of MMP-9 was detected. Culture supernatants activated the recombinant pro-MMP-9 showing that placental leukocytes secrete the activator. A significant increase in MMP-3 secretion by placental leukocytes was observed since 48 h in culture (P≤0.05 and up to 72 h (P≤0.001, when concentration reached its maximum value. Specific activity of MMP-9 decreased significantly (P≤0.005 when an anti-MMP-3 antibody or a specific MMP-3 inhibitor were added to the culture media. Placental leukocytes from term labor produced more MMP-9 and MMP-3 compared to term non-labor cells.In this work we confirm that placental leukocytes from

  2. Gene-environment interactions in multiple sclerosis: Innate and adaptive immune responses to human endogenous retrovirus and herpesvirus antigens and the lectin complement activation pathway

    DEFF Research Database (Denmark)

    Christensen, Tove; Petersen, Thor; Thiel, Steffen

    2007-01-01

    Aspects of gene-environment interactions in multiple sclerosis (MS) were analysed in serum samples from 46 MS families (25 sporadic MS cases and 42 familial MS cases): antibodies to the MS-associated human endogenous retrovirus HERV-H, and levels of three components in the innate pathogen......-associated molecular pattern recognition: mannan-binding lectin (MBL), and MASP-2 and MASP-3. For representative MS families, we also determined herpesvirus serology for HSV-1, VZV, and EBV; and tissue typed for HLA-B, and HLA DR and DQ. In MS, a significant correlation between elevated immune reactivity to HERV-H Env......-H and the antiviral immune response may play a role in MS development, and also underline the tenuous nature of specific genetic contributions to this complex disease....

  3. Gene-environment interactions in multiple sclerosis: innate and adaptive immune responses to human endogenous retrovirus and herpesvirus antigens and the lectin complement activation pathway

    DEFF Research Database (Denmark)

    Christensen, Tove; Petersen, Thor; Thiel, Steffen

    2006-01-01

    Aspects of gene-environment interactions in multiple sclerosis (MS) were analysed in serum samples from 46 MS families (25 sporadic MS cases and 42 familial MS cases): antibodies to the MS-associated human endogenous retrovirus HERV-H, and levels of three components in the innate pathogen......-associated molecular pattern recognition: mannan-binding lectin (MBL), and MASP-2 and MASP-3. For representative MS families, we also determined herpesvirus serology for HSV-1, VZV, and EBV; and tissue typed for HLA-B, and HLA DR and DQ. In MS, a significant correlation between elevated immune reactivity to HERV-H Env...... immune response may play a role in MS development, and also underline the tenuous nature of specific genetic contributions to this complex disease. Udgivelsesdato: 2007-Feb...

  4. Cryogenic Hybrid Magnetic Bearing

    Science.gov (United States)

    Meeks, Crawford R.; Dirusso, Eliseo; Brown, Gerald V.

    1994-01-01

    Cryogenic hybrid magnetic bearing is example of class of magnetic bearings in which permanent magnets and electromagnets used to suspend shafts. Electromagnets provide active control of position of shaft. Bearing operates at temperatures from -320 degrees F (-196 degrees C) to 650 degrees F (343 degrees C); designed for possible use in rocket-engine turbopumps, where effects of cryogenic environment and fluid severely limit lubrication of conventional ball bearings. This and similar bearings also suitable for terrestrial rotating machinery; for example, gas-turbine engines, high-vacuum pumps, canned pumps, precise gimbals that suspend sensors, and pumps that handle corrosive or gritty fluids.

  5. Cryogenic regenerative heat exchangers

    CERN Document Server

    Ackermann, Robert A

    1997-01-01

    An in-depth survey of regenerative heat exchangers, this book chronicles the development and recent commercialization of regenerative devices for cryogenic applications. Chapters cover historical background, concepts, practical applications, design data, and numerical solutions, providing the latest information for engineers to develop advanced cryogenic machines. The discussions include insights into the operation of a regenerator; descriptions of the cyclic and fluid temperature distributions in a regenerator; data for various matrix geometries and materials, including coarse and fine bronze, stainless steel-woven wire mesh screens, and lead spheres; and unique operating features of cryocoolers that produce deviations from ideal regenerator theory.

  6. Simultaneous Activation of Nrf2 and Elevation of Dietary and Endogenous Antioxidant Chemicals for Cancer Prevention in Humans.

    Science.gov (United States)

    Prasad, Kedar N

    2016-01-01

    Despite extensive studies in cancer prevention, the incidence of cancer is increasing. We review studies that have identified several biochemical and genetic defects as well as potential carcinogens in the diet, environmental factors, and lifestyle-related habits. Two of the biochemical abnormalities increased oxidative stress and chronic inflammation, and chronic exposure to carcinogens and mutagens play a significant role in the initiation of multistage carcinogenesis. Therefore, attenuation of these biochemical defects may be useful in reducing the incidence of cancer. Activation of the transcriptional factor called nuclear factor (erythroid-derived 2)-like 2 (Nrf2), which enhances the levels of antioxidant enzymes and phase-2-detoxifying enzymes by complex mechanisms, may be one of the ways to reduce oxidative stress and chronic inflammation. Antioxidant enzymes destroy free radicals by catalysis, whereas phase-2-detoxifying enzymes remove potential carcinogens by converting them to harmless compounds for elimination from the body. However, increasing the levels of antioxidant enzymes by activating Nrf2 may not be sufficient to decrease oxidative stress and chronic inflammation optimally, because antioxidant chemicals, which are decreased in a high oxidative environment, must also be elevated. This review discusses the regulation of activation of Nrf2 and proposes a hypothesis that an elevation of the levels of antioxidant enzymes and dietary and endogenous antioxidant chemicals simultaneously may reduce the incidence of cancer by decreasing oxidative stress and chronic inflammation. The levels of antioxidant chemicals can be increased by supplementation, but increasing the levels of antioxidant enzymes requires activation of Nrf2 by reactive oxygen species (ROS)-dependent and-independent mechanisms. Several phytochemicals and antioxidant chemicals that activate Nrf2 have been identified. This review also describes clinical studies on antioxidants in cancer

  7. Human breast milk contamination with phthalates and alterations of endogenous reproductive hormones in infants three months of age

    DEFF Research Database (Denmark)

    Main, Katharina M; Mortensen, Gerda Krog; Kaleva, Marko M

    2006-01-01

    Phthalates adversely affect the male reproductive system in animals. We investigated whether phthalate monoester contamination of human breast milk had any influence on the postnatal surge of reproductive hormones in newborn boys as a sign of testicular dysgenesis.......Phthalates adversely affect the male reproductive system in animals. We investigated whether phthalate monoester contamination of human breast milk had any influence on the postnatal surge of reproductive hormones in newborn boys as a sign of testicular dysgenesis....

  8. Cryogenics Research and Engineering Experience

    Science.gov (United States)

    Toro Medina, Jaime A.

    2013-01-01

    Energy efficient storage, transfer and use of cryogens and cryogenic propellants on Earth and in space have a direct impact on NASA, government and commercial programs. Research and development on thermal insulation, propellant servicing, cryogenic components, material properties and sensing technologies provides industry, government and research institutions with the cross-cutting technologies to manage low-temperature applications. Under the direction of the Cryogenic Testing Lab at Kennedy Space Center, the work experience acquired allowed me to perform research, testing, design and analysis of current and future cryogenic technologies to be applied in several projects.

  9. Preliminary Thermal Design of Cryogenic Radiation Shielding

    Science.gov (United States)

    Li, Xiaoyi; Mustafi, Shuvo; Boutte, Alvin

    2015-01-01

    Cryogenic Hydrogen Radiation Shielding (CHRS) is the most mass efficient material radiation shielding strategy for human spaceflight beyond low Earth orbit (LEO). Future human space flight, mission beyond LEO could exceed one year in duration. Previous radiation studies showed that in order to protect the astronauts from space radiation with an annual allowable radiation dose less than 500 mSv, 140 kgm2 of polyethylene is necessary. For a typical crew module that is 4 meter in diameter and 8 meter in length. The mass of polyethylene radiation shielding required would be more than 17,500 kg. The same radiation study found that the required hydrogen shielding for the same allowable radiation dose is 40 kgm2, and the mass of hydrogen required would be 5, 000 kg. Cryogenic hydrogen has higher densities and can be stored in relatively small containment vessels. However, the CHRS system needs a sophisticated thermal system which prevents the cryogenic hydrogen from evaporating during the mission. This study designed a cryogenic thermal system that protects the CHRS from hydrogen evaporation for one to up to three year mission. The design also includes a ground based cooling system that can subcool and freeze liquid hydrogen. The final results show that the CHRS with its required thermal protection system is nearly half of the mass of polyethylene radiation shielding.

  10. Seals For Cryogenic Turbomachines

    Science.gov (United States)

    Hendricks, Robert C.; Tam, L. T.; Braun, M. J.; Vlcek, B. L.

    1988-01-01

    Analysis considers effects of seals on stability. Report presents method of calculation of flows of cryogenic fluids through shaft seals. Key to stability is local average velocity in seal. Local average velocity strongly influenced by effects of inlet and outlet and injection of fluid.

  11. High Power Cryogenic Targets

    Energy Technology Data Exchange (ETDEWEB)

    Gregory Smith

    2011-08-01

    The development of high power cryogenic targets for use in parity violating electron scattering has been a crucial ingredient in the success of those experiments. As we chase the precision frontier, the demands and requirements for these targets have grown accordingly. We discuss the state of the art, and describe recent developments and strategies in the design of the next generation of these targets.

  12. Cryogenic current leads

    Energy Technology Data Exchange (ETDEWEB)

    Zizek, F.

    1982-01-01

    Theoretical, technical and design questions are examined of cryogenic current leads for SP of magnetic systems. Simplified mathematical models are presented for the current leads. To illustrate modeling, the calculation is made of the real current leads for 500 A and three variants of current leads for 1500 A for the enterprise ''Shkoda.''

  13. Endogenous gustatory responses and gene expression profile of stably proliferating human taste cells isolated from fungiform papillae.

    Science.gov (United States)

    Hochheimer, Andreas; Krohn, Michael; Rudert, Kerstin; Riedel, Katja; Becker, Sven; Thirion, Christian; Zinke, Holger

    2014-05-01

    Investigating molecular mechanisms underlying human taste sensation requires functionally dedicated and at the same time proliferating human taste cells. Here, we isolated viable human fungiform taste papillae cells from biopsy samples, adenovirally transduced proliferation promoting genes, and obtained stably proliferating cell lines. Analysis of gene expression of 1 human taste cell line termed HTC-8 revealed that these cells express 13 TAS2R bitter taste receptor genes, CD36, OXTR encoding oxytocin receptor, as well as genes implicated with signal transduction and cell fate control. Bitter tastants triggered functionally distinct signaling pathways in HTC-8 cells. Salicin elicited phospholipase C-dependent calcium signaling and no cell depolarization. In contrast, stimulation with saccharin, aristolochic acid, or phenylthiocarbamide triggered cell depolarization and phospholipase C-independent calcium influx. Simultaneous stimulation with salicin and saccharin revealed that saccharin can enhance the phospholipase C-dependent response to salicin indicating crosstalk of signaling pathways. Our results show that HTC-8 cells are programmed to bitter taste reception but are also responsive to fatty acids, oxytocin, and somatosensory stimuli, whereas HTC-8 cells are insensitive to compounds representing other basic taste qualities.

  14. Derepression of an endogenous long terminal repeat activates the CSF1R proto-oncogene in human lymphoma

    NARCIS (Netherlands)

    Lamprecht, Bjoern; Walter, Korden; Kreher, Stephan; Kumar, Raman; Hummel, Michael; Lenze, Dido; Koechert, Karl; Bouhlel, Mohamed Amine; Richter, Julia; Soler, Eric; Stadhouders, Ralph; Joehrens, Korinna; Wurster, Kathrin D.; Callen, David F.; Harte, Michael F.; Giefing, Maciej; Barlow, Rachael; Stein, Harald; Anagnostopoulos, Ioannis; Janz, Martin; Cockerill, Peter N.; Siebert, Reiner; Doerken, Bernd; Bonifer, Constanze; Mathas, Stephan

    2010-01-01

    Mammalian genomes contain many repetitive elements, including long terminal repeats (LTRs), which have long been suspected to have a role in tumorigenesis. Here we present evidence that aberrant LTR activation contributes to lineage-inappropriate gene expression in transformed human cells and that s

  15. NMR identification of endogenous metabolites interacting with fatted and non-fatted human serum albumin in blood plasma: Fatty acids influence the HSA-metabolite interaction

    Science.gov (United States)

    Jupin, Marc; Michiels, Paul J.; Girard, Frederic C.; Spraul, Manfred; Wijmenga, Sybren S.

    2013-03-01

    Metabolites and their concentrations are direct reporters on body biochemistry. Thanks to technical developments metabolic profiling of body fluids, such as blood plasma, by for instance NMR has in the past decade become increasingly accurate enabling successful clinical diagnostics. Human Serum Albumin (HSA) is the main plasma protein (∼60% of all plasma protein) and responsible for the transport of endogenous (e.g. fatty acids) and exogenous metabolites, which it achieves thanks to its multiple binding sites and its flexibility. HSA has been extensively studied with regard to its binding of drugs (exogenous metabolites), but only to a lesser extent with regard to its binding of endogenous (non-fatty acid) metabolites. To obtain correct NMR measured metabolic profiles of blood plasma and/or potentially extract information on HSA and fatty acids content, it is necessary to characterize these endogenous metabolite/plasma protein interactions. Here, we investigate these metabolite-HSA interactions in blood plasma and blood plasma mimics. The latter contain the roughly twenty metabolites routinely detected by NMR (also most abundant) in normal relative concentrations with fatted or non-fatted HSA added or not. First, we find that chemical shift changes are small and seen only for a few of the metabolites. In contrast, a significant number of the metabolites display reduced resonance integrals and reduced free concentrations in the presence of HSA or fatted HSA. For slow-exchange (or strong) interactions, NMR resonance integrals report the free metabolite concentration, while for fast exchange (weak binding) the chemical shift reports on the binding. Hence, these metabolites bind strongly to HSA and/or fatted HSA, but to a limited degree because for most metabolites their concentration is smaller than the HSA concentration. Most interestingly, fatty acids decrease the metabolite-HSA binding quite significantly for most of the interacting metabolites. We further find

  16. Evaluation of CY3A activity in humans using three different parameters based on endogenous cortisol metabolism

    Institute of Scientific and Technical Information of China (English)

    Xi LUO; Xiao-min LI; Zhe-yi HU; Ze-neng CHENG

    2009-01-01

    Aim: Currently, there is considerable debate as to which method is more accurate for measuring the activity of CYP3A in vivo: cortisol 6β-hydroxylation clearance (CI_(m(6β))) or the urinary ratio of 6β-OHF to F (6β-OHF/F). Furthermore, the value of measuring endogenous levels of cortisol over a 24 h period (AUC_F) needs to be confirmed. The aim of the present study was to determine which method was most effective at measuring changes in the in vivo activity of CYP3A: AUC_F, CI_(m(6β)), or 6β-OHF/F. Methods: A two phase, cross-over design was adopted in this study. A total of 24 subjects (12 males and 12 females) were randomly assigned to one of two groups: the test group subjects were given 250 mg clarithromycin tablets twice a day for a period of 4 d, whereas the control group received a placebo twice daily for a similar period. On d 5 of the study, the last dose of either clarithromycin or placebo was supplemented with an oral dose of 7.5 mg midazolam (MDZ); blood and urine samples were then collected at various times. All samples collected at the same sampling times on d 4 were used to evaluate the effects of MDZ administration on cortisol levels and metabolism. The ratio of 1-hydroxymidazolam (1-OHMDZ) concentration to MDZ concentration at 1 h (MR) was taken as a measure of the in vivo CYP3A activity. AUC_F, CI_(m(6β)), and 6β-OHF/F were also used as biomarkers for CYP3A activity. Results: No correlations were found (either before or after inhibition) between CYP3A activity and any of the following measures: AUC_F, CI_(m(6β)), or 6β-OHF/F (r0.05). After 4 d of clarithromycin administration, CYP3A activity (MR) decreased by 75% (P=0.000), whereas AUC_F increased by 19%(P=0.040), and CI_(m(6β)) and 6β-OHF/F decreased by 54.2% (P=0.000) and 50% (P=0.003), respectively. No significant changes in AUC_F(P=0.178), or in the amount of urinary 6β-OHF (P=0.169), or in F(P=0.391) were found over a 24 h time period, either with or without MDZ administration

  17. Development of an androgen reporter gene assay (AR-LUX) utilizing a human cell line with an endogenously regulated androgen receptor.

    Science.gov (United States)

    Blankvoort, B M; de Groene, E M; van Meeteren-Kreikamp, A P; Witkamp, R F; Rodenburg, R J; Aarts, J M

    2001-11-01

    The aim of the work described in this report is to develop and characterize a cell-based androgen reporter assay. For this purpose, the androgen receptor (AR) expressing human breast cancer cell line T47D was stably transfected with a luciferase gene under transcriptional control of the PB-ARE-2 androgen response element. The application of this cell line in an endogenous Androgen Receptor-mediated LUciferase eXpression assay (AR-LUX) was validated. An EC50 value of 86 pM was determined for the standard androgen R1881 with a detection limit of 46 pM. Other androgens like dihydrotestosterone, 17beta-trenbolone, and bolasterone also induced luciferase expression, while anti-androgens suppressed these responses. As expected, AR-mediated responses were also elicited by high concentrations of the steroids progesterone, 17beta-estradiol, d-aldosterone, and dexamethasone, with observed EC50 values 10 to 350,000 times higher than that for R1881. A unique feature of the AR-LUX assay is that effects on modulation of active endogenous AR-levels are reliably reflected in the luciferase induction response, as exemplified by vitamin D, all-trans-retinoic acid, epigallocatechin gallate, and forskolin. This feature is especially useful when assessing complex mixtures, e.g., environmental samples or natural compound libraries. From these data it is concluded that the AR-LUX assay is a reliable in vitro test system for the detection and quantification of AR-mediated biological effects. The 96-well plate format makes the assay particularly suitable for high-throughput screening.

  18. Comprehensive analysis of human endogenous retrovirus group HERV-W locus transcription in multiple sclerosis brain lesions by high-throughput amplicon sequencing.

    Science.gov (United States)

    Schmitt, Katja; Richter, Christin; Backes, Christina; Meese, Eckart; Ruprecht, Klemens; Mayer, Jens

    2013-12-01

    Human endogenous retroviruses (HERVs) of the HERV-W group comprise hundreds of loci in the human genome. Deregulated HERV-W expression and HERV-W locus ERVWE1-encoded Syncytin-1 protein have been implicated in the pathogenesis of multiple sclerosis (MS). However, the actual transcription of HERV-W loci in the MS context has not been comprehensively analyzed. We investigated transcription of HERV-W in MS brain lesions and white matter brain tissue from healthy controls by employing next-generation amplicon sequencing of HERV-W env-specific reverse transcriptase (RT) PCR products, thus revealing transcribed HERV-W loci and the relative transcript levels of those loci. We identified more than 100 HERV-W loci that were transcribed in the human brain, with a limited number of loci being predominantly transcribed. Importantly, relative transcript levels of HERV-W loci were very similar between MS and healthy brain tissue samples, refuting deregulated transcription of HERV-W env in MS brain lesions, including the high-level-transcribed ERVWE1 locus encoding Syncytin-1. Quantitative RT-PCR likewise did not reveal differences in MS regarding HERV-W env general transcript or ERVWE1- and ERVWE2-specific transcript levels. However, we obtained evidence for interindividual differences in HERV-W transcript levels. Reporter gene assays indicated promoter activity of many HERV-W long terminal repeats (LTRs), including structurally incomplete LTRs. Our comprehensive analysis of HERV-W transcription in the human brain thus provides important information on the biology of HERV-W in MS lesions and normal human brain, implications for study design, and mechanisms by which HERV-W may (or may not) be involved in MS.

  19. Modulating Endogenous Electric Currents in Human Corneal Wounds—A Novel Approach of Bioelectric Stimulation Without Electrodes

    Science.gov (United States)

    Reid, Brian; Graue-Hernandez, Enrique O.; Mannis, Mark J.; Zhao, Min

    2011-01-01

    Purpose To measure electric current in human corneal wounds and test the feasibility of pharmacologically enhancing the current to promote corneal wound healing. Methods Using a noninvasive vibrating probe, corneal electric current was measured before and after wounding of the epithelium of donated postmortem human corneas. The effects of drug aminophylline and chloride-free solution on wound current were also tested. Results Unwounded cornea had small outward currents (0.07 μA/cm2). Wounding increased the current more than 5 fold (0.41 μA/cm2). Monitoring the wound current over time showed that it seemed to be actively regulated and maintained above normal unwounded levels for at least 6 hours. The time course was similar to that previously measured in rat cornea. Drug treatment or chloride-free solution more than doubled the size of wound currents. Conclusions Electric current at human corneal wounds can be significantly increased with aminophylline or chloride-free solution. Because corneal wound current directly correlates with wound healing rate, our results suggest a role for chloride-free and/or aminophylline eyedrops to enhance healing of damaged cornea in patients with reduced wound healing such as the elderly or diabetic patient. This novel approach offers bioelectric stimulation without electrodes and can be readily tested in patients. PMID:21099404

  20. Stem/progenitor cells in the cerebral cortex of the human preterm: a resource for an endogenous regenerative neuronal medicine?

    Directory of Open Access Journals (Sweden)

    Laura Vinci

    2016-04-01

    Full Text Available The development of the central nervous system represents a very delicate period of embryogenesis. Premature interruption of neurogenesis in human preterm newborns can lead to motor deficits, including cerebral palsy, and significant cognitive, behavioral or sensory deficits in childhood. Preterm infants also have a higher risk of developing neurodegenerative diseases later in life. In the last decade, great importance has been given to stem/progenitor cells and their possible role in the development and treatment of several neurological disorders. Several studies, mainly carried out on experimental models, evidenced that immunohistochemistry may allow the identification of different neural and glial precursors inside the developing cerebral cortex. However, only a few studies have been performed on markers of human stem cells in the embryonic period.This review aims at illustrating the importance of stem/progenitor cells in cerebral cortex during pre- and post-natal life. Defining the immunohistochemical markers of stem/progenitor cells in the human cerebral cortex during development may be important to develop an “endogenous” target therapy in the perinatal period. Proceedings of the 2nd International Course on Perinatal Pathology (part of the 11th International Workshop on Neonatology · October 26th-31st, 2015 · Cagliari (Italy · October 31st, 2015 · Stem cells: present and future Guest Editors: Gavino Faa, Vassilios Fanos, Antonio Giordano

  1. Human α1-antitrypin binds to heat-shock protein gp96 and protects from endogenous gp96-mediated injury in vivo

    Directory of Open Access Journals (Sweden)

    Eli Chaim Lewis

    2013-10-01

    Full Text Available The extracellular form of the abundant heat shock protein, gp96, is involved in human autoimmune pathologies. In patients with type 1 diabetes, circulating gp96 is found to be elevated, and is bound to the acute-phase protein, α1-antitrypsin (AAT. The two molecules also engage intracellularly during the physiological folding of AAT. AAT therapy promotes pancreatic islet survival in both transplantation and autoimmune diabetes models, and several clinical trials are currently examining AAT therapy for individuals with type 1 diabetes. However, its mechanism of action is yet unknown. Here, we examine whether the protective activity of AAT is related to binding of extracellular gp96. Primary mouse islets, macrophages and dendritic cells were added recombinant gp96 in the presence of clinical-grade human AAT (hAAT, GlassiaTM, Kamada Ltd, Israel. Islet function was evaluated by insulin release. The effect of hAAT on IL-1β/IFNγ-induced gp96 cell surface levels was also evaluated. In vivo, skin transplants were performed for examination of robust immune responses, and systemic inflammation was induced by cecal puncture. Endogenous gp96 was inhibited by gp96-inhibitory peptide (gp96i, Compugen Ltd., Israel in an allogeneic islet transplantation model. Our findings indicate that hAAT binds to gp96 and diminishes gp96-induced inflammatory responses; e.g., hAAT-treated gp96-stimulated islets released less pro-inflammatory cytokines (IL-1β by 6.16-fold and TNFα by 2.69-fold and regained gp96-disrupted insulin release. hAAT reduced cell activation during both skin transplantation and systemic inflammation, as well as lowered inducible surface levels of gp96 on immune cells. Finally, inhibition of gp96 significantly improved immediate islet graft function. These results suggest that hAAT is a regulator of gp96-mediated inflammatory responses, an increasingly appreciated endogenous damage response with relevance to human pathologies that are exacerbated

  2. Asymmetry of the endogenous opioid system in the human anterior cingulate: a putative molecular basis for lateralization of emotions and pain.

    Science.gov (United States)

    Watanabe, Hiroyuki; Fitting, Sylvia; Hussain, Muhammad Z; Kononenko, Olga; Iatsyshyna, Anna; Yoshitake, Takashi; Kehr, Jan; Alkass, Kanar; Druid, Henrik; Wadensten, Henrik; Andren, Per E; Nylander, Ingrid; Wedell, Douglas H; Krishtal, Oleg; Hauser, Kurt F; Nyberg, Fred; Karpyak, Victor M; Yakovleva, Tatjana; Bakalkin, Georgy

    2015-01-01

    Lateralization of the processing of positive and negative emotions and pain suggests an asymmetric distribution of the neurotransmitter systems regulating these functions between the left and right brain hemispheres. By virtue of their ability to selectively mediate euphoria, dysphoria, and pain, the μ-, δ-, and κ-opioid receptors and their endogenous ligands may subserve these lateralized functions. We addressed this hypothesis by comparing the levels of the opioid receptors and peptides in the left and right anterior cingulate cortex (ACC), a key area for emotion and pain processing. Opioid mRNAs and peptides and 5 "classical" neurotransmitters were analyzed in postmortem tissues from 20 human subjects. Leu-enkephalin-Arg (LER) and Met-enkephalin-Arg-Phe, preferential δ-/μ- and κ-/μ-opioid agonists, demonstrated marked lateralization to the left and right ACC, respectively. Dynorphin B (Dyn B) strongly correlated with LER in the left, but not in the right ACC suggesting different mechanisms of the conversion of this κ-opioid agonist to δ-/μ-opioid ligand in the 2 hemispheres; in the right ACC, Dyn B may be cleaved by PACE4, a proprotein convertase regulating left-right asymmetry formation. These findings suggest that region-specific lateralization of neuronal networks expressing opioid peptides underlies in part lateralization of higher functions, including positive and negative emotions and pain in the human brain.

  3. Human endogenous retrovirus W env increases nitric oxide production and enhances the migration ability of microglia by regulating the expression of inducible nitric oxide synthase

    Institute of Scientific and Technical Information of China (English)

    Ran Xiao; Shan Li; Qian Cao; Xiuling Wang; Qiujin Yan; Xiaoning Tu; Ying Zhu; Fan Zhu

    2017-01-01

    Human endogenous retrovirus W env (HERV-W env) plays a critical role in many neuropsychological diseases such as schizophrenia and multiple sclerosis (MS).These diseases are accompanied by immunological reactions in the central nervous system (CNS).Microglia are important immunocytes in brain inflammation that can produce a gasotransmitter-nitric oxide (NO).NO not only plays a role in the function of neuronal cells but also participates in the pathogenesis of various neuropsychological diseases.In this study,we reported increased NO production in CHME-5 microglia cells after they were transfected with HERV-W env.Moreover,HERV-W env increased the expression and function of human inducible nitric oxide synthase (hiNOS) and enhanced the promoter activity of hiNOS.Microglial migration was also enhanced.These data revealed that HERV-W env might contribute to increase NO production and microglial migration ability in neuropsychological disorders by regulating the expression of inducible NOS.Results from this study might lead to the identification of novel targets for the treatment of neuropsychological diseases,including neuroinflammatory diseases,stroke,and neurodegenerative diseases.

  4. Elevated endogenous expression of the dominant negative basic helix-loop-helix protein ID1 correlates with significant centrosome abnormalities in human tumor cells

    Directory of Open Access Journals (Sweden)

    Gutmann Anja

    2010-01-01

    Full Text Available Abstract Background ID proteins are dominant negative inhibitors of basic helix-loop-helix transcription factors that have multiple functions during development and cellular differentiation. Ectopic (over-expression of ID1 extends the lifespan of primary human epithelial cells. High expression levels of ID1 have been detected in multiple human malignancies, and in some have been correlated with unfavorable clinical prognosis. ID1 protein is localized at the centrosomes and forced (over-expression of ID1 results in errors during centrosome duplication. Results Here we analyzed the steady state expression levels of the four ID-proteins in 18 tumor cell lines and assessed the number of centrosome abnormalities. While expression of ID1, ID2, and ID3 was detected, we failed to detect protein expression of ID4. Expression of ID1 correlated with increased supernumerary centrosomes in most cell lines analyzed. Conclusions This is the first report that shows that not only ectopic expression in tissue culture but endogenous levels of ID1 modulate centrosome numbers. Thus, our findings support the hypothesis that ID1 interferes with centrosome homeostasis, most likely contributing to genomic instability and associated tumor aggressiveness.

  5. How Do the Richest 1% Owns 50% of Wealth in a Small-Open Growth Model with Endogenous Wealth and Human Capital

    Directory of Open Access Journals (Sweden)

    Wei-Bin Zhang

    2017-01-01

    Full Text Available This paper extends the growth model for a closed national economy by Zhang (2015 to a small-open economy. We attempt to explain some economic mechanisms of how the richest one per cent of the population own 50% of national wealth. We consider endogenous wealth and human capital accumulation by heterogeneous households with different preferences and learning abilities as the main determinants of growth and inequality. We describe the production technologies and economic structure on the basis of the Uzawa two-sector model. By applying Zhang’s concept of disposable income and approach to household behavior, we describe consumers’ wealth accumulation and consumption behavior. We model human capital accumulation on the basis of Arrow’s learning by doing and Zhang’s creativity with leisure. We simulate the model with three groups of the population, the rich 1 %, the middle 69%, and the poor 20%. We demonstrate the existence of an equilibrium point at which the rich 1% own more than half of the national wealth and the poor 20% less than 10% of the national wealth. We show how the system moves to the equilibrium from an initial state and confirm that the equilibrium point is stable. We also conduct comparative dynamic analysis.

  6. An approximation to the temporal order in endogenous circadian rhythms of genes implicated in human adipose tissue metabolism.

    Science.gov (United States)

    Garaulet, Marta; Ordovás, José M; Gómez-Abellán, Purificación; Martínez, Jose A; Madrid, Juan A

    2011-08-01

    Although it is well established that human adipose tissue (AT) shows circadian rhythmicity, published studies have been discussed as if tissues or systems showed only one or few circadian rhythms at a time. To provide an overall view of the internal temporal order of circadian rhythms in human AT including genes implicated in metabolic processes such as energy intake and expenditure, insulin resistance, adipocyte differentiation, dyslipidemia, and body fat distribution. Visceral and subcutaneous abdominal AT biopsies (n=6) were obtained from morbid obese women (BMI≥40 kg/m(2) ). To investigate rhythmic expression pattern, AT explants were cultured during 24-h and gene expression was analyzed at the following times: 08:00, 14:00, 20:00, 02:00 h using quantitative real-time PCR. Clock genes, glucocorticoid metabolism-related genes, leptin, adiponectin and their receptors were studied. Significant differences were found both in achrophases and relative-amplitude among genes (P30%). When interpreting the phase map of gene expression in both depots, data indicated that circadian rhythmicity of the genes studied followed a predictable physiological pattern, particularly for subcutaneous AT. Interesting are the relationships between adiponectin, leptin, and glucocorticoid metabolism-related genes circadian profiles. Their metabolic significance is discussed. Visceral AT behaved in a different way than subcutaneous for most of the genes studied. For every gene, protein mRNA levels fluctuated during the day in synchrony with its receptors. We have provided an overall view of the internal temporal order of circadian rhythms in human adipose tissue.

  7. Human eosinophil major basic protein is an endogenous allosteric antagonist at the inhibitory muscarinic M2 receptor.

    OpenAIRE

    Jacoby, D B; Gleich, G J; Fryer, A. D.

    1993-01-01

    The effect of human eosinophil major basic protein (MBP) as well as other eosinophil proteins, on binding of [3H]N-methyl-scopolamine ([3H]NMS: 1 x 10(-10) M) to muscarinic M2 receptors in heart membranes and M3 receptors in submandibular gland membranes was studied. MBP inhibited specific binding of [3H]NMS to M2 receptors but not to M3 receptors. MBP also inhibited atropine-induced dissociation of [3H]NMS-receptor complexes in a dose-dependent fashion, demonstrating that the interaction of ...

  8. Human endogenous retrovirus K(HML-2) Gag- and Env-specific T-cell responses are infrequently detected in HIV-1-infected subjects using standard peptide matrix-based screening

    NARCIS (Netherlands)

    R.B. Jones (R. Brad); V.M. John (Vivek); D.V. Hunter (Diana); E. Martin (Eric); S. Mujib (Shariq); V. Mihajlovic (Vesna); P.C. Burgers (Peter); T.M. Luider (Theo); G. Gyenes (Gabor); N.C. Sheppard (Neil); D. SenGupta (Devi); R. Tandon (Ravi); F.-Y. Yue (Feng-Yun); W.S. Benko (William); C. Kovacs (Carrie); R. Nixon; M.A. Ostrowski (Mario)

    2012-01-01

    textabstractT-cell responses to human endogenous retrovirus (HERV) K(HML-2) Gag and Env were mapped in HIV-1-infected subjects using 15mer peptides. Small peptide pools and high concentrations were used to maximize sensitivity. In the 23 subjects studied, only three bona fide HERV-K(HML-2)-specific

  9. Human endogenous retrovirus-FRD envelope protein (syncytin 2 expression in normal and trisomy 21-affected placenta

    Directory of Open Access Journals (Sweden)

    Handschuh Karen

    2008-01-01

    Full Text Available Abstract Human trophoblast expresses two fusogenic retroviral envelope proteins, the widely studied syncytin 1, encoded by HERV-W and the recently characterized syncytin 2 encoded by HERV-FRD. Here we studied syncytin 2 in normal and Trisomy 21-affected placenta associated with abnormal trophoblast differentiation. Syncytin 2 immunolocalization was restricted throughout normal pregnancy to some villous cytotrophoblastic cells (CT. During the second trimester of pregnancy, syncytin 2 was immunolocalized in some cuboidal CT in T21 placentas, whereas in normal placentas it was observed in flat CT, extending into their cytoplasmic processes. In vitro, CT isolated from normal placenta fuse and differentiate into syncytiotrophoblast. At the same time, syncytin 2 transcript levels decreased significantly with syncytiotrophoblast formation. In contrast, CT isolated from T21-affected placentas fused and differentiated poorly and no variation in syncytin 2 transcript levels was observed. Syncytin 2 expression illustrates the abnormal trophoblast differentiation observed in placenta of fetal T21-affected pregnancies.

  10. Human endogenous retrovirus-FRD envelope protein (syncytin 2) expression in normal and trisomy 21-affected placenta

    Science.gov (United States)

    Malassiné, André; Frendo, Jean-Louis; Blaise, Sandra; Handschuh, Karen; Gerbaud, Pascale; Tsatsaris, Vassilis; Heidmann, Thierry; Evain-Brion, Danièle

    2008-01-01

    Human trophoblast expresses two fusogenic retroviral envelope proteins, the widely studied syncytin 1, encoded by HERV-W and the recently characterized syncytin 2 encoded by HERV-FRD. Here we studied syncytin 2 in normal and Trisomy 21-affected placenta associated with abnormal trophoblast differentiation. Syncytin 2 immunolocalization was restricted throughout normal pregnancy to some villous cytotrophoblastic cells (CT). During the second trimester of pregnancy, syncytin 2 was immunolocalized in some cuboidal CT in T21 placentas, whereas in normal placentas it was observed in flat CT, extending into their cytoplasmic processes. In vitro, CT isolated from normal placenta fuse and differentiate into syncytiotrophoblast. At the same time, syncytin 2 transcript levels decreased significantly with syncytiotrophoblast formation. In contrast, CT isolated from T21-affected placentas fused and differentiated poorly and no variation in syncytin 2 transcript levels was observed. Syncytin 2 expression illustrates the abnormal trophoblast differentiation observed in placenta of fetal T21-affected pregnancies. PMID:18215254

  11. Influence of multiple injections of human chorionic gonadotropin (hCG) on urine and serum endogenous steroids concentrations.

    Science.gov (United States)

    Strahm, Emmanuel; Marques-Vidal, Pedro; Pralong, François; Dvorak, Jiri; Saugy, Martial; Baume, Norbert

    2011-12-10

    Since it is established that human chorionic gonadotropin (hCG) affects testosterone production and release in the human body, the use of this hormone as a performance enhancing drug has been prohibited by the World Anti-Doping Agency. Nowadays, the only validated biomarker of a hCG doping is its direct quantification in urine. However, this specific parameter is subjected to large inter-individual variability and its determination is directly dependent on the reliability of hCG immunoassays used. In order to counteract these weaknesses, new biomarkers need to be evidenced. To address this issue, a pilot clinical study was performed on 10 volunteers submitted to 3 subsequent hCG injections. Blood and urine samples were collected during two weeks in order to follow the physiological effects on related compounds such as the steroid profile or hormones involved in the hypothalamo-pituitary axis. The hCG pharmacokinetic observed in all subjects was, as expected, prone to important inter-individual variations. Using ROC plots, level of testosterone and testosterone on luteinizing hormone ratio in both blood and urine were found to be the most relevant biomarker of a hCG abuse, regardless of inter-individual variations. In conclusion, this study showed the crucial importance of reliable quantification methods to assess low differences in hormonal patterns. In regard to these results and to anti-doping requirements and constraints, blood together with urine matrix should be included in the anti-doping testing program. Together with a longitudinal follow-up approach it could constitute a new strategy to detect a hCG abuse, applicable to further forms of steroid or other forbidden drug manipulation.

  12. Cryogenic treatment of gas

    Science.gov (United States)

    Bravo, Jose Luis [Houston, TX; Harvey, III, Albert Destrehan; Vinegar, Harold J [Bellaire, TX

    2012-04-03

    Systems and methods of treating a gas stream are described. A method of treating a gas stream includes cryogenically separating a first gas stream to form a second gas stream and a third stream. The third stream is cryogenically contacted with a carbon dioxide stream to form a fourth and fifth stream. A majority of the second gas stream includes methane and/or molecular hydrogen. A majority of the third stream includes one or more carbon oxides, hydrocarbons having a carbon number of at least 2, one or more sulfur compounds, or mixtures thereof. A majority of the fourth stream includes one or more of the carbon oxides and hydrocarbons having a carbon number of at least 2. A majority of the fifth stream includes hydrocarbons having a carbon number of at least 3 and one or more of the sulfur compounds.

  13. Cryogenic Control System

    Energy Technology Data Exchange (ETDEWEB)

    Goloborod' ko, S.; /Fermilab

    1989-02-27

    The control system (CS) for the cryogenic arrangement of the DO Liquid Argon Calorimeter consists of a Texas instruments 560/565 Programmable Logical Controller (PLC), two remote bases with Remote Base Controllers and a corresponding set of input/output (I/O) modules, and a PC AST Premium 286 (IBM AT Compatible). The PLC scans a set of inputs and provides a set of outputs based on a ladder logic program and PID control loops. The inputs are logic or analog (current, voltage) signals from equipment status switches or transducers. The outputs are logic or analog (current or voltage) signals for switching solenoids and positioning pneumatic actuators. Programming of the PLC is preformed by using the TISOFT2/560/565 package, which is installed in the PC. The PC communicates to the PLC through a serial RS232 port and provides operator interface to the cryogenic process using Xpresslink software.

  14. Cryogenic treatment of gas

    Energy Technology Data Exchange (ETDEWEB)

    Bravo, Jose Luis [Houston, TX; Harvey, III, Albert Destrehan (Kingwood, TX); Vinegar, Harold J [Bellaire, TX

    2012-04-03

    Systems and methods of treating a gas stream are described. A method of treating a gas stream includes cryogenically separating a first gas stream to form a second gas stream and a third stream. The third stream is cryogenically contacted with a carbon dioxide stream to form a fourth and fifth stream. A majority of the second gas stream includes methane and/or molecular hydrogen. A majority of the third stream includes one or more carbon oxides, hydrocarbons having a carbon number of at least 2, one or more sulfur compounds, or mixtures thereof. A majority of the fourth stream includes one or more of the carbon oxides and hydrocarbons having a carbon number of at least 2. A majority of the fifth stream includes hydrocarbons having a carbon number of at least 3 and one or more of the sulfur compounds.

  15. Cryogenic Selective Surfaces

    Science.gov (United States)

    Youngquist, Robert; Nurge, Mark; Gibson, Tracy; Johnson, Wesley

    2017-01-01

    The NASA Innovative Advanced Concept (NIAC) program has been funding work at KSC on a novel coating that should allow cryogenic materials to be stored in deep space. The NIAC Symposium will be the last week of September and it is a requirement that the funded material be presented both orally and at a poster session. This DAA submission is requesting approval to go public with both the presentation and the poster.

  16. Cryogenic Test Technology 1984.

    Science.gov (United States)

    1985-04-01

    aircraft configuration Pathfinder II (Figure 16) made of Vascomax 200, a set of six bodies of revolution (Figure 17) made from 6061 aluminium alloy, a...iron and aluminium alloys appear to be viable candidates. AS loads increase the number of avail- able alloys is severely constrained by toughness...using A-286 screws in four steels and one aluminium alloy. In the absence of loads cryogenic cycling gene- rally produced decreases in breakaway

  17. Advances in Helium Cryogenics

    Science.gov (United States)

    Sciver, S. W. Van

    This review provides a survey of major advances that have occurred in recent years in the area of helium cryogenics. Helium-temperature cryogenics is the enabling technology for a substantial and growing number of low-temperature systems from superconducting magnets to space-based experimental facilities. In recent years there have been many advances in the technology of low-temperature helium, driven mostly by new applications. However, to keep the review from being too broad, this presentation focuses mainly on three of the most significant advances. These are: (1) the development of large-scale recuperative refrigeration systems mainly for superconducting magnet applications in accelerators and other research facilities; (2) the use of stored superfluid helium (He II) as a coolant for spacebased astrophysics experiments; and (3) the application of regenerative cryocoolers operating at liquid helium temperatures primarily for cooling superconducting devices. In each case, the reader should observe that critical technologies were developed to facilitate these applications. In addition to these three primary advances, other significant helium cryogenic technologies are briefly reviewed at the end of this chapter, along with some vision for future developments in these areas.

  18. Rapid and sensitive analysis of phthalate metabolites, bisphenol A, and endogenous steroid hormones in human urine by mixed-mode solid-phase extraction, dansylation, and ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry.

    Science.gov (United States)

    Wang, He-xing; Wang, Bin; Zhou, Ying; Jiang, Qing-wu

    2013-05-01

    Steroid hormone levels in human urine are convenient and sensitive indicators for the impact of phthalates and/or bisphenol A (BPA) exposure on the human steroid hormone endocrine system. In this study, a rapid and sensitive method for determination of 14 phthalate metabolites, BPA, and ten endogenous steroid hormones in urine was developed and validated on the basis of ultra-performance liquid chromatography coupled with electrospray ionization triple quadrupole mass spectrometry. The optimized mixed-mode solid phase-extraction separated the weakly acidic or neutral BPA and steroid hormones from acidic phthalate metabolites in urine: the former were determined in positive ion mode with a methanol/water mobile phase containing 10 mM ammonium formate; the latter were determined in negative ion mode with a acetonitrile/water mobile phase containing 0.1 % acetic acid, which significantly alleviated matrix effects for the analysis of BPA and steroid hormones. Dansylation of estrogens and BPA realized simultaneous and sensitive analysis of the endogenous steroid hormones and BPA in a single chromatographic run. The limits of detection were less than 0.84 ng/mL for phthalate metabolites and less than 0.22 ng/mL for endogenous steroid hormones and BPA. This proposed method had satisfactory precision and accuracy, and was successfully applied to the analyses of human urine samples. This method could be valuable when investigating the associations among endocrine-disrupting chemicals, endogenous steroid hormones, and relevant adverse outcomes in epidemiological studies.

  19. Aerogel Insulation to Support Cryogenic Technologies Project

    Data.gov (United States)

    National Aeronautics and Space Administration — NASA is seeking a high performance thermal insulation material for cryogenic applications in space launch development. Many of the components in cryogenic...

  20. Cryogenic Propellant Storage and Transfer Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The Cryogenic Propellant Storage and Transfer project will demonstrate the capability to safely and efficiently store, transfer and measure cryogenic propellants,...

  1. Human endogenous retrovirus expression is inversely related with the up-regulation of interferon-inducible genes in the skin of patients with lichen planus.

    Science.gov (United States)

    Nogueira, Marcelle Almeida de Sousa; Gavioli, Camila Fátima Biancardi; Pereira, Nátalli Zanete; de Carvalho, Gabriel Costa; Domingues, Rosana; Aoki, Valéria; Sato, Maria Notomi

    2015-04-01

    Lichen planus (LP) is a common inflammatory skin disease of unknown etiology. Reports of a common transactivation of quiescent human endogenous retroviruses (HERVs) support the connection of viruses to the disease. HERVs are ancient retroviral sequences in the human genome and their transcription is often deregulated in cancer and autoimmune diseases. We explored the transcriptional activity of HERV sequences as well as the antiviral restriction factor and interferon-inducible genes in the skin from LP patients and healthy control (HC) donors. The study included 13 skin biopsies from patients with LP and 12 controls. Real-time PCR assay identified significant decrease in the HERV-K gag and env mRNA expression levels in LP subjects, when compared to control group. The expressions of HERV-K18 and HERV-W env were also inhibited in the skin of LP patients. We observed a strong correlation between HERV-K gag with other HERV sequences, regardless the down-modulation of transcripts levels in LP group. In contrast, a significant up-regulation of the cytidine deaminase APOBEC 3G (apolipoprotein B mRNA-editing), and the GTPase MxA (Myxovirus resistance A) mRNA expression level was identified in the LP skin specimens. Other transcript expressions, such as the master regulator of type I interferon-dependent immune responses, STING (stimulator of interferon genes) and IRF-7 (interferon regulatory factor 7), IFN-β and the inflammassome NALP3, had increased levels in LP, when compared to HC group. Our study suggests that interferon-inducible factors, in addition to their role in innate immunity against exogenous pathogens, contribute to the immune control of HERVs. Evaluation of the balance between HERV and interferon-inducible factor expression could possibly contribute to surveillance of inflammatory/malignant status of skin diseases.

  2. 基于人力资本内生的工作搜寻行为研究%Job Searching Behavior Based on Endogenous Human Capital

    Institute of Scientific and Technical Information of China (English)

    肖超群; 周驰; 王秀兰

    2014-01-01

    Job search problem was investigated , in which the job provided by the firms can be either unskilled or skilled while the workers differ in their education level which can be either low -educated or high-educated .By allowing accumulation of human capital, on-the-job, job destruction shock, and death shock, a job search model on different kinds of workers was established according to the optimal principle .And the optimal search strategy was proposed .The structure proportion of the jobs affects whether the high -educated workers will choose the unskilled jobs , and it also yields a new insight on the growth rate of the human capital which is an endogenous variable .%通过研究公司提供非技术性或技术性的工资人力资本合同,风险中立的工人(低学历或高学历)寻找新工作机会下的工作搜寻问题,在允许人力资本累积、在职搜寻、失业冲击和退出冲击下,根据最优性原则,针对不同类别工人建立相应的工作搜寻模型并提出最优搜寻策略。证明了劳动力市场上各类工作的比例结构决定高学历工人是否会选择非技术性工作,并且得到工人人力资本的增长率是一内生变量的结论。

  3. Human endogenous retrovirus family HERV-K(HML-2) RNA transcripts are selectively packaged into retroviral particles produced by the human germ cell tumor line Tera-1 and originate mainly from a provirus on chromosome 22q11.21.

    Science.gov (United States)

    Ruprecht, Klemens; Ferreira, Humberto; Flockerzi, Aline; Wahl, Silke; Sauter, Marlies; Mayer, Jens; Mueller-Lantzsch, Nikolaus

    2008-10-01

    The human germ cell tumor line Tera-1 produces retroviral particles which are encoded by the human endogenous retrovirus family HERV-K(HML-2). We show here, by quantitative reverse transcriptase PCR, that HML-2 gag and env RNA transcripts are selectively packaged into Tera-1 retroviral particles, whereas RNAs from cellular housekeeping genes and from other HERV families (HERV-H and HERV-W) are nonselectively copackaged. Assignment of cloned HML-2 gag and env cDNAs from Tera-1 retroviral particles to individual HML-2 loci in the human genome demonstrated that HML-2 RNA transcripts packaged into Tera-1 retroviral particles originate almost exclusively from an HML-2 provirus on chromosome 22q11.21. Based on relative cloning frequencies, this provirus was the most active among a total of eight transcribed HML-2 loci identified in Tera-1 cells. These data suggest that at least one HML-2 element, that is, the HML-2 provirus on 22q11.21, has retained the capacity for packaging RNA into HML-2-encoded retroviral particles. Given its elevated transcriptional activity and the presence of a full-length Gag open reading frame, the 22q11.21 HML-2 provirus may also significantly contribute to Gag protein and thus particle production in Tera-1 cells. Our findings provide important clues to the generation and biological properties of HML-2-encoded particles. In addition, copackaging of non-HML-2 HERV transcripts in HML-2-encoded particles should inform the debate about endogenous retroviral particles putatively encoded by non-HML-2 HERV families that have previously been described for other human diseases, such as multiple sclerosis.

  4. The Cryogenic Supervision System in NSRRC

    CERN Document Server

    Li, Hsing-Chieh; Chiou, Wen-Song; Hsiao, Feng-Zone; Tsai, Zong-Da

    2005-01-01

    The helium cryogenic system in NSRRC is a fully automatic PLC system using the Siemens SIMATIC 300 controller. Modularization in both hardware and software makes it easy in the program reading, the system modification and the problem debug. Based on the Laview program we had developed a supervision system taking advantage of the Internet technology to get system's real-time information in any place. The functions of this supervision system include the real-time data accessing with more than 300 digital/analog signals, the data restore, the history trend display, and the human machine interface. The data is accessed via a Profibus line connecting the PLC system and the supervision system with a maximum baud rate 1.5 Mbit/s. Due to this supervision system, it is easy to master the status of the cryogenic system within a short time and diagnose the problem.

  5. Endogenous opiates and behavior: 2014.

    Science.gov (United States)

    Bodnar, Richard J

    2016-01-01

    This paper is the thirty-seventh consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2014 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (endogenous opioids and receptors), and the roles of these opioid peptides and receptors in pain and analgesia (pain and analgesia); stress and social status (human studies); tolerance and dependence (opioid mediation of other analgesic responses); learning and memory (stress and social status); eating and drinking (stress-induced analgesia); alcohol and drugs of abuse (emotional responses in opioid-mediated behaviors); sexual activity and hormones, pregnancy, development and endocrinology (opioid involvement in stress response regulation); mental illness and mood (tolerance and dependence); seizures and neurologic disorders (learning and memory); electrical-related activity and neurophysiology (opiates and conditioned place preferences (CPP)); general activity and locomotion (eating and drinking); gastrointestinal, renal and hepatic functions (alcohol and drugs of abuse); cardiovascular responses (opiates and ethanol); respiration and thermoregulation (opiates and THC); and immunological responses (opiates and stimulants). This paper is the thirty-seventh consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2014 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular

  6. An N-terminally truncated envelope protein encoded by a human endogenous retrovirus W locus on chromosome Xq22.3

    Directory of Open Access Journals (Sweden)

    Roebke Christina

    2010-08-01

    Full Text Available Abstract Background We previously showed that the envelope (env sequence of a human endogenous retrovirus (HERV-W locus on chromosome Xq22.3 is transcribed in human peripheral blood mononuclear cells. The env open reading frame (ORF of this locus is interrupted by a premature stop at codon 39, but otherwise harbors a long ORF for an N-terminally truncated 475 amino acid Env protein, starting at an in-frame ATG at codon 68. We set out to characterize the protein encoded by that ORF. Results Transient expression of the 475 amino acid Xq22.3 HERV-W env ORF produced an N-terminally truncated HERV-W Env protein, as detected by the monoclonal anti-HERV-W Env antibodies 6A2B2 and 13H5A5. Remarkably, reversion of the stop at codon 39 in Xq22.3 HERV-W env reconstituted a full-length HERV-W Xq22.3 Env protein. Similar to the full-length HERV-W Env protein Syncytin-1, reconstituted full-length Xq22.3 HERV-W Env is glycosylated, forms oligomers, and is expressed at the cell surface. In contrast, Xq22.3 HERV-W Env is unglycosylated, does not form oligomers, and is located intracellularly, probably due to lack of a signal peptide. Finally, we reconfirm by immunohistochemistry that monoclonal antibody 6A2B2 detects an antigen expressed in placenta and multiple sclerosis brain lesions. Conclusions A partially defective HERV-W env gene located on chromosome Xq22.3, which we propose to designate ERVWE2, has retained coding capacity and can produce ex vivo an N-terminally truncated Env protein, named N-Trenv. Detection of an antigen by 6A2B2 in placenta and multiple sclerosis lesions opens the possibility that N-Trenv could be expressed in vivo. More generally, our findings are compatible with the idea that defective HERV elements may be capable of producing incomplete HERV proteins that, speculatively, may exert functions in human physiology or pathology.

  7. Longitudinal monitoring of endogenous steroids in human serum by UHPLC-MS/MS as a tool to detect testosterone abuse in sports.

    Science.gov (United States)

    Ponzetto, Federico; Mehl, Florence; Boccard, Julien; Baume, Norbert; Rudaz, Serge; Saugy, Martial; Nicoli, Raul

    2016-01-01

    The detection of testosterone abuse in sports is routinely achieved through the 'steroidal module' of the Athlete Biological Passport by GC-MS(/MS) quantification of selected endogenous anabolic androgenic steroids (EAAS) from athletes' urines. To overcome some limitations of the "urinary steroid profile" such as the presence of confounding factors (ethnicity, enzyme polymorphism, bacterial contamination, and ethanol), ultrahigh performance liquid chromatography (UHPLC) measurements of blood concentrations of testosterone, its major metabolites, and precursors could represent an interesting and complementary strategy. In this work, two UHPLC-MS/MS methods were developed for the quantification of testosterone and related compounds in human serum, including major progestogens, corticoids, and estrogens. The validated methods were then used for the analyses of serum samples collected from 19 healthy male volunteers after oral and transdermal testosterone administration. Results from unsupervised multiway analysis allowed variations of target analytes to be assessed simultaneously over a 96-h time period. Except for alteration of concentration values due to the circadian rhythm, which concerns mainly corticosteroids, DHEA, and progesterone, significant variations linked to the oral and transdermal testosterone administration were observed for testosterone, DHT, and androstenedione. As a second step of analysis, the longitudinal monitoring of these biomarkers using intra-individual thresholds showed, in comparison to urine, significant improvements in the detection of testosterone administration, especially for volunteers with del/del genotype for phase II UGT2B17 enzyme, not sensitive to the main urinary marker, T/E ratio. A substantial extension of the detection window after transdermal testosterone administration was also observed in serum matrix. The longitudinal follow-up proposed in this study represents a first example of 'blood steroid profile' in doping control

  8. Role of the human endogenous retrovirus HERV-K18 in autoimmune disease susceptibility: study in the Spanish population and meta-analysis.

    Science.gov (United States)

    de la Hera, Belén; Varadé, Jezabel; García-Montojo, Marta; Lamas, José Ramón; de la Encarnación, Ana; Arroyo, Rafael; Fernández-Gutiérrez, Benjamín; Alvarez-Lafuente, Roberto; Urcelay, Elena

    2013-01-01

    Human endogenous retroviruses (HERVs) are genomic sequences that resulted from ancestral germ-line infections by exogenous retroviruses and therefore are transmitted in a Mendelian fashion. Increased HERV expression and antibodies to HERV antigens have been found in various autoimmune diseases. HERV-K18 in chromosome 1 was previously associated with type one diabetes and multiple sclerosis (MS). The etiology of these complex conditions has not been completely elucidated even after the powerful genome wide association studies (GWAS) performed. Nonetheless, this approach does not scrutinize the repetitive sequences within the genome, and part of the missing heritability could lie behind these sequences. We aimed at evaluating the role of HERV-K18 in chromosome 1 on autoimmune disease susceptibility. Two HERV-K18 SNPs (97Y/C and 154W/Stop substitutions) conforming three haplotypes were genotyped in Spanish cohorts of multiple sclerosis (n = 942), rheumatoid arthritis (n = 462) and ethnically matched controls (n = 601). Our findings were pooled in a meta-analysis including 5312 autoimmune patients and 4032 controls. Significant associations of both HERV-K18 polymorphisms in chromosome 1 with MS patients stratified by HLA-DRB1*15:01 were observed [97Y/C p = 0.02; OR (95% CI) = 1.5 (1.04-2.17) and 154W/Stop: p = 0.001; OR (95% CI) = 1.6 (1.19-2.16)]. Combined meta-analysis of the previously published association studies of HERV-K18 with different autoimmune diseases, together with data derived from Spanish cohorts, yielded a significant association of the HERV-K18.3 haplotype [97Y-154W: p(M-H) = 0.0008; OR(M-H) (95% CI) = 1.22 (1.09-1.38)]. Association of the HERV-K18.3 haplotype in chromosome 1 with autoimmune-disease susceptibility was confirmed through meta-analysis.

  9. The Protective Effects of N-Acetylcysteine on Exogenous Hydrogen Peroxide and Endogenous Superoxide Anion induced DNA Strand Breakage in Human Spermatozoa%`

    Institute of Scientific and Technical Information of China (English)

    徐德祥; 沈汉民; 王俊南

    2001-01-01

    Objective To explore the protective effects of N-Acetylcysteine (NAC) on exogenous hydrogen peroxide and endogenous superoxide anion-induced DNA strand breakage in human spermatozoa by using the single-cell gel electropherosis (SCGE)Methods Sperm cells were exposed to 0. 5 mmol/L of H2O2 or 5. 0 mmol/L of β -NADPH with or without 0. 1, 0. 5, 1. 0 mmol/L of NAC. The percentage of sperm comet cells and the comet tail lengths were measured in the treated sperm cells by using SCGE.Results Both percentage of comet sperm nuclei and mean tail length in sperm cells exposed to 0. 5 mmol/L hydrogen peroxide with different concentrations of NAC decrease significantly in a dose-dependent manner as compared with sperm cells exposed to H2O2 without NAC or catalase. Although mean tail length in sperm cells exposed to 5. 0 mmol/L of β-NADPH with different concentrations of NAC decreases significantly compared with sperm cells exposed to β-NADPH without NAC or SOD,there were no significant differences on the percentage of sperm comet cells between sperm cells exposed to 5. 0 mmol/L of β-NADPH with different concentrations of NAC and sperm cells exposed to 5. 0 mmol/L of β-NADPH without NAC.Conclusion NAC has a protective effect on exogenous hydrogen peroxide-induced DNA damage, while protective effect of NAC against O2- induced DNA strand break age is significant but very weak.

  10. Cryogenic Piezoelectric Actuator

    Science.gov (United States)

    Jiang, Xiaoning; Cook, William B.; Hackenberger, Wesley S.

    2009-01-01

    In this paper, PMN-PT single crystal piezoelectric stack actuators and flextensional actuators were designed, prototyped and characterized for space optics applications. Single crystal stack actuators with footprint of 10 mm x10 mm and the height of 50 mm were assembled using 10 mm x10mm x0.15mm PMN-PT plates. These actuators showed stroke > 65 - 85 microns at 150 V at room temperature, and > 30 microns stroke at 77 K. Flextensional actuators with dimension of 10mm x 5 mm x 7.6 mm showed stroke of >50 microns at room temperature at driving voltage of 150 V. A flextensional stack actuator with dimension of 10 mm x 5 mm x 47 mm showed stroke of approx. 285 microns at 150 V at room temperature and > 100 microns at 77K under driving of 150 V should be expected. The large cryogenic stroke and high precision of these actuators are promising for cryogenic optics applications.

  11. The Endogenous Kalman Filter

    OpenAIRE

    Brad Baxter; Liam Graham; Stephen Wright

    2007-01-01

    We relax the assumption of full information that underlies most dynamic general equilibrium models, and instead assume agents optimally form estimates of the states from an incomplete information set. We derive a version of the Kalman filter that is endogenous to agents' optimising decisions, and state conditions for its convergence. We show the (restrictive) conditions under which the endogenous Kalman filter will at least asymptotically reveal the true states. In general we show that incomp...

  12. Genome-wide profiles of H2AX and γ-H2AX differentiate endogenous and exogenous DNA damage hotspots in human cells.

    Science.gov (United States)

    Seo, Jungmin; Kim, Sang Cheol; Lee, Heun-Sik; Kim, Jung Kyu; Shon, Hye Jin; Salleh, Nur Lina Mohd; Desai, Kartiki Vasant; Lee, Jae Ho; Kang, Eun-Suk; Kim, Jin Sung; Choi, Jung Kyoon

    2012-07-01

    Phosphorylation of the histone variant H2AX forms γ-H2AX that marks DNA double-strand break (DSB). Here, we generated the sequencing-based maps of H2AX and γ-H2AX positioning in resting and proliferating cells before and after ionizing irradiation. Genome-wide locations of possible endogenous and exogenous DSBs were identified based on γ-H2AX distribution in dividing cancer cells without irradiation and that in resting cells upon irradiation, respectively. γ-H2AX-enriched regions of endogenous origin in replicating cells included sub-telomeres and active transcription start sites, apparently reflecting replication- and transcription-mediated stress during rapid cell division. Surprisingly, H2AX itself, prior to phosphorylation, was specifically located at these endogenous hotspots. This phenomenon was only observed in dividing cancer cells but not in resting cells. Endogenous H2AX was concentrated on the transcription start site of actively transcribed genes but was irrelevant to pausing of RNA polymerase II (pol II), which precisely coincided with γ-H2AX of endogenous origin. γ-H2AX enrichment upon irradiation also coincided with actively transcribed regions, but unlike endogenous γ-H2AX, it extended into the gene body and was not specifically concentrated on the pausing site of pol II. Sub-telomeres were less responsive to external DNA damage than to endogenous stress. Our findings provide insight into DNA repair programs of cancer and may have implications for cancer therapy.

  13. Nanodielectrics for Cryogenic Applications

    Energy Technology Data Exchange (ETDEWEB)

    Tuncer, Enis [ORNL; Sauers, Isidor [ORNL; James, David Randy [ORNL; Ellis, Alvin R [ORNL; Pace, Marshall O [ORNL; More, Karren [Oak Ridge National Laboratory (ORNL); Sathyamurthy, Srivatsan [University of Tennessee, Knoxville (UTK); Woodward, Jonathan [ORNL; Rondinone, Adam Justin [ORNL

    2009-01-01

    In this paper we report the recent advances in nanodielectrics that were developed and tested for cryogenic dielectric applications. The systems studied are composed of nanometer size particles. Particles were produced using either an ex-situ or in-situ technique. It is observed that there are clear differences in the structural properties of materials produced using these two approaches. Either no significant degradation or improvement in the electrical insulation properties were observed for ex-situ nano-particle samples processed with an ultrasonic processor and in-situ nano-particle samples. Nanodielectrics have the potential to be tailored with better thermal and mechanical properties without losing their electrical insulation characteristics.

  14. Cryogenic Cam Butterfly Valve

    Science.gov (United States)

    McCormack, Kenneth J. (Inventor)

    2016-01-01

    A cryogenic cam butterfly valve has a body that includes an axially extending fluid conduit formed there through. A disc lug is connected to a back side of a valve disc and has a circular bore that receives and is larger than a cam of a cam shaft. The valve disc is rotatable for a quarter turn within the body about a lug axis that is offset from the shaft axis. Actuating the cam shaft in the closing rotational direction first causes the camming side of the cam of the cam shaft to rotate the disc lug and the valve disc a quarter turn from the open position to the closed position. Further actuating causes the camming side of the cam shaft to translate the valve disc into sealed contact with the valve seat. Opening rotational direction of the cam shaft reverses these motions.

  15. Cryogenic Tracking Detectors

    CERN Multimedia

    Luukka, P R; Tuominen, E M; Mikuz, M

    2002-01-01

    The recent advances in Si and diamond detector technology give hope of a simple solution to the radiation hardness problem for vertex trackers at the LHC. In particular, we have recently demonstrated that operating a heavily irradiated Si detector at liquid nitrogen (LN$_2$) temperature results in significant recovery of Charge Collection Efficiency (CCE). Among other potential benefits of operation at cryogenic temperatures are the use of large low-resistivity wafers, simple processing, higher and faster electrical signal because of higher mobility and drift velocity of carriers, and lower noise of the readout circuit. A substantial reduction in sensor cost could result The first goal of the approved extension of the RD39 program is to demonstrate that irradiation at low temperature in situ during operation does not affect the results obtained so far by cooling detectors which were irradiated at room temperature. In particular we shall concentrate on processes and materials that could significantly reduce th...

  16. Endogenous formation of dimethylamine.

    Science.gov (United States)

    Zeisel, S H; DaCosta, K A; Fox, J G

    1985-01-01

    An understanding of the biosynthesis and metabolism of dimethylamine (DMA) is important because it is a precursor of dimethylnitrosamine (nitroso-DMA). DMA is the major short-chain aliphatic amine in human and rat urine. DMA is formed from trimethylamine (TMA), which, in turn, is a breakdown product of dietary choline. Enzymes within gut bacteria catalyse both of these reactions; it is not known whether mammalian cells can form DMA. To determine the relative importance of dietary choline, bacteria and other mechanisms for the formation of DMA, we measured DMA excretion in the urine of rats fed on a diet devoid of choline, and in urine of rats with no bacterial colonization of the intestines. We also describe an improved gas-chromatographic method for the measurement of methylamines in biological fluids. In control rats there were significant amounts of DMA within several biological fluids [urine, 54.2 +/- 3.0 mumol/kg body wt. per 24 h (556.2 +/- 37.5 nmol/ml); blood, 18.8 +/- 1.9 nmol/ml; gastric juice, 33.5 +/- 10.5 nmol/ml; means +/- S.E.M.]. Animals eating a diet containing no choline excreted as much MMA and DMA as did choline-supplemented rats (25-35 mumol/kg per 24 h), and they excreted slightly less TMA (2 versus 2.5 mumol/kg per 24 h). Rats with no gut bacteria excreted the same amount of DMA in their urine as did the control animals (45-55 mumol/kg per 24 h). They excreted much less MMA (16.3 +/- 1.5 versus 40.3 +/- 2.6 mumol/kg per 24 h; mean +/- S.E.M.; P less than 0.01), TMA (0.7 +/- 0.2 versus 2.5 +/- 0.5 mumol/kg per 24 h; mean +/- S.E.M.; P less than 0.01) and piperidine (2.0 +/- 0.3 versus 6.3 +/- 0.6 mumol/kg per 24 h; mean +/- S.E.M.; P less than 0.01) in their urine. From our studies we conclude that DMA is present in significant amounts within gastric fluid, an environment that is ideal for nitrosamine formation (under acidic conditions, nitroso-DMA is chemically formed by the reaction of nitrite with DMA). Results also indicate that dietary

  17. A Cryogenic Flow Sensor Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Based on the success of the phase I effort, Advanced Technologies Group, Inc. proposes the development of a Cryogenic Flow Sensor (CFS) for determining mass flow of...

  18. Cryogenic Acoustic Suppression Testing Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed project will explore and test the feasibility and effectiveness of using a cryogenic fluid (liquid nitrogen) to facilitate acoustic suppression in a...

  19. Cryogenic MEMS Pressure Sensor Project

    Data.gov (United States)

    National Aeronautics and Space Administration — A directly immersible cryogenic MEMS pressure sensor will be developed. Each silicon die will contain a vacuum-reference and a tent-like membrane. Offsetting thermal...

  20. Lightweight Inflatable Cryogenic Tank Project

    Data.gov (United States)

    National Aeronautics and Space Administration — This proposal describes the development of an inflatable and lightweight polymer-fabric structured pressure vessel designed for the containment of cryogenic fluids....

  1. Cryogenic Systems and Superconductive Power

    Science.gov (United States)

    The report defines, investigates, and experimentally evaluates the key elements of a representative crogenic turborefrigerator subsystem suitable for providing reliable long-lived cryogenic refrigeration for a superconductive ship propulsion system.

  2. Expression and activation by Epstein Barr virus of human endogenous retroviruses-W in blood cells and astrocytes: inference for multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Giuseppe Mameli

    Full Text Available BACKGROUND: Proposed co-factors triggering the pathogenesis of multiple sclerosis (MS are the Epstein Barr virus (EBV, and the potentially neuropathogenic MSRV (MS-associated retrovirus and syncytin-1, of the W family of human endogenous retroviruses. METHODOLOGY/PRINCIPAL FINDINGS: In search of links, the expression of HERV-W/MSRV/syncytin-1, with/without exposure to EBV or to EBV glycoprotein350 (EBVgp350, was studied on peripheral blood mononuclear cells (PBMC from healthy volunteers and MS patients, and on astrocytes, by discriminatory env-specific RT-PCR assays, and by flow cytometry. Basal expression of HERV-W/MSRV/syncytin-1 occurs in astrocytes and in monocytes, NK, and B, but not in T cells. This uneven expression is amplified in untreated MS patients, and dramatically reduced during therapy. In astrocytes, EBVgp350 stimulates the expression of HERV-W/MSRV/syncytin-1, with requirement of the NF-κB pathway. In EBVgp350-treated PBMC, MSRVenv and syncytin-1 transcription is activated in B cells and monocytes, but not in T cells, nor in the highly expressing NK cells. The latter cells, but not the T cells, are activated by proinflammatory cytokines. CONCLUSIONS/SIGNIFICANCE: In vitro EBV activates the potentially immunopathogenic and neuropathogenic HERV-W/MSRV/syncytin-1, in cells deriving from blood and brain. In vivo, pathogenic outcomes would depend on abnormal situations, as in late EBV primary infection, that is often symptomatic, or/and in the presence of particular host genetic backgrounds. In the blood, HERV-Wenv activation might induce immunopathogenic phenomena linked to its superantigenic properties. In the brain, toxic mechanisms against oligodendrocytes could be established, inducing inflammation, demyelination and axonal damage. Local stimulation by proinflammatory cytokines and other factors might activate further HERV-Ws, contributing to the neuropathogenity. In MS pathogenesis, a possible model could include EBV as

  3. Role of the human endogenous retrovirus HERV-K18 in autoimmune disease susceptibility: study in the Spanish population and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Belén de la Hera

    Full Text Available BACKGROUND: Human endogenous retroviruses (HERVs are genomic sequences that resulted from ancestral germ-line infections by exogenous retroviruses and therefore are transmitted in a Mendelian fashion. Increased HERV expression and antibodies to HERV antigens have been found in various autoimmune diseases. HERV-K18 in chromosome 1 was previously associated with type one diabetes and multiple sclerosis (MS. The etiology of these complex conditions has not been completely elucidated even after the powerful genome wide association studies (GWAS performed. Nonetheless, this approach does not scrutinize the repetitive sequences within the genome, and part of the missing heritability could lie behind these sequences. We aimed at evaluating the role of HERV-K18 in chromosome 1 on autoimmune disease susceptibility. METHODS: Two HERV-K18 SNPs (97Y/C and 154W/Stop substitutions conforming three haplotypes were genotyped in Spanish cohorts of multiple sclerosis (n = 942, rheumatoid arthritis (n = 462 and ethnically matched controls (n = 601. Our findings were pooled in a meta-analysis including 5312 autoimmune patients and 4032 controls. RESULTS: Significant associations of both HERV-K18 polymorphisms in chromosome 1 with MS patients stratified by HLA-DRB1*15:01 were observed [97Y/C p = 0.02; OR (95% CI = 1.5 (1.04-2.17 and 154W/Stop: p = 0.001; OR (95% CI = 1.6 (1.19-2.16]. Combined meta-analysis of the previously published association studies of HERV-K18 with different autoimmune diseases, together with data derived from Spanish cohorts, yielded a significant association of the HERV-K18.3 haplotype [97Y-154W: p(M-H = 0.0008; OR(M-H (95% CI = 1.22 (1.09-1.38]. CONCLUSION: Association of the HERV-K18.3 haplotype in chromosome 1 with autoimmune-disease susceptibility was confirmed through meta-analysis.

  4. Structural analysis of the endogenous glycoallergen Hev b 2 (endo-β-1,3-glucanase) from Hevea brasiliensis and its recognition by human basophils

    OpenAIRE

    Rodríguez-Romero, Adela; Hernández-Santoyo, Alejandra; Fuentes-Silva, Deyanira; Palomares, Laura A.; Muñoz-Cruz, Samira; Yépez-Mulia, Lilian; Orozco-Martínez, Socorro

    2014-01-01

    This study describes the three-dimensional structure of the endogenous glycosylated allergen Hev b 2 (endo-β-1,3-glucanase), which exhibits three post-translational modifications that form a patch on the surface of the molecule that is proposed to be an allergenic IgE epitope.

  5. A Piezoelectric Cryogenic Heat Switch

    Science.gov (United States)

    Jahromi, Amir E.; Sullivan, Dan F.

    2014-01-01

    We have measured the thermal conductance of a mechanical heat switch actuated by a piezoelectric positioner, the PZHS (PieZo electric Heat Switch), at cryogenic temperatures. The thermal conductance of the PZHS was measured between 4 K and 10 K, and on/off conductance ratios greater than 100 were achieved when the positioner applied its maximum force of 8 N. We discuss the advantages of using this system in cryogenic applications, and estimate the ultimate performance of an optimized PZHS.

  6. Endogenous MOV10 inhibits the retrotransposition of endogenous retroelements but not the replication of exogenous retroviruses

    Science.gov (United States)

    2012-01-01

    Background The identification of cellular factors that regulate the replication of exogenous viruses and endogenous mobile elements provides fundamental understanding of host-pathogen relationships. MOV10 is a superfamily 1 putative RNA helicase that controls the replication of several RNA viruses and whose homologs are necessary for the repression of endogenous mobile elements. Here, we employ both ectopic expression and gene knockdown approaches to analyse the role of human MOV10 in the replication of a panel of exogenous retroviruses and endogenous retroelements. Results MOV10 overexpression substantially decreased the production of infectious retrovirus particles, as well the propagation of LTR and non-LTR endogenous retroelements. Most significantly, RNAi-mediated silencing of endogenous MOV10 enhanced the replication of both LTR and non-LTR endogenous retroelements, but not the production of infectious retrovirus particles demonstrating that natural levels of MOV10 suppress retrotransposition, but have no impact on infection by exogenous retroviruses. Furthermore, functional studies showed that MOV10 is not necessary for miRNA or siRNA-mediated mRNA silencing. Conclusions We have identified novel specificity for human MOV10 in the control of retroelement replication and hypothesise that MOV10 may be a component of a cellular pathway or process that selectively regulates the replication of endogenous retroelements in somatic cells. PMID:22727223

  7. Unemployment and endogenous growth

    NARCIS (Netherlands)

    van Schaik, A.B.T.M.; de Groot, H.L.F.

    1995-01-01

    In this paper we develop a two-sector endogenous growth model with a dual labour market, based on efficiency wages. Growth is driven by intentional R&D performed in the high-tech and high-wage sector. It is examined how a change in rivalry among firms affects simultaneously growth and unemployment.

  8. Evolution of endogenous analgesia

    NARCIS (Netherlands)

    Niesters, Marieke

    2014-01-01

    Endogenous pain modulation is a complex phenomenon involved in the perception of pain. It consists of top-down inhibitory and facilitatory pathways that originate at higher sites within the central nervous system and converge at dorsal horn neurons in the spinal cord, to modulate incoming afferent n

  9. Streptococcus agalactiae endogenous endophthalmitis

    OpenAIRE

    Saffra, Norman; Rakhamimov, Aleksandr; Husney, Robert; Ghitan, Monica

    2013-01-01

    Streptococcus agalactiae (SA) is a Group B Streptococcus, which is a common pathogen implicated in neonatal and geriatric sepsis. Endogenous bacterial endophthalmitis (EBE) is a condition that results from haematogenous seeding of the globe, during transient or persistent bacteremia. We document a case of a non-septic geriatric patient, who developed EBE after a transient bacteraemia with SA.

  10. Cryogenic holographic distortion testing

    Science.gov (United States)

    Michel, David G.

    1994-06-01

    Hughes cryogenic holographic test facility allows for the rapid characterization of optical components and mechanical structures at elevated and reduced temperatures. The facility consists of a 1.6 meter diameter thermal vacuum chamber, vibration isolated experiment test platform, and a holographic camera assembly. Temperatures as low as 12 Kelvin and as high as 350 Kelvin have been demonstrated. Complex aspheric mirrors are tested without the need for auxiliary null lenses and may be tested in either the polished or unpolished state. Structural elements such as optical benches, solar array panels, and spacecraft antennas have been tested. Types of materials tested include beryllium, silicon carbide, aluminum, graphite epoxy, silicon/aluminum matrix material and injection molded plastics. Sizes have ranged from 7 cm X 15 cm to 825 cm X 1125 cm and have weighed as little as 0.2 Kg and as much as 130 Kg. Surface figure changes as little as (lambda) /10 peak-to-valley ((lambda) equals .514 micrometers ) are routinely measured.

  11. Dual Cryogenic Capacitive Density Sensor

    Science.gov (United States)

    Youngquist, Robert; Mata, Carlos; Vokrot, Peter; Cox, Robert

    2009-01-01

    A dual cryogenic capacitive density sensor has been developed. The device contains capacitive sensors that monitor two-phase cryogenic flow density to within 1% accuracy, which, if temperature were known, could be used to determine the ratio of liquid to gas in the line. Two of these density sensors, located a known distance apart, comprise the sensor, providing some information on the velocity of the flow. This sensor was constructed as a proposed mass flowmeter with high data acquisition rates. Without moving parts, this device is capable of detecting the density change within a two-phase cryogenic flow more than 100 times a second. Detection is enabled by a series of two sets of five parallel plates with stainless steel, cryogenically rated tubing. The parallel plates form the two capacitive sensors, which are measured by electrically isolated digital electronics. These capacitors monitor the dielectric of the flow essentially the density of the flow and can be used to determine (along with temperature) the ratio of cryogenic liquid to gas. Combining this information with the velocity of the flow can, with care, be used to approximate the total two-phase mass flow. The sensor can be operated at moderately high pressures and can be lowered into a cryogenic bath. The electronics have been substantially improved over the older sensors, incorporating a better microprocessor, elaborate ground loop protection and noise limiting circuitry, and reduced temperature sensitivity. At the time of this writing, this design has been bench tested at room temperature, but actual cryogenic tests are pending

  12. Cryogenics bringing the temperature down, underground

    CERN Multimedia

    2005-01-01

    The first 600m of the LHC cryogenic distribution line (QRL), which will feed the accelerator's superconducting magnets, has passed initial validating tests of its mechanical design at room and cryogenic temperatures.

  13. Cryogenic engineering fifty years of progress

    CERN Document Server

    Reed, Richard

    2007-01-01

    Cryogenic Engineering: Fifty Years of Progress is a benchmark reference work which chronicles the major developments in the field. Starting with an historical background dating to the 1850s, this book reviews the development of data resources now available for cryogenic fields and properties of materials. The advances in cryogenic fundamentals are covered by reviews of cryogenic principles, cryogenic insulation, low-loss storage systems, modern liquefaction processes, helium cryogenics and low-temperature thermometry. Several well-established applications resulting from cryogenic advances include aerospace cryocoolers and refrigerators, use of LTS and HTS systems in electrical applications, and recent changes in cryopreservation. Extensive references are provided for the readers interested in the details of these cryogenic engineering advances.

  14. Stimulating endogenous cardiac regeneration

    Directory of Open Access Journals (Sweden)

    Amanda eFinan

    2015-09-01

    Full Text Available The healthy adult heart has a low turnover of cardiac myocytes. The renewal capacity, however, is augmented after cardiac injury. Participants in cardiac regeneration include cardiac myocytes themselves, cardiac progenitor cells, and peripheral stem cells, particularly from the bone marrow compartment. Cardiac progenitor cells and bone marrow stem cells are augmented after cardiac injury, migrate to the myocardium, and support regeneration. Depletion studies of these populations have demonstrated their necessary role in cardiac repair. However, the potential of these cells to completely regenerate the heart is limited. Efforts are now being focused on ways to augment these natural pathways to improve cardiac healing, primarily after ischemic injury but in other cardiac pathologies as well. Cell and gene therapy or pharmacological interventions are proposed mechanisms. Cell therapy has demonstrated modest results and has passed into clinical trials. However, the beneficial effects of cell therapy have primarily been their ability to produce paracrine effects on the cardiac tissue and recruit endogenous stem cell populations as opposed to direct cardiac regeneration. Gene therapy efforts have focused on prolonging or reactivating natural signaling pathways. Positive results have been demonstrated to activate the endogenous stem cell populations and are currently being tested in clinical trials. A potential new avenue may be to refine pharmacological treatments that are currently in place in the clinic. Evidence is mounting that drugs such as statins or beta blockers may alter endogenous stem cell activity. Understanding the effects of these drugs on stem cell repair while keeping in mind their primary function may strike a balance in myocardial healing. To maximize endogenous cardiac regeneration,a combination of these approaches couldameliorate the overall repair process to incorporate the participation ofmultiple cell players.

  15. Endogenizing technological progress: The MESEMET model

    NARCIS (Netherlands)

    P.A.G. van Bergeijk (Peter); G.H.A. van Hagen; R.A. de Mooij (Ruud); J. van Sinderen (Jarig)

    1997-01-01

    textabstractThis paper endogenizes technology and human capital formation in the MESEM model that was developed by van Sinderen (Economic Modelling, 1993, 13, 285-300). Tax allowances for private R&D expenditures and public expenditures on both education and R& D are effective instruments to stimula

  16. Human Endogenous Retrovirus K(HML-2) Gag- and Env-Specific T-Cell Responses Are Infrequently Detected in HIV-1-Infected Subjects Using Standard Peptide Matrix-Based Screening

    Science.gov (United States)

    John, Vivek M.; Hunter, Diana V.; Martin, Eric; Mujib, Shariq; Mihajlovic, Vesna; Burgers, Peter C.; Luider, Theo M.; Gyenes, Gabor; Sheppard, Neil C.; SenGupta, Devi; Tandon, Ravi; Yue, Feng-Yun; Benko, Erika; Kovacs, Colin; Nixon, Douglas F.; Ostrowski, Mario A.

    2012-01-01

    T-cell responses to human endogenous retrovirus (HERV) K(HML-2) Gag and Env were mapped in HIV-1-infected subjects using 15mer peptides. Small peptide pools and high concentrations were used to maximize sensitivity. In the 23 subjects studied, only three bona fide HERV-K(HML-2)-specific responses were detected. At these high peptide concentrations, we detected false-positive responses, three of which were mapped to an HIV-1 Gag peptide contaminant. Thus, HERV-K(HML-2) Gag- and Env-specific T-cell responses are infrequently detected by 15mer peptide mapping. PMID:22205657

  17. Xenotransplantation and pig endogenous retroviruses.

    Science.gov (United States)

    Magre, Saema; Takeuchi, Yasuhiro; Bartosch, Birke

    2003-01-01

    Xenotransplantation, in particular transplantation of pig cells, tissues and organs into human patients, may alleviate the current shortage of suitable allografts available for human transplantation. This overview addresses the physiological, immunological and virological factors considered with regard to xenotransplantation. Among the issues reviewed are the merits of using pigs as xenograft source species, the compatibility of pig and human organ physiology and the immunological hindrances with regard to the various types of rejection and attempts at abrogating rejection. Advances in the prevention of pig organ rejection by creating genetically modified pigs that are more suited to the human microenvironment are also discussed. Finally, with regard to virology, possible zoonotic infections emanating from pigs are reviewed, with special emphasis on the pig endogenous retrovirus (PERV). An in depth account of PERV studies, comprising their discovery as well as recent knowledge of the virus, is given. To date, all retrospective studies on patients with pig xenografts have shown no evidence of PERV transmission, however, many factors make us interpret these results with caution. Although the lack of PERV infection in xenograft recipients up to now is encouraging, more basic research and controlled animal studies that mimic the pig to human xenotransplantation setting more closely are required for safety assessment.

  18. [Investigation of Predisposition Biomarkers to Identify Risk Factors for Drug-induced Liver Injury in Humans: Analyses of Endogenous Metabolites in an Animal Model Mimicking Human Responders to APAP-induced Hepatotoxicity].

    Science.gov (United States)

    Kobayashi, Akio; Kondo, Kazuma; Sugai, Shoichiro

    2015-01-01

    Drug-induced liver injury is a main reason of regulatory action pertaining to drugs, including restrictions to clinical indications and withdrawal from the marketplace. Acetaminophen (APAP) is a commonly used and effective analgesic/antipyretic agent and relatively safe drug even in long-term treatment. However, it is known that APAP at therapeutic doses may cause hepatotoxicity in some individuals. Hence great efforts have been made to identify risk factors for APAP-induced chronic hepatotoxicity. We investigated the contribution of undernourishment to susceptibility to APAP-induced chronic hepatotoxicity using an animal model. We employed daytime restricted fed (RF) rats as a modified-nutritional state model for human APAP-induced hepatotoxicity. RF and ad libitum fed (ALF) rats were given APAP at 0, 300, and 500 mg/kg for 3 months. Plasma and urinary glutathione-related metabolomes and liver function parameters were measured during the dosing period. Endogenous metabolites forming at different levels between the RF and ALF rats could be potential predisposition biomarkers for APAP-induced hepatotoxicity. In addition, RF rats were considered a useful model to estimate the contribution of nutritional state of patients to APAP-induced chronic hepatotoxicity. In this article we report our current research focusing on nutritional state as risk factor for APAP-induced chronic hepatotoxicity and our findings of hepatotoxicity biomarkers.

  19. Thermodynamic properties of cryogenic fluids

    CERN Document Server

    Leachman, Jacob; Lemmon, Eric; Penoncello, Steven

    2017-01-01

    This update to a classic reference text provides practising engineers and scientists with accurate thermophysical property data for cryogenic fluids. The equations for fifteen important cryogenic fluids are presented in a basic format, accompanied by pressure-enthalpy and temperature-entropy charts and tables of thermodynamic properties. It begins with a chapter introducing the thermodynamic relations and functional forms for equations of state, and goes on to describe the requirements for thermodynamic property formulations, needed for the complete definition of the thermodynamic properties of a fluid. The core of the book comprises extensive data tables and charts for the most commonly-encountered cryogenic fluids. This new edition sees significant updates to the data presented for air, argon, carbon monoxide, deuterium, ethane, helium, hydrogen, krypton, nitrogen and xenon. The book supports and complements NIST’s REFPROP - an interactive database and tool for the calculation of thermodynamic propertie...

  20. Cryogenic safety organisation at CERN

    CERN Document Server

    CERN. Geneva

    2016-01-01

    With Safety being a top priority of CERN’s general policy, the Organisation defines and implements a Policy that sets out the general principles governing Safety at CERN. To the end of the attainment of said Safety objectives, the organic units (owners/users of the equipment) are assigned the responsibility for the implementation of the CERN Safety Policy at all levels of the organization, whereas the Health and Safety and Environmental Protection Unit (HSE) has the role of providing assistance for the implementation of the Safety Policy, and a monitoring role related to the implementation of continuous improvement of Safety, compliance with the Safety Rules and the handling of emergency situations. This talk will elaborate on the roles, responsibilities and organisational structure of the different stakeholders within the Organization with regards to Safety, and in particular to cryogenic safety. The roles of actors of particular importance such as the Cryogenic Safety Officers (CSOs) and the Cryogenic Sa...

  1. Cryogenic needs for future tokamaks

    Science.gov (United States)

    Katheder, H.

    The ITER tokamak is a machine using superconducting magnets. The windings of these magnets will be subjected to high heat loads resulting from a combination of nuclear energy absorption and AC-losses. It is estimated that about 100 kW at 4.5 K are needed. The total cooling mass flow rate will be around 10 - 15 kg/s. In addition to the large cryogenic power required for the superconducting magnets cryogenic power is also needed for refrigerated radiation shield, various cryopumps, fuel processing and test beds. A general description of the overall layout and the envisaged refrigerator cycle, necessary cold pumps and ancillary equipment is given. The basic cryogenic layout for the ITER tokakmak design, as developed during the conceptual design phase and a short overview about existing tokamak designs using superconducting magnets is given.

  2. Magnetic bearings for cryogenic turbomachines

    Science.gov (United States)

    Iannello, Victor; Sixsmith, Herbert

    1991-01-01

    Magnetic bearings offer a number of advantages over gas bearings for the support of rotors in cryogenic turboexpanders and compressors. Their performance is relatively independent of the temperature or pressure of the process gas for a large range of conditions. Active magnetic bearing systems that use capacitive sensors have been developed for high speed compressors for use in cryogenic refrigerators. Here, the development of a magnetic bearing system for a miniature ultra high speed compressor is discussed. The magnetic bearing has demonstrated stability at rotational speeds exceeding 250,000 rpm. This paper describes the important features of the magnetic bearing and presents test results demonstrating its performance characteristics.

  3. The Endogenous Feedback Network

    DEFF Research Database (Denmark)

    Augustenborg, Claudia Carrara

    2010-01-01

    proposals, it will first be considered the extents of their reciprocal compatibility, tentatively shaping an integrated, theoretical profile of consciousness. A new theory, the Endogenous Feedback Network (EFN) will consequently be introduced which, beside being able to accommodate the main tenets...... of the reviewed theories, appears able to compensate for the explanatory gaps they leave behind. The EFN proposes consciousness as the phenomenon emerging from a distinct network of neural paths broadcasting the neural changes associated to any mental process. It additionally argues for the need to include a 5th...

  4. Endogenous price leadership

    OpenAIRE

    van Damme, E.E.C.; Hurkens, S.

    1998-01-01

    We consider a linear price setting duopoly game with di®erentiated products and determine endogenously which of the players will lead and which will follow. While the follower role is most attractive for each firm, we show that waiting is more risky for the low cost firm so that, consequently, risk dominance considerations, as in Harsanyi and Selten (1988), allow the conclusion that only the high cost firm will choose to wait. Hence, the low cost firm will emerge as the end...

  5. Tectonic conditionality endogenic geoecological processes on a shelf

    Science.gov (United States)

    Kholmiansky, Mikhail; Anokhin, Vladimir; Kholmianskaia, Galina

    2014-05-01

    water area Barents and Kara seas is the first attempt to combine exogenic and endogenic dangers. On the map are allocated ecological geological formation zones (ekologo-formation zones), characterised by us, as: «ekologo-formation zone - the existential set of natural-technogenic processes characterised by general facial, geochemical, geocriological, engineering - geological, geodynamic signs and the same display of ecological functions litosphere». In total it is allocated eight ekologo-formation zones: Kola, Central Barents, Prinovozemelsky, Amdermsky, Central Kara, Obskoenisejsky, Northern, Boundary shelf. The most difficult ecogeological conditions differ central Barents and amderma zones where dangerous cryogenic processes are developed along with the raised seismicity, active accumulation of heavy metals and the high maintenance of a suspension in sea water.

  6. Cryogenic technology for tracking detectors

    CERN Document Server

    Granata, V; Watts, S; Borer, K; Janos, S; Pretzl, Klaus P; Dezillie, B; Li, Z; Casagrande, L; Collins, P; Grohmann, S; Heijne, Erik H M; Lourenço, C; Niinikoski, T O; Palmieri, V G; Sonderegger, P; Borchi, E; Bruzzi, Mara; Pirollo, S; Chapuy, S; Dimcovski, Zlatomir; Grigoriev, E; Bell, W; Devine, S R H; O'Shea, V; Ruggiero, G; Smith, K; Berglund, P; de Boer, Wim; Hauler, F; Heising, S; Jungermann, L; Abreu, M C; Rato-Mendes, P; Sousa, P; Cindro, V; Mikuz, M; Zavrtanik, M; Esposito, A P; Konorov, I; Paul, S; Buontempo, S; D'Ambrosio, D; Pagano, S; Eremin, V V; Verbitskaya, E

    2001-01-01

    A low-mass cryogenic cooling technique for silicon sensor modules has been developed in the framework of the RD39 Collaboration at CERN. A prototype low-mass beam tracker cryostat has been designed, constructed and tested for applications in fixed target experiments. We shall report here briefly the main features and results of the system. (2 refs).

  7. USAF Space Sensing Cryogenic Considerations

    Science.gov (United States)

    2010-01-01

    capacitance dilatometer for measuring thermal expansion and magnetostriction Rev. Sci. Instrum. 83, 095102 (2012) Compact radio-frequency resonator...enhancing when the refrigeration system is considered as part of an overall optimization problem. INTRODUCTION The use of cryogenics in space sensing

  8. LHC Cryogenics on the mend

    CERN Multimedia

    2004-01-01

    On 29 September, repairs began on the LHC cryogenic distribution line, or QRL, to replace a faulty part that occurs in the hundreds of elements of the line that are already on-site. The Accelerator Technology Department is designing a work programme to finish the repairs as soon as possible and minimize delays to the rest of the LHC project.

  9. Champagne for the cryogenics teams

    CERN Multimedia

    2005-01-01

    Christmas has come early for the LHC as a complete sector of the cryogenic distribution line has been operating at 10 degrees Kelvin (-263°C) for the past two weeks, just a few degrees above the machine's nominal operating temperature.

  10. Background reduction in cryogenic detectors

    Energy Technology Data Exchange (ETDEWEB)

    Bauer, Daniel A.; /Fermilab

    2005-04-01

    This paper discusses the background reduction and rejection strategy of the Cryogenic Dark Matter Search (CDMS) experiment. Recent measurements of background levels from CDMS II at Soudan are presented, along with estimates for future improvements in sensitivity expected for a proposed SuperCDMS experiment at SNOLAB.

  11. Survey of cryogenic semiconductor devices

    Energy Technology Data Exchange (ETDEWEB)

    Talarico, L.J.; McKeever, J.W.

    1996-04-01

    Improved reliability and electronic performance can be achieved in a system operated at cryogenic temperatures because of the reduction in mechanical insult and in disruptive effects of thermal energy on electronic devices. Continuing discoveries of new superconductors with ever increasing values of T{sub c} above that of liquid nitrogen temperature (LNT) have provided incentive for developing semiconductor electronic systems that may also operate in the superconductor`s liquid nitrogen bath. Because of the interest in high-temperature superconductor (HTS) devices, liquid nitrogen is the cryogen of choice and LNT is the temperature on which this review is focused. The purpose of this survey is to locate and assemble published information comparing the room temperature (298 K), performance of commercially available conventional and hybrid semiconductor device with their performance at LNT (77K), to help establish their candidacy as cryogenic electronic devices specifically for use at LNT. The approach to gathering information for this survey included the following activities. Periodicals and proceedings were searched for information on the behavior of semiconductor devices at LNT. Telephone calls were made to representatives of semiconductor industries, to semiconductor subcontractors, to university faculty members prominent for their research in the area of cryogenic semiconductors, and to representatives of the National Aeronautics and Space Administration (NASA) and NASA subcontractors. The sources and contacts are listed with their responses in the introduction, and a list of references appears at the end of the survey.

  12. A Magnetically Coupled Cryogenic Pump

    Science.gov (United States)

    Hatfield, Walter; Jumper, Kevin

    2011-01-01

    Historically, cryogenic pumps used for propellant loading at Kennedy Space Center (KSC) and other NASA Centers have a bellows mechanical seal and oil bath ball bearings, both of which can be problematic and require high maintenance. Because of the extremely low temperatures, the mechanical seals are made of special materials and design, have wearing surfaces, are subject to improper installation, and commonly are a potential leak path. The ball bearings are non-precision bearings [ABEC-1 (Annular Bearing Engineering Council)] and are lubricated using LOX compatible oil. This oil is compatible with the propellant to prevent explosions, but does not have good lubricating properties. Due to the poor lubricity, it has been a goal of the KSC cryogenics community for the last 15 years to develop a magnetically coupled pump, which would eliminate these two potential issues. A number of projects have been attempted, but none of the pumps was a success. An off-the-shelf magnetically coupled pump (typically used with corrosive fluids) was procured that has been used for hypergolic service at KSC. The KSC Cryogenics Test Lab (CTL) operated the pump in cryogenic LN2 as received to determine a baseline for modifications required. The pump bushing, bearings, and thrust rings failed, and the pump would not flow liquid (this is a typical failure mode that was experienced in the previous attempts). Using the knowledge gained over the years designing and building cryogenic pumps, the CTL determined alternative materials that would be suitable for use under the pump design conditions. The CTL procured alternative materials for the bearings (bronze, aluminum bronze, and glass filled PTFE) and machined new bearing bushings, sleeves, and thrust rings. The designed clearances among the bushings, sleeves, thrust rings, case, and case cover were altered once again using experience gained from previous cryogenic pump rebuilds and designs. The alternative material parts were assembled into

  13. A surrogate analyte-based LC-MS/MS method for the determination of γ-hydroxybutyrate (GHB) in human urine and variation of endogenous urinary concentrations of GHB.

    Science.gov (United States)

    Kang, Soyoung; Oh, Seung Min; Chung, Kyu Hyuck; Lee, Sooyeun

    2014-09-01

    γ-Hydroxybutyrate (GHB) is a drug of abuse with a strong anesthetic effect; however, proving its ingestion through the quantification of GHB in biological specimens is not straightforward due to the endogenous presence of GHB in human blood, urine, saliva, etc. In the present study, a surrogate analyte approach was applied to accurate quantitative determination of GHB in human urine using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in order to overcome this issue. For this, (2)H6-GHB and (13)C2-dl-3-hydroxybutyrate were used as a surrogate standard and as an internal standard, respectively, and parallelism between the surrogate analyte approach and standard addition was investigated at the initial step. The validation results proved the method to be selective, accurate, and precise, with acceptable linearity within calibration ranges (0.1-1μg/ml). The limit of detection and the limit of quantification of (2)H6-GHB were 0.05 and 0.1μg/ml, respectively. No significant variations were observed among urine matrices from different sources. The stability of (2)H6-GHB was satisfactory under sample storage and in-process conditions. However, in vitro production of endogenous GHB was observed when the urine sample was kept under the in-process condition for 4h and under the storage conditions of 4 and -20°C. In order to facilitate the practical interpretation of urinary GHB, endogenous GHB was accurately measured in urine samples from 79 healthy volunteers using the surrogate analyte-based LC-MS/MS method developed in the present study. The unadjusted and creatinine-adjusted GHB concentrations in 74 urine samples with quantitative results ranged from 0.09 to 1.8μg/ml and from 4.5 to 530μg/mmol creatinine, respectively. No significant correlation was observed between the unadjusted and creatinine-adjusted GHB concentrations. The urinary endogenous GHB concentrations were affected by gender and age while they were not significantly influenced by habitual

  14. Proliferative responses to altered 17beta-hydroxysteroid dehydrogenase (17HSD) type 2 expression in human breast cancer cells are dependent on endogenous expression of 17HSD type 1 and the oestradiol receptors.

    Science.gov (United States)

    Jansson, A; Gunnarsson, C; Stål, O

    2006-09-01

    The primary source of oestrogen in premenopausal women is the ovary but, after menopause, oestrogen biosynthesis in peripheral tissue is the exclusive site of formation. An enzyme group that affects the availability of active oestrogens is the 17beta-hydroxysteroid dehydrogenase (17HSD) family. In breast cancer, 17HSD type 1 and type 2 have been mostly investigated and seem to be the principal 17HSD enzymes involved thus far. The question whether 17HSD type 1 or type 2 is of greatest importance in breast tumour development is still not clear. The aim of this study was to investigate how the loss of 17HSD type 2 expression, using siRNA in the non-tumour breast epithelial cells HMEC (human mammal epithelial cells) and MCF10A, and gain of 17HSD type 2 expression, using transient transfection in the breast cancer derived cell lines MCF7 and T47D, affect oestradiol conversion and proliferation rate measured as S-phase fraction. We further investigated how this was related to the endogenous expression of 17HSD type 1 and oestradiol receptors in the examined cell lines. The oestradiol level in the medium changed significantly in the MCF7 transfected cells and the siRNA-treated HMEC cells, but not in T47D or MCF10A. The S-phase fraction decreased in the 17HSD type 2-transfected MCF7 cells and the siRNA-treated HMEC cells. The results seemed to be dependent on the endogenous expression of 17HSD type 1 and the oestradiol receptors. In conclusion, we found that high or low levels of 17HSD type 2 affected the oestradiol concentration significantly. However, the response was dependent on the endogenous expression of 17HSD type 1. Expression of 17HSD type 1 seems to be dominant to 17HSD type 2. Therefore, it may be important to investigate a ratio between 17HSD type 1 and 17HSD type 2.

  15. ENDOGENEITY OF INDONESIAN MONEY SUPPLY

    OpenAIRE

    Meutia Safrina Rachma

    2011-01-01

    There has been a long debate about the endogeneity of money supply. The main objective of this article is to identify whether money supply in Indonesia is an exogenous or an endogenous variable. Using a Vector Autoregressive model and monthly data 1997(5)-2010(6), the estimation result shows that money supply in Indonesia is an endogenous variable. The movement of broad money supply does influence the movement of base money and Consumer Price Index. Consequently, the central bank does not hav...

  16. The endogenous hallucinogen and trace amine N,N-dimethyltryptamine (DMT displays potent protective effects against hypoxia via sigma-1 receptor activation in human primary iPSC-derived cortical neurons and microglia-like immune cells

    Directory of Open Access Journals (Sweden)

    Attila Szabo

    2016-09-01

    Full Text Available N,N-dimethyltryptamine (DMT is a potent endogenous hallucinogen present in the brain of humans and other mammals. Despite extensive research, its physiological role remains largely unknown. Recently, DMT has been found to activate the sigma-1 receptor (Sig-1R, an intracellular chaperone fulfilling an interface role between the endoplasmic reticulum (ER and mitochondria. It ensures the correct transmission of ER stress into the nucleus resulting in the enhanced production of antistress and antioxidant proteins. Due to this function, the activation of Sig-1R can mitigate the outcome of hypoxia or oxidative stress. In this paper we aimed to test the hypothesis that DMT plays a neuroprotective role in the brain by activating the Sig-1R. We tested whether DMT can mitigate hypoxic stress in in vitro cultured human cortical neurons (derived from induced pluripotent stem cells, and in monocyte-derived macrophages and dendritic cells. Here we report that DMT robustly increases the survival of these cell types in severe hypoxia (0.5% O2 through the Sig-1R. Furthermore, this phenomenon is associated with the decreased expression and function of the alpha subunit of the hypoxia-inducible factor 1 (HIF-1 suggesting that DMT-mediated Sig-1R activation may alleviate hypoxia-induced cellular stress and increase survival in a HIF-1-independent manner. Our results reveal a novel and important role of DMT in human cellular physiology. We postulate that this compound may be endogenously generated in situations of stress, ameliorating the adverse effects of hypoxic/ischemic insult to the brain.

  17. The Endogenous Hallucinogen and Trace Amine N,N-Dimethyltryptamine (DMT) Displays Potent Protective Effects against Hypoxia via Sigma-1 Receptor Activation in Human Primary iPSC-Derived Cortical Neurons and Microglia-Like Immune Cells.

    Science.gov (United States)

    Szabo, Attila; Kovacs, Attila; Riba, Jordi; Djurovic, Srdjan; Rajnavolgyi, Eva; Frecska, Ede

    2016-01-01

    N,N-dimethyltryptamine (DMT) is a potent endogenous hallucinogen present in the brain of humans and other mammals. Despite extensive research, its physiological role remains largely unknown. Recently, DMT has been found to activate the sigma-1 receptor (Sig-1R), an intracellular chaperone fulfilling an interface role between the endoplasmic reticulum (ER) and mitochondria. It ensures the correct transmission of ER stress into the nucleus resulting in the enhanced production of antistress and antioxidant proteins. Due to this function, the activation of Sig-1R can mitigate the outcome of hypoxia or oxidative stress. In this paper, we aimed to test the hypothesis that DMT plays a neuroprotective role in the brain by activating the Sig-1R. We tested whether DMT can mitigate hypoxic stress in in vitro cultured human cortical neurons (derived from induced pluripotent stem cells, iPSCs), monocyte-derived macrophages (moMACs), and dendritic cells (moDCs). Results showed that DMT robustly increases the survival of these cell types in severe hypoxia (0.5% O2) through the Sig-1R. Furthermore, this phenomenon is associated with the decreased expression and function of the alpha subunit of the hypoxia-inducible factor 1 (HIF-1) suggesting that DMT-mediated Sig-1R activation may alleviate hypoxia-induced cellular stress and increase survival in a HIF-1-independent manner. Our results reveal a novel and important role of DMT in human cellular physiology. We postulate that this compound may be endogenously generated in situations of stress, ameliorating the adverse effects of hypoxic/ischemic insult to the brain.

  18. The relationship of endogenous plasma concentrations of β-Hydroxy β-Methyl Butyrate (HMB) to age and total appendicular lean mass in humans.

    Science.gov (United States)

    Kuriyan, Rebecca; Lokesh, Deepa P; Selvam, Sumithra; Jayakumar, J; Philip, Mamatha G; Shreeram, Sathyavageeswaran; Kurpad, Anura V

    2016-08-01

    The maintenance of muscle mass and muscle strength is important for reducing the risk of chronic diseases. The age- related loss of muscle mass and strength is associated with adverse outcomes of physical disability, frailty and death. β-Hydroxy β-Methyl Butyrate (HMB), a metabolite of leucine, has beneficial effects on muscle mass and strength under various catabolic conditions. The objectives of the present study were to determine if age- related differences existed in endogenous plasma HMB levels, and to assess if HMB levels correlated to total appendicular lean mass and forearm grip strength. Anthropometry, dietary and physical activity assessment, and the estimation of fasting plasma HMB concentrations and handgrip strength were performed on the 305 subjects (children, young adults and older adults). Lean mass, which serves as a surrogate for muscle mass was measured using dual energy X-ray absorptiometry (DEXA). Mean plasma HMB concentrations were significantly lower with increasing age groups, with children having highest mean HMB concentration (plean mass normalized for body weight (%), appendicular lean mass (r=0.37; plean mass and hand grip strength in young adults and older adults group.

  19. Omega-3 N-acylethanolamines are endogenously synthesised from omega-3 fatty acids in different human prostate and breast cancer cell lines.

    Science.gov (United States)

    Brown, I; Wahle, K W J; Cascio, M G; Smoum-Jaouni, R; Mechoulam, R; Pertwee, R G; Heys, S D

    2011-12-01

    Omega-3 (n-3) fatty acids inhibit breast and prostate cancer cell growth. We previously showed that N-acylethanolamine derivatives of n-3 (n-3-NAE) are endocannabinoids, which regulate cancer cell proliferation. These n-3-NAE are synthesised in certain cells/tissues, after supplementing with fatty acids, however, no one has assessed whether and to what extent this occurs in cancer cells. We determined levels of endogenous n-3-NAEs in hormone sensitive and insensitive prostate and breast cancer cells and subsequent effects on other endocannabinoids (anandamide and 2-arachidonoylglycerol), before and after supplementing with DHA and EPA fatty acids, using HPLC tandem mass spectrometry. This is the first study reporting that n-3-NAEs are synthesised from their parent n-3 fatty acids in cancer cells, regardless of tumour type, hormone status or the presence of fatty acid amide hydrolase. This could have important implications for the use of n-3 fatty acids as therapeutic agents in breast and prostate cancers expressing cannabinoid receptors.

  20. Nuclear Cryogenic Propulsion Stage Affordable Development Strategy

    Science.gov (United States)

    Doughty, Glen E.; Gerrish, H. P.; Kenny, R. J.

    2014-01-01

    The development of nuclear power for space use in nuclear thermal propulsion (NTP) systems will involve significant expenditures of funds and require major technology development efforts. The development effort must be economically viable yet sufficient to validate the systems designed. Efforts are underway within the National Aeronautics and Space Administration's (NASA) Nuclear Cryogenic Propulsion Stage Project (NCPS) to study what a viable program would entail. The study will produce an integrated schedule, cost estimate and technology development plan. This will include the evaluation of various options for test facilities, types of testing and use of the engine, components, and technology developed. A "Human Rating" approach will also be developed and factored into the schedule, budget and technology development approach.

  1. A cryogenic receiver for EPR.

    Science.gov (United States)

    Narkowicz, R; Ogata, H; Reijerse, E; Suter, D

    2013-12-01

    Cryogenic probes have significantly increased the sensitivity of NMR. Here, we present a compact EPR receiver design capable of cryogenic operation. Compared to room temperature operation, it reduces the noise by a factor of ≈2.5. We discuss in detail the design and analyze the resulting noise performance. At low microwave power, the input noise density closely follows the emission of a cooled 50Ω resistor over the whole measurement range from 20K up to room temperature. To minimize the influence of the microwave source noise, we use high microwave efficiency (≈1.1-1.7mTW(-1/2)) planar microresonators. Their efficient conversion of microwave power to magnetic field permits EPR measurements with very low power levels, typically ranging from a few μW down to fractions of nW. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. The Cryogenic Dark Matter Search

    Science.gov (United States)

    Sander, Joel

    2004-05-01

    The Cryogenic Dark Matter Search (CDMS) is an experiment to search for Weakly Interacting Massive Particles (WIMPs). The experiment initially was deployed at a shallow underground site, and is currently deployed at a deep underground site at the Soudan Mine in Minnesota. The detectors operate at cryogenic temperature, and are capable of distinguishing nuclear recoils from WIMP interactions from various backgrounds. The detectors are shielded from background by both active and passive elements. We will describe the components of the overall experiment, and focus on the novel data acquisition system that has been develop to control and monitor the experiment via the World Wide Web. Preliminary signals from the operation at Soudan will be discussed.

  3. Cryogenic High-Sensitivity Magnetometer

    Science.gov (United States)

    Day, Peter; Chui, Talso; Goodstein, David

    2005-01-01

    A proposed magnetometer for use in a cryogenic environment would be sensitive enough to measure a magnetic-flux density as small as a picogauss (10(exp -16) Tesla). In contrast, a typical conventional flux-gate magnetometer cannot measure a magnetic-flux density smaller that about 1 microgauss (10(exp -10) Tesla). One version of this device, for operation near the low end of the cryogenic temperature range, would include a piece of a paramagnetic material on a platform, the temperature of which would be controlled with a periodic variation. The variation in temperature would be measured by use of a conventional germanium resistance thermometer. A superconducting coil would be wound around the paramagnetic material and coupled to a superconducting quantum interference device (SQUID) magnetometer.

  4. Cryogenic Flange and Seal Evaluation

    Science.gov (United States)

    Ramirez, Adrian

    2014-01-01

    The assembly of flanges, seals, and pipes are used to carry cryogenic fluid from a storage tank to the vehicle at launch sites. However, after a certain amount of cycles these raised face flanges with glass-filled Teflon gaskets have been found to have torque relaxation and are as a result susceptible to cryogenic fluid leakage if not re-torqued. The intent of this project is to identify alternate combinations of flanges and seals which may improve thermal cycle performance and decrease re-torque requirements. The general approach is to design a test fixture to evaluate leak characteristics between spiral and concentric serrations and to test alternate flange and seal combinations. Due to insufficient time, it was not possible to evaluate these different types of combinations for the combination that improved thermal cycle performance the most. However, the necessary drawings for the test fixture were designed and assembled along with the collection of the necessary parts.

  5. Therapeutic IgG4 antibodies engage in Fab-arm exchange with endogenous human IgG4 in vivo

    NARCIS (Netherlands)

    A.F. Labrijn; A.O. Buijsse; E.T.J. van den Bremer; A.Y.W. Verwilligen; W.K. Bleeker; S.J. Thorpe; J. Killestein; C.H. Polman; R.C. Aalberse; J. Schuurman; J.G.J. van de Winkel; P.W.H.I. Parren

    2009-01-01

    Two humanized IgG4 antibodies, natalizumab and gemtuzumab, are approved for human use, and several others, like TGN1412, are or have been in clinical development. Although IgG4 antibodies can dynamically exchange half-molecules(1), Fab-arm exchange with therapeutic antibodies has not been demonstrat

  6. The cryogenic storage ring project

    Energy Technology Data Exchange (ETDEWEB)

    Hahn, Robert von; Blaum, Klaus; Becker, Arno; Fellenberger, Florian; George, Sebastian; Grieser, Manfred; Grussie, Florian; Herwig, Philipp; Krantz, Claude; Kreckel, Holger; Lange, Michael; Menk, Sebastian; Repnow, Roland; Vogel, Stephen; Wolf, Andreas [Max-Planck-Institut fuer Kernphysik, Heidelberg (Germany); Spruck, Kaija [Justus-Liebig-Universitaet, Giessen (Germany)

    2014-07-01

    At MPIK the electrostatic cryogenic storage ring CSR is nearing completion. At beam energies of 20 to 300 keV per charge unit and 35 m circumference the CSR will allow experiments in a cryogenic environment providing conditions of extremely low vacuum and heat radiation. By using liquid helium at 2 K for cryopumping, the projected vacuum (confirmed at a prototype) lies at 1E-13 mbar or below, ensuring long storage times for slow singly charged and highly charged ions, molecules and clusters. Moreover, phase space cooling by electrons will be implemented. The internal quantum states of molecular and cluster ions can be cooled to low temperature, yielding well defined vibrational and for smaller systems also rotational structures. In the CSR construction, the cryogenic ion beam vacuum system has been set up. Extensive tests confirming the criteria on heat flow, alignment and high-voltage stability were successfully completed on the first quadrant. In addition beam diagnostic units for electric pickup signals and spatial profiles, detectors for neutral and charged fragments, the injection beam line, and an electron cooling device are under construction.

  7. ZERODUR TAILORED for cryogenic application

    Science.gov (United States)

    Jedamzik, R.; Westerhoff, T.

    2014-07-01

    ZERODUR® glass ceramic from SCHOTT is known for its very low thermal expansion coefficient (CTE) at room temperature and its excellent CTE homogeneity. It is widely used for ground-based astronomical mirrors but also for satellite applications. Many reference application demonstrate the excellent and long lasting performance of ZERODUR® components in orbit. For space application a low CTE of the mirror material is required at cryogenic temperatures together with a good match of the thermal expansion to the supporting structure material. It is possible to optimize the coefficient of thermal expansion of ZERODUR® for cryogenic applications. This paper reports on measurements of thermal expansion of ZERODUR® down to cryogenic temperatures of 10 K performed by the PTB (Physikalisch Technische Bundesanstallt, Braunschweig, Germany, the national metrology laboratory). The ZERODUR® TAILORED CRYO presented in this paper has a very low coefficient of thermal expansion down to 70 K. The maximum absolute integrated thermal expansion down to 10 K is only about 20 ppm. Mirror blanks made from ZERODUR® TAILORED CRYO can be light weighted to almost 90% with our modern processing technologies. With ZERODUR® TAILORED CRYO, SCHOTT offers the mirror blank material for the next generation of space telescope applications.

  8. Positronium production in cryogenic environments

    Science.gov (United States)

    Cooper, B. S.; Alonso, A. M.; Deller, A.; Liszkay, L.; Cassidy, D. B.

    2016-03-01

    We report measurements of positronium (Ps) formation following positron irradiation of mesoporous SiO2 films and Ge(100) single crystals at temperatures ranging from 12-700 K. As both of these materials generate Ps atoms via nonthermal processes, they are able to function as positron-positronium converters at cryogenic temperatures. Our data show that such Ps formation is possibly provided the targets are not compromised by adsorption of residual gas. In the case of SiO2 films, we observe a strong reduction in the Ps formation efficiency following irradiation with UV laser light (λ =243.01 nm) below 250 K, in accordance with previous observations of radiation-induced surface paramagnetic centers. Conversely, Ps emission from Ge is enhanced by irradiation with visible laser light (λ =532 nm) via a photoemission process that persists at cryogenic temperatures. Both mesoporous SiO2 films and Ge crystals were found to produce Ps efficiently in cryogenic environments. Accordingly, these materials are likely to prove useful in several areas of research, including Ps mediated antihydrogen formation conducted in the cold bore of a superconducting magnet, the production of Rydberg Ps for experiments in which the effects of black-body radiation must be minimized, and the utilization of mesoporous structures that have been modified to produce cold Ps atoms.

  9. The evolution of cryogenic safety at Fermilab

    Energy Technology Data Exchange (ETDEWEB)

    Stanek, R.; Kilmer, J.

    1992-12-01

    Over the past twenty-five years, Fermilab has been involved in cryogenic technology as it relates to pursuing experimentation in high energy physics. The Laboratory has instituted a strong cryogenic safety program and has maintained a very positive safety record. The solid commitment of management and the cryogenic community to incorporating safety into the system life cycle has led to policies that set requirements and help establish consistency for the purchase and installation of equipment and the safety analysis and documentation.

  10. Identification of the endogenous key substrates of the human organic cation transporter OCT2 and their implication in function of dopaminergic neurons.

    Directory of Open Access Journals (Sweden)

    Dirk Taubert

    Full Text Available BACKGROUND: The etiology of neurodegenerative disorders, such as the accelerated loss of dopaminergic neurons in Parkinson's disease, is unclear. Current hypotheses suggest an abnormal function of the neuronal sodium-dependent dopamine transporter DAT to contribute to cell death in the dopaminergic system, but it has not been investigated whether sodium-independent amine transporters are implicated in the pathogenesis of Parkinson's disease. METHODOLOGY/PRINCIPAL FINDINGS: By the use of a novel tandem-mass spectrometry-based substrate search technique, we have shown that the dopaminergic neuromodulators histidyl-proline diketopiperazine (cyclo(his-pro and salsolinol were the endogenous key substrates of the sodium-independent organic cation transporter OCT2. Quantitative real-time mRNA expression analysis revealed that OCT2 in contrast to its related transporters was preferentially expressed in the dopaminergic regions of the substantia nigra where it colocalized with DAT and tyrosine hydroxylase. By assessing cell viability with the MTT reduction assay, we found that salsolinol exhibited a selective toxicity toward OCT2-expressing cells that was prevented by cyclo(his-pro. A frequent genetic variant of OCT2 with the amino acid substitution R400C reduced the transport efficiency for the cytoprotective cyclo(his-pro and thereby increased the susceptibility to salsolinol-induced cell death. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that the OCT2-regulated interplay between cyclo(his-pro and salsolinol is crucial for nigral cell integrity and that a shift in transport efficiency may impact the risk of Parkinson's disease.

  11. The DNA copy number of human endogenous retrovirus-W (MSRV-type is increased in multiple sclerosis patients and is influenced by gender and disease severity.

    Directory of Open Access Journals (Sweden)

    Marta Garcia-Montojo

    Full Text Available BACKGROUND: Multiple sclerosis is an autoimmune disease more prevalent in women than in men. Multiple Sclerosis Associated Retrovirus element (MSRV is a member of type-W endogenous retrovirus family (HERV-W, known to be associated to MS. Most HERVs are unable to replicate but MSRV expression associated with reverse-transcriptase activity in MS would explain reported DNA copy number increase in MS patients. A potential link between HERV-W copies on chromosome X and gender differential prevalence has been suggested. The present study addresses MSRV-type DNA load in relation with the gender differences and clinical status in MS and healthy controls. RESULTS: 178 MS patients (62.9% women and 124 controls (56.5% women were included. MSRV env load (copies/pg of DNA was analyzed by real time qPCR with specific primers and probe for its env gene, in DNA from peripheral blood mononuclear cells (PBMCs. MSRV load was more elevated in MS patients than in controls (p = 4.15e-7. MS women presented higher MSRV load than control women (p = 0.009 and MS men also had higher load than control men (p = 2.77e-6. Besides, women had higher levels than men, both among patients (p = 0.007 and controls (p = 1.24e-6. Concordantly, EDSS and MSSS scores were higher among female patients with an elevated MSRV load (p = 0.03 and p = 0.04, respectively. CONCLUSIONS: MSRV increases its copy number in PBMC of MS patients and particularly in women with high clinical scores. This may explain causes underlying the higher prevalence of MS in women. The association with the clinical severity calls for further investigations on MSRV load in PBMCs as a biomarker for MS.

  12. Calcium-sensing receptor antagonist (calcilytic) NPS 2143 specifically blocks the increased secretion of endogenous Aβ42 prompted by exogenous fibrillary or soluble Aβ25-35 in human cortical astrocytes and neurons-therapeutic relevance to Alzheimer's disease.

    Science.gov (United States)

    Armato, Ubaldo; Chiarini, Anna; Chakravarthy, Balu; Chioffi, Franco; Pacchiana, Raffaella; Colarusso, Enzo; Whitfield, James F; Dal Prà, Ilaria

    2013-10-01

    The "amyloid-β (Aβ) hypothesis" posits that accumulating Aβ peptides (Aβs) produced by neurons cause Alzheimer's disease (AD). However, the Aβs contribution by the more numerous astrocytes remains undetermined. Previously we showed that fibrillar (f)Aβ25-35, an Aβ42 proxy, evokes a surplus endogenous Aβ42 production/accumulation in cortical adult human astrocytes. Here, by using immunocytochemistry, immunoblotting, enzymatic assays, and highly sensitive sandwich ELISA kits, we investigated the effects of fAβ25-35 and soluble (s)Aβ25-35 on Aβ42 and Aβ40 accumulation/secretion by human cortical astrocytes and HCN-1A neurons and, since the calcium-sensing receptor (CaSR) binds Aβs, their modulation by NPS 2143, a CaSR allosteric antagonist (calcilytic). The fAβ25-35-exposed astrocytes and surviving neurons produced, accumulated, and secreted increased amounts of Aβ42, while Aβ40 also accrued but its secretion was unchanged. Accordingly, secreted Aβ42/Aβ40 ratio values rose for astrocytes and neurons. While slightly enhancing Aβ40 secretion by fAβ25-35-treated astrocytes, NPS 2143 specifically suppressed the fAβ25-35-elicited surges of endogenous Aβ42 secretion by astrocytes and neurons. Therefore, NPS 2143 addition always kept Aβ42/Aβ40 values to baseline or lower levels. Mechanistically, NPS 2143 decreased total CaSR protein complement, transiently raised proteasomal chymotrypsin activity, and blocked excess NO production without affecting the ongoing increases in BACE1/β-secretase and γ-secretase activity in fAβ25-35-treated astrocytes. Compared to fAβ25-35, sAβ25-35 also stimulated Aβ42 secretion by astrocytes and neurons and NPS 2143 specifically and wholly suppressed this effect. Therefore, since NPS 2143 thwarts any Aβ/CaSR-induced surplus secretion of endogenous Aβ42 and hence further vicious cycles of Aβ self-induction/secretion/spreading, calcilytics might effectively prevent/stop the progression to full-blown AD.

  13. Exogenous versus endogenous recovery of 25-hydroxyvitamins D2 and D3 in human samples using high-performance liquid chromatography and the DiaSorin LIAISON Total-D Assay.

    Science.gov (United States)

    Horst, Ronald L

    2010-07-01

    Demand for circulating 25-hydroxyvitamin D [25(OH)D] measurements has exploded due to its relationship with many serious health problems. The present study was designed to investigate the validity of samples "spiked" with 25-hydroxyvitamin D2 [25(OH)D2] or 25-hydroxyvitamin D3 [25(OH)D3] to determine their analytical recovery by the DiaSorin LIAISON 25 OH Vitamin D Total Assay (DiaSorin Assay) and high-performance liquid chromatography (HPLC). 25(OH)D was measured in nine volunteers taking large daily doses of vitamin D2 for 2 weeks. Samples were obtained pre-supplementation and 1 week following vitamin D2. Pre-supplementation samples were used for exogenous recovery studies by adding 25(OH)D2 or 25(OH)D3. Endogenous 25(OH)D [25(OH)D2 plus 25(OH)D3] concentrations reported by the DiaSorin Assay or detected by HPLC were in excellent agreement. However, exogenously added 25(OH)D2 and 25(OH)D3 were under-recovered by the DiaSorin Assay. NIST vitamin D standards containing serum from another species (horse) or exogenous 25(OH)D2 were similarly affected when using the DiaSorin Assay. Exogenous 25(OH)D2, 25(OH)D3 or serum from other species added to human samples is inappropriate in determining the analytical recovery of vitamin D compounds when using the DiaSorin Assay. Only endogenous 25(OH)D2 and/or 25(OH)D3 contained in human blood samples should be utilized for this purpose.

  14. Genomic analysis of ERVWE2 locus in patients with Multiple sclerosis: absence of genetic association but potential role of Human Endogenous retrovirus type W elements in molecular mimicry with myelin antigen.

    Directory of Open Access Journals (Sweden)

    Guilherme S Olival

    2013-06-01

    Full Text Available Human endogenous retroviruses (HERVs arise from ancient infections of the host germline cells by exogenous retroviruses, constituting 8% of the human genome. Elevated level of envelope transcripts from HERVs-W has been detected in CSF, plasma and brain tissues from patients with Multiple Sclerosis (MS, most of them from Xq22.3, 15q21.3 and 6q21 chromosomes. However, since the locus Xq22.3 (ERVWE2 lack the 5' LTR promoter and the putative protein should be truncated due to a stop codon, we investigated the ERVWE2 genomic loci from 84 individuals, including MS patients with active HERV-W expression detected in PBMC. In addition, an automated search for promoter sequences in 20kb nearby region of ERVWE2 reference sequence was performed. Several putative binding sites for cellular cofactors and enhancers were found, suggesting that transcription may occur via alternative promoters. However, ERVWE2 DNA sequencing of MS and healthy individuals revealed that all of them harbor a stop codon at site 39, undermining the expression of a full-length protein. Finally, since plaque formation in CNS of MS patients is attributed to immunological mechanisms triggered by autoimmune attack against myelin, we also investigated the level of similarity between envelope protein and myelin oligodendrocyte glycoprotein (MOG. Comparison of the MOG to the envelope identified five retroviral regions similar to the Ig-like domain of MOG. Interestingly, one of them includes T and B cell epitopes, capable to induce T effector functions and circulating Abs in rats. In sum, although no DNA substitutions that would link ERVWE2 to the MS pathogeny was found, the similarity between the envelope protein to MOG extends the idea that ERVEW2 may be involved on the immunopathogenesis of MS, maybe facilitating the MOG recognizing by the immune system. Although awaiting experimental evidences, the data presented here may expand the scope of the endogenous retroviruses involvement on MS

  15. High Reliability Cryogenic Piezoelectric Valve Actuator Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Cryogenic fluid valves are subject to harsh exposure and actuators to drive these valves require robust performance and high reliability. DSM's piezoelectric...

  16. Cryogenic MEMS Technology for Sensing Applications Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The development of cryogenic microwave components, such as focal plane polarization modulators, first requires an RF MEMS switching technology that operates...

  17. Contemporaryperspective on endogenous myocardial regeneration

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Considering the complex nature of the adult heart,it is no wonder that innate regenerative processes,while maintaining adequate cardiac function, fall shortin myocardial jeopardy. In spite of these enchaining limitations, cardiac rejuvenation occurs as well asrestricted regeneration. In this review, the backgroundas well as potential mechanisms of endogenousmyocardial regeneration are summarized. We presentand analyze the available evidence in three subsequentsteps. First, we examine the experimental researchdata that provide insights into the mechanisms andorigins of the replicating cardiac myocytes, includingcell populations referred to as cardiac progenitor cells(i.e. , c-kit+ cells). Second, we describe the role ofclinical settings such as acute or chronic myocardialischemia, as initiators of pathways of endogenousmyocardial regeneration. Third, the hitherto conductedclinical studies that examined different approachesof initiating endogenous myocardial regeneration infailing human hearts are analyzed. In conclusion, wepresent the evidence in support of the notion thatregaining cardiac function beyond cellular replacementof dysfunctional myocardium via initiation of innateregenerative pathways could create a new perspectiveand a paradigm change in heart failure therapeutics.Reinitiating cardiac morphogenesis by reintroducingdevelopmental pathways in the adult failing heart mightprovide a feasible way of tissue regeneration. Basedon our hypothesis "embryonic recall", we present firstsupporting evidence on regenerative impulses in themyocardium, as induced by developmental processes.

  18. Cryogenic Operation Methodology and Cryogen Management at CERN over the last 15 Years

    CERN Document Server

    Delikaris, D; Claudet, S; Gayet, Ph; Passardi, Giorgio; Serio, L; Tavian, L

    2009-01-01

    CERN, the European Organization for Nuclear Research has progressively implemented and brought into operation an impressive number of cryogenic units (34). The paper will present the evolution of CERN’s cryogenic infrastructure and summarize results from cryogenic operation cumulating 590’000 running hours over the last fifteen years. The implemented methodology allowing reaching a high level of plant reliability will be described. CERN also becomes an intensive user of cryogens. Contracts for the delivery of 320 t of liquid helium and 70’000 t of liquid nitrogen have been adjudicated. The paper will describe the procurement strategy, the storage infrastructure and cryogen inventory.

  19. To Ensure the Integrity of the Cryogenic Propellant Depot Tank Within the Expected Radiation and Space Debris Environment Project

    Data.gov (United States)

    National Aeronautics and Space Administration — We intend to develop the technology for lightweight composite structure suitable for both cryogenic fuel depot storage as well as human in-space habitat. These will...

  20. Development of an androgen reporter gene assay (AR-LUX) utilizing a human cell line with an endogenously regulated androgen receptor

    NARCIS (Netherlands)

    Blankvoort, B.M.G.; Groene, E.M. de; Meeteren-Kreikamp, A.P. van; Witkamp, R.F.; Rodenburg, R.J.T.; Aarts, J.M.M.J.G.

    2001-01-01

    The aim of the work described in this report is to develop and characterize a cell-based androgen reporter assay. For this purpose, the androgen receptor (AR) expressing human breast cancer cell line T47D was stably transfected with a luciferase gene under transcriptional control of the PB-ARE-2 and

  1. The Nuclear Cryogenic Propulsion Stage

    Science.gov (United States)

    Houts, Michael G.; Kim, Tony; Emrich, William J.; Hickman, Robert R.; Broadway, Jeramie W.; Gerrish, Harold P.; Belvin, Anthony D.; Borowski, Stanley K.; Scott, John H.

    2014-01-01

    Nuclear Thermal Propulsion (NTP) development efforts in the United States have demonstrated the technical viability and performance potential of NTP systems. For example, Project Rover (1955 - 1973) completed 22 high power rocket reactor tests. Peak performances included operating at an average hydrogen exhaust temperature of 2550 K and a peak fuel power density of 5200 MW/m3 (Pewee test), operating at a thrust of 930 kN (Phoebus-2A test), and operating for 62.7 minutes in a single burn (NRX-A6 test). Results from Project Rover indicated that an NTP system with a high thrust-to-weight ratio and a specific impulse greater than 900 s would be feasible. Excellent results were also obtained by the former Soviet Union. Although historical programs had promising results, many factors would affect the development of a 21st century nuclear thermal rocket (NTR). Test facilities built in the US during Project Rover no longer exist. However, advances in analytical techniques, the ability to utilize or adapt existing facilities and infrastructure, and the ability to develop a limited number of new test facilities may enable affordable development, qualification, and utilization of a Nuclear Cryogenic Propulsion Stage (NCPS). Bead-loaded graphite fuel was utilized throughout the Rover/NERVA program, and coated graphite composite fuel (tested in the Nuclear Furnace) and cermet fuel both show potential for even higher performance than that demonstrated in the Rover/NERVA engine tests.. NASA's NCPS project was initiated in October, 2011, with the goal of assessing the affordability and viability of an NCPS. FY 2014 activities are focused on fabrication and test (non-nuclear) of both coated graphite composite fuel elements and cermet fuel elements. Additional activities include developing a pre-conceptual design of the NCPS stage and evaluating affordable strategies for NCPS development, qualification, and utilization. NCPS stage designs are focused on supporting human Mars

  2. Drosophila lines with mutant and wild type human TDP-43 replacing the endogenous gene reveals phosphorylation and ubiquitination in mutant lines in the absence of viability or lifespan defects.

    Science.gov (United States)

    Chang, Jer-Cherng; Morton, David B

    2017-01-01

    Mutations in TDP-43 are associated with proteinaceous inclusions in neurons and are believed to be causative in neurodegenerative diseases such as frontotemporal dementia or amyotrophic lateral sclerosis. Here we describe a Drosophila system where we have engineered the genome to replace the endogenous TDP-43 orthologue with wild type or mutant human TDP-43(hTDP-43). In contrast to other models, these flies express both mutant and wild type hTDP-43 at similar levels to those of the endogenous gene and importantly, no age-related TDP-43 accumulation observed among all the transgenic fly lines. Immunoprecipitation of TDP-43 showed that flies with hTDP-43 mutations had increased levels of ubiquitination and phosphorylation of the hTDP-43 protein. Furthermore, histologically, flies expressing hTDP-43 M337V showed global, robust neuronal staining for phospho-TDP. All three lines: wild type hTDP-43, -G294A and -M337V were homozygous viable, with no defects in development, life span or behaviors observed. The primary behavioral defect was that flies expressing either hTDP-43 G294A or M337V showed a faster decline with age in negative geotaxis. Together, these observations implied that neurons could handle these TDP-43 mutations by phosphorylation- and ubiquitin-dependent proteasome systems, even in a background without the wild type TDP-43. Our findings suggest that these two specific TDP-43 mutations are not inherently toxic, but may require additional environmental or genetic factors to affect longevity or survival.

  3. Foam vessel for cryogenic fluid storage

    Science.gov (United States)

    Spear, Jonathan D [San Francisco, CA

    2011-07-05

    Cryogenic storage and separator vessels made of polyolefin foams are disclosed, as are methods of storing and separating cryogenic fluids and fluid mixtures using these vessels. In one embodiment, the polyolefin foams may be cross-linked, closed-cell polyethylene foams with a density of from about 2 pounds per cubic foot to a density of about 4 pounds per cubic foot.

  4. Neutron Detection with Cryogenics and Semiconductors

    Energy Technology Data Exchange (ETDEWEB)

    bell, Z.W.; Carpenter, D.A.; Cristy, S.S.; Lamberti, V.E.

    2005-03-10

    The common methods of neutron detection are reviewed with special attention paid to the application of cryogenics and semiconductors to the problem. The authors' work with LiF- and boron-based cryogenic instruments is described as well as the use of CdTe and HgI{sub 2} for direct detection of neutrons.

  5. Low Mn alloy steel for cryogenic service

    Science.gov (United States)

    Morris, J.W. Jr.; Niikura, M.

    A ferritic cryogenic steel which has a relatively low (about 4 to 6%) manganese content and which has been made suitable for use at cryogenic temperatures by a thermal cycling treatment followed by a final tempering. The steel includes 4 to 6% manganese, 0.02 to 0.06% carbon, 0.1 to 0.4% molybdenum and 0 to 3% nickel.

  6. Continuous-Reading Cryogen Level Sensor

    Science.gov (United States)

    Barone, F. E.; Fox, E.; Macumber, S.

    1984-01-01

    Two pressure transducers used in system for measuring amount of cryogenic liquid in tank. System provides continuous measurements accurate within 0.03 percent. Sensors determine pressure in liquid and vapor in tank. Microprocessor uses pressure difference to compute mass of cryogenic liquid in tank. New system allows continuous sensing; unaffected by localized variations in composition and density as are capacitance-sensing schemes.

  7. Cryogenic fluid management program flight concept definition

    Science.gov (United States)

    Kroeger, Erich

    1987-01-01

    The Lewis Research Center's cryogenic fluid management program flight concept definition is presented in viewgraph form. Diagrams are given of the cryogenic fluid management subpallet and its configuration with the Delta launch vehicle. Information is given in outline form on feasibility studies, requirements definition, and flight experiments design.

  8. Residual contact restraints in cryogenics

    Science.gov (United States)

    Cretegny, J. F.; Demonicault, J. M.

    The use of residual stress measurements to evaluate the state of cryogenic turbomachines, whose surfaces are worn by the working conductions in dry contact, is addressed. Their contribution to the understanding of the reasons of possible ruptures is considered. It is stated that residual stress measurements should be used as a complementary tool rather than as input data for models. It is shown, thanks to two examples concerning the ball bearings and splines of the liquid hydrogen turbopump of the Vulcain engine, what can be expected from such techniques. Total exploitation of the results has still to be done, but preliminary results are quite encouraging.

  9. ISOCAM experiment cryogenic test results

    Science.gov (United States)

    de Sa, L.; Collaudin, B.

    The thermal requirements for ISOCAM, an IR camera to be mounted aboard the ISO satellite, are reviewed, and model predictions are matched with test results. The degree of model validation suggested by analytical prediction vs test results is described. Predictions of thermal conduction through mounting screws, from ball bearings, and of the heat distribution in the rotor and stator of a cryogenic stepper motor correlate well with actual test results. It is shown that ISOCAM meets the thermal requirements necessary for successful on-orbit operation. The model predicted such phenomena as 'chopped' motor function and the twofold increase in temperature resulting from continuous motor operation.

  10. Structural characterization of the binding interactions of various endogenous estrogen metabolites with human estrogen receptor α and β subtypes: a molecular modeling study.

    Directory of Open Access Journals (Sweden)

    Pan Wang

    Full Text Available In the present study, we used the molecular docking approach to study the binding interactions of various derivatives of 17β-estradiol (E2 with human estrogen receptor (ER α and β. First, we determined the suitability of the molecular docking method to correctly predict the binding modes and interactions of two representative agonists (E2 and diethylstilbesterol in the ligand binding domain (LBD of human ERα. We showed that the docked structures of E2 and diethylstilbesterol in the ERα LBD were almost exactly the same as the known crystal structures of ERα in complex with these two estrogens. Using the same docking approach, we then characterized the binding interactions of 27 structurally similar E2 derivatives with the LBDs of human ERα and ERβ. While the binding modes of these E2 derivatives are very similar to that of E2, there are distinct subtle differences, and these small differences contribute importantly to their differential binding affinities for ERs. In the case of A-ring estrogen derivatives, there is a strong inverse relationship between the length of the hydrogen bonds formed with ERs and their binding affinity. We found that a better correlation between the computed binding energy values and the experimentally determined logRBA values could be achieved for various A-ring derivatives by re-adjusting the relative weights of the van der Waals interaction energy and the Coulomb interaction energy in computing the overall binding energy values.

  11. ENDOGENEITY OF INDONESIAN MONEY SUPPLY

    Directory of Open Access Journals (Sweden)

    Meutia Safrina Rachma

    2011-09-01

    Full Text Available There has been a long debate about the endogeneity of money supply. The main objective of this article is to identify whether money supply in Indonesia is an exogenous or an endogenous variable. Using a Vector Autoregressive model and monthly data 1997(5-2010(6, the estimation result shows that money supply in Indonesia is an endogenous variable. The movement of broad money supply does influence the movement of base money and Consumer Price Index. Consequently, the central bank does not have control power on money supply. The bank is only able to maintain the stability and control the movement of broad money supply. Keywords: Endogenous variable, money supply, vector autoregressionJEL classification numbers: E51, E52, E58

  12. Endogenous money and effective demand

    OpenAIRE

    Steve Keen

    2014-01-01

    Endogenous money is a core component of post-Keynesian economics, but it has not been fully integrated into its macroeconomics. To do so requires replacing the accounting truism that ex post expenditure equals ex post income with the endogenous money insight that ex post expenditure equals ex ante income plus the ex post turnover of new debt. This paper derives this result after exploring precedents to this concept in the work of Schumpeter, Minsky, Keynes and Pigou.

  13. 实施人力资源培训工程,增强景颇族经济发展内生动力%To Implement Human Resource Training Project, Enhance Endogenous Power of Jingpo's Economic Development

    Institute of Scientific and Technical Information of China (English)

    郑颖; 高延芳

    2012-01-01

    人力资源是经济发展中最具活力和弹性的因素,是经济发展的原生经济资源之一,是国民财富的最终基础,是实现经济可持续发展的关键要素.景颇族作为德宏州的主体民族之一,人力资源的数量比较充裕,但人力资源的质量不高,影响了自然、能量、信息等经济资源向经济发展优势和区域财政优势的转化.实施人力资源培训工程,提高景颇人民的知识、技能和健康素质,对于提升景颇族经济发展内生动力,构建民族团结进步边疆繁荣稳定示范区有着重大的现实意义.%The human resource is the most dynamic and flexible factor in economic development, is one of the primary economic resources of economic development, is the ultimate foundation of national wealth, is the key element to achieve sustainable economic development. Jingpo As one of the main ethnics of Dehong, the number of human resources in Jingpo nationality is relatively abundant, but the quality of human resources is not high, affecting the conversion to economic development advantage and regional financial advantage from economic resources, such as nature, energy, information etc. To implement human resource training project, the Jingpo people's knowledge, skills and quality of health has great practical significance for enhancing endogenous power of Jingpo's economic development and building demonstration area of national unity and progress and frontier prosperity and stability.

  14. The cryogenic storage ring CSR.

    Science.gov (United States)

    von Hahn, R; Becker, A; Berg, F; Blaum, K; Breitenfeldt, C; Fadil, H; Fellenberger, F; Froese, M; George, S; Göck, J; Grieser, M; Grussie, F; Guerin, E A; Heber, O; Herwig, P; Karthein, J; Krantz, C; Kreckel, H; Lange, M; Laux, F; Lohmann, S; Menk, S; Meyer, C; Mishra, P M; Novotný, O; O'Connor, A P; Orlov, D A; Rappaport, M L; Repnow, R; Saurabh, S; Schippers, S; Schröter, C D; Schwalm, D; Schweikhard, L; Sieber, T; Shornikov, A; Spruck, K; Sunil Kumar, S; Ullrich, J; Urbain, X; Vogel, S; Wilhelm, P; Wolf, A; Zajfman, D

    2016-06-01

    An electrostatic cryogenic storage ring, CSR, for beams of anions and cations with up to 300 keV kinetic energy per unit charge has been designed, constructed, and put into operation. With a circumference of 35 m, the ion-beam vacuum chambers and all beam optics are in a cryostat and cooled by a closed-cycle liquid helium system. At temperatures as low as (5.5 ± 1) K inside the ring, storage time constants of several minutes up to almost an hour were observed for atomic and molecular, anion and cation beams at an energy of 60 keV. The ion-beam intensity, energy-dependent closed-orbit shifts (dispersion), and the focusing properties of the machine were studied by a system of capacitive pickups. The Schottky-noise spectrum of the stored ions revealed a broadening of the momentum distribution on a time scale of 1000 s. Photodetachment of stored anions was used in the beam lifetime measurements. The detachment rate by anion collisions with residual-gas molecules was found to be extremely low. A residual-gas density below 140 cm(-3) is derived, equivalent to a room-temperature pressure below 10(-14) mbar. Fast atomic, molecular, and cluster ion beams stored for long periods of time in a cryogenic environment will allow experiments on collision- and radiation-induced fragmentation processes of ions in known internal quantum states with merged and crossed photon and particle beams.

  15. Cryogenics for HL-LHC

    CERN Document Server

    Tavian, L; Claudet, S; Ferlin, G; Wagner, U; van Weelderen, R

    2015-01-01

    The discovery of a Higgs boson at CERN in 2012 is the start of a major program of work to measure this particle's properties with the highest possible precision for testing the validity of the Standard Model and to search for further new physics at the energy frontier. The LHC is in a unique position to pursue this program. Europe's top priority is the exploitation of the full potential of the LHC, including the high-luminosity upgrade of the machine and detectors with an objective to collect ten times more data than in the initial design, by around 2030. To reach this objective, the LHC cryogenic system must be upgraded to withstand higher beam current and higher luminosity at top energy while keeping the same operation availability by improving the collimation system and the protection of electronics sensitive to radiation. This chapter will present the conceptual design of the cryogenic system upgrade with recent updates in performance requirements, the corresponding layout and architecture of the system a...

  16. The cryogenic storage ring CSR

    Science.gov (United States)

    von Hahn, R.; Becker, A.; Berg, F.; Blaum, K.; Breitenfeldt, C.; Fadil, H.; Fellenberger, F.; Froese, M.; George, S.; Göck, J.; Grieser, M.; Grussie, F.; Guerin, E. A.; Heber, O.; Herwig, P.; Karthein, J.; Krantz, C.; Kreckel, H.; Lange, M.; Laux, F.; Lohmann, S.; Menk, S.; Meyer, C.; Mishra, P. M.; Novotný, O.; O'Connor, A. P.; Orlov, D. A.; Rappaport, M. L.; Repnow, R.; Saurabh, S.; Schippers, S.; Schröter, C. D.; Schwalm, D.; Schweikhard, L.; Sieber, T.; Shornikov, A.; Spruck, K.; Sunil Kumar, S.; Ullrich, J.; Urbain, X.; Vogel, S.; Wilhelm, P.; Wolf, A.; Zajfman, D.

    2016-06-01

    An electrostatic cryogenic storage ring, CSR, for beams of anions and cations with up to 300 keV kinetic energy per unit charge has been designed, constructed, and put into operation. With a circumference of 35 m, the ion-beam vacuum chambers and all beam optics are in a cryostat and cooled by a closed-cycle liquid helium system. At temperatures as low as (5.5 ± 1) K inside the ring, storage time constants of several minutes up to almost an hour were observed for atomic and molecular, anion and cation beams at an energy of 60 keV. The ion-beam intensity, energy-dependent closed-orbit shifts (dispersion), and the focusing properties of the machine were studied by a system of capacitive pickups. The Schottky-noise spectrum of the stored ions revealed a broadening of the momentum distribution on a time scale of 1000 s. Photodetachment of stored anions was used in the beam lifetime measurements. The detachment rate by anion collisions with residual-gas molecules was found to be extremely low. A residual-gas density below 140 cm-3 is derived, equivalent to a room-temperature pressure below 10-14 mbar. Fast atomic, molecular, and cluster ion beams stored for long periods of time in a cryogenic environment will allow experiments on collision- and radiation-induced fragmentation processes of ions in known internal quantum states with merged and crossed photon and particle beams.

  17. Simulations of Cavitating Cryogenic Inducers

    Science.gov (United States)

    Dorney, Dan (Technical Monitor); Hosangadi, Ashvin; Ahuja, Vineet; Ungewitter, Ronald J.

    2004-01-01

    Simulations of cavitating turbopump inducers at their design flow rate are presented. Results over a broad range of Nss, numbers extending from single-phase flow conditions through the critical head break down point are discussed. The flow characteristics and performance of a subscale geometry designed for water testing are compared with the fullscale configuration that employs LOX. In particular, thermal depression effects arising from cavitation in cryogenic fluids are identified and their impact on the suction performance of the inducer quantified. The simulations have been performed using the CRUNCH CFD[R] code that has a generalized multi-element unstructured framework suitable for turbomachinery applications. An advanced multi-phase formulation for cryogenic fluids that models temperature depression and real fluid property variations is employed. The formulation has been extensively validated for both liquid nitrogen and liquid hydrogen by simulating the experiments of Hord on hydrofoils; excellent estimates of the leading edge temperature and pressure depression were obtained while the comparisons in the cavity closure region were reasonable.

  18. Two-photon excited endogenous fluorescence for label-free in vivo imaging ingestion of disease-causing bacteria by human leukocytes

    Science.gov (United States)

    Zeng, Yan; Yan, Bo; Sun, Qiqi; Teh, Seng Khoon; Zhang, Wei; Wen, Zilong; Qu, Jianan Y.

    2013-02-01

    Real time and in vivo monitoring leukocyte behavior provides unique information to understand the physiological and pathological process of infection. In this study, we demonstrate that two-photon excited reduced nicotinamide adenine dinucleotide (NADH) fluorescence provides imaging contrast to distinguish granulocyte and agranulocyte. By using spectral and time-resolved NADH fluorescence, we study the immune response of human neutrophils against bacterial infection (Escherichia coli). The two-photon excited NADH fluorescence images clearly review the morphological changes from resting neutrophils (round shape) to activated neutrophils (ruffle shape) during phagocytosis. The free-tobound NADH ratio of neutrophils decreases after ingesting disease-causing pathogen: Escherichia coli. This finding may provide a new optical tool to investigate inflammatory processes by using NADH fluorescence in vivo.

  19. Induction of Neurorestoration From Endogenous Stem Cells.

    Science.gov (United States)

    Yu, Ji Hea; Seo, Jung-Hwa; Lee, Ji Yong; Lee, Min-Young; Cho, Sung-Rae

    2016-01-01

    Neural stem cells (NSCs) persist in the subventricular zone lining the ventricles of the adult brain. The resident stem/progenitor cells can be stimulated in vivo by neurotrophic factors, hematopoietic growth factors, magnetic stimulation, and/or physical exercise. In both animals and humans, the differentiation and survival of neurons arising from the subventricular zone may also be regulated by the trophic factors. Since stem/progenitor cells present in the adult brain and the production of new neurons occurs at specific sites, there is a possibility for the treatment of incurable neurological diseases. It might be feasible to induce neurogenesis, which would be particularly efficacious in the treatment of striatal neurodegenerative conditions such as Huntington's disease, as well as cerebrovascular diseases such as ischemic stroke and cerebral palsy, conditions that are widely seen in the clinics. Understanding of the molecular control of endogenous NSC activation and progenitor cell mobilization will likely provide many new opportunities as therapeutic strategies. In this review, we focus on endogenous stem/progenitor cell activation that occurs in response to exogenous factors including neurotrophic factors, hematopoietic growth factors, magnetic stimulation, and an enriched environment. Taken together, these findings suggest the possibility that functional brain repair through induced neurorestoration from endogenous stem cells may soon be a clinical reality.

  20. Comparison of the effect of timegadine, levamisole, and D-penicillamine on human neutrophil metabolism of endogenous arachidonic acid and chemotaxis

    Energy Technology Data Exchange (ETDEWEB)

    Nielsen, O.H.; Ahnfelt-Roenne, I. Department of Pharmacology, Leo Pharmaceutical Products, Ballerup; Elmgreen, J.

    1988-01-01

    The effect of timegadine, a novel experimental antirheumatic drug, on human neutrophil (PMN) 5-lipoxygenase activity and leukotriene B/sub 4/ (LTB/sub 4/) chemotaxis was compared with that of two second-line antiinflammatory drugs, D-penicillamine and levamisole. 1-/sup 14/C-Arachidonic acid (AA) was incorporated into the purified cells until steady state conditions were obtained. After preincubation with serial dilutions of the three drugs, AA release and metabolism was stimulated with calcium ionophore A23187. The radioactive eicosanoids released were extracted and separated by thinlayer chromatography, followed by autoradiography and quantitative laser densitometry. Chemotaxi of PMNs towards LTB/sub 4/ was measured in a modified Boyden chamber. Timegardine showed dose-dependent inhibition of both the 5-lipoxygenase pathway (IC50 3.4 x 10/sup -5/ M), and of chemotaxis (IC50 3 x 10/sup -4/ M). Inhibition of the release of AA from phospholipids, however, occurred only at therapeutically irrelevant doses (millimolar concentrations). Levamisole and D-penicillamine did not inhibit any of the cell functions investigated. Inhibition of both neutrophil motility and cellular synthesis of pro-inflammatory eicosanoids, may thus contribute to the clinical effects of timegadine in rheumatoid arthritis.

  1. 内源性IL-12决定人PBMC产生干扰素γ的水平%Endogenous production of IL-12 is critical for optimal production of interferon-γby human PBMC

    Institute of Scientific and Technical Information of China (English)

    孙晗笑; 杨滨燕; 李波; 娄阁; 吴长有

    2002-01-01

    Objective: IFN-γ is produced by both activated T andNK cells in response to mitogen or antigen and has a broad range of immunoregulatory activity. IL- 12 has been described as a strong inducer of IFN-γ production and promotes the differentiation of naive C D4+ T cells toward the Thl phenotype,priming them for IFN-γproduction,and consequent induction ofcell-mediated immunity. Aim is to know endogenous production of IL- 12 from PBMC inducing production of IFN-γ in vitro, which is involving in mechanism of T cells to be activated. Methods: Induced IFN-γ secretion from human PBMC by stimulated with anfi-CD3,PHA,anti-CD3 plus anti-CD28 and antigen(MLC).Also inhibited IFNγ production by neutralizing antibodies to IL-12 and IL-12Rβ1 significantly. Results: IFN-γ secretion from human activated PBMC is endogenous IL-12 dependent, and activated T cells induce the production ofIL-12 from APC by a mechanism involving the interaction between CD40L on T cells and CD40 on APC. Conclusion: These results suggest that endogenous IL- 12.plays an important role in the normal host defense against infection by a variety of intracellular pathogens and also plays a central role in the genesis of some forms of immunopathology including autoimmune diseases and transplantation rejections.%目的:IFN-γ是由被有丝分裂原或抗原所激活的T细胞和NK细胞所产生,它具有广泛的免疫调节活性,现认为IL-12(外源性)是诱导IFN-γ产生的强诱导剂,并可促进静息CD4+T细胞朝向Thl表型分化,即诱导细胞免疫.目的是为了解由PBMC产生的内源性R-12是否在体外可诱导IFN-γ的产生及通过何机制诱导细胞免疫.方法:用抗CD3抗体、PHA、抗CD3抗体加抗CD28抗体和抗原(MLC)来检测被刺激的PBMC细胞的IFN-γ的产生,同时也用IL-12和IL-12Rβ1的中和抗体来抑制IFN-γ的产生.结果:激活的人PBMC中IFN-γ分泌依赖于内源性IL-12的产生,而且激活的T细胞可诱导APC细胞产生IL-l2,此过

  2. Hybrid Composite Cryogenic Tank Structure

    Science.gov (United States)

    DeLay, Thomas

    2011-01-01

    A hybrid lightweight composite tank has been created using specially designed materials and manufacturing processes. The tank is produced by using a hybrid structure consisting of at least two reinforced composite material systems. The inner composite layer comprises a distinct fiber and resin matrix suitable for cryogenic use that is a braided-sleeve (and/or a filamentwound layer) aramid fiber preform that is placed on a removable mandrel (outfitted with metallic end fittings) and is infused (vacuum-assisted resin transfer molded) with a polyurethane resin matrix with a high ductility at low temperatures. This inner layer is allowed to cure and is encapsulated with a filamentwound outer composite layer of a distinct fiber resin system. Both inner and outer layer are in intimate contact, and can also be cured at the same time. The outer layer is a material that performs well for low temperature pressure vessels, and it can rely on the inner layer to act as a liner to contain the fluids. The outer layer can be a variety of materials, but the best embodiment may be the use of a continuous tow of carbon fiber (T-1000 carbon, or others), or other high-strength fibers combined with a high ductility epoxy resin matrix, or a polyurethane matrix, which performs well at low temperatures. After curing, the mandrel can be removed from the outer layer. While the hybrid structure is not limited to two particular materials, a preferred version of the tank has been demonstrated on an actual test tank article cycled at high pressures with liquid nitrogen and liquid hydrogen, and the best version is an inner layer of PBO (poly-pphenylenebenzobisoxazole) fibers with a polyurethane matrix and an outer layer of T-1000 carbon with a high elongation epoxy matrix suitable for cryogenic temperatures. A polyurethane matrix has also been used for the outer layer. The construction method is ideal because the fiber and resin of the inner layer has a high strain to failure at cryogenic

  3. Endogenous rhythms influence interpersonal synchrony.

    Science.gov (United States)

    Zamm, Anna; Wellman, Chelsea; Palmer, Caroline

    2016-05-01

    Interpersonal synchrony, the temporal coordination of actions between individuals, is fundamental to social behaviors from conversational speech to dance and music-making. Animal models indicate constraints on synchrony that arise from endogenous rhythms: Intrinsic periodic behaviors or processes that continue in the absence of change in external stimulus conditions. We report evidence for a direct causal link between endogenous rhythms and interpersonal synchrony in a music performance task, which places high demands on temporal coordination. We first establish that endogenous rhythms, measured by spontaneous rates of individual performance, are stable within individuals across stimulus materials, limb movements, and time points. We then test a causal link between endogenous rhythms and interpersonal synchrony by pairing each musician with a partner who is either matched or mismatched in spontaneous rate and by measuring their joint behavior up to 1 year later. Partners performed melodies together, using either the same or different hands. Partners who were matched for spontaneous rate showed greater interpersonal synchrony in joint performance than mismatched partners, regardless of hand used. Endogenous rhythms offer potential to predict optimal group membership in joint behaviors that require temporal coordination.

  4. Cryogenic vacuumm RF feedthrough device

    Science.gov (United States)

    Wu, Genfa [Yorktown, VA; Phillips, Harry Lawrence [Hayes, VA

    2008-12-30

    A cryogenic vacuum rf feedthrough device comprising: 1) a probe for insertion into a particle beam; 2) a coaxial cable comprising an inner conductor and an outer conductor, a dielectric/insulating layer surrounding the inner conductor, the latter being connected to the probe for the transmission of higher mode rf energy from the probe; and 3) a high thermal conductivity stub attached to the coaxial dielectric about and in thermal contact with the inner conductor which high thermal conductivity stub transmits heat generated in the vicinity of the probe efficiently and radially from the area of the probe and inner conductor all while maintaining useful rf transmission line characteristics between the inner and outer coaxial conductors.

  5. The Nuclear Cryogenic Propulsion Stage

    Science.gov (United States)

    Houts, Michael G.; Kim, Tony; Emrich, William J.; Hickman, Robert R.; Broadway, Jeramie W.; Gerrish, Harold P.; Doughty, Glen; Belvin, Anthony; Borowski, Stanley K.; Scott, John

    2014-01-01

    The fundamental capability of Nuclear Thermal Propulsion (NTP) is game changing for space exploration. A first generation Nuclear Cryogenic Propulsion Stage (NCPS) based on NTP could provide high thrust at a specific impulse above 900 s, roughly double that of state of the art chemical engines. Characteristics of fission and NTP indicate that useful first generation systems will provide a foundation for future systems with extremely high performance. The role of the NCPS in the development of advanced nuclear propulsion systems could be analogous to the role of the DC-3 in the development of advanced aviation. Progress made under the NCPS project could help enable both advanced NTP and advanced Nuclear Electric Propulsion (NEP). Nuclear propulsion can be affordable and viable compared to other propulsion systems and must overcome a biased public fear due to hyper-environmentalism and a false perception of radiation and explosion risk.

  6. Photomultiplier Tubes at Cryogenic Temperatures

    Science.gov (United States)

    Saunders, Nathan

    2016-09-01

    Liquid noble gas scintillators are widely used in experiments searching for physics beyond the Standard Model. Photomultiplier Tubes (PMTs) working at cryogenic temperatures have been developed as the primary light readout device in those experiments. Three PMTs from Hamamatsu Photonics K.K. (R6041, R11065, and R8520) have been systematically characterized at liquid nitrogen temperature. The high voltage dividing circuits for two of the PMTs were custom-built to make sure there is similar performance at both room and liquid nitrogen temperatures. Their dark count rates at both temperatures were measured. Also measured were their single photoelectron responses at both temperatures using 300, 340, 370, and 420 nm LEDs. The intention is to couple these PMTs directly with inorganic scintillators at liquid nitrogen temperature to achieve high light yeilds for rare-event searches.

  7. A Cryogenic Infrared Calibration Target

    Science.gov (United States)

    Wollack, E. J.; Kinzer, R. E., Jr.; Rinehart, S. A.

    2014-01-01

    A compact cryogenic calibration target is presented that has a peak diffuse reflectance, R < or = 0.003, from 800 to 4800/cm (12 - 2 microns ). Upon expanding the spectral range under consideration to 400-10,000/ cm-1 (25 - 1 microns) the observed performance gracefully degrades to R < or = 0.02 at the band edges. In the implementation described, a high-thermal-conductivity metallic substrate is textured with a pyramidal tiling and subsequently coated with a thin lossy dielectric coating that enables high absorption and thermal uniformity across the target. The resulting target assembly is lightweight, has a low-geometric profile, and has survived repeated thermal cycling from room temperature to approx.4 K. Basic design considerations, governing equations, and test data for realizing the structure described are provided. The optical properties of selected absorptive materials-Acktar Fractal Black, Aeroglaze Z306, and Stycast 2850 FT epoxy loaded with stainless steel powder-are characterized and presented

  8. Computed tomography of cryogenic cells

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, Gerd; Anderson, E.; Vogt, S.; Knochel, C.; Weiss, D.; LeGros, M.; Larabell, C.

    2001-08-30

    Due to the short wavelengths of X-rays and low numerical aperture of the Fresnel zone plates used as X-ray objectives, the depth of field is several microns. Within the focal depth, imaging a thick specimen is to a good approximation equivalent to projecting the specimen absorption. Therefore, computed tomography based on a tilt series of X-ray microscopic images can be used to reconstruct the local linear absorption coefficient and image the three-dimensional specimen structure. To preserve the structural integrity of biological objects during image acquisition, microscopy is performed at cryogenic temperatures. Tomography based on X-ray microscopic images was applied to study the distribution of male specific lethal 1 (MSL-1), a nuclear protein involved in dosage compensation in Drosophila melanogaster, which ensures that males with single X chromosome have the same amount of most X-linked gene products as females with two X chromosomes. Tomographic reconstructions of X-ray microscopic images were used to compute the local three-dimensional linear absorption coefficient revealing the arrangement of internal structures of Drosophila melanogaster cells. Combined with labelling techniques, nanotomography is a new technique to study the 3D distribution of selected proteins inside whole cells. We want to improve this technique with respect to resolution and specimen preparation. The resolution in the reconstruction can be significantly improved by reducing the angular step size to collect more viewing angles, which requires an automated data acquisition. In addition, fast-freezing with liquid ethane instead of cryogenic He gas will be applied to improve the vitrification of the hydrated samples. We also plan to apply cryo X-ray nanotomography in order to study different types of cells and their nuclear protein distributions.

  9. Endogenous surfactant metabolism in critically ill infants measured with stable isotope labeled fatty acids

    NARCIS (Netherlands)

    Cogo, PE; Carnielli, VP; Bunt, JEH; Badon, T; Giordano, G; Zacchello, F; Sauer, PJJ; Zimmermann, LJI

    1999-01-01

    Little is known about endogenous surfactant metabolism in infants, because radioactive isotopes used for this purpose in animals cannot be used in humans. We developed a novel and safe method to measure the endogenous surfactant kinetics in vivo in humans by using stable isotope labeled fatty acids.

  10. Longitudinal testing of hippocampal plasticity reveals the onset and maintenance of endogenous human Aß-induced synaptic dysfunction in individual freely behaving pre-plaque transgenic rats: rapid reversal by anti-Aß agents.

    Science.gov (United States)

    Qi, Yingjie; Klyubin, Igor; Harney, Sarah C; Hu, NengWei; Cullen, William K; Grant, Marianne K; Steffen, Julia; Wilson, Edward N; Do Carmo, Sonia; Remy, Stefan; Fuhrmann, Martin; Ashe, Karen H; Cuello, A Claudio; Rowan, Michael J

    2014-12-24

    Long before synaptic loss occurs in Alzheimer's disease significant harbingers of disease may be detected at the functional level. Here we examined if synaptic long-term potentiation is selectively disrupted prior to extracellular deposition of Aß in a very complete model of Alzheimer's disease amyloidosis, the McGill-R-Thy1-APP transgenic rat. Longitudinal studies in freely behaving animals revealed an age-dependent, relatively rapid-onset and persistent inhibition of long-term potentiation without a change in baseline synaptic transmission in the CA1 area of the hippocampus. Thus the ability of a standard 200 Hz conditioning protocol to induce significant NMDA receptor-dependent short- and long-term potentiation was lost at about 3.5 months of age and this deficit persisted for at least another 2-3 months, when plaques start to appear. Consistent with in vitro evidence for a causal role of a selective reduction in NMDA receptor-mediated synaptic currents, the deficit in synaptic plasticity in vivo was associated with a reduction in the synaptic burst response to the conditioning stimulation and was overcome using stronger 400 Hz stimulation. Moreover, intracerebroventricular treatment for 3 days with an N-terminally directed monoclonal anti- human Aß antibody, McSA1, transiently reversed the impairment of synaptic plasticity. Similar brief treatment with the BACE1 inhibitor LY2886721 or the γ-secretase inhibitor MRK-560 was found to have a comparable short-lived ameliorative effect when tracked in individual rats. These findings provide strong evidence that endogenously generated human Aß selectively disrupts the induction of long-term potentiation in a manner that enables potential therapeutic options to be assessed longitudinally at the pre-plaque stage of Alzheimer's disease amyloidosis.

  11. Sprayable Thermal Insulation for Cryogenic Tanks Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The Sprayable Thermal Insulation for Cryogenic Tanks (STICT) is a thermal management system applied by either an automated or manual spraying process with less...

  12. Cryogenic fatigue data developed for Inconel 718

    Science.gov (United States)

    Schmidt, E. H.

    1967-01-01

    Data were obtained on the cryogenic fatigue properties of Inconel 718 bar using axial loading and rotating beam fatigue tests. Results also disclosed the fatigue properties of Inconel 718 sheet materials.

  13. Temperature Stratification in a Cryogenic Fuel Tank

    Data.gov (United States)

    National Aeronautics and Space Administration — A reduced dynamical model describing temperature stratification effects driven by natural convection in a liquid hydrogen cryogenic fuel tank has been developed. It...

  14. Advanced Insulation Techniques for Cryogenic Tanks Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The ability to store large amounts of cryogenic fluids for long durations has a profound effect on the success of many future space programs using these fluids for...

  15. Cryogenic and Vacuum Compatible Metrology Systems Project

    Data.gov (United States)

    National Aeronautics and Space Administration — In this Phase I SBIR project for NASA, Flexure Engineering of Greenbelt, MD will leverage the work we did in our current SBIR project entitled: Cryogenic Optical...

  16. A brief overview of cryogenics in China

    Science.gov (United States)

    Li, S.-M.

    In this paper general aspects of cryogenics in China are introduced, and applications of cryogenics in the space programme are described briefly, such as its application to the Long March 3 rocket vehicles with LH2/LO2 engines, the development of a 750 dm 3 hr -1 liquid hydrogen plant and railway tank cars with 60 and 70 m 3 capacities. In addition, the progress of various cryogenic techniques in China is presented, such as the FY-1 radiation refrigerator loaded on a meteorology satellite, regenerative cryocoolers of the Gifford-McMahon, Solvay, Vuilleumier, Stirling and pulse tube types, and the KM-3 and KM-4 space simulation facilities. Finally, the paper discusses current education about refrigeration and cryogenics for undergraduates and graduates.

  17. Cryogenic Safety Rules and Guidelines at CERN

    CERN Document Server

    CERN. Geneva

    2016-01-01

    CERN defines and implements a Safety Policy that sets out the general principles governing safety at CERN. As an intergovernmental organisation, CERN further establishes its own Safety Rules as necessary for its proper functioning. In this process, it takes into account the laws and regulation of the Host States (France and Switzerland), EU regulations and directives, as well as international regulations, standards and directives. For the safety of cryogenic equipment, this is primarily covered by the Safety Regulation for Mechanical Equipment and the General Safety Instruction for Cryogenic Equipment. In addition, CERN has also developed Safety Guidelines to support the implementation of these safety rules, covering cryogenic equipment and oxygen deficiency hazard assessment and mitigation. An overview of the cryogenic safety rules and these safety guidelines will be presented.

  18. Small Scroll Pump for Cryogenic Liquids Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The innovation is a compact, reliable, light weight, electrically driven pump capable of pumping cryogenic liquids, based on scroll pump technology. This pump will...

  19. Sprayable Thermal Insulation for Cryogenic Tanks Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The innovation addressed in this proposal is Sprayable Thermal Insulation for Cryogenic Tanks, or STICT. This novel system could be applied in either an automated or...

  20. Visual-Inspection Probe For Cryogenic Chamber

    Science.gov (United States)

    Friend, Steve; Valenzuela, James; Yoshinaga, Jay

    1990-01-01

    Visual-inspection probe that resembles borescope enables observer at ambient temperature to view objects immersed in turbulent flow of liquid oxygen, liquid nitrogen, or other cryogenic fluid. Design of probe fairly conventional, except special consideration given to selection of materials and to thermal expansion to provide for expected range of operating temperatures. Penetrates wall of cryogenic chamber to provide view of interior. Similar probe illuminates scene. View displayed on video monitor.

  1. Academic Training: Introduction to cryogenic Engineering

    CERN Multimedia

    Françoise Benz

    2005-01-01

    2005-2006 ACADEMIC TRAINING PROGRAMME LECTURE SERIES 5, 6, 7, 8 and 9 December from 11:00 to 12:00 - Main Auditorium, bldg. 500 Introduction to cryogenic Engineering by G. Perinic - CERN-AT Cryogenic engineering is one of the key technologies at CERN. It is widely used in research and has many applications in industry and last but not least in medicine. In research cryogenic engineering and its applications are omnipresent from the smallest laboratories to fusion reactors, hughe detectors and accelerators. With the termination of the LHC, CERN will in fact become the world's largest cryogenic installation. This series of talks intends to introduce the non-cryogenist to the basic principles and challenges of cryogenic engineering and its applications. The course will also provide a basis for practical application as well as for further learning. From history to modern refrigeration cycles (1/5) Refrigerants, standard cryostats, cryogenic design (2/5) Heat transfer and insulation (3/5) Safety in cryoge...

  2. Academic Training: Introduction to cryogenic Engineering

    CERN Multimedia

    Françoise Benz

    2005-01-01

    2005-2006 ACADEMIC TRAINING PROGRAMME LECTURE SERIES 5, 6, 7, 8 and 9 December from 11:00 to 12:00 - Main Auditorium, bldg. 500 Introduction to cryogenic Engineering by G. Perinic - CERN-AT Cryogenic engineering is one of the key technologies at CERN. It is widely used in research and has many applications in industry and last but not least in medicine. In research cryogenic engineering and its applications are omnipresent from the smallest laboratories to fusion reactors, huge detectors and accelerators. With the termination of the LHC, CERN will in fact become the world’s largest cryogenic installation. This series of talks intends to introduce the non-cryogenist to the basic principles and challenges of cryogenic engineering and its applications. The course will also provide a basis for practical application as well as for further learning. Monday 5.12.2005 Introduction: From History to Modern Refrigeration Cycles (Goran Perinic) Tuesday 6.12.2005 Refrigerants, Standard Cryostats, Cryogenic Des...

  3. Flight Performance of the AKARI Cryogenic System

    CERN Document Server

    Nakagawa, Takao; Hirabayashi, Masayuki; Kaneda, Hidehiro; Kii, Tsuneo; Kimura, Yoshiyuki; Matsumoto, Toshio; Murakami, Hiroshi; Murakami, Masahide; Narasaki, Katsuhiro; Narita, Masanao; Ohnishi, Akira; Tsunematsu, Shoji; Yoshida, Seiji

    2007-01-01

    We describe the flight performance of the cryogenic system of the infrared astronomical satellite AKARI, which was successfully launched on 2006 February 21 (UT). AKARI carries a 68.5 cm telescope together with two focal plane instruments, Infrared Cameras (IRC) and Far Infrared Surveyor (FIS), all of which are cooled down to cryogenic temperature to achieve superior sensitivity. The AKARI cryogenic system is a unique hybrid system, which consists of cryogen (liquid helium) and mechanical coolers (2-stage Stirling coolers). With the help of the mechanical coolers, 179 L (26.0 kg) of super-fluid liquid helium can keep the instruments cryogenically cooled for more than 500 days. The on-orbit performance of the AKARI cryogenics is consistent with the design and pre-flight test, and the boil-off gas flow rate is as small as 0.32 mg/s. We observed the increase of the major axis of the AKARI orbit, which can be explained by the thrust due to thermal pressure of vented helium gas.

  4. L-arginine activates expression of endogenous coagulation factor Ⅷ in human normal liver cells%L-精氨酸对人肝细胞中内源凝血因子Ⅷ表达的激活作用

    Institute of Scientific and Technical Information of China (English)

    朱重阳; 李鑫; 温泉; 张军

    2012-01-01

    目的 探讨L-精氨酸对人肝细胞LO2中内源凝血因子Ⅷ(Coagulation factorⅧ,FⅧ)表达的激活作用.方法 将LO2细胞分为试验组和对照组,试验组加入L-精氨酸(终浓度为10 mmol/L)分别培养24、36、48和60 h,对照组用等体积的灭菌水取代L-精氨酸培养.采用RT-PCR法检测LO2细胞中人FⅧ基因mRNA的转录水平并测序鉴定,一期法检测细胞培养上清液中人FⅧ的促凝活性(FⅧ:C),Western blot检测24、48 h时相点LO2细胞中人FⅧ蛋白的表达,免疫荧光染色结合激光共聚焦显微镜观察L-精氨酸作用48 h后LO2细胞中人FⅧ的表达.结果 加入L-精氨酸培养36、48、60 h后,LO2细胞中有人FⅧ基因mRNA的转录,而对照组未出现人FⅧ基因mRNA的转录;各时相点两组细胞培养上清液中人FⅧ:C的水平差异均无统计学意义(P>0.05);Western blot及激光共聚焦均观察到加L-精氨酸培养48 h后LO2细胞中出现人FⅧ的表达,而对照组细胞中均无人FⅧ的表达.结论 L-精氨酸可激活人正常肝细胞中内源FⅧ的表达.%Objective To explore the activating effect of L-arginine on expression of endogenous coagulation factor Ⅷ (Ⅷ) in human normal liver LO2 cells. Methods LO2 cells were divided into test and control groups. The cells in test group were treated with L-arginine (at afinal concentration of 10 mmol/L) for 24, 36, 48 and 60 h respectively, while those in control group with physiological saline. The transcription level of FⅧ mRNA in LO2 cells was determined by RT-PCR, and the PCR product was sequenced. The cell culture supernatant was collected and determined for clotting activity of human FⅧ (FⅧ : C) by one-stage method. The expressions of Ⅷ in LO2 cells 24 and 48 h after treatment were determined by Western blot, and that 48 h after treatment by IFA combined with laser confocal microscopy. Results Transcription of FⅧ mRNA was observed in the cells 36, 48 and 60 h after treatment with L

  5. ENDOGENOUS SCHEDULING PREFERENCES AND CONGESTION

    DEFF Research Database (Denmark)

    Fosgerau, Mogens; Small, Kenneth

    2017-01-01

    We consider the timing of activities through a dynamic model of commuting with congestion, in which workers care solely about leisure and consumption. Implicit preferences for the timing of the commute form endogenously due to temporal agglomeration economies. Equilibrium exists uniquely and is i...

  6. Endogenous Fibrinolysis and Vascular Disease

    Institute of Scientific and Technical Information of China (English)

    彭林

    2004-01-01

    @@ The fate of a forming thrombus is determined through the delicate balance between the coagulation cascade (favouring clot formation) and the fibrinolytic system (favouring clot lysis). These processes occur simultaneously, and enhancement of endogenous fibrinolysis has been shown to reduce occlusive thrombus formation in animal models.

  7. A note on endogenous transfers

    NARCIS (Netherlands)

    S. Brakman (Steven); J.G.M. van Marrewijk (Charles)

    1991-01-01

    textabstractIn a competitive and Walrasian stable world with two goods transfer paradoxes are very robust to endogenization (relating the size of the transfer to either the donor's or the recipient's GNP). Donor enrichment and/or recipient impoverishment occur in very general formulations of

  8. Light-Weight Injector Technology for Cryogenic Mars Ascent Engines

    Science.gov (United States)

    Trihn, Huu Phuoc; Cramer, John M.

    1998-01-01

    Preliminary mission studies for human exploration of Mars have been performed at Marshall Space Flight Center (MSFC). These studies indicate that for chemical rockets only a cryogenic propulsion system would provide high enough performance to be considered for a Mars ascent vehicle. Although the mission is possible with Earth-supplied propellants for this vehicle, utilization of in-situ propellants is highly attractive. This option would significantly reduce the overall mass of launch vehicles. Consequently, the cost of the mission would be greatly reduced because the number and size of the Earth launch vehicle(s) needed for the mission decrease. NASA/Johnson Space Center has initiated several concept studies of in-situ propellant production plants. Liquid oxygen (LOX) is the primary candidate for an in-situ oxidizer. In-situ fuel candidates include methane (CH4), ethylene (C2H4), and methanol (CH3OH). MSFC initiated a technology development program for a cryogenic propulsion system for the Mars human exploration mission in 1998. One part of this technology program is the effort described here: an evaluation of propellant injection concepts for a LOX/liquid methane Mars Ascent Engine (MAE) with an emphasis on light-weight, high efficiency, reliability, and thermal compatibility. In addition to the main objective, hot-fire tests of the subject injectors will be used to test other key technologies including light-weight combustion chamber materials and advanced ignition concepts. This state-of-the-art technology will then be applied to the development of a cryogenic propulsion system that will meet the requirements of the planned Mars sample return (MSR) mission. The current baseline propulsion system for the MSR mission uses a storable propellant combination [monomethyl hydrazine/mixed oxides of nitrogen-25. However, a mission option that incorporates in-situ propellant production and utilization for the ascent stage is being carefully considered as a subscale

  9. Cryogenic ion chemistry and spectroscopy.

    Science.gov (United States)

    Wolk, Arron B; Leavitt, Christopher M; Garand, Etienne; Johnson, Mark A

    2014-01-21

    The use of mass spectrometry in macromolecular analysis is an incredibly important technique and has allowed efficient identification of secondary and tertiary protein structures. Over 20 years ago, Chemistry Nobelist John Fenn and co-workers revolutionized mass spectrometry by developing ways to non-destructively extract large molecules directly from solution into the gas phase. This advance, in turn, enabled rapid sequencing of biopolymers through tandem mass spectrometry at the heart of the burgeoning field of proteomics. In this Account, we discuss how cryogenic cooling, mass selection, and reactive processing together provide a powerful way to characterize ion structures as well as rationally synthesize labile reaction intermediates. This is accomplished by first cooling the ions close to 10 K and condensing onto them weakly bound, chemically inert small molecules or rare gas atoms. This assembly can then be used as a medium in which to quench reactive encounters by rapid evaporation of the adducts, as well as provide a universal means for acquiring highly resolved vibrational action spectra of the embedded species by photoinduced mass loss. Moreover, the spectroscopic measurements can be obtained with readily available, broadly tunable pulsed infrared lasers because absorption of a single photon is sufficient to induce evaporation. We discuss the implementation of these methods with a new type of hybrid photofragmentation mass spectrometer involving two stages of mass selection with two laser excitation regions interfaced to the cryogenic ion source. We illustrate several capabilities of the cryogenic ion spectrometer by presenting recent applications to peptides, a biomimetic catalyst, a large antibiotic molecule (vancomycin), and reaction intermediates pertinent to the chemistry of the ionosphere. First, we demonstrate how site-specific isotopic substitution can be used to identify bands due to local functional groups in a protonated tripeptide designed to

  10. THE PROCESSES OF ENDOGENIZING IN THE ENDOGENOUS GROWTH: THE CASE OF TURKEY

    Directory of Open Access Journals (Sweden)

    OSMAN DEMİR

    2013-06-01

    Full Text Available The aim of this study is to state how the main inputs of endogenous growth, i.e. knowledge, human capital and technological progress are made endogenous by education, R&D, university-industry cooperation, learning by doing and diffusion within the production process. Competitiveness of firms and countries would increase as educated people enter into workforce; as R&D produces new technologies which are used in the production process; as theoretical knowledge meets with practice by university-industry cooperation; and as workers have more experience by learning by doing. In empirical analysis for Turkey is made by using data of 1970-2001 term it was found that a positive relationship among labour and capital factors and GNP and a negative relationship among education expenditures and foreign trade volume and capital stock.

  11. Cryogenic deformation in soils and their engineering geology consequence

    Energy Technology Data Exchange (ETDEWEB)

    Danilov, I.D. [Moscow State Univ., Moscow (Russian Federation); Roujansky, V.E. [EBA Engineering Consultants Ltd., Edmonton, AB (Canada)

    1994-12-31

    Cryogenic soil deformation was studied. Three basic types were considered, i. e. cryogenic-lithogenic, cryogenic-disjunctive and cryogenic-plastic. Different mechanisms of their formation were explained. The diversity of cryogenic deformations and their morphological resemblance to the tectonic dislocations pointed towards a specific type of the exogenic tectogenesis, namely, the `cryogenic tectogenesis`. Investigation of these phenomena were described. Results suggested that to prevent the development of severe permafrost-related engineering geology processes, such as soil instability, differential thaw settlement, and thermal erosion, appropriate precautions should be taken since they could potentially result in loss of support and damage to engineering structures erected on permafrost. 10 refs.

  12. 两部门内生增长模型中财政政策的短期分析%SHORT-RUN ANALYSIS OF FISCAL POLICY IN A TWO-SECTOR ENDOGENOUS GROWTH MODEL WITH HUMAN CAPITAL ACCUMULATION

    Institute of Scientific and Technical Information of China (English)

    崔小勇; 龚六堂

    2011-01-01

    在一个两部门内生增长模型中,讨论政府财政政策变化对居民消费,资本积累以及经济增长的长期影响和短期影响.发现在短期内,政府增加资本收入税不仅可以增加居民消费,而且可以刺激人力资本积累,从而刺激短期经济增长.但是政府财政政策改变对长期经济增长不产生影响,而且资本收入税会降低长期的消费水平和资本存量.另外,从经济增长形态和消费者福利两个角度讨论了资本收入税的无效性.%In a two-sector endogenous growth model, this paper studies the long-run and short-run effects of fiscal policy on private consumption, capital accumulation, and economic growth. It is found that: The increase in the capital income tax not only increases private consumption, but also increases the human capital accumulation, and in turn increases economic growth. However, government policy has no long-run effect on the economic growth, and the increasing of capital income tax rate will decrease the long-run consumption and physical capital accumulation. The welfare effects of fiscal policy is investigated too.

  13. Different regulation of human delta-opioid receptors by SNC-80 [(+)-4-[(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide] and endogenous enkephalins.

    Science.gov (United States)

    Lecoq, I; Marie, N; Jauzac, Ph; Allouche, S

    2004-08-01

    Among the different mechanisms underlying opioid tolerance, receptor desensitization would represent a major cellular adaptation process in which the role of receptor internalization is still a matter of debate. In the present study, we examined desensitization of the human delta-opioid receptor (hDOR) produced by endogenous opioid peptides Leu-enkephalin (Tyr-Gly-Gly-Phe-Leu) and Met-enkephalin (Tyr-Gly-Gly-Phe-Met), and the contribution of internalization in this process. Results obtained with natural peptides were compared with those produced by a synthetic opioid agonist, SNC-80 [(+)-4-[(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide). After a 30-min treatment, we observed a different regulation of hDOR between agonists. SNC-80 produced a stronger and faster desensitization and was associated with a loss of opioid binding sites by 50%. SNC-80 also caused a marked hDOR down-regulation by 30% as observed by Western blot. Immunocytochemistry revealed that SNC-80 induced a complete redistribution of hDOR from cell surface into intracellular compartments, whereas a partial internalization was visualized upon enkephalin exposure. In contrast, a stronger hDOR recycling and resensitization were measured after enkephalin treatment compared with SNC-80. These data strongly suggested a differential sorting of the internalized receptors caused by enkephalins and SNC-80 that was further confirmed by chloroquine as a lysosomal degradation blocker and monensin as a recycling endosome inhibitor. Finally, by preventing hDOR internalization with 0.5 M sucrose, we demonstrated that hDOR internalization contributes partially to desensitization. In conclusion, hDOR desensitization depends both on its internalization and its sorting either to the recycling pathway or to lysosomes.

  14. How Active Are Porcine Endogenous Retroviruses (PERVs?

    Directory of Open Access Journals (Sweden)

    Joachim Denner

    2016-08-01

    Full Text Available Porcine endogenous retroviruses (PERVs represent a risk factor if porcine cells, tissues, or organs were to be transplanted into human recipients to alleviate the shortage of human transplants; a procedure called xenotransplantation. In contrast to human endogenous retroviruses (HERVs, which are mostly defective and not replication-competent, PERVs are released from normal pig cells and are infectious. PERV-A and PERV-B are polytropic viruses infecting cells of several species, among them humans; whereas PERV-C is an ecotropic virus infecting only pig cells. Virus infection was shown in co-culture experiments, but also in vivo, in the pig, leading to de novo integration of proviruses in certain organs. This was shown by measurement of the copy number per cell, finding different numbers in different organs. In addition, recombinations between PERV-A and PERV-C were observed and the recombinant PERV-A/C were found to be integrated in cells of different organs, but not in the germ line of the animals. Here, the evidence for such in vivo activities of PERVs, including expression as mRNA, protein and virus particles, de novo infection and recombination, will be summarised. These activities make screening of pigs for provirus number and PERV expression level difficult, especially when only blood or ear biopsies are available for analysis. Highly sensitive methods to measure the copy number and the expression level will be required when selecting pigs with low copy number and low expression of PERV as well as when inactivating PERVs using the clustered regularly interspaced short palindromic repeats (CRISPR/CRISPR-associated nuclease (CRISPR/Cas technology.

  15. How Active Are Porcine Endogenous Retroviruses (PERVs)?

    Science.gov (United States)

    Denner, Joachim

    2016-01-01

    Porcine endogenous retroviruses (PERVs) represent a risk factor if porcine cells, tissues, or organs were to be transplanted into human recipients to alleviate the shortage of human transplants; a procedure called xenotransplantation. In contrast to human endogenous retroviruses (HERVs), which are mostly defective and not replication-competent, PERVs are released from normal pig cells and are infectious. PERV-A and PERV-B are polytropic viruses infecting cells of several species, among them humans; whereas PERV-C is an ecotropic virus infecting only pig cells. Virus infection was shown in co-culture experiments, but also in vivo, in the pig, leading to de novo integration of proviruses in certain organs. This was shown by measurement of the copy number per cell, finding different numbers in different organs. In addition, recombinations between PERV-A and PERV-C were observed and the recombinant PERV-A/C were found to be integrated in cells of different organs, but not in the germ line of the animals. Here, the evidence for such in vivo activities of PERVs, including expression as mRNA, protein and virus particles, de novo infection and recombination, will be summarised. These activities make screening of pigs for provirus number and PERV expression level difficult, especially when only blood or ear biopsies are available for analysis. Highly sensitive methods to measure the copy number and the expression level will be required when selecting pigs with low copy number and low expression of PERV as well as when inactivating PERVs using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nuclease (CRISPR/Cas) technology. PMID:27527207

  16. Repeatability of Cryogenic Multilayer Insulation

    Science.gov (United States)

    Johnson, W. L.; Vanderlaan, M.; Wood, J. J.; Rhys, N. O.; Guo, W.; Van Sciver, S.; Chato, D. J.

    2017-01-01

    Due to the variety of requirements across aerospace platforms, and one off projects, the repeatability of cryogenic multilayer insulation has never been fully established. The objective of this test program is to provide a more basic understanding of the thermal performance repeatability of MLI systems that are applicable to large scale tanks. There are several different types of repeatability that can be accounted for: these include repeatability between multiple identical blankets, repeatability of installation of the same blanket, and repeatability of a test apparatus. The focus of the work in this report is on the first two types of repeatability. Statistically, repeatability can mean many different things. In simplest form, it refers to the range of performance that a population exhibits and the average of the population. However, as more and more identical components are made (i.e. the population of concern grows), the simple range morphs into a standard deviation from an average performance. Initial repeatability testing on MLI blankets has been completed at Florida State University. Repeatability of five GRC provided coupons with 25 layers was shown to be +/- 8.4 whereas repeatability of repeatedly installing a single coupon was shown to be +/- 8.0. A second group of 10 coupons have been fabricated by Yetispace and tested by Florida State University, through the first 4 tests, the repeatability has been shown to be +/- 16. Based on detailed statistical analysis, the data has been shown to be statistically significant.

  17. The Cryogenic Storage Ring CSR

    CERN Document Server

    von Hahn, Robert; Berg, Felix; Blaum, Klaus; Breitenfeldt, Christian; Fadil, Hisham; Fellenberger, Florian; Froese, Michael; George, Sebastian; Göck, Jürgen; Grieser, Manfred; Grussie, Florian; Guerin, Elisabeth A; Heber, Oded; Herwig, Philipp; Karthein, Jonas; Krantz, Claude; Kreckel, Holger; Lange, Michael; Laux, Felix; Lohmann, Svenja; Menk, Sebastian; Meyer, Christian; Mishra, Preeti M; Novotný, Oldřich; Connor, Aodh P O; Orlov, Dmitry A; Rappaport, Michael L; Repnow, Roland; Saurabh, Sunny; Schippers, Stefan; Schröter, Claus Dieter; Schwalm, Dirk; Schweikhard, Lutz; Sieber, Thomas; Shornikov, Andrey; Spruck, Kaija; Kumar, Sudhakaran Sunil; Ullrich, Joachim; Urbain, Xavier; Vogel, Stephen; Wilhelm, Patrick; Wolf, Andreas; Zajfman, Daniel

    2016-01-01

    An electrostatic cryogenic storage ring, CSR, for beams of anions and cations with up to 300 keV kinetic energy per unit charge has been designed, constructed and put into operation. With a circumference of 35 m, the ion-beam vacuum chambers and all beam optics are in a cryostat and cooled by a closed-cycle liquid helium system. At temperatures as low as (5.5 $\\pm$ 1) K inside the ring, storage time constants of several minutes up to almost an hour were observed for atomic and molecular, anion and cation beams at an energy of 60 keV. The ion-beam intensity, energy-dependent closed-orbit shifts (dispersion) and the focusing properties of the machine were studied by a system of capacitive pickups. The Schottky-noise spectrum of the stored ions revealed a broadening of the momentum distribution on a time scale of 1000 s. Photodetachment of stored anions was used in the beam lifetime measurements. The detachment rate by anion collisions with residual-gas molecules was found to be extremely low. A residual-gas den...

  18. Cryogenic silicon surface ion trap

    CERN Document Server

    Niedermayr, Michael; Kumph, Muir; Partel, Stefan; Edlinger, Johannes; Brownnutt, Michael; Blatt, Rainer

    2014-01-01

    Trapped ions are pre-eminent candidates for building quantum information processors and quantum simulators. They have been used to demonstrate quantum gates and algorithms, quantum error correction, and basic quantum simulations. However, to realise the full potential of such systems and make scalable trapped-ion quantum computing a reality, there exist a number of practical problems which must be solved. These include tackling the observed high ion-heating rates and creating scalable trap structures which can be simply and reliably produced. Here, we report on cryogenically operated silicon ion traps which can be rapidly and easily fabricated using standard semiconductor technologies. Single $^{40}$Ca$^+$ ions have been trapped and used to characterize the trap operation. Long ion lifetimes were observed with the traps exhibiting heating rates as low as $\\dot{\\bar{n}}=$ 0.33 phonons/s at an ion-electrode distance of 230 $\\mu$m. These results open many new avenues to arrays of micro-fabricated ion traps.

  19. A Cryogenic Infrared Calibration Target

    CERN Document Server

    Wollack, Edward J; Rinehart, Stephan A

    2014-01-01

    A compact cryogenic calibration target is presented that has a peak diffuse reflectance, $R \\le 0.003$, from $800-4,800\\,{\\rm cm}^{-1}$ $(12-2\\,\\mu$m). Upon expanding the spectral range under consideration to $400-10,000\\,{\\rm cm}^{-1}$ $(25-1\\,\\mu$m) the observed performance gracefully degrades to $R \\le 0.02$ at the band edges. In the implementation described, a high-thermal-conductivity metallic substrate is textured with a pyramidal tiling and subsequently coated with a thin lossy dielectric coating that enables high absorption and thermal uniformity across the target. The resulting target assembly is lightweight, has a low-geometric profile, and has survived repeated thermal cycling from room temperature to $\\sim4\\,$K. Basic design considerations, governing equations, and test data for realizing the structure described are provided. The optical properties of selected absorptive materials -- Acktar Fractal Black, Aeroglaze Z306, and Stycast 2850 FT epoxy loaded with stainless steel powder -- are character...

  20. The future of cryogenic propulsion

    Science.gov (United States)

    Palerm, S.; Bonhomme, C.; Guelou, Y.; Chopinet, J. N.; Danous, P.

    2015-07-01

    As the French Space Agency, CNES is funding an ambitious program to identify, develop and evaluate the technologies and skills that will enable to design cost efficient future launchers. This program deals together with, researches for mastering complex physical phenomena, set ups of robust and efficient numerical tools for design and justification, and identification of innovative manufacturing processes and hardware. It starts from low Technical Readiness Level (TRL 2) up to a maturation of TRL 6 with the use of demonstrators, level that allows to be ready for a development. This paper focuses on cryogenic propulsion activities conducted with SNECMA and French laboratories to prepare next generation engines. The physics in that type of hardware addresses a large range of highly complex phenomena, among them subcritical and supercritical combustion and possible associated High Frequency oscillations in combustion devices, tribology in bearings and seals, cavitation and rotordynamics in turbopump. The research activities conducted to master those physical phenomena are presented. Moreover, the operating conditions of these engines are very challenging, both thermally and mechanically. The innovative manufacturing processes and designs developed to cope with these conditions while filling cost reduction requirements are described. Finally, the associated demonstrators put in place to prepare the implementation of these new technologies on future engines are presented.

  1. Cryogenic Fluid Management Technology Development Roadmaps

    Science.gov (United States)

    Stephens, J. R.; Johnson, W. L.

    2017-01-01

    Advancement in Cryogenic Fluid Management (CFM) Technologies is essential for achieving NASA's future long duration missions. Propulsion systems utilizing cryogens are necessary to achieve mission success. Current State Of the Art (SOA) CFM technologies enable cryogenic propellants to be stored for several hours. However, some envisioned mission architectures require cryogens to be stored for two years or longer. The fundamental roles of CFM technologies are long term storage of cryogens, propellant tank pressure control and propellant delivery. In the presence of heat, the cryogens will "boil-off" over time resulting in excessive pressure buildup, off-nominal propellant conditions, and propellant loss. To achieve long term storage and tank pressure control, the CFM elements will intercept and/or remove any heat from the propulsion system. All functions are required to perform both with and without the presence of a gravitational field. Which CFM technologies are required is a function of the cryogens used, mission architecture, vehicle design and propellant tank size. To enable NASA's crewed mission to the Martian surface, a total of seventeen CFM technologies have been identified to support an In-Space Stage and a Lander/Ascent Vehicle. Recognizing that FY2020 includes a Decision Point regarding the In-Space Stage Architecture, a set of CFM Technology Development Roadmaps have been created identifying the current Technology Readiness Level (TRL) of each element, current technology "gaps", and existing technology development efforts. The roadmaps include a methodical approach and schedule to achieve a flight demonstration in FY2023, hence maturing CFM technologies to TRL 7 for infusion into the In-Space Stage Preliminary Design.

  2. Procedures for cryogenic X-ray ptychographic imaging of biological samples

    Science.gov (United States)

    Yusuf, M.; Zhang, F.; Chen, B.; Bhartiya, A.; Cunnea, K.; Wagner, U.; Cacho-Nerin, F.; Schwenke, J.; Robinson, I. K.

    2017-01-01

    Biological sample-preparation procedures have been developed for imaging human chromosomes under cryogenic conditions. A new experimental setup, developed for imaging frozen samples using beamline I13 at Diamond Light Source, is described. This manuscript describes the equipment and experimental procedures as well as the authors’ first ptychographic reconstructions using X-rays.

  3. Procedures for cryogenic X-ray ptychographic imaging of biological samples.

    Science.gov (United States)

    Yusuf, M; Zhang, F; Chen, B; Bhartiya, A; Cunnea, K; Wagner, U; Cacho-Nerin, F; Schwenke, J; Robinson, I K

    2017-03-01

    Biological sample-preparation procedures have been developed for imaging human chromosomes under cryogenic conditions. A new experimental setup, developed for imaging frozen samples using beamline I13 at Diamond Light Source, is described. This manuscript describes the equipment and experimental procedures as well as the authors' first ptychographic reconstructions using X-rays.

  4. Procedures for cryogenic X-ray ptychographic imaging of biological samples

    Directory of Open Access Journals (Sweden)

    M. Yusuf

    2017-03-01

    Full Text Available Biological sample-preparation procedures have been developed for imaging human chromosomes under cryogenic conditions. A new experimental setup, developed for imaging frozen samples using beamline I13 at Diamond Light Source, is described. This manuscript describes the equipment and experimental procedures as well as the authors' first ptychographic reconstructions using X-rays.

  5. [Memory processes in endogenous depression].

    Science.gov (United States)

    Radziwiłłowicz, W; Radziwiłłowicz, P

    1998-01-01

    The thesis aims to answer the questions about the profile of mental ability in endogenous depression and to decide whether self-estimation of depressive symptoms influences the results achieved by patients in memory tests. Fifty six patients suffering from endogenous depression have been examined. The following methods have been applied: Mini Mental State Examination, Benton Visual Retention Test, Beck Depression Inventory, hold tests: Vocabulary, Information, Comprehension and Digit Span of Wechsler Adult Intelligence Scale (WAIS), Rey-Osterrieth Complex Figure, Auditory Verbal Learning Test, DCS Weidlich. General status of cognitive functions correlates with the profile of specific kinds of memory results, particularly with delayed memory. Self-estimation of depressive symptoms intensity is mostly influenced by memory capacity, visuomotorial factor, functions of perception and lingual factor. High correlation between verbal and non verbal learning shows uniform influence of depression on the process of learning.

  6. Endogenous neuromodulation at infralow frequencies.

    Science.gov (United States)

    Othmer, Siegfried; Othmer, Susan F; Kaiser, David A; Putman, John

    2013-12-01

    Neuromodulation in the bioelectrical domain is an attractive option for the remediation of functionally based deficits. Most of the interest to date has focused on exogenous methods, such as repetitive transcranial magnetic stimulation, transient direct current stimulation, vagus nerve stimulation, and deep brain stimulation. Much less attention has been given to endogenous methods of exploiting latent brain plasticity. These have reached a level of sophistication and maturity that invites attention. Over the last 7 years, the domain of infralow frequencies has been exploited productively for the enhancement of neuroregulation. The principal mechanism is putatively the renormalization of functional connectivity of our resting-state networks. The endogeneous techniques are particularly attractive for the pediatric population, where they can be utilized before dysfunctional patterns of brain behavior become consolidated and further elaborated into clinical syndromes. © 2013 Published by Elsevier Inc.

  7. Endogenous Opiates and Behavior: 2006

    OpenAIRE

    Bodnar, Richard J.

    2007-01-01

    This paper is the twenty-ninth consecutive installment of the annual review of research concerning the endogenous opioid system, now spanning thirty years of research. It summarizes papers published during 2006 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localiz...

  8. Money, banks and endogenous volatility

    OpenAIRE

    Pere Gomis-Porqueras

    2000-01-01

    In this paper I consider a monetary growth model in which banks provide liquidity, and the government fixes a constant rate of money creation. There are two underlying assets in the economy, money and capital. Money is dominated in rate of return. In contrast to other papers with a larger set of government liabilities, I find a unique equilibrium when agents' risk aversion is moderate. However, indeterminacies and endogenous volatility can be observed when agents are relatively risk averse.

  9. The Origins of Endogenous Growth

    OpenAIRE

    ROMER, Paul M.

    1994-01-01

    This paper describes two strands of work that converged under the heading of 'endogenous growth.' One strand, which is primarily empirical, asks whether there is a general tendency for poor countries to catch up with rich countries. The other strand, which is primarily theoretical, asks what modifications are necessary to construct a theory of aggregate growth that takes the economics of discovery, innovation, and technological change seriously. The paper argues that the second strand of work...

  10. Endogenous Fusarium Endophthalmitis in Diabetes Mellitus

    National Research Council Canada - National Science Library

    Balamurugan, S; Khodifad, Ashish

    2016-01-01

      Endogenous endophthalmitis accounts for 2% to 8% of cases of endophthalmitis. Immunocompromised state and intravenous drug use are the 2 most common causes of endogenous endophthalmitis due to molds fungi...

  11. NASA's Cryogenic Fluid Management Technology Project

    Science.gov (United States)

    Tramel, Terri L.; Motil, Susan M.

    2008-01-01

    The Cryogenic Fluid Management (CFM) Project's primary objective is to develop storage, transfer, and handling technologies for cryogens that will support the enabling of high performance cryogenic propulsion systems, lunar surface systems and economical ground operations. Such technologies can significantly reduce propellant launch mass and required on-orbit margins, reduce or even eliminate propellant tank fluid boil-off losses for long term missions, and simplify vehicle operations. This paper will present the status of the specific technologies that the CFM Project is developing. The two main areas of concentration are analysis models development and CFM hardware development. The project develops analysis tools and models based on thermodynamics, hydrodynamics, and existing flight/test data. These tools assist in the development of pressure/thermal control devices (such as the Thermodynamic Vent System (TVS), and Multi-layer insulation); with the ultimate goal being to develop a mature set of tools and models that can characterize the performance of the pressure/thermal control devices incorporated in the design of an entire CFM system with minimal cryogen loss. The project does hardware development and testing to verify our understanding of the physical principles involved, and to validate the performance of CFM components, subsystems and systems. This database provides information to anchor our analytical models. This paper describes some of the current activities of the NASA's Cryogenic Fluid Management Project.

  12. Cryogenic System for the Spallation Neutron Source

    Science.gov (United States)

    Arenius, D.; Chronis, W.; Creel, J.; Dixon, K.; Ganni, V.; Knudsen, P.

    2004-06-01

    The Spallation Neutron Source (SNS) is a neutron-scattering facility being built at Oak Ridge, TN for the US Department of Energy. The SNS accelerator linac consists of superconducting radio-frequency (SRF) cavities in cryostats (cryomodules). The linac cryomodules are cooled to 2.1 K by a 2300 watt cryogenic refrigeration system. As an SNS partner laboratory, Jefferson Lab is responsible for the installed integrated cryogenic system design for the SNS linac accelerator consisting of major subsystem equipment engineered and procured from industry. Jefferson Lab's work included developing the major vendor subsystem equipment procurement specifications, equipment procurement, and the integrated system engineering support of the field installation and commissioning. The major cryogenic system components include liquid nitrogen storage, gaseous helium storage, cryogen distribution transfer line system, 2.1-K cold box consisting of four stages of cold compressors, 4.5-K cold box, warm helium compressors with its associated oil removal, gas management, helium purification, gas impurity monitoring systems, and the supportive utilities of electrical power, cooling water and instrument air. The system overview, project organization, the important aspects, and the capabilities of the cryogenic system are described.

  13. Advanced Devices for Cryogenic Thermal Management

    Science.gov (United States)

    Bugby, D.; Stouffer, C.; Garzon, J.; Beres, M.; Gilchrist, A.

    2006-04-01

    This paper describes six advanced cryogenic thermal management devices/subsystems developed by Swales Aerospace for ground/space-based applications of interest to NASA, DoD, and the commercial sector. The devices/subsystems described herein include the following: (a) a differential thermal expansion cryogenic thermal switch (DTE-CTSW) constructed with high purity aluminum end-pieces and an Ultem support rod for the 6 K Mid-Infrared Instrument (MIRI) on the James Webb Space Telescope (JWST) (b) a quad-redundant DTE-CTSW assembly for the 35 K science instruments (NIRCam, NIRSpec, and FGS) mounted on the JWST Integrated Science Instrument Module (ISIM) (c) a cryogenic diode heat pipe (CDHP) thermal switching system using methane as the working fluid for the 100 K CRISM hyperspectral mapping instrument on the Mars Reconnaissance Orbiter (MRO) and (d) three additional devices/subsystems developed during the AFRL-sponsored CRYOTOOL program, which include a dual DTE-CTSW/dual cryocooler test bed, a miniaturized neon cryogenic loop heat pipe (mini-CLHP), and an across gimbal cryogenic thermal transport system (GCTTS). For the first three devices/subsystems mentioned above, this paper describes key aspects of the development efforts including concept definition, design, fabrication, and testing. For the latter three, this paper provides brief overview descriptions as key details are provided in a related paper.

  14. Cryogenic Applications of Commercial Electronic Components

    Science.gov (United States)

    Buchanan, Ernest D.; Benford, Dominic J.; Forgione, Joshua B.; Moseley, S. Harvey; Wollack, Edward J.

    2012-01-01

    We have developed a range of techniques useful for constructing analog and digital circuits for operation in a liquid Helium environment (4.2K), using commercially available low power components. The challenges encountered in designing cryogenic electronics include finding components that can function usefully in the cold and possess low enough power dissipation so as not to heat the systems they are designed to measure. From design, test, and integration perspectives it is useful for components to operate similarly at room and cryogenic temperatures; however this is not a necessity. Some of the circuits presented here have been used successfully in the MUSTANG and in the GISMO camera to build a complete digital to analog multiplexer (which will be referred to as the Cryogenic Address Driver board). Many of the circuit elements described are of a more general nature rather than specific to the Cryogenic Address Driver board, and were studied as a part of a more comprehensive approach to addressing a larger set of cryogenic electronic needs.

  15. Advanced Sprayable Composite Coating for Cryogenic Insulation Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Advanced Materials Technology, Inc (AMTI) responds to the NASA solicitation X10 "Cryogenic Propellant Storage and Transfer" under subtopic X.01 "Cryogenic Fluid...

  16. Low evaporation rate storage media for cryogenic liquids Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Considerable design work has been devoted to the development of cryogenic liquid storage containers. Containers which hold cryogenic liquids such as liquid nitrogen,...

  17. Manufacture of Novel Cryogenic Thermal Protection Materials Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Advanced Materials Technology, Inc (AMTI) responds to the NASA SBIR solicitation X8 "Space Cryogenic Systems" under subtopic X8.01, "Cryogenic Fluid Transfer and...

  18. In-Space Cryogenic VOST Connect/Disconnect Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Two novel cryogenic couplings will be designed, fabricated and tested. Intended for in-space use at cryogenic propellant depots, the couplings are based on patented...

  19. In-Space Cryogenic VOST Connect/Disconnect Project

    Data.gov (United States)

    National Aeronautics and Space Administration — A novel cryogenic coupling will be designed and modeled. Intended for in-space use at cryogenic propellant depots, the coupling is based on patented Venturi-Offset...

  20. Energy Efficient Cryogenics on Earth and in Space

    Science.gov (United States)

    Fesmire, James E.

    2012-01-01

    The Cryogenics Test Laboratory, NASA Kennedy Space Center, works to provide practical solutions to low-temperature problems while focusing on long-term technology targets for energy-efficient cryogenics on Earth and in space.

  1. REFERENCE MODELS OF ENDOGENOUS ECONOMIC GROWTH

    Directory of Open Access Journals (Sweden)

    GEAMĂNU MARINELA

    2012-05-01

    Full Text Available The new endogenous growth theories are a very important research area for shaping the most effective policies and long term sustainable development strategies.Endogenous growth theory has emerged as a reaction to the imperfections of neoclassical theory, by the fact that the economic growth is the endogenous product of an economical system.

  2. A Reference Guide for Cryogenic Properties of Materials

    Energy Technology Data Exchange (ETDEWEB)

    Weisend, John G

    2003-09-16

    A thorough knowledge of the behavior of materials at cryogenic temperatures is critical for the design of successful cryogenic systems. Over the past 50 years, a tremendous amount of material properties at cryogenic temperatures have been measured and published. This guide lists resources for finding these properties. It covers online databases, computer codes, conference proceedings, journals, handbooks, overviews and monographs. It includes references for finding reports issued by government laboratories and agencies. Most common solids and fluids used in cryogenics are covered.

  3. Cryogenic cooling system for HTS cable

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Shigeru [Taiyo Nippon Sanso, Tsukuba (Japan)

    2017-06-15

    Recently, Research and development activity of HTS (High Temperature Superconducting) power application is very progressive worldwide. Especially, HTS cable system and HTSFCL (HTS Fault current limiter) system are proceeding to practical stages. In such system and equipment, cryogenic cooling system, which makes HTS equipment cooled lower than critical temperature, is one of crucial components. In this article, cryogenic cooling system for HTS application, mainly cable, is reviewed. Cryogenic cooling system can be categorized into conduction cooling system and immersion cooling system. In practical HTS power application area, immersion cooling system with sub-cooled liquid nitrogen is preferred. The immersion cooling system is besides grouped into open cycle system and closed cycle system. Turbo-Brayton refrigerator is a key component for closed cycle system. Those two cooling systems are focused in this article. And, each design and component of the cooling system is explained.

  4. Process Identification through Test on Cryogenic System

    CERN Document Server

    Pezzetti, M; Chadli, M; Coppier, H

    2008-01-01

    UNICOS (UNified Industrial Control System) is the CERN object-based control standard for the cryogenics of the LHC and its experiments. It includes a variety of embedded functions, dedicated to the specific cryogenic processes. To enlarge the capabilities of the standard it is proposed to integrate the parametrical identification step in the control system of large scale cryogenic plants. Different methods of parametrical identification have been tested and the results were combined to obtain a better model. The main objective of the work is to find a compromise between an easy-to-use solution and a good level of process identification model. The study focuses on identification protocol for large delayed system, the measurement consistency and correlation between different inputs and outputs. Furthermore the paper describes in details, the results and the tests carried out on parametrical identification investigations with large scale systems.

  5. Cryogenic hydrogen-induced air liquefaction technologies

    Science.gov (United States)

    Escher, William J. D.

    1990-01-01

    Extensively utilizing a special advanced airbreathing propulsion archives database, as well as direct contacts with individuals who were active in the field in previous years, a technical assessment of cryogenic hydrogen-induced air liquefaction, as a prospective onboard aerospace vehicle process, was performed and documented. The resulting assessment report is summarized. Technical findings are presented relating the status of air liquefaction technology, both as a singular technical area, and also that of a cluster of collateral technical areas including: compact lightweight cryogenic heat exchangers; heat exchanger atmospheric constituents fouling alleviation; para/ortho hydrogen shift conversion catalysts; hydrogen turbine expanders, cryogenic air compressors and liquid air pumps; hydrogen recycling using slush hydrogen as heat sink; liquid hydrogen/liquid air rocket-type combustion devices; air collection and enrichment systems (ACES); and technically related engine concepts.

  6. Technical presentation: BGM Cryogenic Engineering Limited

    CERN Multimedia

    Caroline Laignel - FI Department

    2006-01-01

    13 - 14 June 2006 TECHNICAL PRESENTATION BGM Cryogenic Engineering Limited 09:00 - 18:00, 60-2-016, Main Building. Presentation on BGM: 11:00 - 12:00, 60-2-016, Main Building. BGM Cryogenic Engineering Limited manufactures assemblies, sub-assemblies and machined components for the cryogenic technology sector. The primary markets served include superconducting magnets used in the healthcare sector (eg MRI body scanners), spectroscopy and NMR equipment for numerous R & D and technology applications, high vacuum applications and particle physics research. BGM has specialist assembly capability including stainless steel and aluminium welding, vacuum testing, electromechanical assembly and metal finishing. BGM offers a ‘one stop shop'facility to satisfy any customer requirement. Through our design partner we can offer a full design and modelling service, including 3D modelling and production of 2D drawings on your own borders. We can conduct heat load and force calculations and advise on the best...

  7. Cryogenics for Particle Accelerators and Detectors

    CERN Document Server

    Lebrun, P; Vandoni, Giovanna; Wagner, U

    2002-01-01

    Cryogenics has become a key ancillary technology of particle accelerators and detectors, contributing to their sustained development over the last fifty years. Conversely, this development has produced new challenges and markets for cryogenics, resulting in a fruitful symbiotic relation which materialized in significant technology transfer and technical progress. This began with the use of liquid hydrogen and deuterium in the targets and bubble chambers of the 1950s, 1960s and 1970s. It developed more recently with increasing amounts of liquefied noble gases - mainly argon, but also krypton and even today xenon - in calorimeters. In parallel with these applications, the availability of practical type II superconductors from the early 1960s triggered the use of superconductivity in large spectrometer magnets - mostly driven by considerations of energy savings - and the corresponding development of helium cryogenics. It is however the generalized application of superconductivity in particle accelerators - RF ac...

  8. Characterization of a cryogenic ion guide at IGISOL

    NARCIS (Netherlands)

    Saastamoinen, A.; Moore, I. D.; Ranjan, M.; Dendooven, P.; Penttila, H.; Perajarvi, K.; Popov, A.; Aysto, J.

    2012-01-01

    A small volume cryogenic ion guide has been characterized at the IGISOL facility, Jyvaskyla, as a prototype to verify whether there are any major obstacles to the use of high-density cryogenic helium gas for the stopping and extraction of high-energy ions from a large volume cryogenic ion catcher.

  9. 49 CFR 173.319 - Cryogenic liquids in tank cars.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Cryogenic liquids in tank cars. 173.319 Section... REQUIREMENTS FOR SHIPMENTS AND PACKAGINGS Gases; Preparation and Packaging § 173.319 Cryogenic liquids in tank cars. (a) General requirements. (1) A tank car containing a flammable cryogenic liquid may not be...

  10. 49 CFR 173.316 - Cryogenic liquids in cylinders.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Cryogenic liquids in cylinders. 173.316 Section... REQUIREMENTS FOR SHIPMENTS AND PACKAGINGS Gases; Preparation and Packaging § 173.316 Cryogenic liquids in cylinders. (a) General requirements. (1) A cylinder may not be loaded with a cryogenic liquid colder than...

  11. 21 CFR 882.4250 - Cryogenic surgical device.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cryogenic surgical device. 882.4250 Section 882...) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Surgical Devices § 882.4250 Cryogenic surgical device. (a) Identification. A cryogenic surgical device is a device used to destroy nervous tissue or produce...

  12. 49 CFR 173.320 - Cryogenic liquids; exceptions.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Cryogenic liquids; exceptions. 173.320 Section 173... REQUIREMENTS FOR SHIPMENTS AND PACKAGINGS Gases; Preparation and Packaging § 173.320 Cryogenic liquids; exceptions. (a) Atmospheric gases and helium, cryogenic liquids, in Dewar flasks, insulated cylinders...

  13. 49 CFR 173.318 - Cryogenic liquids in cargo tanks.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Cryogenic liquids in cargo tanks. 173.318 Section... REQUIREMENTS FOR SHIPMENTS AND PACKAGINGS Gases; Preparation and Packaging § 173.318 Cryogenic liquids in cargo tanks. (a) General requirements. (1) A cargo tank may not be loaded with a cryogenic liquid colder than...

  14. Cryogenic Propellant Storage and Transfer (CPST) Technology Demonstration Mission (TDM)

    Science.gov (United States)

    Chojnacki, Kent

    2013-01-01

    Objectives: 1) Store cryogenic propellants in a manner that maximizes their availability for use regardless of mission duration. 2) Efficiently transfer conditioned cryogenic propellant to an engine or tank situated in a microgravity environment. 3) Accurately monitor and gauge cryogenic propellants situated in a microgravity environment.

  15. Characterization of a cryogenic ion guide at IGISOL

    NARCIS (Netherlands)

    Saastamoinen, A.; Moore, I. D.; Ranjan, M.; Dendooven, P.; Penttila, H.; Perajarvi, K.; Popov, A.; Aysto, J.

    2012-01-01

    A small volume cryogenic ion guide has been characterized at the IGISOL facility, Jyvaskyla, as a prototype to verify whether there are any major obstacles to the use of high-density cryogenic helium gas for the stopping and extraction of high-energy ions from a large volume cryogenic ion catcher. T

  16. Transfection of small RNAs globally perturbs gene regulation by endogenous microRNAs

    DEFF Research Database (Denmark)

    Khan, Aly A; Betel, Doron; Miller, Martin L

    2009-01-01

    among the transfected small RNAs and the endogenous pool of miRNAs for the intracellular machinery that processes small RNAs. To test this hypothesis, we analyzed genome-wide transcript responses from 151 published transfection experiments in seven different human cell types. We show that targets...... of endogenous miRNAs are expressed at significantly higher levels after transfection, consistent with impaired effectiveness of endogenous miRNA repression. This effect exhibited concentration and temporal dependence. Notably, the profile of endogenous miRNAs can be largely inferred by correlating miRNA sites...

  17. Resolving Ultrafast Heating of Dense Cryogenic Hydrogen

    Science.gov (United States)

    Zastrau, U.; Sperling, P.; Harmand, M.; Becker, A.; Bornath, T.; Bredow, R.; Dziarzhytski, S.; Fennel, T.; Fletcher, L. B.; Förster, E.; Göde, S.; Gregori, G.; Hilbert, V.; Hochhaus, D.; Holst, B.; Laarmann, T.; Lee, H. J.; Ma, T.; Mithen, J. P.; Mitzner, R.; Murphy, C. D.; Nakatsutsumi, M.; Neumayer, P.; Przystawik, A.; Roling, S.; Schulz, M.; Siemer, B.; Skruszewicz, S.; Tiggesbäumker, J.; Toleikis, S.; Tschentscher, T.; White, T.; Wöstmann, M.; Zacharias, H.; Döppner, T.; Glenzer, S. H.; Redmer, R.

    2014-03-01

    We report on the dynamics of ultrafast heating in cryogenic hydrogen initiated by a ≲300 fs, 92 eV free electron laser x-ray burst. The rise of the x-ray scattering amplitude from a second x-ray pulse probes the transition from dense cryogenic molecular hydrogen to a nearly uncorrelated plasmalike structure, indicating an electron-ion equilibration time of ˜0.9 ps. The rise time agrees with radiation hydrodynamics simulations based on a conductivity model for partially ionized plasma that is validated by two-temperature density-functional theory.

  18. Compact insert design for cryogenic pressure vessels

    Science.gov (United States)

    Aceves, Salvador M.; Ledesma-Orozco, Elias Rigoberto; Espinosa-Loza, Francisco; Petitpas, Guillaume; Switzer, Vernon A.

    2017-06-14

    A pressure vessel apparatus for cryogenic capable storage of hydrogen or other cryogenic gases at high pressure includes an insert with a parallel inlet duct, a perpendicular inlet duct connected to the parallel inlet. The perpendicular inlet duct and the parallel inlet duct connect the interior cavity with the external components. The insert also includes a parallel outlet duct and a perpendicular outlet duct connected to the parallel outlet duct. The perpendicular outlet duct and the parallel outlet duct connect the interior cavity with the external components.

  19. Cryogenic Yb: YAG Thin-Disk Laser

    Science.gov (United States)

    2016-09-09

    Spitzberg, "Cryogenic Yb3+-Doped Solid-State Lasers," IEEE Journ. of Sel. Topics in Quant. Elect., 13(3), 448-459 (2007). [3] S. Tokita, J. Kawanaka, M...Europe ( IEEE ,2005) ,CTu3 (2005). [4] D. C. Brown, J. M. Singley, E. Yager, J. W. Kuper, B. J. Lotito, L. L. Bennett, "Innovative high-power CW...Y. Sun, and R. W. Equall, "Yb:YAG Absorption at Ambient and Cryogenic Temperatures," IEEE Journ. Sel. Topics Quant. Elect. 11(3), 604-612 (2005

  20. MCP-based Photodetectors for Cryogenic Applications

    CERN Document Server

    Dharmapalan, Ranjan; Byrum, Karen; Demarteau, Marcel; Elam, Jeffrey; May, Edward; Wagner, Robert; Walters, Dean; Xia, Lei; Xie, Junqi; Zhao, Huyue; Wang, J

    2016-01-01

    The Argonne MCP-based photo detector is an offshoot of the Large Area Pico-second Photo Detector (LAPPD) project, wherein 6 cm x 6 cm sized detectors are made at Argonne National Laboratory. We have successfully built and tested our first detectors for pico-second timing and few mm spatial resolution. We discuss our efforts to customize these detectors to operate in a cryogenic environment. Initial plans aim to operate in liquid argon. We are also exploring ways to mitigate wave length shifting requirements and also developing bare-MCP photodetectors to operate in a gaseous cryogenic environment.

  1. Population ageing policy reforms and endogenous growth in Japan: a computable overlapping generations approach

    OpenAIRE

    Shimasawa, Manabu

    2004-01-01

    We have developed a multi-period computable endogenous growth overlapping generations model generated by the accumulation of human capital. To study whether ageing itself and policy reform that aims to cope with aging make any quantitative impact through human capital formation on the Japanese economy, we simulate two policy change scenarios and compare the results of those with endogenous growth to those with exogenous growth. Three main results are obtained: (1) the human capital investment...

  2. Endogenous infection and hospital's civil liability - a case study.

    Science.gov (United States)

    Wąsik, D; Wąsik, N; Sygit, B; Dubiel, M

    2014-01-01

    The subject matter of this publication is the legal assessment of endogenous infection - the specific type of hospital infections. The main aim of the publication is to answer the question of whether medical and legal grounds exist for civil liability for endogenous infections and for treating those infections as cases of medical malpractice or medical events. The research method adopted is a case study. The authors have analysed a civil lawsuit for compensation instituted by an infected patient against a Polish hospital, adjudicated in 2013. The main conclusion of the publication is to postulate distinguishing medical malpractice from complications resulting from the reactions of the human body to treatment. The authors argue that endogenous infections should be treated as the latter-mentioned of these two cases.

  3. Endogenous psychoactive tryptamines reconsidered: an anxiolytic role for dimethyltryptamine.

    Science.gov (United States)

    Jacob, Michael S; Presti, David E

    2005-01-01

    The presence of the potent hallucinogenic psychoactive chemical N,N-dimethyltryptamine (DMT) in the human body has puzzled scientists for decades. Endogenous DMT was investigated in the 1960s and 1970s and it was proposed that DMT was involved in psychosis and schizophrenia. This hypothesis developed from comparisons of the blood and urine of schizophrenic and control subjects. However, much of this research proved inconclusive and conventional thinking has since held that trace levels of DMT, and other endogenous psychoactive tryptamines, are insignificant metabolic byproducts. The recent discovery of a G-protein-coupled, human trace amine receptor has triggered a reappraisal of the role of compounds present in limited concentrations in biological systems. Interestingly enough, DMT and other psychoactive tryptamine hallucinogens elicit a robust response at the trace amine receptor. While it is currently accepted that serotonin 5-HT(2A) receptors play a pivotal role in the activity of hallucinogenic/psychedelic compounds, we propose that the effects induced by exogenous DMT administration, especially at low doses, are due in part to activity at the trace amine receptor. Furthermore, we suggest that endogenous DMT interacts with the TA receptor to produce a calm and relaxed mental state, which may suppress, rather than promote, symptoms of psychosis. This hypothesis may help explain the inconsistency in the early analysis of endogenous DMT in humans. Finally, we propose that amphetamine action at the TA receptor may contribute to the calming effects of amphetamine and related drugs, especially at low doses.

  4. Endogenous money, circuits and financialization

    OpenAIRE

    Malcolm Sawyer

    2013-01-01

    This paper locates the endogenous money approach in a circuitist framework. It argues for the significance of the credit creation process for the evolution of the economy and the absence of any notion of ‘neutrality of money’. Clearing banks are distinguished from other financial institutions as the providers of initial finance in a circuit whereas other financial institutions operate in a final finance circuit. Financialization is here viewed in terms of the growth of financial assets an...

  5. Monopoly Insurance and Endogenous Information

    DEFF Research Database (Denmark)

    Lagerlöf, Johan N. M.; Schottmüller, Christoph

    2017-01-01

    We study a monopoly insurance model with endogenous information acquisi- tion. Through a continuous effort choice, consumers can determine the precision of a privately observed signal that is informative about their accident risk. The equilibrium effort is, depending on parameter values, either...... zero (implying symmetric information) or positive (implying privately informed consumers). Regardless of the nature of the equilibrium, all offered contracts, also at the top, involve underinsurance, which discourages information gathering. We identify a missorting effect that explains why the insurer...... wants to discourage information acquisition. Moreover, lower information gathering costs can hurt both consumer and insurer....

  6. Endogenous fertility, mortality and growth.

    Science.gov (United States)

    Blackburn, K; Cipriani, G P

    1998-01-01

    This paper presents a model that illustrates the joint determination of population and development. "Economic and demographic outcomes are determined jointly in a choice-theoretic model of fertility, mortality and capital accumulation.... In addition to choosing savings and births, parents may reduce (infant) deaths by incurring expenditures on health-care which is also provided by the government. A generalised production technology accounts for long-run endogenous growth with short-run transitional dynamics. The analysis yields testable time series and cross-section implications which accord with the empirical evidence on the relationship between demography and development."

  7. Endogenous scheduling preferences and congestion

    DEFF Research Database (Denmark)

    Fosgerau, Mogens; Small, Kenneth

    2010-01-01

    Dynamic models of congestion so far rely on exogenous scheduling preferences of travelers, based for example on disutility of deviation from a preferred departure or arrival time for a trip. This paper provides a more fundamental view in which travelers derive utility just from consumption...... and leisure, but agglomeration economies at home and at work lead to scheduling preferences forming endogenously. Using bottleneck congestion technology, we obtain an equilibrium queuing pattern consistent with a general version of the Vickrey bottleneck model. However, the policy implications are different...

  8. An Overview of Recent Cryogenic Fluid Management Developments

    Science.gov (United States)

    Hedayat, A.; Johnson, W. L.; Stephens, J. R.

    2017-01-01

    Long-term storage, supply, and transfer of cryogenic fluids are critical capabilities needed to advance the human exploration of space. Technologies and advanced development programs have been pursued to address issues likely to confront the designers and developers of future cryogenic fluid management (CFM) subsystems and propulsion systems. NASA and aerospace industries have continued to conduct research and development for the propulsion applications of cryogenic fluids. From the well known in-space applications, to new applications involving superconducting motors within multiple different aircraft, and a renewed interest in production of oxygen on Mars, NASA continues to probe cryogenic applications within propulsion. This article presents brief reviews of several of the current CFM efforts to support future space missions. NASA GRC is currently focusing on understanding some of the finer points in the application of multilayer insulation. GRC recently finished the activation of a new calorimeter that operates at 20 K with a warm boundary that can operate either around 90 K or at 300 K. Current testing is focused on investigating multiple different seam concepts, initially between temperatures of 300 K and 20 K, and between 20 K and 90 K. One of the larger recent NASA investments has been on the Structural Heat Intercept, Insulation, and Vibration Experiment Rig (SHIIVER). SHIIVER is a 4 m diameter tank that is approximately 1/2 scale of the planned upper stage of the new Space Launch System (SLS) rocket. SHIIVER is focused on demonstrating the thermal benefits of multilayer insulation on the tank domes and boil-off vapor cooling on structural cylinders that hold the tank in-line on the rocket. It will also quantify any damage that may incur during the acoustic environment of over 160 decibels that SLS will experience on its trip to Earth orbit. In support of the possible production of oxygen out of the Mars' atmosphere, a team comprised of four NASA centers

  9. Endogenous Receptor Agonists: Resolving Inflammation

    Directory of Open Access Journals (Sweden)

    Gerhard Bannenberg

    2007-01-01

    Full Text Available Controlled resolution or the physiologic resolution of a well-orchestrated inflammatory response at the tissue level is essential to return to homeostasis. A comprehensive understanding of the cellular and molecular events that control the termination of acute inflammation is needed in molecular terms given the widely held view that aberrant inflammation underlies many common diseases. This review focuses on recent advances in the understanding of the role of arachidonic acid and ω-3 polyunsaturated fatty acids (PUFA–derived lipid mediators in regulating the resolution of inflammation. Using a functional lipidomic approach employing LC-MS-MS–based informatics, recent studies, reviewed herein, uncovered new families of local-acting chemical mediators actively biosynthesized during the resolution phase from the essential fatty acids eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA. These new families of local chemical mediators are generated endogenously in exudates collected during the resolution phase, and were coined resolvins and protectins because specific members of these novel chemical families control both the duration and magnitude of inflammation in animal models of complex diseases. Recent advances on the biosynthesis, receptors, and actions of these novel anti-inflammatory and proresolving lipid mediators are reviewed with the aim to bring to attention the important role of specific lipid mediators as endogenous agonists in inflammation resolution.

  10. Endogeneity in prison risk classification.

    Science.gov (United States)

    Shermer, Lauren O'Neill; Bierie, David M; Stock, Amber

    2013-10-01

    Security designation tools are a key feature of all prisons in the United States, intended as objective measures of risk that funnel inmates into security levels-to prison environments varying in degree of intrusiveness, restriction, dangerousness, and cost. These tools are mostly (if not all) validated by measuring inmates on a set of characteristics, using scores from summations of that information to assign inmates to prisons of varying security level, and then observing whether inmates assumed more risky did in fact offend more. That approach leaves open the possibility of endogeneity--that the harsher prisons are themselves bringing about higher misconduct and thus biasing coefficients assessing individual risk. The current study assesses this potential bias by following an entry cohort of inmates to more than 100 facilities in the Federal Bureau of Prisons (BOP) and exploiting the substantial variation in classification scores within a given prison that derive from systematic overrides of security-level designations for reasons not associated with risk of misconduct. By estimating pooled models of misconduct along with prison-fixed effects specifications, the data show that a portion of the predictive accuracy thought associated with the risk-designation tool used in BOP was a function of facility-level contamination (endogeneity).

  11. Cryogenic crashworthiness of LNG fuel storage tanks

    NARCIS (Netherlands)

    Atli-Veltin, B.; Vredeveldt, A.W.

    2014-01-01

    Shipping is gradually embracing natural gas as bunker fuel. The most viable way to store natural gas on board is in its liquid form. Gas needs to be cooled to cryogenic temperatures and in practice moderately pressurized. On board ships, solely double walled pressure tanks are used for this purpose.

  12. Transient boiling crisis of cryogenic liquids

    NARCIS (Netherlands)

    Deev, [No Value; Kharitonov, VS; Kutsenko, KV; Lavrukhin, AA

    2004-01-01

    This paper introduces a new physical model of boiling crisis under rapid increase of power on the heated surface. The calculation of the time interval of the transition to film boiling in cryogenic liquids was carried out depending on heat flux and pressure. The obtained results are in good

  13. Exergy Analysis of Cryogenic Air Separation

    NARCIS (Netherlands)

    Cornelissen, Rene; Hirs, Gerard

    1998-01-01

    An exergy analysis is performed to analyse the possibilities of fuel saving in the cryogenic distillation process, which is the main method of air separation. It is shown that more than half of the exergy loss takes place in the liquefaction unit and almost one-third in the air compression unit.

  14. Impact resistance cryogenic bunker fuel tanks

    NARCIS (Netherlands)

    Voormeeren, L.O.; Atli-Veltin, B.; Vredeveldt, A.W.

    2014-01-01

    The increasing use of liquefied natural gas (LNG) as bunker fuel in ships, calls for an elaborate study regarding the risks involved. One particular issue is the vulnerability of cryogenic LNG storage tanks with respect to impact loadings, such as ship collisions and dropped objects. This requires a

  15. Cryogenic crashworthiness of LNG fuel storage tanks

    NARCIS (Netherlands)

    Atli-Veltin, B.; Vredeveldt, A.W.

    2014-01-01

    Shipping is gradually embracing natural gas as bunker fuel. The most viable way to store natural gas on board is in its liquid form. Gas needs to be cooled to cryogenic temperatures and in practice moderately pressurized. On board ships, solely double walled pressure tanks are used for this purpose.

  16. Cryogenic Propellant Boil-Off Reduction System

    Science.gov (United States)

    Plachta, D. W.; Christie, R. J.; Carlberg, E.; Feller, J. R.

    2008-03-01

    Lunar missions under consideration would benefit from incorporation of high specific impulse propellants such as LH2 and LO2, even with their accompanying boil-off losses necessary to maintain a steady tank pressure. This paper addresses a cryogenic propellant boil-off reduction system to minimize or eliminate boil-off. Concepts to do so were considered under the In-Space Cryogenic Propellant Depot Project. Specific to that was an investigation of cryocooler integration concepts for relatively large depot sized propellant tanks. One concept proved promising—it served to efficiently move heat to the cryocooler even over long distances via a compressed helium loop. The analyses and designs for this were incorporated into NASA Glenn Research Center's Cryogenic Analysis Tool. That design approach is explained and shown herein. Analysis shows that, when compared to passive only cryogenic storage, the boil-off reduction system begins to reduce system mass if durations are as low as 40 days for LH2, and 14 days for LO2. In addition, a method of cooling LH2 tanks is presented that precludes development issues associated with LH2 temperature cryocoolers.

  17. Transient boiling crisis of cryogenic liquids

    NARCIS (Netherlands)

    Deev, [No Value; Kharitonov, VS; Kutsenko, KV; Lavrukhin, AA

    2004-01-01

    This paper introduces a new physical model of boiling crisis under rapid increase of power on the heated surface. The calculation of the time interval of the transition to film boiling in cryogenic liquids was carried out depending on heat flux and pressure. The obtained results are in good agreemen

  18. Composite aerogel insulation for cryogenic liquid storage

    Science.gov (United States)

    Kyeongho, Kim; Hyungmook, Kang; Soojin, Shin; In Hwan, Oh; Changhee, Son; Hyung, Cho Yun; Yongchan, Kim; Sarng Woo, Karng

    2017-02-01

    High porosity materials such as aerogel known as a good insulator in a vacuum range (10-3 ∼ 1 Torr) was widely used to storage and to transport cryogenic fluids. It is necessary to be investigated the performance of aerogel insulations for cryogenic liquid storage in soft vacuum range to atmospheric pressure. A one-dimensional insulating experimental apparatus was designed and fabricated to consist of a cold mass tank, a heat absorber and an annular vacuum space with 5-layer (each 10 mm thickness) of the aerogel insulation materials. Aerogel blanket for cryogenic (used maximum temperature is 400K), aerogel blanket for normal temperature (used maximum temperature is 923K), and combination of the two kinds of aerogel blankets were 5-layer laminated between the cryogenic liquid wall and the ambient wall in vacuum space. Also, 1-D effective thermal conductivities of the insulation materials were evaluated by measuring boil-off rate from liquid nitrogen and liquid argon. In this study, the effective thermal conductivities and the temperature-thickness profiles of the two kinds of insulators and the layered combination of the two different aerogel blankets were presented.

  19. Robust Multilayer Insulation for Cryogenic Systems

    Science.gov (United States)

    Fesmire, J. E.; Scholtens, B. F.; Augustynowicz, S. D.

    2007-01-01

    New requirements for thermal insulation include robust Multilayer insulation (MU) systems that work for a range of environments from high vacuum to no vacuum. Improved MLI systems must be simple to install and maintain while meeting the life-cycle cost and thermal performance objectives. Performance of actual MLI systems has been previously shown to be much worse than ideal MLI. Spacecraft that must contain cryogens for both lunar service (high vacuum) and ground launch operations (no vacuum) are planned. Future cryogenic spacecraft for the soft vacuum environment of Mars are also envisioned. Industry products using robust MLI can benefit from improved cost-efficiency and system safety. Novel materials have been developed to operate as excellent thermal insulators at vacuum levels that are much less stringent than the absolute high vacuum requirement of current MLI systems. One such robust system, Layered Composite Insulation (LCI), has been developed by the Cryogenics Test Laboratory at NASA Kennedy Space Center. The experimental testing and development of LCI is the focus of this paper. LCI thermal performance under cryogenic conditions is shown to be six times better than MLI at soft vacuum and similar to MLI at high vacuum. The experimental apparent thermal conductivity (k-value) and heat flux data for LCI systems are compared with other MLI systems.

  20. Exergy analysis of cryogenic air separation

    NARCIS (Netherlands)

    Cornelissen, R.L.; Hirs, G.G.

    1998-01-01

    An exergy analysis is performed to analyse the possibilities of fuel saving in the cryogenic distillation process, which is the main method of air separation. It is shown that more than half of the exergy loss takes place in the liquefaction unit and almost one-third in the air compression unit. Min

  1. Testing the LHC magnet cryogenic systems

    CERN Multimedia

    Laurent Guiraud

    1999-01-01

    The magnets in the LHC will be cooled to 1.9 K (- 270.3°C). To keep this 27 km long machine at such a low temperatures requires one of the largest refrigeration systems in the world. These pictures show the cryogenics plant in the testing area.

  2. Stabilizing stainless steel components for cryogenic service

    Science.gov (United States)

    Holden, C. F.

    1967-01-01

    Warpage and creep in stainless steel valve components are decreased by a procedure in which components are machined to a semifinish and then cold soaked in a bath of cryogenic liquid. After the treatment they are returned to ambient temperature and machine finished to the final drawing dimensions.

  3. Cryogenic Heat Exchanger with Turbulent Flows

    Science.gov (United States)

    Amrit, Jay; Douay, Christelle; Dubois, Francis; Defresne, Gerard

    2012-01-01

    An evaporator-type cryogenic heat exchanger is designed and built for introducing fluid-solid heat exchange phenomena to undergraduates in a practical and efficient way. The heat exchanger functions at liquid nitrogen temperature and enables cooling of N[subscript 2] and He gases from room temperatures. We present first the experimental results of…

  4. Cryogenic Laser Calorimetry for Impurity Analysis

    Science.gov (United States)

    Swimm, R. T.

    1985-01-01

    The results of a one-year effort to determine the applicability of laser-calorimetric spectroscopy to the study of deep-level impurities in silicon are presented. Critical considerations for impurity analysis by laser-calorimetric spectroscopy are discussed, the design and performance of a cryogenic laser calorimeter is described, and measurements of background absorption in high-purity silicon are presented.

  5. Cryogenic Heat Exchanger with Turbulent Flows

    Science.gov (United States)

    Amrit, Jay; Douay, Christelle; Dubois, Francis; Defresne, Gerard

    2012-01-01

    An evaporator-type cryogenic heat exchanger is designed and built for introducing fluid-solid heat exchange phenomena to undergraduates in a practical and efficient way. The heat exchanger functions at liquid nitrogen temperature and enables cooling of N[subscript 2] and He gases from room temperatures. We present first the experimental results of…

  6. Energy Efficient Storage and Transfer of Cryogens

    Science.gov (United States)

    Fesmire, James E.

    2013-01-01

    Cryogenics is globally linked to energy generation, storage, and usage. Thermal insulation systems research and development is an enabling part of NASA's technology goals for Space Launch and Exploration. New thermal testing methodologies and materials are being transferred to industry for a wide range of commercial applications.

  7. Cryogenic Liquid Fluctuations in a Motionless Tank

    Directory of Open Access Journals (Sweden)

    Min Vin Ai

    2014-01-01

    Full Text Available The article considers approximate numerical methods to determine own frequencies of cryogenic liquid fluctuations stratification of which changes under any law. The increasing use of cryogenic liquids, liquefied gas, superfluid solutions, and slush liquids in modern mechanical engineering define relevance of a perspective. Interest in the considered problem is also caused by the fact that in cryogenic liquid along with superficial waves there can be internal wave movements penetrating all thickness of liquid in a tank and therefore playing important role in many hydro-dynamic processes.This article considers problems of determining the own frequencies of cryogenic liquid fluctuations, partially filling cylindrical tank of any cross section. It is supposed that the change of the liquid particles density due to thermal stratification of entire liquid mass can proceed continuously under any law. To solve numerically a similar problem, a method of trigonometric series (MTS and a method of final elements (MFE were used. When using the MTS method the unknown solution and variable coefficients of the equation were presented in the form of trigonometric series. Further, after multiplication of series and the subsequent mathematical operations the frequency equation was obtained. Bubnov-Galyorkin's approach was used to obtain solutions by the MFE method. Reliability of received numerical results is confirmed by coincidence with frequency results calculated by analytical formulas of solutions of differential equations with constant frequency of buoyancy.

  8. Cryogenics system: strategy to achieve nominal performance and reliable operation

    CERN Document Server

    Bremer, J; Casas, J; Claudet, S; Delikaris, D; Delruelle, N; Ferlin, G; Fluder, C; Perin, A; Perinic, G; Pezzetti, M; Pirotte, O; Tavian, L; Wagner, U

    2012-01-01

    During the LHC operation in 2010 and 2011, the cryogenic system has achieved an availability level fulfilling the overall requirement. To reach this level, the cryogenic system has profited like many other beam-dependent systems from the reduced beam parameters. Therefore, impacts of some failures occurred during the LHC operation were mitigated by using the overcapacity margin, the existing built-in redundancy in between adjacent sector cryogenic plants and the "cannibalization" of spares on two idle cryogenic plants. These two first years of operation were also crucial to identify the weaknesses of the present cryogenic maintenance plan and new issues like SEUs. After the LS1, nominal beam parameters are expected and the mitigated measures will be less effective or not applicable at all. Consequently, a consolidation plan to improve the MTBF and the MTTR of the LHC cryogenic system is under definition. Concerning shutdown periods, the present cryogenic sectorization imposes some restrictions in the type of ...

  9. ATLAS magnet common cryogenic, vacuum, electrical and control systems

    CERN Document Server

    Miele, P; Delruelle, N; Geich-Gimbel, C; Haug, F; Olesen, G; Pengo, R; Sbrissa, E; Tyrvainen, H; ten Kate, H H J

    2004-01-01

    The superconducting Magnet System for the ATLAS detector at the LHC at CERN comprises a Barrel Toroid, two End Cap Toroids and a Central Solenoid with overall dimensions of 20 m diameter by 26 m length and a stored energy of 1.6 GJ. Common proximity cryogenic and electrical systems for the toroids are implemented. The Cryogenic System provides the cooling power for the 3 toroid magnets considered as a single cold mass (600 tons) and for the CS. The 21 kA toroid and the 8 kA solenoid electrical circuits comprise both a switch-mode power supply, two circuit breakers, water cooled bus bars, He cooled current leads and the diode resistor ramp-down unit. The Vacuum System consists of a group of primary rotary pumps and sets of high vacuum diffusion pumps connected to each individual cryostat. The Magnet Safety System guarantees the magnet protection and human safety through slow and fast dump treatment. The Magnet Control System ensures control, regulation and monitoring of the operation of the magnets. The update...

  10. Retinal photodamage by endogenous and xenobiotic agents.

    Science.gov (United States)

    Wielgus, Albert R; Roberts, Joan E

    2012-01-01

    The human eye is constantly exposed to sunlight and artificial lighting. Light transmission through the eye is fundamental to its unique biological functions of directing vision and circadian rhythm and therefore light absorbed by the eye must be benign. However, exposure to the very intense ambient radiation can pose a hazard particularly if the recipient is over 40 years of age. There are age-related changes in the endogenous (natural) chromophores (lipofuscin, A2E and all-trans-retinal derivatives) in the human retina that makes it more susceptible to visible light damage. Intense visible light sources that do not filter short blue visible light (400-440 nm) used for phototherapy of circadian imbalance (i.e. seasonal affective disorder) increase the risk for age-related light damage to the retina. Moreover, many drugs, dietary supplements, nanoparticles and diagnostic dyes (xenobiotics) absorb ocular light and have the potential to induce photodamage to the retina, leading to transient or permanent blinding disorders. This article will review the underlying reasons why visible light in general and short blue visible light in particular dramatically raises the risk of photodamage to the human retina.

  11. Overproduction of a kinetic subclass of VLDL-apoB, and direct catabolism of VLDL-apoB in human endogenous hypertriglyceridemia: an analytical model solution of tracer data

    Energy Technology Data Exchange (ETDEWEB)

    Eaton, R.P.; Allen, R.C.; Schade, D.S.

    1983-10-01

    To investigate the participation of the major apoprotein involved in triglyceride transport in the pathogenesis of endogenous hypertriglyceridemia, five kinetic studies of apoprotein B were conducted in volunteer normolipidemic subjects and six studies in four patients with endogenous hypertriglyceridemia. The transport of apoprotein B within four kinetic subclasses of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) was studied by injection of (/sup 75/Se)selenomethionine. A 24-fold increase in the entry of newly synthesized apoprotein B at the initial kinetic subclass of the four-compartment VLDL delipidation sequence characterized the hypertriglyceridemic studies relative to normal subjects. Moreover, approximately 75 mg/kg per day of VLDL-B turnover reflected direct catabolism independent of conversion to IDL and/or to LDL, in contrast to the 8 mg/kg per day observed in controls. IDL-B was derived from VLDL-B in both normal and hypertriglyceridemic subjects, and was responsible for greater than 70% of all LDL-B synthesis. LDL-B pool size and turnover were indistinguishable in hypertriglyceridemic subjects from that observed in normal subjects. These studies suggest that two kinetic phenomena may characterize the pathophysiology of endogenous hypertriglyceridemia: a) over-production of apoB within a kinetic subclass of VLDL and b) preferential catabolism of hypertriglyceridemic VLDL without prior conversion to IDL/LDL.

  12. Cooperation Networks: Endogeneity and Complexity

    CERN Document Server

    Angus, S

    2006-01-01

    Insights from the Complex Systems literature are employed to develop a computational model of truly endogenous strategic network formation. Artificial Adaptive Agents, implemented as Finite State Automata (FSA), play a modified two-player IPD game with an option to further develop the interaction space as part of their strategy. Several insights result from this minor modification: first, I find that network formation is a necessary condition for cooperation to be sustainable but that both the frequency of interaction and the degree to which edge formation impacts agent mixing are both necessary conditions for cooperative networks. Second, within the FSA-modified IPD frame-work, a rich ecology of agents and network topologies is observed and described. Third, the system dynamics are investigated and reveal that initially simple dynamics with small interaction length between agents gives way to complex, a-periodic dynamics with self-organized critical properties when interaction lengths are increased by a sing...

  13. Endogenous, Imperfectly Competitive Business Cycles

    DEFF Research Database (Denmark)

    Whitta-Jacobsen, Hans Jørgen

    by monopolistic competition. An implicit assumption of barriers to entry justifies that the number of firms is fixed even when positive profits occur. It turns out that both market power of firms on the product markets and market power of unions on the labor markets make the occurrence of cycles more likely......We investigate how imperfect competition affects the occurrence and the properties of endogenous, rational expectations business cycles in an overlapping generations model with constant returns to scale in production. The model has explicit product and labor markets all characterized....... In particular, imperfect competition on the product markets and the positive profits associated with it may have the effect that there is a cycle even if the labor supply curve is increasing in the real-wage rate. For competitive cycles is required not only a decreasing labor supply curve, but a wage elasticity...

  14. Endogenous scheduling preferences and congestion

    DEFF Research Database (Denmark)

    Fosgerau, Mogens; Small, Kenneth

    2010-01-01

    Dynamic models of congestion so far rely on exogenous scheduling preferences of travelers, based for example on disutility of deviation from a preferred departure or arrival time for a trip. This paper provides a more fundamental view in which travelers derive utility just from consumption...... and leisure, but agglomeration economies at home and at work lead to scheduling preferences forming endogenously. Using bottleneck congestion technology, we obtain an equilibrium queuing pattern consistent with a general version of the Vickrey bottleneck model. However, the policy implications are different....... Compared to the predictions of an analyst observing untolled equilibrium and taking scheduling preferences as exogenous, we find that both the optimal capacity and the marginal external cost of congestion have changed. The benefits of tolling are greater, and the optimal time varying toll is different....

  15. Detection of endogenous cortisol in human hair by high performance liquid chromatography tandem mass spectrometry%头发中内源性氢化可的松的高效液相色谱/串联质谱检测

    Institute of Scientific and Technical Information of China (English)

    谢巧珍; 皋伟; 李季峰; 乔婷; 邓慧华; 陆祖宏

    2011-01-01

    A new method for detection of endogenous cortisol in human hair was developed based on high performance liquid chromatography tandem mass spectrometry (HPLC/MS/MS), and the results detected was compared with that determined by high performance liquid chromatography with fluorescence detector (HPLC/FLU). Hair sample (50 mg ) was incubated in methanol after being washed and pulverized, and then the extraction was purified by C18 solid phase extraction column. Cortisol identification was performed by electro-spray ionization (ESI) in negative mode using multiple reaction monitoring (MRM) and the quantification was performed using external standard method. The limit of quantification is 2 pg/mg, and the linear range is 2 to 100 pg/mg. The recovery of cortisol spiked at 50 pg/mg is (99. 4 ±9. 1 ) %, intra-day precision is 7. 6 %, inter-day precision is 8. 3 %. Because of the differences in hair pretreatment method, cortisol extraction method, matrix effect and quantitative method, cortisol concentration detected by HPLC/MS/MS is significantly lower than that determined by HPLC/FLU. However, Pearson correlation analysis showed that there is a significant linear correlation (r =0. 749, p <0. 01 ) between hair cortisol contents analyzed by these two methods.%基于高效液相色谱/串联质谱(HPLC/MS/MS)建立了一种检测头发中内源性氢化可的松含量的方法,并与高效液相色谱/荧光法(HPLC/FLU)的测定结果进行比较.头发样品(50 mg)经过清洗与研磨、甲醇提取和C18固相萃取后,在电喷雾(ESI)负离子模式和多反应监测(MRM)方式下进行定性,以外标法进行定量.方法的定量限为2 pg/mg,工作曲线的线性范围为2~100 pg/mg;在空白头发添加50 pg/mg外标时,方法的回收率为(99.4±9.1)%,日内精密度为7.6%,日间精密度为8.3%.由于前处理提取方法、基质效应和定量方法不同,所以HPLC/MS/MS法的测定结果明显低于HPLC/FLU法的测定

  16. Cryogenic Detectors (Narrow Field Instruments)

    Science.gov (United States)

    Hoevers, H.; Verhoeve, P.

    Two cryogenic imaging spectrometer arrays are currently considered as focal plane instruments for XEUS. The narrow field imager 1 (NFI 1) will cover the energy range from 0.05 to 3 keV with an energy resolution of 2 eV, or better, at 500 eV. A second narrow field imager (NFI 2) covers the energy range from 1 to 15 keV with an energy resolution of 2 eV (at 1 keV) and 5 eV (at 7 keV), creating some overlap with part of the NFI 1 energy window. Both narrow field imagers have a 0.5 arcmin field of view. Their imaging capabilities are matched to the XEUS optics of 2 to 5 arcsec leading to 1 arcsec pixels. The detector arrays will be cooled by a closed cycle system comprising a mechanical cooler with a base temperature of 2.5 K and either a low temperature 3He sorption pump providing the very low temperature stage and/or an Adiabatic Demagnetization Refrigerator (ADR). The ADR cooler is explicitly needed to cool the NFI 2 array. The narrow field imager 1} Currently a 48 times 48 element array of superconducting tunnel junctions (STJ) is envisaged. Its operating temperature is in the range between 30 and 350 mK. Small, single Ta STJs (20-50 mum on a side) have shown 3.5 eV (FWHM) resolution at E = 525 eV and small arrays have been successfully demonstrated (6 times 6 pixels), or are currently tested (10 times 12 pixels). Alternatively, a prototype Distributed Read-Out Imaging Device (DROID), consisting of a linear superconducting Ta absorber of 20 times 100 mum2, including a 20 times 20 mum STJ for readout at either end, has shown a measured energy resolution of 2.4 eV (FWHM) at E = 500 eV. Simulations involving the diffusion properties as well as loss and tunnel rates have shown that the performance can be further improved by slight modifications in the geometry, and that the size of the DROIDS can be increased to 0.5-1.0 mm without loss in energy resolution. The relatively large areas and good energy resolution compared to single STJs make DROIDS good candidates for the

  17. Endogenous K-ras signaling in erythroid differentiation.

    Science.gov (United States)

    Zhang, Jing; Lodish, Harvey F

    2007-08-15

    K-ras is one of the most frequently mutated genes in virtually all types of human cancers. Using mouse fetal liver erythroid progenitors as a model system, we studied the role of endogenous K-ras signaling in erythroid differentiation. When oncogenic K-ras is expressed from its endogenous promoter, it hyperactivates cytokine-dependent signaling pathways and results in a partial block in erythroid differentiation. In erythroid progenitors deficient in K-ras, cytokine-dependent Akt activation is greatly reduced, leading to delays in erythroid differentiation. Thus, both loss- and gain-of-Kras functions affect erythroid differentiation through modulation of cytokine signaling. These results support the notion that in human cancer patients oncogenic Ras signaling might be controlled by antagonizing essential cytokines.

  18. Cryogenic Insulation Standard Data and Methodologies Project

    Science.gov (United States)

    Summerfield, Burton; Thompson, Karen; Zeitlin, Nancy; Mullenix, Pamela; Fesmire, James; Swanger, Adam

    2015-01-01

    Extending some recent developments in the area of technical consensus standards for cryogenic thermal insulation systems, a preliminary Inter-Laboratory Study of foam insulation materials was performed by NASA Kennedy Space Center and LeTourneau University. The initial focus was ambient pressure cryogenic boil off testing using the Cryostat-400 flat-plate instrument. Completion of a test facility at LETU has enabled direct, comparative testing, using identical cryostat instruments and methods, and the production of standard thermal data sets for a number of materials under sub-ambient conditions. The two sets of measurements were analyzed and indicate there is reasonable agreement between the two laboratories. Based on cryogenic boiloff calorimetry, new equipment and methods for testing thermal insulation systems have been successfully developed. These boiloff instruments (or cryostats) include both flat plate and cylindrical models and are applicable to a wide range of different materials under a wide range of test conditions. Test measurements are generally made at large temperature difference (boundary temperatures of 293 K and 78 K are typical) and include the full vacuum pressure range. Results are generally reported in effective thermal conductivity (ke) and mean heat flux (q) through the insulation system. The new cryostat instruments provide an effective and reliable way to characterize the thermal performance of materials under subambient conditions. Proven in through thousands of tests of hundreds of material systems, they have supported a wide range of aerospace, industry, and research projects. Boiloff testing technology is not just for cryogenic testing but is a cost effective, field-representative methodology to test any material or system for applications at sub-ambient temperatures. This technology, when adequately coupled with a technical standards basis, can provide a cost-effective, field-representative methodology to test any material or system

  19. Design of the NIF Cryogenic Target System

    Energy Technology Data Exchange (ETDEWEB)

    Gibson, C; Baltz, J; Malsbury, T; Atkinson, D; Brugmann, V; Coffield, F; Edwards, O; Haid, B; Locke, S; Shiromizu, S; Skulina, K

    2008-06-10

    The United States Department of Energy has embarked on a campaign to conduct credible fusion ignition experiments on the National Ignition Facility (NIF) at the Lawrence Livermore National Laboratory in 2010. The target assembly specified for this campaign requires the formation of a deuterium/tritium (DT) fuel ice layer in a 2 mm diameter capsule at the center of a 9 mm long by 5 mm diameter cylinder, called a hohlraum. The ice layer must be formed and maintained at temperatures below 20 K. At laser shot time, the target is positioned at the center of the NIF target chamber, aligned to the laser beams and held stable to less than 7 {micro}m rms. We have completed the final design of the Cryogenic Target System and are integrating the devices necessary to create, characterize and position the cryogenic target for ignition experiments. These designs, with supporting analysis and prototype test results, will be presented.

  20. A cryogenic valve for spacecraft applications

    Science.gov (United States)

    Salerno, L. J.; Spivak, A. L.

    1982-01-01

    Space-compatible cryogenic valves are now required to operate between room and liquid helium temperatures. A remotely controllable cryogenic valve is described, which is made of bellows-type stainless steel and is operated by a miniature dc motor with integral gearset (485:1) at a nominal voltage of 28 Vdc. The power transmission provides a further reduction of 7.2:1 to give an overall gear ratio of nearly 3500:1, assuring reliability of operation at low temperatures. Valve performance (leak rate) data are presented at LN2, LHe, and SfHe temperatures at delivered torques of 18, 27, 31, and 35 N-m. At a closing torque of 31 N-m, a leak rate of 0.028 scc/sec was achieved at 2 K, while at a torque of 18 N-m the leak rate at 300 K was less than 3 x 10 to the -9th scc/sec.

  1. Absorber Materials at Room and Cryogenic Temperatures

    Energy Technology Data Exchange (ETDEWEB)

    F. Marhauser, T.S. Elliott, A.T. Wu, E.P. Chojnacki, E. Savrun

    2011-09-01

    We recently reported on investigations of RF absorber materials at cryogenic temperatures conducted at Jefferson Laboratory (JLab). The work was initiated to find a replacement material for the 2 Kelvin low power waveguide Higher Order Mode (HOM) absorbers employed within the original cavity cryomodules of the Continuous Electron Beam Accelerator Facility (CEBAF). This effort eventually led to suitable candidates as reported in this paper. Furthermore, though constrained by small funds for labor and resources, we have analyzed a variety of lossy ceramic materials, several of which could be usable as HOM absorbers for both normal conducting and superconducting RF structures, e.g. as loads in cavity waveguides and beam tubes either at room or cryogenic temperatures and, depending on cooling measures, low to high operational power levels.

  2. Progress of the FAIR Cryogenic System

    Science.gov (United States)

    Kauschke, M.; Kollmus, H.; Martinez-Lopez, M.

    2017-02-01

    The planning revision of the cryogenic system for the Facility of Antiproton and Ion Research (FAIR, Darmstadt, Germany) resulted in the choice of a single universal plant, which should provide a wide range of cryogenic operation modes, as refrigeration capacity at 4.4K, liquefaction or intermediate temperature levels. The adaptation to the FAIR specific requirements will be done later by adding a second plant. One major demand for the plant is the short term adaptation to variations in the load requirements in the system. An exemplary integration into the overall FAIR system will be shown with the experiments in the Compressed Baryonic Matter (CBM) cave. The CBM cave will house an already existing magnet, HADES, and a new magnet for the CBM experiment, which is still under design. The scheduling of the different operation modes related to the operation of the main consumers as SIS100 or SuperFRS is shown.

  3. Cryogenic cooling for high power laser amplifiers

    Directory of Open Access Journals (Sweden)

    Perin J.P.

    2013-11-01

    Full Text Available Using DPSSL (Diode Pumped Solid State Lasers as pumping technology, PW-class lasers with enhanced repetition rates are developed. Each of the Yb YAG amplifiers will be diode-pumped at a wavelength of 940 nm. This is a prerequisite for achieving high repetition rates (light amplification duration 1 millisecond and repetition rate 10 Hz. The efficiency of DPSSL is inversely proportional to the temperature, for this reason the slab amplifier have to be cooled at a temperature in the range of 100 K–170 K with a heat flux of 1 MW*m−2. This paper describes the thermo-mechanical analysis for the design of the amplification laser head, presents a preliminary proposal for the required cryogenic cooling system and finally outlines the gain of cryogenic operation for the efficiency of high pulsed laser.

  4. A Scanning Quantum Cryogenic Atom Microscope

    CERN Document Server

    Yang, Fan; Taylor, Stephen F; Turner, Richard W; Lev, Benjamin L

    2016-01-01

    Microscopic imaging of local magnetic fields provides a window into the organizing principles of complex and technologically relevant condensed matter materials. However, a wide variety of intriguing strongly correlated and topologically nontrivial materials exhibit poorly understood phenomena outside the detection capability of state-of-the-art high-sensitivity, high-resolution scanning probe magnetometers. We introduce a quantum-noise-limited scanning probe magnetometer that can operate from room-to-cryogenic temperatures with unprecedented DC-field sensitivity and micron-scale resolution. The Scanning Quantum Cryogenic Atom Microscope (SQCRAMscope) employs a magnetically levitated atomic Bose-Einstein condensate (BEC), thereby providing immunity to conductive and blackbody radiative heating. The SQCRAMscope has a noise floor of 300 pT and provides a 100x improvement in magnetic flux sensitivity over previous atomic scanning probe magnetometers. These capabilities are carefully benchmarked by imaging magnet...

  5. Design of a rapidly cooled cryogenic mirror

    Science.gov (United States)

    Plummer, Ron; Hsu, Ike

    1993-01-01

    The paper discusses the design, analysis, and testing of a rapidly cooled beryllium cryogenic mirror, which is the primary mirror in the four-element optical system for the Long Wavelength Infrared Advanced Technology Seeker. The mirror is shown to meet the requirement of five minutes for cooling to cryogenic operating temperature; it also maintains its optical figure and vacuum integrity and meets the nuclear specification. Results of a detailed thermal analysis on the mirror showed that, using nitrogen gas at 80 K as coolant, the front face of the mirror can be cooled from an initial temperature of 300 K to less than 90 K within five minutes. In a vacuum chamber, using liquid nitrogen as coolant, the mirror can be cooled to 80 K within 1.5 min. The mirror is well thermally insulated, so that it can be maintained at less than its operating temperature for a long time without active cooling.

  6. LHC’s cryogenic magnet test facility

    CERN Multimedia

    1994-01-01

    This string of magnets was designed to test the cryogenic systems that will keep the LHC colder than 270 degrees below zero. The LHC’s beams will be accelerated to an energy of 7 TeV so powerful superconducting magnets must be used to hold the beams on course as they race around the giant accelerator. These magnets are kept at 1.9 K (-270.3°C).

  7. Cryogenic Boil-Off Reduction System

    Science.gov (United States)

    Plachta, David W.; Guzik, Monica C.

    2014-03-01

    A computational model of the cryogenic boil-off reduction system being developed by NASA as part of the Cryogenic Propellant Storage and Transfer technology maturation project has been applied to a range of propellant storage tanks sizes for high-performing in-space cryogenic propulsion applications. This effort focuses on the scaling of multi-layer insulation (MLI), cryocoolers, broad area cooling shields, radiators, solar arrays, and tanks for liquid hydrogen propellant storage tanks ranging from 2 to 10 m in diameter. Component scaling equations were incorporated into the Cryogenic Analysis Tool, a spreadsheet-based tool used to perform system-level parametric studies. The primary addition to the evolution of this updated tool is the integration of a scaling method for reverse turbo-Brayton cycle cryocoolers, as well as the development and inclusion of Self-Supporting Multi-Layer Insulation. Mass, power, and sizing relationships are traded parametrically to establish the appropriate loiter period beyond which this boil-off reduction system application reduces mass. The projected benefit compares passive thermal control to active thermal control, where active thermal control is evaluated for reduced boil-off with a 90 K shield, zero boil-off with a single heat interception stage at the tank wall, and zero boil-off with a second interception stage at a 90 K shield. Parametric studies show a benefit over passive storage at loiter durations under one month, in addition to showing a benefit for two-stage zero boil-off in terms of reducing power and mass as compared to single stage zero boil-off. Furthermore, active cooling reduces the effect of varied multi-layer insulation performance, which, historically, has been shown to be significant.

  8. Signal processing in cryogenic particle detection

    Energy Technology Data Exchange (ETDEWEB)

    Yuryev, Y.N. [Department of Physics and Astronomy, Seoul National University, Seoul (Korea, Republic of); Korea Research Institute of Standards and Science (KRISS), Daejeon (Korea, Republic of); Jang, Y.S. [Korea Research Institute of Standards and Science (KRISS), Daejeon (Korea, Republic of); Kim, S.K. [Department of Physics and Astronomy, Seoul National University, Seoul (Korea, Republic of); Lee, K.B.; Lee, M.K. [Korea Research Institute of Standards and Science (KRISS), Daejeon (Korea, Republic of); Lee, S.J. [Department of Physics and Astronomy, Seoul National University, Seoul (Korea, Republic of); Korea Research Institute of Standards and Science (KRISS), Daejeon (Korea, Republic of); Yoon, W.S. [Korea Research Institute of Standards and Science (KRISS), Daejeon (Korea, Republic of); Kim, Y.H., E-mail: yhkim@kriss.re.k [Korea Research Institute of Standards and Science (KRISS), Daejeon (Korea, Republic of)

    2011-04-11

    We describe a signal-processing program for a data acquisition system for cryogenic particle detectors. The program is based on an optimal-filtering method for high-resolution measurement of calorimetric signals with a significant amount of noise of unknown origin and non-stationary behavior. The program was applied to improve the energy resolution of the alpha particle spectrum of an {sup 241}Am source.

  9. High-aperture cryogenic light microscopy

    Science.gov (United States)

    LE GROS, M.A.; McDERMOTT, G.; UCHIDA, M.; KNOECHEL, C.G.; LARABELL, C.A.

    2012-01-01

    Summary We report here the development of instruments and protocols for carrying out high numerical aperture immersion light microscopy on cryogenic specimens. Imaging by this modality greatly increases the lifetimes of fluorescence probes, including those commonly used for protein localization studies, while retaining the ability to image the specimen with high fidelity and spatial resolution. The novel use of a cryogenic immersion fluid also minimizes the refractive index mismatch between the sample and lens, leading to a more efficient coupling of the light from the sample to the image forming system. This enhancement is applicable to both fluorescence and transmitted light microscopy techniques. The design concepts used for the cryogenic microscope can be applied to virtually any existing light-based microscopy technique. This prospect is particularly exciting in the context of ‘super-resolution’ techniques, where enhanced fluorescence lifetime probes are especially useful. Thus, using this new modality it is now possible to observe dynamic events in a live cell, and then rapidly vitrify the specimen at a specific time point prior to carrying out high-resolution imaging. The techniques described can be used in conjunction with other imaging modalities in correlated studies. We have also developed instrumentation to perform cryo-light imaging together with soft X-ray tomography on the same cryo-fixed specimen as a means of carrying out high content, quantifiable correlated imaging analyses. These methods are equally applicable to correlated light and electron microscopy of frozen biological objects. PMID:19566622

  10. Influence of Thermal Cycling on Cryogenic Thermometers

    CERN Document Server

    Balle, C; Rieubland, Jean Michel; Suraci, A; Togny, F; Vauthier, N

    1999-01-01

    The stringent requirements on temperature control of the superconducting magnets for the Large Hadron Collider (LHC), impose that the cryogenic temperature sensors meet compelling demands such as long-term stability, radiation hardness, readout accuracy better than 5 mK at 1.8 K and compatibility with industrial control equipment. This paper presents the results concerning long-term stability of resistance temperature sensors submitted to cryogenic thermal cycles. For this task a simple test facility has been designed, constructed and put into operation for cycling simultaneously 115 cryogenic thermometers between 300 K and 4.2 K. A thermal cycle is set to last 71/4 hours: 3 hours for either cooling down or warming up the sensors and 1 respectively 1/4 hour at steady temperature conditions at each end of the temperature cycle. A Programmable Logic Controller (PLC) drives automatically this operation by reading 2 thermometers and actuating on 3 valves and 1 heater. The first thermal cycle was accomplished in a...

  11. Polyamide 66 as a cryogenic dielectric

    Science.gov (United States)

    Tuncer, Enis; Polizos, Georgios; Sauers, Isidor; Randy James, D.; Ellis, Alvin R.; Messman, Jamie M.; Aytuğ, Tolga

    2009-09-01

    Improvements in superconductor and cryogenic technologies enable novel power apparatus, e.g., cables, transformers, fault current limiters, generators, it etc., with better device characteristics than their conventional counterparts. In these applications electrical insulation materials play an important role in system weight, footprint (size), and voltage level. The trend in the electrical insulation material selection has been to adapt or to employ conventional insulation materials to these new systems. However, at low temperatures, thermal contraction and loss of mechanical strength in many materials make them unsuitable for superconducting power applications. In this paper, a widely used commercial material was characterized as a potential cryogenic dielectric. The material is used in "oven bags" which is a heat-resistant polyamide (nylon) used in cooking (produced by ; this value is approximately 46kVmm higher than PPLP™. Comparison of the mechanical properties of PA and PPLP™ indicates that PA66 has low storage and loss moduli than PPLP™. It is concluded that PA66 may be a good candidate for cryogenic applications. Finally, a summary of dielectric properties of some of the commercial tape insulation materials and various polymers is also provided.

  12. Thermoelectric Generators used as Cryogenic Heat Engines

    Science.gov (United States)

    Smith, D. E.; Ordonez, C. A.

    1997-03-01

    A future experiment is being planned at the University of North Texas to design, build, and test a cryogenic heat engine(C. A. Ordonez, Am. J. Phys. 64), 479 (1996). suitable as an electric-vehicle power system. The power system shall then be installed in a demonstration vehicle. This will be a next-generation vehicle following the current project described in the accompanying poster, ``Experimental Car Which Uses Liquid Nitrogen as Its Fuel" by M. E. Parker et al. The cryogenic heat engine electric vehicle power system will incorporate both a thermoelectric generator and an ambient-temperature turbine or pneumatic-motor/generator. The thermoelectric generator shall use liquid nitrogen (under pressure) as its cold reservoir. Energy is produced with the thermoelectric generator by using the liquid/gas phase change to absorb heat. At the present time a study is being carried out to determine the efficiency of thermoelectric devices which are used as cryogenic heat engines. Initial data is being taken using frozen H_2O and CO2 as cold reservoirs. The results of the study shall be presented.

  13. Liquid Cryogenic Target Development for Fast Ignition*

    Science.gov (United States)

    Hanson, D. L.; Russell, C.; Vesey, R. A.; Schroen, D. G.; Taylor, J. L.; Back, C. A.; Steinman, D.; Nikroo, A.; Kaae, J. L.; Giraldez, E.; Johnston, R. R.; Youngman, K.

    2007-11-01

    As an alternative to foam-stabilized cryogenic solid D-T fuel layers for indirect-drive fast ignitor targets, which will tend to β-layer to a nonuniform distribution in a reentrant cone geometry [1], we are investigating hemispherical cryogenic fast ignition capsules with a liquid fuel layer confined between a thick outer ablator shell and a thin inner shell [2]. The shape and surface quality of the fuel layer is determined entirely by the characteristics of the bounding shells. In the present design, structural support for the thin (4.5 um) hemispherical GDP inner shell is provided by a mounting ring. Fabrication of stronger thin Be hemi-shells is also being investigated. Technology issues for liquid cryogenic fuel capsule development and progress toward demonstration of a working target will be presented. [1] J.K. Hoffer et al., Fusion Sci. Technol. 50, 15 (2006). [2] D.L. Hanson et al., Fusion Sci. Technol. 49, 500 (2006). *Sandia is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin Company, for the United States Department of Energy's National Nuclear Security Administration under Contract DE-AC04-94AL85000.

  14. Demonstration of Microsphere Insulation in Cryogenic Vessels

    Science.gov (United States)

    Baumgartner, R. G.; Myers, E. A.; Fesmire, J. E.; Morris, D. L.; Sokalski, E. R.

    2006-04-01

    While microspheres have been recognized as a legitimate insulation material for decades, actual use in full-scale cryogenic storage tanks has not been demonstrated until now. The performance and life-cycle-cost advantages previously predicted have now been proven. Most bulk cryogenic storage tanks are insulated with either multilayer insulation (MLI) or perlite. Microsphere insulation, consisting of hollow glass bubbles, combines in a single material the desirable properties that other insulations only have individually. The material has high crush strength, low density, is noncombustible, and performs well in soft vacuum. These properties were proven during recent field testing of two 22,700-L (6,000-gallon) liquid nitrogen tanks, one insulated with microsphere insulation and the other with perlite. Normal evaporation rates (NER) for both tanks were monitored with precision test equipment and insulation levels within the tanks were observed through view ports as an indication of insulation compaction. Specific industrial applications were evaluated based on the test results and beneficial properties of microsphere insulation. Over-the-road trailers previously insulated with perlite will benefit not only from the reduced heat leak, but also the reduced mass of microsphere insulation. Economic assessments for microsphere-insulated cryogenic vessels including life-cycle cost are also presented.

  15. Expandable Purge Chambers Would Protect Cryogenic Fittings

    Science.gov (United States)

    Townsend, Ivan I., III

    2004-01-01

    Expandable ice-prevention and cleanliness-preservation (EIP-CP) chambers have been proposed to prevent the accumulation of ice or airborne particles on quick-disconnect (QD) fittings, or on ducts or tubes that contain cryogenic fluids. In the original application for which the EIP-CP chambers were conceived, there is a requirement to be able to disconnect and reconnect the QD fittings in rapid succession. If ice were to form on the fittings by condensation and freezing of airborne water vapor on the cold fitting surfaces, the ice could interfere with proper mating of the fittings, making it necessary to wait an unacceptably long time for the ice to thaw before attempting reconnection. By keeping water vapor away from the cold fitting surfaces, the EIP-CP chambers would prevent accumulation of ice, preserving the ability to reconnect as soon as required. Basically, the role of an EIP-CP chamber would be to serve as an enclosure for a flow of dry nitrogen gas that would keep ambient air away from QD cryogenic fittings. An EIP-CP chamber would be an inflatable device made of a fabriclike material. The chamber would be attached to an umbilical plate holding a cryogenic QD fitting.

  16. Design Tool for Cryogenic Thermal Insulation Systems

    Energy Technology Data Exchange (ETDEWEB)

    Demko, Jonathan A [ORNL; Fesmire, J. E. [NASA Kennedy Space Center, Kennedy Space Center, Florida; Augustynowicz, S. D. [Sierra Lobo Inc., Kennedy Space Center, Florida

    2008-01-01

    Thermal isolation of low-temperature systems from ambient environments is a constant issue faced by practitioners of cryogenics. For energy-efficient systems and processes to be realized, thermal insulation must be considered as an integrated system, not merely an add-on element. A design tool to determine the performance of insulation systems for comparative trade-off studies of different available material options was developed. The approach is to apply thermal analysis to standard shapes (plane walls, cylinders, spheres) that are relatively simple to characterize with a one-dimensional analytical or numerical model. The user describes the system hot and cold boundary geometry and the operating environment. Basic outputs such as heat load and temperature profiles are determined. The user can select from a built-in insulation material database or input user defined materials. Existing information has been combined with the new experimental thermal conductivity data produced by the Cryogenics Test Laboratory for cryogenic and vacuum environments, including high vacuum, soft vacuum, and no vacuum. Materials in the design tool include multilayer insulation, aerogel blankets, aerogel bulk-fill, foams, powders, composites, and other insulation system constructions. A comparison of the design tool to a specific composite thermal insulation system is given.

  17. Realization and performance of cryogenic selection mechanisms

    Science.gov (United States)

    Aitink-Kroes, Gabby; Bettonvil, Felix; Kragt, Jan; Elswijk, Eddy; Tromp, Niels

    2014-07-01

    Within Infra-Red large wavelength bandwidth instruments the use of mechanisms for selection of observation modes, filters, dispersing elements, pinholes or slits is inevitable. The cryogenic operating environment poses several challenges to these cryogenic mechanisms; like differential thermal shrinkage, physical property change of materials, limited use of lubrication, high feature density, limited space etc. MATISSE the mid-infrared interferometric spectrograph and imager for ESO's VLT interferometer (VLTI) at Paranal in Chile coherently combines the light from 4 telescopes. Within the Cold Optics Bench (COB) of MATISSE two concepts of selection mechanisms can be distinguished based on the same design principles: linear selection mechanisms (sliders) and rotating selection mechanisms (wheels).Both sliders and wheels are used at a temperature of 38 Kelvin. The selection mechanisms have to provide high accuracy and repeatability. The sliders/wheels have integrated tracks that run on small, accurately located, spring loaded precision bearings. Special indents are used for selection of the slider/wheel position. For maximum accuracy/repeatability the guiding/selection system is separated from the actuation in this case a cryogenic actuator inside the cryostat. The paper discusses the detailed design of the mechanisms and the final realization for the MATISSE COB. Limited lifetime and performance tests determine accuracy, warm and cold and the reliability/wear during life of the instrument. The test results and further improvements to the mechanisms are discussed.

  18. A novel endogenous betaretrovirus group characterized from polar bears (Ursus maritimus) and giant pandas (Ailuropoda melanoleuca).

    Science.gov (United States)

    Mayer, Jens; Tsangaras, Kyriakos; Heeger, Felix; Avila-Arcos, María; Stenglein, Mark D; Chen, Wei; Sun, Wei; Mazzoni, Camila J; Osterrieder, Nikolaus; Greenwood, Alex D

    2013-08-15

    Transcriptome analysis of polar bears (Ursus maritimus) yielded sequences with highest similarity to the human endogenous retrovirus group HERV-K(HML-2). Further analysis of the polar bear draft genome identified an endogenous betaretrovirus group comprising 26 proviral copies and 231 solo LTRs. Molecular dating indicates the group originated before the divergence of bears from a common ancestor but is not present in all carnivores. Closely related sequences were identified in the giant panda (Ailuropoda melanoleuca) and characterized from its genome. We have designated the polar bear and giant panda sequences U. maritimus endogenous retrovirus (UmaERV) and A. melanoleuca endogenous retrovirus (AmeERV), respectively. Phylogenetic analysis demonstrated that the bear virus group is nested within the HERV-K supergroup among bovine and bat endogenous retroviruses suggesting a complex evolutionary history within the HERV-K group. All individual remnants of proviral sequences contain numerous frameshifts and stop codons and thus, the virus is likely non-infectious.

  19. Population aging and endogenous economic growth.

    Science.gov (United States)

    Prettner, Klaus

    2013-04-01

    We investigate the consequences of population aging for long-run economic growth perspectives. Our framework incorporates endogenous growth models and semi-endogenous growth models as special cases. We show that (1) increases in longevity have a positive impact on per capita output growth, (2) decreases in fertility have a negative impact on per capita output growth, (3) the positive longevity effect dominates the negative fertility effect in case of the endogenous growth framework, and (4) population aging fosters long-run growth in the endogenous growth framework, while its effect depends on the relative change between fertility and mortality in the semi-endogenous growth framework.Electronic supplementary material The online version of this article (doi:10.1007/s00148-012-0441-9) contains supplementary material, which is available to authorized users.

  20. Cryogenic Safety HSE Seminar | 21 - 23 September 2016

    CERN Multimedia

    2016-01-01

    With the LHC being the world’s largest superconducting installation, it’s not surprising that CERN is a world leader in cryogenic safety. On 21 and 22 September, over 100 experts in cryogenic safety will be coming to CERN to take part in CERN’s first Cryogenic Safety Seminar, which aims to stimulate collaboration and further the state of the art in this increasingly important field.  

  1. Cryogenic Tm: YAG Laser in the Near Infrared

    Science.gov (United States)

    2015-05-29

    REPLACE THIS LINE WITH YOUR PAPER IDENTIFICATION NUMBER (DOUBLE-CLICK HERE TO EDIT) < Cryogenic Tm:YAG Laser in the Near Infrared* Tso Yee Fan...therefore limits operation. However, operation at cryogenic temperature depopulates the lower laser level, reduces laser threshold, increases...efficiency, and greatly mitigates thermo-optic effects in crystalline host materials [21]-[23]. Here, we have used cryogenic cooling to enable laser

  2. Advances in cryogenic engineering, Volume 39, Part B

    Energy Technology Data Exchange (ETDEWEB)

    Kittel, P. [ed.

    1994-12-31

    This book provides a review of the latest work in cryogenic engineering and technology as related to a number of differing disciplines. It should serve as a valuable reference to researchers and engineers in cryogenics, materials science, low-temperature physics, polymer science, and solid-state physics. This volume contains articles under the following general areas: instrumentation and control; cryocoolers; heat exchangers and cryopumps; heat and mass transfer; cryogenic properties. Separate articles have been indexed into the database.

  3. Cryogenic resonator design for trapped ion experiments in Paul traps

    CERN Document Server

    Brandl, Matthias F; Monz, Thomas; Blatt, Rainer

    2016-01-01

    Trapping ions in Paul traps requires high radio-frequency voltages, which are generated using resonators. When operating traps in a cryogenic environment, an in-vacuum resonator showing low loss is crucial to limit the thermal load to the cryostat. In this study, we present a guide for the design and production of compact, shielded cryogenic resonators. We produced and characterized three different types of resonators and furthermore demonstrate efficient impedance matching of these resonators at cryogenic temperatures.

  4. Passive Capillary Pumped Cryocooling System for Zero-Boil-Off Cryogen Storage Tanks Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Significant cost and weight savings of a space mission can be achieved by improving the cryogenic storage technology. Added cryogen mass due to the cryogen boil-off,...

  5. Technology Maturation in Preparation for the Cryogenic Propellant Storage and Transfer (CPST) Technology Demonstration Mission (TDM)

    Science.gov (United States)

    Meyer, Michael L.; Doherty, Michael P.; Moder, Jeffrey P.

    2014-01-01

    In support of its goal to find an innovative path for human space exploration, NASA embarked on the Cryogenic Propellant Storage and Transfer (CPST) Project, a Technology Demonstration Mission (TDM) to test and validate key cryogenic capabilities and technologies required for future exploration elements, opening up the architecture for large in-space cryogenic propulsion stages and propellant depots. Recognizing that key Cryogenic Fluid Management (CFM) technologies anticipated for on-orbit (flight) demonstration would benefit from additional maturation to a readiness level appropriate for infusion into the design of the flight demonstration, the NASA Headquarters Space Technology Mission Directorate (STMD) authorized funding for a one-year technology maturation phase of the CPST project. The strategy, proposed by the CPST Project Manager, focused on maturation through modeling, concept studies, and ground tests of the storage and fluid transfer of CFM technology sub-elements and components that were lower than a Technology Readiness Level (TRL) of 5. A technology maturation plan (TMP) was subsequently approved which described: the CFM technologies selected for maturation, the ground testing approach to be used, quantified success criteria of the technologies, hardware and data deliverables, and a deliverable to provide an assessment of the technology readiness after completion of the test, study or modeling activity. The specific technologies selected were grouped into five major categories: thick multilayer insulation, tank applied active thermal control, cryogenic fluid transfer, propellant gauging, and analytical tool development. Based on the success of the technology maturation efforts, the CPST project was approved to proceed to flight system development.

  6. Investigation of woven composites as potential cryogenic tank materials

    Science.gov (United States)

    Islam, Md. S.; Melendez-Soto, E.; Castellanos, A. G.; Prabhakar, P.

    2015-12-01

    In this paper, carbon fiber and Kevlar® fiber woven composites were investigated as potential cryogenic tank materials for storing liquid fuel in spacecraft or rocket. Towards that end, both carbon and Kevlar® fiber composites were manufactured and tested with and without cryogenic exposure. The focus was on the investigation of the influence of initial cryogenic exposure on the degradation of the composite. Tensile, flexural and inter laminar shear strength (ILSS) tests were conducted, which indicate that Kevlar® and carbon textile composites are potential candidates for use under cryogenic exposure.

  7. Cryogenic optical tests of a lightweight HIP beryllium mirror

    Science.gov (United States)

    Melugin, Ramsey K.; Miller, Jacob H.; Young, J. A.; Howard, Steven D.; Pryor, G. Mark

    Five interferometric tests were conducted at cryogenic temperatures on a lightweight, 50 cm diameter, hot isostatic pressed (HIP) beryllium mirror in the Ames Research Center (ARC) Cryogenic Optics Test Facility. The purpose of the tests was to determine the stability of the mirror's figure when cooled to cryogenic temperatures. Test temperatures ranged from room ambient to 8 K. One cycle to 8 K and five cycles to 80 K were performed. Optical and thermal test methods are described. Data is presented to show the amount of cryogenic distortion and hysteresis present in the mirror when measured with an earlier, Shack interferometer, and with a newly-acquired, phase-measuring interferometer.

  8. Cryogenic Fluid Transfer Components Using Single Crystal Piezoelectric Actuators Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Cryogenic fluid transfer components using single crystal piezoelectric actuators are proposed to enable low thermal mass, minimal heat leak, low power consumption...

  9. Cryogenic Fluid Transfer Components Using Single Crystal Piezoelectric Actuators Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Cryogenic fluid transfer components using single crystal piezoelectric actuators are proposed to enable low thermal mass, minimal heat leak, low power consumption...

  10. Highly Flexible and Extremely Durable Polyimide Cryogenic Insulation Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed innovative insulation would greatly enhance the usability of, and reduce the inherent losses associated with, cryogenic fuel delivery and storage...

  11. Wrapped-MLI: Thermal Insulation for Cryogenic Piping Project

    Data.gov (United States)

    National Aeronautics and Space Administration — New NASA vehicles (EDS, Orion, landers & orbiting fuel depots) need improved cryogenic propellant transfer & storage for long duration missions. Current...

  12. Cryopumping in Cryogenic Insulations for a Reusable Launch Vehicle

    Science.gov (United States)

    Johnson, Theodore F.; Weiser, Erik S.; Grimsley, Brian W.; Jensen, Brian J.

    2003-01-01

    Testing at cryogenic temperatures was performed to verify the material characteristics and manufacturing processes of reusable propellant tank cryogenic insulations for a Reusable Launch Vehicle (RLV). The unique test apparatus and test methods developed for the investigation of cryopumping in cryogenic insulations are described. Panel level test specimens with various types of cryogenic insulations were subjected to a specific thermal profile where the temperature varied from -262 C to 21 C. Cryopumping occurred if the interior temperature of the specimen exhibited abnormal temperature fluctuations, such as a sudden decrease in temperature during the heating phase.

  13. Advances in cryogenic engineering. Volume 41, Part A & B

    Energy Technology Data Exchange (ETDEWEB)

    Kittel, P. [ed.

    1996-12-31

    This proceedings is of the 1995 Cryogenic Engineering Conference. It consists of 252 published papers covering the latest developments in all aspects of cryogenic engineering research. Contributions touch on fields including: cryobiology; heat and mass transfer (including data on boiling and superfluid helium); magnet technology; large-scale cryogenic systems, such as the large hadron collider and the TeV Electron Superconducting Linear Accelerator; cryofuels; minesweeping applications; space cryocooler applications; research on miscellaneous cryogenic machinery, techniques, and safety concerns. Separate abstracts have been submitted for contributions from this proceedings.

  14. Advances in cryogenic engineering. Volume 29 - Proceedings of the Cryogenic Engineering Conference, Colorado Springs, CO, August 15-17, 1983

    Science.gov (United States)

    Fast, R. W.

    Applications of superconductivity are discussed, taking into account the thermal performance of the MFTF magnets, the design and testing of a large bore superconducting magnet test facility, the development of a 12-tesla multifilamentary Nb3Sn magnet, a superconducting magnet for solid NMR studies, advanced applications of superconductors, transition and recovery of a cryogenically stable superconductor, and finite-difference modeling of the cryostability of helium II cooled conductor packs. Other topics explored are related to resource availability, heat exchangers, heat transfer to He I, liquid nitrogen, heat transfer in He II, refrigeration for superconducting and cryopump systems, refrigeration of cryogenic systems, refrigeration and liquefaction, dilution and magnetic refrigeration, cryocoolers, refrigeration for space applications, cryogenic applications, cryogenic instrumentation and data acquisition, and properties of fluids. Attention is given to biomedical applications of cryogenics in China, long-term cryogen storage in space, and a passive orbital disconnect strut.

  15. 33S nuclear magnetic resonance spectroscopy of biological samples obtained with a laboratory model 33S cryogenic probe.

    Science.gov (United States)

    Hobo, Fumio; Takahashi, Masato; Saito, Yuta; Sato, Naoki; Takao, Tomoaki; Koshiba, Seizo; Maeda, Hideaki

    2010-05-01

    (33)S nuclear magnetic resonance (NMR) spectroscopy is limited by inherently low NMR sensitivity because of the quadrupolar moment and low gyromagnetic ratio of the (33)S nucleus. We have developed a 10 mm (33)S cryogenic NMR probe, which is operated at 9-26 K with a cold preamplifier and a cold rf switch operated at 60 K. The (33)S NMR sensitivity of the cryogenic probe is as large as 9.8 times that of a conventional 5 mm broadband NMR probe. The (33)S cryogenic probe was applied to biological samples such as human urine, bile, chondroitin sulfate, and scallop tissue. We demonstrated that the system can detect and determine sulfur compounds having SO(4)(2-) anions and -SO(3)(-) groups using the (33)S cryogenic probe, as the (33)S nuclei in these groups are in highly symmetric environments. The NMR signals for other common sulfur compounds such as cysteine are still undetectable by the (33)S cryogenic probe, as the (33)S nuclei in these compounds are in asymmetric environments. If we shorten the rf pulse width or decrease the rf coil diameter, we should be able to detect the NMR signals for these compounds.

  16. Digoxin and its related endogenous factors.

    Science.gov (United States)

    Jortani, S A; Valdes, R

    1997-01-01

    The digitalis drugs are plant-derived cardenolide compounds used medicinally for several hundred years. These drugs elicit inotropic and chronotropic effects on the heart, but they also affect many other tissues. The mechanism of action involves inhibition of the ion-transport activity of a membrane-associated protein called Na, K-ATPase (sodium pump). Present theory holds that the sodium pump is the principal molecular receptor for the digitalis drugs. Recent evidence indicates the presence of naturally occurring digitalis-like compounds in mammals. It is believed these compounds, collectively known as either digitalis-like (DLF) or ouabain-like (OLF) factors, may be endogenous hormones regulating the biological activity of the sodium pump and its isoforms. The presence of deglycosylated and other congeners of one specific DLF, the digoxin-like immunoreactive factor (DLIF), has very recently been described in humans. Digoxin as a drug is the most widely prescribed digitalis in the U.S., and its measurement in serum has established a model for present-day therapeutic drug monitoring (TDM). Historically, the accurate measurement of digoxin in blood has been difficult. This article focuses on the present understanding of the clinical use of digoxin, factors that affect the accuracy of measuring digoxin, the principle of measuring metabolically active species of digoxin, and the effects of DLIF and other interfering substances in digoxin immunoassay.

  17. Endogenous Retroviruses: With Us and Against Us

    Science.gov (United States)

    Meyer, Thomas J.; Rosenkrantz, Jimi L.; Carbone, Lucia; Chavez, Shawn L.

    2017-04-01

    Mammalian genomes are scattered with thousands of copies of endogenous retroviruses (ERVs), mobile genetic elements that are relics of ancient retroviral infections. After inserting copies into the germ line of a host, most ERVs accumulate mutations that prevent the normal assembly of infectious viral particles, becoming trapped in host genomes and unable to leave to infect other cells. While most copies of ERVs are inactive, some are transcribed and encode the proteins needed to generate new insertions at novel loci. In some cases, old copies are removed via recombination and other mechanisms. This creates a shifting landscape of ERV copies within host genomes. New insertions can disrupt normal expression of nearby genes via directly inserting into key regulatory elements or by containing regulatory motifs within their sequences. Further, the transcriptional silencing of ERVs via epigenetic modification may result in changes to the epigenetic regulation of adjacent genes. In these ways, ERVs can be potent sources of regulatory disruption as well as genetic innovation. Here, we provide a brief review of the association between ERVs and gene expression, especially as observed in pre-implantation development and placentation. Moreover, we will describe the roles ERVs may play in somatic tissues, mostly in the context of human disease, including cancer, neurodegenerative disorders, and schizophrenia. Lastly, we discuss the recent discovery that some ERVs may have been pressed into the service of their host genomes to aid in the innate immune response to exogenous viral infections.

  18. Cryogenic Clamp-on Ultrasonic Flowmeters using Single Crystal Piezoelectric Transducers Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Clamp-on ultrasound cryogenic flowmeters using single crystal piezoelectric transducers are proposed to enable reliable, accurate cryogenic instrumentation needs in...

  19. Endogenous cardiac stem cells for the treatment of heart failure

    Directory of Open Access Journals (Sweden)

    Fuentes T

    2013-03-01

    Full Text Available Tania Fuentes, Mary Kearns-Jonker Department of Pathology and Human Anatomy, Loma Linda University School of Medicine, Loma Linda, CA, USA Abstract: Stem cell-based therapies hold promise for regenerating the myocardium after injury. Recent data obtained from phase I clinical trials using endogenous cardiovascular progenitors isolated directly from the heart suggest that cell-based treatment for heart patients using stem cells that reside in the heart provides significant functional benefit and an improvement in patient outcome. Methods to achieve improved engraftment and regeneration may extend this therapeutic benefit. Endogenous cardiovascular progenitors have been tested extensively in small animals to identify cells that improve cardiac function after myocardial infarction. However, the relative lack of large animal models impedes translation into clinical practice. This review will exclusively focus on the latest research pertaining to humans and large animals, including both endogenous and induced sources of cardiovascular progenitors. Keywords: Isl1, iPSC, large animal, c-kit, cardiosphere

  20. Proceedings of the 26th International Cryogenic Engineering Conference - International Cryogenic Material Conference 2016

    Science.gov (United States)

    Datta, T. S.; Sharma, R. G.; Kar, S.

    2017-02-01

    International Conference ICEC 26 - ICMC 2016 was organized at New Delhi, India during March 7-11, 2016. Previous conference ICEC25-ICMC 2014 was held at the University of Twente, The Netherlands in July 2014. Next Conference ICEC 27- ICMC 2018 will be held at Oxford, UK during September 3-7, 2018 1. Introduction This is a biennial international conference on cryogenic engineering and cryogenics materials organized by the International Cryogenic Engineering Committee and the International Cryogenic Material Committee. For some years, the host country has been alternating between Europe and Asia. The present conference was held at the Manekshaw Convention Centre, New Delhi, India during March 7-11, 2016 and hosted jointly by the Indian Cryogenics Council (ICC) and the Inter-University Accelerator Centre (IUAC), New Delhi. Put all together as many as 547 persons participated in the conference. Out of these 218 were foreign delegates coming from 25 countries and the rest from India. 2. Inaugural Session & Course Lectures The pre conference short course lectures on “Cryocoolers” and “Superconducting Materials for Power Applications” were organized on 7th March. Cryocooler course was given jointly by Dr. Chao Wang from M/s. Cryomech, USA and Prof. Milind Atrey from IIT Bombay, India. The Course on Superconducting Materials was given by Prof. Venkat Selvamanickam from the University of Houston, USA. The conference was inaugurated in the morning of March 8th in a typical Indian tradition and in the presence of the Chief Guest, Dr. R Chidambaram (Principle Scientific Adviser to Govt. of India), Guest of Honour, Prof. H Devaraj (Vice Chairman University Grant Commission), Prof Marcel ter Brake ( Chair, ICEC Board), Prof. Wilfried Goldacker (Chair, ICMC board), Dr. D Kanjilal (Director IUAC), Dr R K Bhandari, (President, Indian Cryogenic Council ). Dr. T S Datta, Chair Local Organizing Committee coordinated the proceedings of the inaugural function. 3. Technical