WorldWideScience

Sample records for underlying pathophysiological mechanisms

  1. [Pathophysiology of neuropathic pain: molecular mechanisms underlying central sensitization in the dorsal horn in neuropathic pain].

    Science.gov (United States)

    Yamanaka, Hiroki; Noguchi, Koichi

    2012-11-01

    Neuropathic pain syndromes are clinically characterized by spontaneous pain and evoked pain (hyperalgesia and allodynia). The optimal treatment approach for neuropathic pain is still under development because of the complex pathological mechanisms underlying this type of pain. The spinal cord is an important gateway thorough which peripheral pain signals are transmitted to the brain, and sensitization of the spinal neurons is one of the important mechanisms underlying neuropathic pain. Central sensitization represents enhancement of the function of neuronal circuits in nociceptive pathways and is a manifestation of the remarkable plasticity of the somatosensory nervous system after nerve injury. This review highlights the pathological features of central sensitization, which develops because of (1) injury-induced abnormal inputs from primary afferents, (2) increase in the excitability of dorsal horn neurons, and (3) activated glial cell-derived signals.

  2. Pathophysiological mechanisms of insulin resistance

    NARCIS (Netherlands)

    Brands, M.

    2013-01-01

    In this thesis we studied pathophysiological mechanisms of insulin resistance in different conditions in humans, i.e. in obesity, during lipid infusions, after hypercaloric feeding, and glucocorticoid treatment. We focused on 3 important hypotheses that are suggested to be implicated in the

  3. StartReact effects support different pathophysiological mechanisms underlying freezing of gait and postural instability in Parkinson's disease.

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    Jorik Nonnekes

    Full Text Available The pathophysiology underlying postural instability in Parkinson's disease is poorly understood. The frequent co-existence with freezing of gait raises the possibility of shared pathophysiology. There is evidence that dysfunction of brainstem structures contribute to freezing of gait. Here, we evaluated whether dysfunction of these structures contributes to postural instability as well. Brainstem function was assessed by studying the StartReact effect (acceleration of latencies by a startling acoustic stimulus (SAS.We included 25 patients, divided in two different ways: 1 those with postural instability (HY = 3, n = 11 versus those without (HY<3, n = 14; and 2 those with freezing (n = 11 versus those without freezing (n = 14. We also tested 15 matched healthy controls. We tested postural responses by translating a balance platform in the forward direction, resulting in backward balance perturbations. In 25% of trials, the start of the balance perturbation was accompanied by a SAS.The amplitude of automatic postural responses and length of the first balance correcting step were smaller in patients with postural instability compared to patients without postural instability, but did not differ between freezers and non-freezers. In contrast, the StartReact effect was intact in patients with postural instability but was attenuated in freezers.We suggest that the mechanisms underlying freezing of gait and postural instability in Parkinson's disease are at least partly different. Underscaling of automatic postural responses and balance-correcting steps both contribute to postural instability. The attenuated StartReact effect was seen only in freezers and likely reflects inadequate representation of motor programs at upper brainstem level.

  4. Pathophysiologic mechanisms of biomedical nanomaterials

    International Nuclear Information System (INIS)

    Wang, Liming; Chen, Chunying

    2016-01-01

    Nanomaterials (NMs) have been widespread used in biomedical fields, daily consuming, and even food industry. It is crucial to understand the safety and biomedical efficacy of NMs. In this review, we summarized the recent progress about the physiological and pathological effects of NMs from several levels: protein-nano interface, NM-subcellular structures, and cell–cell interaction. We focused on the detailed information of nano-bio interaction, especially about protein adsorption, intracellular trafficking, biological barriers, and signaling pathways as well as the associated mechanism mediated by nanomaterials. We also introduced related analytical methods that are meaningful and helpful for biomedical effect studies in the future. We believe that knowledge about pathophysiologic effects of NMs is not only significant for rational design of medical NMs but also helps predict their safety and further improve their applications in the future. - Highlights: • Rapid protein adsorption onto nanomaterials that affects biomedical effects • Nanomaterials and their interaction with biological membrane, intracellular trafficking and specific cellular effects • Nanomaterials and their interaction with biological barriers • The signaling pathways mediated by nanomaterials and related biomedical effects • Novel techniques for studying translocation and biomedical effects of NMs

  5. Pathophysiological mechanisms ofurbanisation-related ...

    African Journals Online (AJOL)

    Subjects had their blood pressures measured at least three times before the study. Initial blood pressure recordings were generally high compared with those .... Elevated. TXA2/PGI2 appears to be an additional mechanism leading to increased blood pressure in the hypertensives subjected to increased dietary salt intake.

  6. [Hypercapnic respiratory failure. Pathophysiology, indications for mechanical ventilation and management].

    Science.gov (United States)

    Kreppein, U; Litterst, P; Westhoff, M

    2016-04-01

    Acute hypercapnic respiratory failure is mostly seen in patients with chronic obstructive pulmonary disease (COPD) and obesity hypoventilation syndrome (OHS). Depending on the underlying cause it may be associated with hypoxemic respiratory failure and places high demands on mechanical ventilation. Presentation of the current knowledge on indications and management of mechanical ventilation in patients with hypercapnic respiratory failure. Review of the literature. Important by the selection of mechanical ventilation procedures is recognition of the predominant pathophysiological component. In hypercapnic respiratory failure with a pH ventilation (NIV) is primarily indicated unless there are contraindications. In patients with severe respiratory acidosis NIV requires a skilled and experienced team and close monitoring in order to perceive a failure of NIV. In acute exacerbation of COPD ventilator settings need a long expiration and short inspiration time to avoid further hyperinflation and an increase in intrinsic positive end-expiratory pressure (PEEP). Ventilation must be adapted to the pathophysiological situation in patients with OHS or overlap syndrome. If severe respiratory acidosis and hypercapnia cannot be managed by mechanical ventilation therapy alone extracorporeal venous CO2 removal may be necessary. Reports on this approach in awake patients are available. The use of NIV is the predominant treatment in patients with hypercapnic respiratory failure but close monitoring is necessary in order not to miss the indications for intubation and invasive ventilation. Methods of extracorporeal CO2 removal especially in awake patients need further evaluation.

  7. Pathophysiological Mechanisms in Sclerosing Skin Diseases

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    Beate Eckes

    2017-08-01

    Full Text Available Sclerosing skin diseases represent a large number of distinct disease entities, which include systemic sclerosis, localized scleroderma, and scleredema adultorum. These pathologies have a common clinical appearance and share histological features. However, the specific interplay between cytokines and growth factors, which activate different mesenchymal cell populations and production of different extracellular matrix components, determines the biomechanical properties of the skin and the clinical features of each disease. A better understanding of the mechanisms underlying these events is prerequisite for developing novel targeted therapeutic approaches.

  8. Visceral hypersensitivity in Irritable Bowel Syndrome:pathophysiological mechanisms

    NARCIS (Netherlands)

    Kerckhoffs, A.P.M.

    2009-01-01

    Irritable Bowel Syndrome (IBS) is a functional bowel disease characterized by abdominal pain or discomfort associated with a disordered defecation. No unique pathophysiological mechanism has been identified. It is most likely a multifactorial disease involving alterations in intestinal microbiota

  9. Chikungunya Virus: Pathophysiology, Mechanism, and Modeling

    Science.gov (United States)

    Ganesan, Vaishnavi K.; Reid, St Patrick

    2017-01-01

    Chikungunya virus (CHIKV), a mosquito-transmitted alphavirus, is recurring in epidemic waves. In the past decade and a half, the disease has resurged in several countries around the globe, with outbreaks becoming increasingly severe. Though CHIKV was first isolated in 1952, there remain significant gaps in knowledge of CHIKV biology, pathogenesis, transmission, and mechanism. Diagnosis is largely simplified and based on symptoms, while treatment is supportive rather than curative. Here we present an overview of the disease, the challenges that lie ahead for future research, and what directions current studies are headed towards, with emphasis on improvement of current animal models and potential use of 3D models. PMID:29194359

  10. Streptozotocin-Induced Diabetes Models: Pathophysiological Mechanisms and Fetal Outcomes

    Directory of Open Access Journals (Sweden)

    D. C. Damasceno

    2014-01-01

    Full Text Available Glucose homeostasis is controlled by endocrine pancreatic cells, and any pancreatic disturbance can result in diabetes. Because 8% to 12% of diabetic pregnant women present with malformed fetuses, there is great interest in understanding the etiology, pathophysiological mechanisms, and treatment of gestational diabetes. Hyperglycemia enhances the production of reactive oxygen species, leading to oxidative stress, which is involved in diabetic teratogenesis. It has also been suggested that maternal diabetes alters embryonic gene expression, which might cause malformations. Due to ethical issues involving human studies that sometimes have invasive aspects and the multiplicity of uncontrolled variables that can alter the uterine environment during clinical studies, it is necessary to use animal models to better understand diabetic pathophysiology. This review aimed to gather information about pathophysiological mechanisms and fetal outcomes in streptozotocin-induced diabetic rats. To understand the pathophysiological mechanisms and factors involved in diabetes, the use of pancreatic regeneration studies is increasing in an attempt to understand the behavior of pancreatic beta cells. In addition, these studies suggest a new preventive concept as a treatment basis for diabetes, introducing therapeutic efforts to minimize or prevent diabetes-induced oxidative stress, DNA damage, and teratogenesis.

  11. POTENTIAL PATHOPHYSIOLOGICAL MECHANISMS OF ULTRAFINE PARTICLE TOXIC EFFECTS IN HUMANS

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    JASMINA JOVIĆ-STOŠIĆ

    2008-03-01

    Full Text Available Epidemiological and clinical studies suggested the association of the particulate matter ambient air pollution and the increased morbidity and mortality, mainly from respiratory and cardiovascular diseases. The size of particles has great influence on their toxicity, because it determines the site in the respiratory tract where they deposit. The most well established theory explaining the mechanisms behind the increased toxicity of ultrafine particles (UFP, < 0.1 µm is that it has to do with the increased surface area and/or the combination with the increased number of particles. Biological effects of UFP are also determined by their shape and chemical composition, so it is not possible to estimate their toxicity in a general way. General hypothesis suggested that exposure to inhaled particles induces pulmonary alveolar inflammation as a basic pathophysiological event, triggering release of various proinflammatory cytokines. Chronic inflammation is a very important underlying mechanism in the genesis of atherosclerosis and cardiovascular diseases. UFP can freely move through the circulation, but their effects on the secondary organs are not known yet, so more studies on recognizing toxicological endpoints of UFP are needed. Determination of UFP toxicity and the estimation of their internal and biologically active dose are necessary for the evidence based conclusions connecting air pollution by UFP and human diseases.

  12. Obesity and Pulmonary Hypertension: A Review of Pathophysiologic Mechanisms

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    Scott E. Friedman

    2012-01-01

    Full Text Available Pulmonary hypertension (PH is a potentially life-threatening condition arising from a wide variety of pathophysiologic mechanisms. Effective treatment requires a systematic diagnostic approach to identify all reversible mechanisms. Many of these mechanisms are relevant to those afflicted with obesity. The unique mechanisms of PH in the obese include obstructive sleep apnea, obesity hypoventilation syndrome, anorexigen use, cardiomyopathy of obesity, and pulmonary thromboembolic disease. Novel mechanisms of PH in the obese include endothelial dysfunction and hyperuricemia. A wide range of effective therapies exist to mitigate the disability of PH in the obese.

  13. Focal venous hypertension as a pathophysiologic mechanism for tissue hypertrophy, port-wine stains, the Sturge-Weber syndrome, and related disorders: proof of concept with novel hypothesis for underlying etiological cause (an American Ophthalmological Society thesis).

    Science.gov (United States)

    Parsa, Cameron F

    2013-09-01

    To provide an in-depth re-examination of assumed causes of tissue hypertrophy, port-wine stains, and the Sturge-Weber, Cobb, Klippel-Trénaunay, and related syndromes to support an alternative unifying pathophysiologic mechanism of venous dysplasia producing focal venous hypertension with attendant tissue responses; to provide proof of concept with new patient data; to propose a novel etiological hypothesis for the venous dysplasia in these syndromes and find supportive evidence. Data from 20 patients with port-wine stains and corneal pachymetry readings was collected prospectively by the author in an institutional referral-based practice. The literature was searched using MEDLINE, and articles and textbooks were obtained from the bibliographies of these publications. Newly obtained dermatologic, corneal pachymetry, fundus ophthalmoscopic, ocular and orbital venous Doppler ultrasonography, and magnetic resonance imaging findings in patients with the Sturge-Weber syndrome or isolated port-wine stains, along with published data, reveal diffusely thickened tissues and neural atrophy in all areas associated with venous congestion. Contrary to traditional understanding, signs and symptoms in the Sturge-Weber and related syndromes, including both congenital and acquired port-wine stains, are shown to arise from effects of localized primary venous dysplasia or acquired venous obstruction rather than neural dysfunction, differentiating these syndromes from actual phacomatoses. Effects of focal venous hypertension are transmitted to nearby areas via compensatory collateral venous channels in the above conditions, as in the Parkes Weber syndrome. A novel underlying etiology-prenatal venous thrombo-occlusion-is proposed to be responsible for the absence of veins with persistence and enlargement of collateral circulatory pathways with data in the literature backing this offshoot hypothesis. The mechanism for isolated pathologic tissue hypertrophy in these syndromes clarifies

  14. Focal Venous Hypertension as a Pathophysiologic Mechanism for Tissue Hypertrophy, Port-Wine Stains, the Sturge-Weber Syndrome, and Related Disorders: Proof of Concept with Novel Hypothesis for Underlying Etiological Cause (An American Ophthalmological Society Thesis)

    Science.gov (United States)

    Parsa, Cameron F.

    2013-01-01

    Purpose: To provide an in-depth re-examination of assumed causes of tissue hypertrophy, port-wine stains, and the Sturge-Weber, Cobb, Klippel-Trénaunay, and related syndromes to support an alternative unifying pathophysiologic mechanism of venous dysplasia producing focal venous hypertension with attendant tissue responses; to provide proof of concept with new patient data; to propose a novel etiological hypothesis for the venous dysplasia in these syndromes and find supportive evidence. Methods: Data from 20 patients with port-wine stains and corneal pachymetry readings was collected prospectively by the author in an institutional referral-based practice. The literature was searched using MEDLINE, and articles and textbooks were obtained from the bibliographies of these publications. Results: Newly obtained dermatologic, corneal pachymetry, fundus ophthalmoscopic, ocular and orbital venous Doppler ultrasonography, and magnetic resonance imaging findings in patients with the Sturge-Weber syndrome or isolated port-wine stains, along with published data, reveal diffusely thickened tissues and neural atrophy in all areas associated with venous congestion. Conclusions: Contrary to traditional understanding, signs and symptoms in the Sturge-Weber and related syndromes, including both congenital and acquired port-wine stains, are shown to arise from effects of localized primary venous dysplasia or acquired venous obstruction rather than neural dysfunction, differentiating these syndromes from actual phacomatoses. Effects of focal venous hypertension are transmitted to nearby areas via compensatory collateral venous channels in the above conditions, as in the Parkes Weber syndrome. A novel underlying etiology—prenatal venous thrombo-occlusion—is proposed to be responsible for the absence of veins with persistence and enlargement of collateral circulatory pathways with data in the literature backing this offshoot hypothesis. The mechanism for isolated pathologic

  15. Pathophysiological mechanisms of death resistance in colorectal carcinoma.

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    Huang, Ching-Ying; Yu, Linda Chia-Hui

    2015-11-07

    Colon cancers develop adaptive mechanisms to survive under extreme conditions and display hallmarks of unlimited proliferation and resistance to cell death. The deregulation of cell death is a key factor that contributes to chemoresistance in tumors. In a physiological context, balance between cell proliferation and death, and protection against cell damage are fundamental processes for maintaining gut epithelial homeostasis. The mechanisms underlying anti-death cytoprotection and tumor resistance often bear common pathways, and although distinguishing them would be a challenge, it would also provide an opportunity to develop advanced anti-cancer therapeutics. This review will outline cell death pathways (i.e., apoptosis, necrosis, and necroptosis), and discuss cytoprotective strategies in normal intestinal epithelium and death resistance mechanisms of colon tumor. In colorectal cancers, the intracellular mechanisms of death resistance include the direct alteration of apoptotic and necroptotic machinery and the upstream events modulating death effectors such as tumor suppressor gene inactivation and pro-survival signaling pathways. The autocrine, paracrine and exogenous factors within a tumor microenvironment can also instigate resistance against apoptotic and necroptotic cell death in colon cancers through changes in receptor signaling or transporter uptake. The roles of cyclooxygenase-2/prostaglandin E2, growth factors, glucose, and bacterial lipopolysaccharides in colorectal cancer will be highlighted. Targeting anti-death pathways in the colon cancer tissue might be a promising approach outside of anti-proliferation and anti-angiogenesis strategies for developing novel drugs to treat refractory tumors.

  16. Pathophysiology of major depressive disorder: mechanisms involved in etiology are not associated with clinical progression

    OpenAIRE

    Verduijn, J; Milaneschi, Y; Schoevers, R A; van Hemert, A M; Beekman, A T F; Penninx, B W J H

    2015-01-01

    Meta-analyses support the involvement of different pathophysiological mechanisms (inflammation, hypothalamic-pituitary (HPA)-axis, neurotrophic growth and vitamin D) in major depressive disorder (MDD). However, it remains unknown whether dysregulations in these mechanisms are more pronounced when MDD progresses toward multiple episodes and/or chronicity. We hypothesized that four central pathophysiological mechanisms of MDD are not only involved in etiology, but also associated with clinical ...

  17. Metabolomics Insights Into Pathophysiological Mechanisms of Interstitial Cystitis

    Science.gov (United States)

    Fiehn, Oliver

    2014-01-01

    Interstitial cystitis (IC), also known as painful bladder syndrome or bladder pain syndrome, is a chronic lower urinary tract syndrome characterized by pelvic pain, urinary urgency, and increased urinary frequency in the absence of bacterial infection or identifiable clinicopathology. IC can lead to long-term adverse effects on the patient's quality of life. Therefore, early diagnosis and better understanding of the mechanisms underlying IC are needed. Metabolomic studies of biofluids have become a powerful method for assessing disease mechanisms and biomarker discovery, which potentially address these important clinical needs. However, limited intensive metabolic profiles have been elucidated in IC. The article is a short review on metabolomic analyses that provide a unique fingerprint of IC with a focus on its use in determining a potential diagnostic biomarker associated with symptoms, a response predictor of therapy, and a prognostic marker. PMID:25279237

  18. Meconium aspiration syndrome: possible pathophysiological mechanisms and future potential therapies.

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    Lindenskov, Paal Helge Haakonsen; Castellheim, Albert; Saugstad, Ola Didrik; Mollnes, Tom Eirik

    2015-01-01

    Does meconium cause meconium aspiration syndrome (MAS) or is meconium discharge only a marker of fetal hypoxia? This dispute has lasted for centuries, but since the 1960s, detrimental effects of meconium itself on the lungs have been demonstrated in animal experiments. In clinical MAS, persistent pulmonary hypertension of the newborn is the leading cause of death in MAS. Regarding the complex chemical composition of meconium, it is difficult to identify a single agent responsible for the pathophysiology. However, considering that meconium is stored in the intestines, partly unexposed to the immune system, aspirated meconium could be recognized as ‘danger', representing damaged self. The common denominator in the pathophysiology could therefore be activation of innate immunity. Thus, a bulk of evidence implies that meconium is a potent activator of inflammatory mediators, including cytokines, complement, prostaglandins and reactive oxygen species. We hypothesize that the two main recognition systems of innate immunity, the Toll-like receptors and the complement system, recognize meconium as ‘danger', which leads not only to lung dysfunction but also to a systemic inflammatory response. This might have therapeutic implications in the future.

  19. EGFR transactivation: mechanisms, pathophysiology and potential therapies in cardiovascular system

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    Forrester, Steven J.; Kawai, Tatsuo; Elliott, Katherine J.; O’Brien, Shannon; Thomas, Walter; Harris, Raymond C.; Eguchi, Satoru

    2017-01-01

    Accumulating studies suggest that the epidermal growth factor receptor (EGFR) activation is associated with the physiology and pathophysiology of the cardiovascular system, and inhibition of EGFR activity is emerging as a potential therapeutic strategy to treat diseases, including hypertension, cardiac hypertrophy, renal fibrosis and abdominal aortic aneurysm. The capacity of G protein-coupled receptor (GPCR) agonists, such as angiotensin II (AngII), to promote EGFR signaling is well described – a process termed EGFR “transactivation” – yet delineating the molecular processes and functional relevance of this crosstalk has been challenging. Moreover, these critical findings are dispersed among many different fields. The aim of our review is to highlight the recent advancement of the signaling cascades and downstream consequences of EGFR transactivation within the cardiovascular renal system in vitro and in vivo. We will also focus on linking EGFR transactivation to animal models of the disease as well as the potential therapeutic applications. PMID:26566153

  20. Splanchnic vein thrombosis in myeloproliferative neoplasms: pathophysiology and molecular mechanisms of disease

    Science.gov (United States)

    How, Joan; Zhou, Amy; Oh, Stephen T.

    2016-01-01

    Myeloproliferative neoplasms (MPNs) are the most common underlying prothrombotic disorder found in patients with splanchnic vein thrombosis (SVT). Clinical risk factors for MPN-associated SVTs include younger age, female sex, concomitant hypercoagulable disorders, and the JAK2 V617F mutation. These risk factors are distinct from those associated with arterial or deep venous thrombosis (DVT) in MPN patients, suggesting disparate disease mechanisms. The pathophysiology of SVT is thought to derive from local interactions between activated blood cells and the unique splanchnic endothelial environment. Other mutations commonly found in MPNs, including CALR and MPL, are rare in MPN-associated SVT. The purpose of this article is to review the clinical and molecular risk factors for MPN-associated SVT, with particular focus on the possible mechanisms of SVT formation in MPN patients. PMID:28246554

  1. Identifying the genetic components underlying the pathophysiology of movement disorders

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    Ezquerra M

    2011-06-01

    Full Text Available Mario Ezquerra, Yaroslau Compta, Maria J MartiParkinson’s Disease and Movement Disorders Unit, Service of Neurology, Institute of Clinical Neurosciences, Hospital Clinic of Barcelona, IDIBAPS, CIBERNED, SpainAbstract: Movement disorders are a heterogeneous group of neurological conditions, few of which have been classically described as bona fide hereditary illnesses (Huntington’s chorea, for instance. Most are considered to be either sporadic or to feature varying degrees of familial aggregation (parkinsonism and dystonia. In the late twentieth century, Mendelian monogenic mutations were found for movement disorders with a clear and consistent family history. Although important, these findings apply only to very rare forms of movement disorders. Already in the twenty-first century, and taking advantage of the modern developments in genetics and molecular biology, growing attention is being paid to the complex genetics of movement disorders. The search for risk genetic variants (polymorphisms in large cohorts and the identification of different risk variants across different populations and ethnic groups are under way, with the most relevant findings to date corresponding to recent genome wide association studies in Parkinson’s disease. These new approaches focusing on risk variants may enable the design of screening tests for early or even preclinical disease, and the identification of likely therapeutic targets.Keywords: genetics, movement disorders, Parkinson’s disease, parkinsonism, dystonia

  2. Recent Advances in Methamphetamine Neurotoxicity Mechanisms and Its Molecular Pathophysiology

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    Shaobin Yu

    2015-01-01

    Full Text Available Methamphetamine (METH is a sympathomimetic amine that belongs to phenethylamine and amphetamine class of psychoactive drugs, which are widely abused for their stimulant, euphoric, empathogenic, and hallucinogenic properties. Many of these effects result from acute increases in dopamine and serotonin neurotransmission. Subsequent to these acute effects, METH produces persistent damage to dopamine and serotonin release in nerve terminals, gliosis, and apoptosis. This review summarized the numerous interdependent mechanisms including excessive dopamine, ubiquitin-proteasome system dysfunction, protein nitration, endoplasmic reticulum stress, p53 expression, inflammatory molecular, D3 receptor, microtubule deacetylation, and HIV-1 Tat protein that have been demonstrated to contribute to this damage. In addition, the feasible therapeutic strategies according to recent studies were also summarized ranging from drug and protein to gene level.

  3. Complement in immune and inflammatory disorders: pathophysiological mechanisms

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    Ricklin, Daniel; Lambris, John D.

    2013-01-01

    While acute or chronic inflammation is a common component of many clinical disorders, the underlying processes can be highly distinct. In recent years, the complement system has been associated with a growing number of immunological and inflammatory conditions that include degenerative diseases, cancer and transplant rejection. It becomes evident that excessive activation or insufficient control of complement activation on host cells can cause an immune imbalance that may fuel a vicious cycle between complement, inflammatory cells and tissue damage that exacerbates clinical complications. Although the exact involvement of complement needs to be carefully investigated for each disease, therapeutic modulation of complement activity emerges as attractive target for upstream inhibition of inflammatory processes. This review provides an update about the functional and collaborative capabilities of complement, highlights major disease areas with known complement contribution, and indicates the potential for complement as focal point in immunomodulatory strategies for treating inflammatory diseases. PMID:23564577

  4. Cytomegalovirus: pathophysiological mechanisms of the cytomegalovirus-induced cellular responses

    International Nuclear Information System (INIS)

    Nokta, M.A.

    1986-01-01

    Cytomegalovirus (CMV) infection of fibroblasts of human origin is associated with a cascade of morphologic cellular responses which in other systems have been associated with regulation of intracellular free (IF) [Ca ++ ]. In the present study, the relationship of specific ion fluxes (Ca ++ , Na + ) to the development of cytomegalovirus (CMV)-induced morphologic cellular responses was investigated. An influx of Ca ++ was observed by the first hour after CMV infection (PI), and total calcium sequestered by infected cells was enhanced by 5 hr Pl. A gradual rise in intracellular free (IF) [Ca ++ ] was observed that continued through 48 hour postinfection (hr Pl). The IF [Ca ++ ] response to CMV infection was shown to be multiplicity dependent, require viable virus, and occur under conditions consistent with the expression of immediate early CMV genes. Development and progression of cytomegaly was found to be independent of CMV DNA synthesis and appeared to be dependent on the IF [Ca ++ ] response. Ca ++ influx blockers (e.g. verapamil) and cyclic nucleotide modulators (e.g. papaverine) inhibited both Ca ++ responses and cytomegaly. Quabain-sensitive 86 Rb uptake and sequestering of Ca ++ increased in parallel with development of cytomegaly. There may be a relationship between Ca ++ influx, IF [Ca ++ ], activation of the Na + /H + exchanger, induction of Na + , Cl - , HCO 3 cotransport, Na + entry, Na + /K + ATPase activity and development of CMV-induced morphologic cellular responses including cytomegaly

  5. The controversial relationship between exercise and atrial fibrillation: clinical studies and pathophysiological mechanisms.

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    D'Ascenzi, Flavio; Cameli, Matteo; Ciccone, Marco M; Maiello, Maria; Modesti, Pietro A; Mondillo, Sergio; Muiesan, Maria L; Scicchitano, Pietro; Novo, Salvatore; Palmiero, Pasquale; Saba, Pier S; Pedrinelli, Roberto

    2015-12-01

    Atrial fibrillation is the most common clinically significant arrhythmia observed both in the general population and in competitive athletes. The most important risk factors are all preventable by regular physical activity. However, although the benefits of moderate physical activity in controlling cardiovascular risk factors and decreasing the risk of atrial fibrillation have been extensively proved, concerns have arisen about the potential negative effects of vigorous exercise, particularly in endurance athletes. Furthermore, in a subset of patients with atrial fibrillation younger than 60 years, routine evaluation does not reveal any cardiovascular disease or any other known causal factor. This condition is called 'lone atrial fibrillation', and the potential mechanisms underlying this condition are speculative and remain to be clarified. Atrial ectopy, increased vagal tone, changes in electrolytes, left atrial dilatation, and fibrosis have been proposed among others as potential mechanisms. However, no convincing data still exist. Particularly, the increase in left atrial size represents in athletes a physiological adaptation to exercise conditioning and the presence of biatrial fibrosis has not been demonstrated in humans. Thus, contrary to patients with cardiovascular disorders, the atrial substrate seems to play a secondary role in healthy athletes. This review article analyzes the controversial relationship between atrial fibrillation and physical activity, with a particular attention on the pathophysiological mechanisms that could be responsible for atrial fibrillation in the athletic population.

  6. An update on pathophysiological mechanisms related to idiopathic oro-facial pain conditions with implications for management.

    Science.gov (United States)

    Forssell, H; Jääskeläinen, S; List, T; Svensson, P; Baad-Hansen, L

    2015-04-01

    Chronic oro-facial pain conditions such as persistent idiopathic facial pain (PIFP), atypical odontalgia (AO) and burning mouth syndrome (BMS), usually grouped together under the concept of idiopathic oro-facial pain, remain a diagnostic and therapeutic challenge. Lack of understanding of the underlying pathophysiological mechanisms of these pain conditions is one of the important reasons behind the problems in diagnostic and management. During the last two decades, neurophysiological, psychophysical, brain imaging and neuropathological methods have been systematically applied to study the trigeminal system in idiopathic oro-facial pain. The findings in these studies have provided evidence for neuropathic involvement in the pathophysiology of PIFP, AO and BMS. The present qualitative review is a joint effort of a group of oro-facial pain specialists and researchers to appraise the literature on idiopathic oro-facial pain with special focus on the currently available studies on their pathophysiological mechanisms. The implications of the findings of these studies for the clinical diagnosis and treatment of idiopathic oro-facial pain conditions are discussed. © 2014 John Wiley & Sons Ltd.

  7. Child abuse: underlying mechanisms

    OpenAIRE

    Martínez, Gladys S.

    2009-01-01

    Exposure to traumatic stress during childhood, in the form of abuse or neglect, is related to an increased vulnerability resulting in the development of several pathologies, this relation has been confi rmed by epidemiological studies; however, the neural mechanisms underlying such abnormalities are still unknown. Most of the research done has focused on the effects in the infant, and only recently it has begun to focus on the neurobiological changes in the abusive parents. In this article, I...

  8. Principles of hemodynamic for mechanical circulatory support: patho-physiological key aspects of assisted PCI.

    Science.gov (United States)

    Basile, Eloisa; Russo, Giulio; Leone, Antonio M

    2018-03-15

    It is essential to understand the pathophysiology of cardiogenic shock and the possible deterioration of contractile function during high-risk PCI in order to select those patients who could benefit from mechanical support thus choosing the most suitable device in every situation. Percutaneous Ventricular Assist Devices (pVAD) provide hemodynamic support by improving cardiac output and mean arterial pressure, but their specific features result in different hemodynamic effects and degrees of myocardial ischemic protection and LV unloading. These features, together with ease of use, specific contraindications and individual risk of complications, must be taken into account in the evaluation and selection of the device. Ai of this review is to illustrate the principles of left ventricular mechanic, including the pressure- volume loop analysis, in order to better understand, to quantify the different hemodynamic effects of pVAD supports and to explain the key pathophysiological aspects of assisted PCI.

  9. Study protocol subacromial impingement syndrome: the identification of pathophysiologic mechanisms (SISTIM

    Directory of Open Access Journals (Sweden)

    de Witte Pieter

    2011-12-01

    muscle activation controlled acromiohumeral translation assessments; Clinical phenotyping (Constant Score, DASH, WORC, and SF-36 scores. Discussion By relating anatomic properties, kinematics and muscle dynamics to subacromial volume, we expect to identify one or more predominant pathophysiological mechanisms in every SIS patient. These differences in underlying mechanisms are a reflection of the variations in symptoms, clinical scores and outcomes reported in literature. More insight in these mechanisms is necessary in order to optimize future diagnostic and treatment strategies for patients with SIS symptoms. Trial registration Dutch Trial Registry (Nederlands Trial Register NTR2283.

  10. The contribution of inspiratory muscles function to exercise limitation in heart failure: pathophysiological mechanisms

    OpenAIRE

    Ribeiro,Jorge P.; Chiappa,Gaspar R.; Callegaro,Carine C.

    2012-01-01

    BACKGROUND: Heart failure induces histological, metabolic and functional adaptations in the inspiratory muscles. This inspiratory muscle weakness, which occurs in 30% to 50% of the heart failure patients, is associated with reduction in the functional capacity, reduction in the quality of life and with a poor prognosis in these individuals. OBJECTIVES: The objective of this review was to discuss the pathophysiological mechanisms that may explain the role of the inspiratory muscles in the exer...

  11. High fructose diet-induced metabolic syndrome: Pathophysiological mechanism and treatment by traditional Chinese medicine.

    Science.gov (United States)

    Pan, Ying; Kong, Ling-Dong

    2018-02-19

    Fructose is a natural monosaccharide broadly used in modern society. Over the past few decades, epidemiological studies have demonstrated that high fructose intake is an etiological factor of metabolic syndrome (MetS). This review highlights research advances on fructose-induced MetS, especially the underlying pathophysiological mechanism as well as pharmacotherapy by traditional Chinese medicine (TCM), using the PubMed, Web of science, China National Knowledge Infrastructure, China Science and Technology Journal and Wanfang Data. This review focuses on de novo lipogenesis (DNL) and uric acid (UA) production, two unique features of fructolysis different from glucose glycolysis. High level of DNL and UA production can result in insulin resistance, the key pathological event in developing MetS, mostly through oxidative stress and inflammation. Some other pathologies like the disturbance in brain and gut microbiota in the development of fructose-induced MetS in the past years, are also discussed. In management of MetS, TCM is an excellent representative in alternative and complementary medicine with a complete theory system and substantial herbal remedies. TCMs against MetS or MetS components, including Chinese patent medicines, TCM compound formulas, single TCM herbs and active compounds of TCM herbs, are reviewed on their effects and molecular mechanisms. TCMs with hypouricemic activity, which specially target fructose-induced MetS, are highlighted. And new technologies and strategies (such as high-throughput assay and systems biology) in this field are further discussed. In summary, fructose-induced MetS is a multifactorial disorder with the underlying complex mechanisms. Current clinical and pre-clinical evidence supports the potential of TCMs in management of MetS. Additionally, TCMs may show some advantages against complex MetS as their holistic feature through multiple target actions. However, further work is needed to confirm the effectivity and safety of TCMs

  12. The Pathophysiology of Insomnia

    Science.gov (United States)

    Levenson, Jessica C.; Kay, Daniel B.

    2015-01-01

    Insomnia disorder is characterized by chronic dissatisfaction with sleep quantity or quality that is associated with difficulty falling asleep, frequent nighttime awakenings with difficulty returning to sleep, and/or awakening earlier in the morning than desired. Although progress has been made in our understanding of the nature, etiology, and pathophysiology of insomnia, there is still no universally accepted model. Greater understanding of the pathophysiology of insomnia may provide important information regarding how, and under what conditions, the disorder develops and is maintained as well as potential targets for prevention and treatment. The aims of this report are (1) to summarize current knowledge on the pathophysiology of insomnia and (2) to present a model of the pathophysiology of insomnia that considers evidence from various domains of research. Working within several models of insomnia, evidence for the pathophysiology of the disorder is presented across levels of analysis, from genetic to molecular and cellular mechanisms, neural circuitry, physiologic mechanisms, sleep behavior, and self-report. We discuss the role of hyperarousal as an overarching theme that guides our conceptualization of insomnia. Finally, we propose a model of the pathophysiology of insomnia that integrates the various types of evidence presented. PMID:25846534

  13. HbE/β-Thalassemia and Oxidative Stress: The Key to Pathophysiological Mechanisms and Novel Therapeutics.

    Science.gov (United States)

    Hirsch, Rhoda Elison; Sibmooh, Nathawut; Fucharoen, Suthat; Friedman, Joel M

    2017-05-10

    Oxidative stress and generation of free radicals are fundamental in initiating pathophysiological mechanisms leading to an inflammatory cascade resulting in high rates of morbidity and death from many inherited point mutation-derived hemoglobinopathies. Hemoglobin (Hb)E is the most common point mutation worldwide. The β E -globin gene is found in greatest frequency in Southeast Asia, including Thailand, Malaysia, Indonesia, Vietnam, Cambodia, and Laos. With the wave of worldwide migration, it is entering the gene pool of diverse populations with greater consequences than expected. While HbE by itself presents as a mild anemia and a single gene for β-thalassemia is not serious, it remains unexplained why HbE/β-thalassemia (HbE/β-thal) is a grave disease with high morbidity and mortality. Patients often exhibit defective physical development, severe chronic anemia, and often die of cardiovascular disease and severe infections. Recent Advances: This article presents an overview of HbE/β-thal disease with an emphasis on new findings pointing to pathophysiological mechanisms derived from and initiated by the dysfunctional property of HbE as a reduced nitrite reductase concomitant with excess α-chains exacerbating unstable HbE, leading to a combination of nitric oxide imbalance, oxidative stress, and proinflammatory events. Additionally, we present new therapeutic strategies that are based on the emerging molecular-level understanding of the pathophysiology of this and other hemoglobinopathies. These strategies are designed to short-circuit the inflammatory cascade leading to devastating chronic morbidity and fatal consequences. Antioxid. Redox Signal. 26, 794-813.

  14. Management of Psychosis in Parkinson’s Disease: Emphasizing Clinical Subtypes and Pathophysiological Mechanisms of the Condition

    Directory of Open Access Journals (Sweden)

    Raquel N. Taddei

    2017-01-01

    Full Text Available Investigation into neuropsychiatric symptoms in Parkinson’s disease (PD is sparse and current drug development is mainly focused on the motor aspect of PD. The tight association of psychosis with an impaired quality of life in PD, together with an important underreporting of this comorbid condition, contributes to its actual insufficient assessment and management. Furthermore, the withdrawal from access to readily available treatment interventions is unacceptable and has an impact on PD prognosis. Despite its impact, to date no standardized guidelines to the adequate management of PD psychosis are available and they are therefore highly needed. Readily available knowledge on distinct clinical features as well as early biomarkers of psychosis in PD justifies the potential for its timely diagnosis and for early intervention strategies. Also, its specific characterisation opens up the possibility of further understanding the underlying pathophysiological mechanisms giving rise to more targeted therapeutic developments in the nearer future. A literature review on the most recent knowledge with special focus on specific clinical subtypes and pathophysiological mechanisms will not only contribute to an up to date practical approach of this condition for the health care providers, but furthermore open up new ideas for research in the near future.

  15. Mechanism of nitrogen metabolism-related parameters and enzyme activities in the pathophysiology of autism

    Directory of Open Access Journals (Sweden)

    Abu Shmais Ghada A

    2012-02-01

    Full Text Available Abstract Background There is evidence that impaired metabolism play an important role in the etiology of many neuropsychiatric disorders. Although this has not been investigated to date, several recent studies proposed that nitrogen metabolism-related parameters may have a pathophysiological role in autism. Methods The study enrolled 20 Saudi boys with autism aged 4 to 12 years and 20 healthy controls matched for age and gender. Levels of creatine, urea, ammonia, gamma-aminobutyric acid (GABA, glutamate:glutamine (Glu:Gln ratio, and enzymatic activities of glutamate dehydrogenase, 5'-nucleotidase, and adenosine deaminase (ADA were determined in plasma samples from both groups. Results We found a significant elevation of creatine, 5'-nucleotidase, GABA, and glutamic acid and a significant decrease in the enzymatic activity of ADA and glutamine level in patients with autism compared with healthy controls. The most significant variation between the two groups was found in the Glu:Gln ratio. Conclusion A raised Glu:Gln ratio together with positive correlations in creatine, GABA, and 5'-nucleotidase levels could contribute to the pathophysiology of autism, and might be useful diagnostic markers. The mechanism through which these parameters might be related to autism is discussed in detail.

  16. Association of Ozone Exposure With Cardiorespiratory Pathophysiologic Mechanisms in Healthy Adults.

    Science.gov (United States)

    Day, Drew B; Xiang, Jianbang; Mo, Jinhan; Li, Feng; Chung, Mingkei; Gong, Jicheng; Weschler, Charles J; Ohman-Strickland, Pamela A; Sundell, Jan; Weng, Wenguo; Zhang, Yinping; Zhang, Junfeng Jim

    2017-09-01

    Exposure to ozone has been associated with cardiovascular mortality, but the underlying biological mechanisms are not yet understood. To examine the association between ozone exposure and cardiopulmonary pathophysiologic mechanisms. A longitudinal study involving 89 healthy adult participants living on a work campus in Changsha City, China, was conducted from December 1, 2014, to January 31, 2015. This unique quasiexperimental setting allowed for better characterization of air pollutant exposure effects because the participants spent most of their time in controlled indoor environments. Concentrations of indoor and outdoor ozone, along with the copollutants particulate matter, nitrogen dioxide, and sulfur dioxide, were monitored throughout the study period and then combined with time-activity information and filtration conditions of each residence and office to estimate 24-hour and 2-week combined indoor and outdoor mean exposure concentrations. Associations between each exposure measure and outcome measure were analyzed using single-pollutant and 2-pollutant linear mixed models controlling for ambient temperature, secondhand smoke exposure, and personal-level time-varying covariates. Biomarkers indicative of inflammation and oxidative stress, arterial stiffness, blood pressure, thrombotic factors, and spirometry were measured at 4 sessions. Of the 89 participants, 25 (28%) were women and the mean (SD) age was 31.5 (7.6) years. The 24-hour ozone exposure concentrations ranged from 1.4 to 19.4 parts per billion (ppb), corresponding to outdoor concentrations ranging from 4.3 to 47.9 ppb. Within this range, in models controlling for a second copollutant and other potential confounders, a 10-ppb increase in 24-hour ozone was associated with mean increases of 36.3% (95% CI, 29.9%-43.0%) in the level of platelet activation marker soluble P-selectin, 2.8% (95% CI, 0.6%-5.1%) in diastolic blood pressure, 18.1% (95% CI, 4.5%-33.5%) in pulmonary inflammation markers

  17. Unfolding the mechanism of cisplatin induced pathophysiology in spleen and its amelioration by carnosine.

    Science.gov (United States)

    Banerjee, Sharmistha; Sinha, Krishnendu; Chowdhury, Sayantani; Sil, Parames C

    2018-01-05

    cis-Diamminedichloroplatinum (cisplatin) is an effective chemotherapeutic and is widely used for the treatment of various types of solid tumors. Bio-distribution of cisplatin to other organs due to poor targeting towards only cancer cells constitutes the backbone of cisplatin-induced toxicity. The adverse effect of this drug on spleen is not well characterized so far. Therefore, we have set our goal to explore the mechanism of the cisplatin-induced pathophysiology of the spleen and would also like to evaluate whether carnosine, an endogenous neurotransmitter and antioxidant, can ameliorate this pathophysiological response. We found a dose and time-dependent increase of the pro-inflammatory cytokine, TNF-α, in the spleen tissue of the experimental mice exposed to 10 and 20 mg/kg body weight of cisplatin. The increase in inflammatory cytokine can be attributed to the activation of the transcription factor, NF-ĸB. This also aids in the transcription of other pro-inflammatory cytokines and cellular adhesion molecules. Exposure of animals to cisplatin at both the doses resulted in ROS and NO production leading to oxidative stress. The MAP Kinase pathway, especially JNK activation, was also triggered by cisplatin. Eventually, the persistence of inflammatory response and oxidative stress lead to apoptosis through extrinsic pathway. Carnosine has been found to restore the expression of inflammatory molecules and catalase to normal levels through inhibition of pro-inflammatory cytokines, oxidative stress, NF-ĸB and JNK. Carnosine also protected the splenic cells from apoptosis. Our study elucidated the detailed mechanism of cisplatin-induced spleen toxicity and use of carnosine as a protective agent against this cytotoxic response. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Oscillation mechanics of the respiratory system in never-smoking patients with silicosis: pathophysiological study and evaluation of diagnostic accuracy.

    Science.gov (United States)

    Sá, Paula Morisco de; Lopes, Agnaldo José; Jansen, José Manoel; Melo, Pedro Lopes de

    2013-05-01

    Silicosis is a chronic and incurable occupational disease that can progress even after the cessation of exposure. Recent studies suggest that the forced oscillation technique may help to clarify the changes in lung mechanics resulting from silicosis as well as the detection of these changes. We investigated the effects of airway obstruction in silicosis on respiratory impedance and evaluated the diagnostic efficacy of the forced oscillation technique in these patients. Spirometry was used to classify the airway obstruction, which resulted in four subject categories: controls (n=21), patients with a normal exam (n=12), patients with mild obstruction (n=22), and patients with moderate-to-severe obstruction (n=12). Resistive data were interpreted using the zero-intercept resistance (R0), the resistance at 4 Hz (Rrs4), and the mean resistance. We also analyzed the mean reactance (Xm) and the dynamic compliance. The total mechanical load was evaluated using the absolute value of the respiratory impedance (Z4Hz). The diagnostic potential was evaluated by investigating the area under the receiver operating characteristic curve. ClinicalTrials.gov: NCT01725971. We observed significant (p0.80) and highly accurately in the detection of moderate-to-severe obstruction (area under the curve>0.90). The forced oscillation technique may contribute to the study of the pathophysiology of silicosis and may improve the treatment offered to these patients, thus representing an alternative and/or complementary tool for evaluating respiratory mechanics.

  19. The Interface of Mechanics and Nociception in Joint Pathophysiology: Insights From the Facet and Temporomandibular Joints

    Science.gov (United States)

    Sperry, Megan M.; Ita, Meagan E.; Kartha, Sonia; Zhang, Sijia; Yu, Ya-Hsin; Winkelstein, Beth

    2017-01-01

    Chronic joint pain is a widespread problem that frequently occurs with aging and trauma. Pain occurs most often in synovial joints, the body's load bearing joints. The mechanical and molecular mechanisms contributing to synovial joint pain are reviewed using two examples, the cervical spinal facet joints and the temporomandibular joint (TMJ). Although much work has focused on the macroscale mechanics of joints in health and disease, the combined influence of tissue mechanics, molecular processes, and nociception in joint pain has only recently become a focus. Trauma and repeated loading can induce structural and biochemical changes in joints, altering their microenvironment and modifying the biomechanics of their constitutive tissues, which themselves are innervated. Peripheral pain sensors can become activated in response to changes in the joint microenvironment and relay pain signals to the spinal cord and brain where pain is processed and perceived. In some cases, pain circuitry is permanently changed, which may be a potential mechanism for sustained joint pain. However, it is most likely that alterations in both the joint microenvironment and the central nervous system (CNS) contribute to chronic pain. As such, the challenge of treating joint pain and degeneration is temporally and spatially complicated. This review summarizes anatomy, physiology, and pathophysiology of these joints and the sensory pain relays. Pain pathways are postulated to be sensitized by many factors, including degeneration and biochemical priming, with effects on thresholds for mechanical injury and/or dysfunction. Initiators of joint pain are discussed in the context of clinical challenges including the diagnosis and treatment of pain. PMID:28056123

  20. Regulation of Nox enzymes expression in vascular pathophysiology: Focusing on transcription factors and epigenetic mechanisms.

    Science.gov (United States)

    Manea, Simona-Adriana; Constantin, Alina; Manda, Gina; Sasson, Shlomo; Manea, Adrian

    2015-08-01

    NADPH oxidases (Nox) represent a family of hetero-oligomeric enzymes whose exclusive biological function is the generation of reactive oxygen species (ROS). Nox-derived ROS are essential modulators of signal transduction pathways that control key physiological activities such as cell growth, proliferation, migration, differentiation, and apoptosis, immune responses, and biochemical pathways. Enhanced formation of Nox-derived ROS, which is generally associated with the up-regulation of different Nox subtypes, has been established in various pathologies, namely cardiovascular diseases, diabetes, obesity, cancer, and neurodegeneration. The detrimental effects of Nox-derived ROS are related to alterations in cell signalling and/or direct irreversible oxidative damage of nucleic acids, proteins, carbohydrates, and lipids. Thus, understanding of transcriptional regulation mechanisms of Nox enzymes have been extensively investigated in an attempt to find ways to counteract the excessive formation of Nox-derived ROS in various pathological states. Despite the numerous existing data, the molecular pathways responsible for Nox up-regulation are not completely understood. This review article summarizes some of the recent advances and concepts related to the regulation of Nox expression in the vascular pathophysiology. It highlights the role of transcription factors and epigenetic mechanisms in this process. Identification of the signalling molecules involved in Nox up-regulation, which is associated with the onset and development of cardiovascular dysfunction may contribute to the development of novel strategies for the treatment of cardiovascular diseases. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  1. The features of HPOA on dynamic bone scintigraphy: A reflection of underlying pathophysiology

    Energy Technology Data Exchange (ETDEWEB)

    Bernard, E.J.; Howman-Giles, R.; Macauley, D.I.; Uren, R.F. [Royal Alexander Hospital for Children, Sydney, NSW (Australia)

    1998-03-01

    Full text: Hypertrophic pulmonary osteoarthropathy (HPOA) is the clinical syndrome of clubbing, arthritis and periostitis which may accompany a spectrum of underlying disease processes. Increased blood flow through involved extremities is an invariable accompaniment of the syndrome and it is hypothesised that the chronic increase in peripheral blood flow results in the known pathological changes of periosteal inflammation and proliferation, oedema, synovial congestion and exudation and hyperplasia of the finger pulp. The dynamic and blood pool phases of bone scintigraphy provide a unique tool for examining the vascular changes in bone and soft tissues and we describe the previously unreported features of the dynamic bone scan in HPOA. We performed three-phase bone scans on two adolescent patients with cystic fibrosis with knee discomfort. Both studies showed marked hyperaemia to the knees. On the blood pool phase, hyperaemia was seen to the tissues closely related to the periosteum of the long bones in upper and lower limbs, periarticular tissues and finger pulps. The delayed images showed the classic features of HPOA with linear uptake of tracer in the shafts and metaphyseal regions of the long bones and minor periarticular uptake of tracer. A WBC scan performed in one patient showed WBC accumulation in the periosteum of the metaphyseal regions, extending in the shafts, of the distal femurs and proximal tibias. Negligible WBC accumulation was seen in the synovium of the knees reflecting the non-inflammatory nature of the articular changes as is described in most patients with HPOA. In conclusion, the dynamic phases of the bone scan examination in HPOA reflect the pivotal underlying pathophysiological process of abnormally increased blood flow to the periosteal and periarticular tissues of involved long bones and finger pulps and further expands the known diagnostic features of this disease on bone scintigraphy.

  2. Endometriosis-associated infertility: aspects of pathophysiological mechanisms and treatment options.

    Science.gov (United States)

    Tanbo, Tom; Fedorcsak, Peter

    2017-06-01

    Endometriosis is a common condition in women of reproductive age. In addition to pain, endometriosis may also reduce fertility. The causes of infertility in women with endometriosis may range from anatomical distortions due to adhesions and fibrosis to endocrine abnormalities and immunological disturbances. In some cases, the various pathophysiological disturbances seem to interact through mechanisms so far not fully understood. Whether surgery should be offered as a treatment option in endometriosis-associated infertility has become controversial, partly due to its modest or undocumented effect. Medical or hormonal treatment alone has little or no effect and should only be used in conjunction with assisted reproductive technology (ART). Of the various methods of ART, intrauterine insemination, due to its simplicity, can be recommended in women with minimal or mild peritoneal endometriosis, even though insemination may yield a lower success rate than in women without endometriosis. In vitro fertilization (IVF) is an effective treatment option in less-advanced disease stages, and the success rates are similar to the results in other causes of infertility. However, women with more advanced stages of endometriosis have lower success rates with IVF. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

  3. Venous System in Acute Brain Injury: Mechanisms of Pathophysiological Change and Function

    Science.gov (United States)

    Xu, Liang; Matei, Nathanael; Tang, Jiping; Feng, Hua; Zhang, JohnH

    2015-01-01

    Cerebral vascular injury is a major component of acute brain injury. Currently, neuroprotective strategies primarily focus on the recanalization of cerebral arteries and capillaries, and the protection of insulted neurons. Hitherto, the role of vein drainage in the pathophysiology of acute brain injury has been overlooked, due to an under appreciation of the magnitude of the impact of veins in circulation. In this review, we summarize the changes in the vein morphology and functions that are known, or likely to occur related to acute brain injury, and aim to advance the therapeutic management of acute brain injury by shifting the focus from reperfusion to another term: recirculation. Recent progress in the neurobiological understanding of the vascular neural network has demonstrated that cerebral venous systems are able to respond to acute brain injury by regulating the blood flow disharmony following brain edema, blood brain barrier disruption, ischemia, and hemorrhage. With the evidence presented in this review, future clinical management of acutely brain injured patients will expand to include the recirculation concept, establishing a harmony between arterial and venous systems, in addition to the established recanalization and reperfusion strategies. PMID:25783658

  4. Underlying Mechanisms Affecting Institutionalisation of ...

    African Journals Online (AJOL)

    This paper discusses the underlying causal mechanisms that enabled or constrained institutionalisation of environmental education in 12 institutions in eight countries in southern Africa. The study was carried out in the context of the Southern Africa Development Community Regional Environmental Education Support ...

  5. Underlying Mechanisms Affecting Institutionalisation of ...

    African Journals Online (AJOL)

    doctoral study and draws on critical realism as the ontological lens. Data analysis was done by means of a retroductive mode of inference, as articulated by Danermark, Ekström, Jakosben and Karlsson (2002). The paper demonstrates that there are a number of underlying causal mechanisms, which may enable or.

  6. Molecular mechanisms underlying bacterial persisters

    DEFF Research Database (Denmark)

    Maisonneuve, Etienne; Gerdes, Kenn

    2014-01-01

    All bacteria form persisters, cells that are multidrug tolerant and therefore able to survive antibiotic treatment. Due to the low frequencies of persisters in growing bacterial cultures and the complex underlying molecular mechanisms, the phenomenon has been challenging to study. However, recent...

  7. Obesity: Pathophysiology and Intervention

    Directory of Open Access Journals (Sweden)

    Yi Zhang

    2014-11-01

    Full Text Available Obesity presents a major health hazard of the 21st century. It promotes co-morbid diseases such as heart disease, type 2 diabetes, obstructive sleep apnea, certain types of cancer, and osteoarthritis. Excessive energy intake, physical inactivity, and genetic susceptibility are main causal factors for obesity, while gene mutations, endocrine disorders, medication, or psychiatric illnesses may be underlying causes in some cases. The development and maintenance of obesity may involve central pathophysiological mechanisms such as impaired brain circuit regulation and neuroendocrine hormone dysfunction. Dieting and physical exercise offer the mainstays of obesity treatment, and anti-obesity drugs may be taken in conjunction to reduce appetite or fat absorption. Bariatric surgeries may be performed in overtly obese patients to lessen stomach volume and nutrient absorption, and induce faster satiety. This review provides a summary of literature on the pathophysiological studies of obesity and discusses relevant therapeutic strategies for managing obesity.

  8. The proportion of xanthine oxidase activity of total xanthine oxidoreductase activity in situ remains constant in rat liver under various (patho)physiological conditions

    NARCIS (Netherlands)

    Frederiks, W. M.; Bosch, K. S.

    1996-01-01

    Activity of xanthine oxidoreductase (total xanthine dehydrogenase plus xanthine oxidase) and xanthine oxidase was determined cytophotometrically in periportal and pericentral areas of livers of rats under various (patho)physiological conditions that are known to affect the content of reduced

  9. [General concept and pathophysiological mechanisms of progression of macrovascular complications in diabetes].

    Science.gov (United States)

    Kashiwagi, Atsunori

    2010-05-01

    Macrovascular complications in diabetes consist of 2 basic pathophysiological characteristics such as obstructive atherosclerotic lesions and non-obstructive sclerotic arterial lesions. The patients with former lesions are frequently complicated with postprandial hyperglycemia, insulin resistance, hyperinsulinemia, metabolic syndrome, smoking or high LDL-C concentrations. The latter lesions are usually characterized by diffuse, multi-vessel diseases and typically found in patients with long duration of diabetes and advanced diabetic retinopathy as well as nephropathy. Cardiovascular events or death in diabetes are as equally high as non-diabetic patients with a previous history of ischemic coronary artery diseases in not only Finish study but also Japanese J-ACCES study. It is now very clear that the progression of macrovascular complications in diabetes can be efficiently prevented by a strict multifactorial control of all coronary risk factors including hyperglycemia.

  10. Does Parkinson's disease and type-2 diabetes mellitus present common pathophysiological mechanisms and treatments?

    Science.gov (United States)

    Lima, Marcelo M S; Targa, Adriano D S; Noseda, Ana C D; Rodrigues, Lais S; Delattre, Ana Marcia; dos Santos, Fabiola V; Fortes, Mariana H; Maturana, Maira J; Ferraz, Anete C

    2014-04-01

    Parkinson's disease (PD) is the second most common neurodegenerative disease afflicting about 1% of people over 65 years old and 4-5% of people over 85 years. It is proposed that a cascade of deleterious factors is set in motion within that neuron made not of one, but rather of multiple factors such as free radicals, excitotoxicity, neuroinflammation, and apoptosis to cite only some of the most salient. In this scenario, chronic systemic inflammation, as well as impaired mitochondrial metabolism, have also been suspected of playing a role in the development of type-2 diabetes, and the possibility of a shared pathophysiology of PD and type-2 diabetes has been proposed. The discussion about the interactions between PD and type-2 diabetes mellitus began in the 1960's and there is still controversy. Insulin and dopamine may exert reciprocal regulation hence; hypoinsulinemia induced by streptozotocin decreased the amounts of dopamine transporter and tyrosine hydroxylase transcripts in the substantia nigra pars compacta. Accordingly, dopamine depletion in the striatum is able to decreases insulin signaling in basal ganglia, indicating that, perhaps, PD may be considered as a risk factor for the development of type-2 diabetes mellitus. In this sense, it is described that peroxisome proliferator-activated receptor-γ, ATP-sensitive K(+) channels, AMP-activated protein kinase, glucagon-like peptide-1 and dipeptidyl peptidase-4 are important therapeutic targets for PD and reinforces the association with diabetes. Therefore, the objective of the present review is to contextualize the mutual pathophysiological interactions between PD and type-2 diabetes mellitus, as well as the potential common treatments.

  11. Systemic cobalt toxicity from total hip arthroplasties: review of a rare condition Part 1 - history, mechanism, measurements, and pathophysiology.

    Science.gov (United States)

    Cheung, A C; Banerjee, S; Cherian, J J; Wong, F; Butany, J; Gilbert, C; Overgaard, C; Syed, K; Zywiel, M G; Jacobs, J J; Mont, M A

    2016-01-01

    Recently, the use of metal-on-metal articulations in total hip arthroplasty (THA) has led to an increase in adverse events owing to local soft-tissue reactions from metal ions and wear debris. While the majority of these implants perform well, it has been increasingly recognised that a small proportion of patients may develop complications secondary to systemic cobalt toxicity when these implants fail. However, distinguishing true toxicity from benign elevations in cobalt ion levels can be challenging. The purpose of this two part series is to review the use of cobalt alloys in THA and to highlight the following related topics of interest: mechanisms of cobalt ion release and their measurement, definitions of pathological cobalt ion levels, and the pathophysiology, risk factors and treatment of cobalt toxicity. Historically, these metal-on-metal arthroplasties are composed of a chromium-cobalt articulation. The release of cobalt is due to the mechanical and oxidative stresses placed on the prosthetic joint. It exerts its pathological effects through direct cellular toxicity. This manuscript will highlight the pathophysiology of cobalt toxicity in patients with metal-on-metal hip arthroplasties. Patients with new or evolving hip symptoms with a prior history of THA warrant orthopaedic surgical evaluation. Increased awareness of the range of systemic symptoms associated with cobalt toxicity, coupled with prompt orthopaedic intervention, may forestall the development of further complications. ©2016 The British Editorial Society of Bone & Joint Surgery.

  12. Hypothermia – mechanism of action and pathophysiological changes in the human body

    Directory of Open Access Journals (Sweden)

    Przemysław Sosnowski

    2015-01-01

    Full Text Available This review focuses on the physiological responses and pathophysiological changes induced by hypothermia. Normal body function depends on its ability to maintain thermal homeostasis. The human body can be divided arbitrarily into two thermal compartments: a core compartment (trunk and head, with precisely regulated temperature around 37°C, and a peripheral compartment (skin and extremities with less strictly controlled temperature, and lower than the core temperature. Thermoregulatory processes occur in three phases: afferent thermal sensing, central regulation, mainly by the preoptic area of the anterior hypothalamus, and efferent response. Exposure to cold induces thermoregulatory responses including cutaneous vasoconstriction, shivering and non-shivering thermogenesis, and behavioral changes. Alterations of body temperature associated with impaired thermoregulation, decreased heat production or increased heat loss can lead to hypothermia. Hypothermia is defined as a core body temperature below 35ºC, and may be classified according to the origin as accidental (e.g. caused by exposure to a cold environment, drugs, or illness or intentional (i.e. therapeutic, or by the degree of hypothermia as mild, moderate or severe. Classification by temperature is not universal. Lowering of body temperature disrupts the physiological processes at the molecular, cellular and system level, but hypothermia induced prior to cardiosurgical or neurosurgical procedures, by the decrease in tissue oxygen demand, can reduce the risk of cerebral or cardiac ischemic damage. Therapeutic hypothermia has been recommended as a clinical procedure in situations characterized by ischemia, such as cardiac arrest, stroke and brain injuries.

  13. Pathophysiological mechanisms of Staphylococcus non-aureus bone and joint infection: interspecies homogeneity and specific behaviour of S. pseudintermedius

    Directory of Open Access Journals (Sweden)

    Yousef Maali

    2016-07-01

    Full Text Available Implicated in more than 60% of bone and joint infections (BJIs, Staphylococci have a particular tropism for osteoarticular tissue and lead to difficult-to-treat clinical infections. To date, Staphylococcus aureus internalization in non-professional phagocytic cells (NPPCs is a well-explored virulence mechanism involved in BJI chronicity. Conversely, the pathophysiological pathways associated with Staphylococcus non-aureus (SNA BJIs have scarcely been studied despite their high prevalence. In this study, fifteen reference strains from 15 different SNA species were compared in terms of (i adhesion to human fibronectin based on adhesion microplate assays and (ii internalization ability, intracellular persistence and cytotoxicity based on an in vitro infection model using human osteoblasts. Compared to S. aureus, Staphylococcus pseudintermedius was the only species that significantly adhered to human fibronectin. This species was also associated with high (even superior to S. aureus internalization ability, intracellular persistence and cytotoxicity. These findings were confirmed using a panel of 17 different S. pseudintermedius isolates. Additionally, S. pseudintermedius internalization by osteoblasts was completely abolished in β1 integrin-deficient murine osteoblasts. These results suggest the involvement of β1 integrin in the invasion process, although this mechanism was previously restricted to S. aureus. In summary, our results suggest that internalization into NPPCs is not a classical pathophysiologic mechanism of SNA BJIs. S. pseudintermedius appears to be an exception, and its ability to invade and subsequently induce cytotoxicity in NPPCs could explain its severe and necrotic forms of infection, notably in dogs, which exhibit a high prevalence of S. pseudintermedius infection.

  14. Distribution and possible function of lysosomal enzymes in the inner ear under normal and pathophysiological conditions.

    Science.gov (United States)

    Schätzle, W

    1976-05-31

    The normal distribution of several lysosomal enzymes was studied in 20 guinea pigs. In the outer hair cells lysosomal enzymes are mainly localized at the apical cell pole, while in inner hair cells the distribution was uniform. Nonlysosomal enzymes like alcaline phosphatase are of predominantly basal localization. The concentration of some lysosomal enzymes like N-acetyl-beta-glucosaminidase was higher in outer than in inner hair cells while others like acid phosphatase, beta-glucuronidase and sulfatase showed a stronger reaction in the inner hair cells. After 10 days of sound overstimulation with 120 dB for 1 h a day, there was an increase of lysosomal enzyme content namely in the outer hair cells. There was no change of non-lysosomal enzymes. Under these conditions there might be a partial destruction of cellular organelles eliminated by lysosomal activity without loss of a total cell. In addition the distribution and possible function of lysosomal enzymes in other labyrinthine tissues was discussed.

  15. Modelling accidental hypothermia effects on a human body under different pathophysiological conditions.

    Science.gov (United States)

    Coccarelli, Alberto; Boileau, Etienne; Parthimos, Dimitris; Nithiarasu, Perumal

    2017-12-01

    Accidental exposure to cold water environment is one of the most challenging situations in which hypothermia occurs. In the present work, we aim to characterise the energy balance of a human body subjected to such extreme environmental conditions. This study is carried out using a recently developed computational model and by setting boundary conditions needed to simulate the effect of cold surrounding environment. A major finding is the capacity of the body core regions to maintain their temperature high for a substantial amount of time, even under the most extreme environmental conditions. We also considered two disease states that highlight the spectrum of possible pathologies implicated in thermal regulation of the human body. These states are (i) cardiomyopathy, which affects the operating capacity of the heart, and (ii) malnutrition, which directly impairs the body's ability to regulate heat exchange with the environment. We have found that cardiomyopathy has little influence on the thermal balance of the human body, whereas malnutrition has a profound negative effect on the thermal balance and leads to dramatic reduction in core temperature.

  16. MECHANISMS IN ENDOCRINOLOGY: Diabetic cardiomyopathy: pathophysiology and potential metabolic interventions state of the art review.

    Science.gov (United States)

    Levelt, Eylem; Gulsin, Gaurav; Neubauer, Stefan; McCann, Gerry P

    2018-04-01

    Heart failure is a major cause of morbidity and mortality in type 2 diabetes. Type 2 diabetes contributes to the development of heart failure through a variety of mechanisms, including disease-specific myocardial structural, functional and metabolic changes. This review will focus on the contemporary contributions of state of the art non-invasive technologies to our understanding of diabetic cardiomyopathy, including data on cardiac disease phenotype, cardiac energy metabolism and energetic deficiency, ectopic and visceral adiposity, diabetic liver disease, metabolic modulation strategies and cardiovascular outcomes with new classes of glucose-lowering therapies. © 2018 The authors.

  17. First report of the characterization of the pathophysiological mechanisms caused by the freshwater catfish Pimelodus maculatus (order: Siluriformes).

    Science.gov (United States)

    Sarmiento, Beatriz Elena; Rangel, Marisa; Gonçalves, Jacqueline Coimbra; Pereira, Lilibete; Rego, Solange; Campos, Leandro Ambrósio; Haddad, Vidal; Mortari, Márcia Renata; Schwartz, Elisabeth F

    2015-07-01

    Injuries caused by aquatic animals in Brazil in most cases are provoked by marine and freshwater catfish. Pimelodus maculatus is a freshwater catfish very common in Brazilian basins that causes frequent accidents mainly amongst fishermen, and whose venom characteristics and pathological mechanisms of the venom are poorly known. In the present study for the first time, we have characterized the main pathophysiological mechanisms associated with the clinical manifestation (pain, local inflammation and edema) of the envenomations caused by P. maculatus crude venom. It was estimated that the crude venom of one P. maculatus stinger contains approximately 100 μg of protein, likely the quantity involved in the envenomation. P. maculatus crude venom induced marked nociceptive and edematogenic effects and caused vascular permeability alterations at doses from 30 to 100 μg/animal. Additionally, P. maculatus crude venom caused a decrease in the contraction force in in situ frog heart, did not cause hemorrhage or alterations in clotting times (prothrombin time and activated partial thromboplastin time), but induced significant changes in the levels of CK and its isoenzyme CK-MB in mice. In the present work, we present a correlation between the effects obtained experimentally and the main symptoms observed in the human accidents provoked by P. maculatus. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Irritable bowel syndrome and visceral hypersensitivity : risk factors and pathophysiological mechanisms.

    Science.gov (United States)

    Deiteren, A; de Wit, A; van der Linden, L; De Man, J G; Pelckmans, P A; De Winter, B Y

    2016-03-01

    Irritable bowel syndrome (IBS) is a common functional gastro-intestinal disorder, characterized by abdominal pain and altered intestinal motility. Visceral hypersensitivity is an important hallmark feature of IBS and is believed to underlie abdominal pain in patients with IBS. The two main risk factors associated with the development of IBS are gastrointestinal inflammation and psychological distress. On a peripheral level, visceral sensitivity seems to be modulated by several mechanisms. Immune cells in the mucosal wall, such as mast cells, and enterochromaffin cells may sensitize afferent nerves by release of their mediators. Furthermore, increased mucosal permeability, altered intestinal microflora and dietary habits may contribute to this feature. On a central level, an increased prevalence of psychiatric comorbidities is demonstrated in IBS patients, alongside alterations in the hormonal brain-gut axis, increased vigilance towards intestinal stimuli and functional and structural changes in the brain. The pathogenesis of IBS is complicated and multifactorial and the treatment remains clinically challenging. Dietary measures and symptomatic control are the cornerstones for IBS treatment and may be sufficient for patients experiencing mild symptoms, alongside education, reassurance and an effective therapeutic physician-patient relationship. New pharmacological therapies are aimed at interfering with mediator release and/or blockade of the relevant receptors within the gut wall, while modulation of the intestinal flora and diet may also be of therapeutic benefit. Tricyclic anti-depressants and serotonin reuptake inhibitors act both on a central and peripheral level by modulating pain signalling pathways. © Acta Gastro-Enterologica Belgica.

  19. Botulinum Toxin A and Lower Urinary Tract Dysfunction: Pathophysiology and Mechanisms of Action

    Directory of Open Access Journals (Sweden)

    Jia-Fong Jhang

    2016-04-01

    Full Text Available The use of onabotulinumtoxinA (BoNT-A for the treatment of lower urinary tract diseases (LUTD has increased markedly in recent years. The indications for BoNT-A treatment of LUTD now include neurogenic or idiopathic detrusor overactivity, interstitial cystitis/bladder pain syndrome and voiding dysfunction. The mechanisms of BoNT-A action on LUTDs affect many different aspects. Traditionally, the effects of BoNT-A were believed to be attributable to inhibition of acetylcholine release from the presynaptic efferent nerves at the neuromuscular junctions in the detrusor or urethral sphincter. BoNT-A injection in the bladder also regulated sensory nerve function by blocking neurotransmitter release and reducing receptor expression in the urothelium. In addition, recent studies revealed an anti-inflammatory effect for BoNT-A. Substance P and nerve growth factor in the urine and bladder tissue decreased after BoNT-A injection. Mast cell activation in the bladder also decreased. BoNT-A-induced improvement of urothelium function plays an important mitigating role in bladder dysfunction. Vascular endothelial growth factor expression in urothelium decreased after BoNT-A injection, as did apoptosis. Studies also revealed increased apoptosis in the prostate after BoNT-A injection. Although BoNT-A injection has been widely used to treat different LUTDs refractory to conventional treatment, currently, onabotulinumtoxinA has been proven effective only on urinary incontinence due to IDO and NDO in several large-scale clinical trials. The effects of onabotulinumtoxinA on other LUTDs such as interstitial cystitis, benign prostatic hyperplasia, dysfunctional voiding or detrusor sphincter dyssynergia have not been well demonstrated.

  20. Epigenetic mechanisms underlying nervous system diseases.

    Science.gov (United States)

    Qureshi, Irfan A; Mehler, Mark F

    2018-01-01

    Epigenetic mechanisms act as control systems for modulating genomic structure and activity in response to evolving profiles of cell-extrinsic, cell-cell, and cell-intrinsic signals. These dynamic processes are responsible for mediating cell- and tissue-specific gene expression and function and gene-gene and gene-environmental interactions. The major epigenetic mechanisms include DNA methylation and hydroxymethylation; histone protein posttranslational modifications, nucleosome remodeling/repositioning, and higher-order chromatin reorganization; noncoding RNA regulation; and RNA editing. These mechanisms are intimately involved in executing fundamental genomic programs, including gene transcription, posttranscriptional RNA processing and transport, translation, X-chromosome inactivation, genomic imprinting, retrotransposon regulation, DNA replication, and DNA repair and the maintenance of genomic stability. For the nervous system, epigenetics offers a novel and robust framework for explaining how brain development and aging occur, neural cellular diversity is generated, synaptic and neural network connectivity and plasticity are mediated, and complex cognitive and behavioral phenotypes are inherited transgenerationally. Epigenetic factors and processes are, not surprisingly, implicated in nervous system disease pathophysiology through several emerging paradigms - mutations and genetic variation in genes encoding epigenetic factors; impairments in epigenetic factor expression, localization, and function; epigenetic mechanisms modulating disease-associated factors and pathways; and the presence of deregulated epigenetic profiles in central and peripheral tissues. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Metacognitive mechanisms underlying lucid dreaming.

    Science.gov (United States)

    Filevich, Elisa; Dresler, Martin; Brick, Timothy R; Kühn, Simone

    2015-01-21

    Lucid dreaming is a state of awareness that one is dreaming, without leaving the sleep state. Dream reports show that self-reflection and volitional control are more pronounced in lucid compared with nonlucid dreams. Mostly on these grounds, lucid dreaming has been associated with metacognition. However, the link to lucid dreaming at the neural level has not yet been explored. We sought for relationships between the neural correlates of lucid dreaming and thought monitoring. Human participants completed a questionnaire assessing lucid dreaming ability, and underwent structural and functional MRI. We split participants based on their reported dream lucidity. Participants in the high-lucidity group showed greater gray matter volume in the frontopolar cortex (BA9/10) compared with those in the low-lucidity group. Further, differences in brain structure were mirrored by differences in brain function. The BA9/10 regions identified through structural analyses showed increases in blood oxygen level-dependent signal during thought monitoring in both groups, and more strongly in the high-lucidity group. Our results reveal shared neural systems between lucid dreaming and metacognitive function, in particular in the domain of thought monitoring. This finding contributes to our understanding of the mechanisms enabling higher-order consciousness in dreams. Copyright © 2015 the authors 0270-6474/15/351082-07$15.00/0.

  2. Molecular Mechanisms Underlying Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Christian Trepo

    2009-11-01

    Full Text Available Hepatocarcinogenesis is a complex process that remains still partly understood. That might be explained by the multiplicity of etiologic factors, the genetic/epigenetic heterogeneity of tumors bulks and the ignorance of the liver cell types that give rise to tumorigenic cells that have stem cell-like properties. The DNA stress induced by hepatocyte turnover, inflammation and maybe early oncogenic pathway activation and sometimes viral factors, leads to DNA damage response which activates the key tumor suppressive checkpoints p53/p21Cip1 and p16INK4a/pRb responsible of cell cycle arrest and cellular senescence as reflected by the cirrhosis stage. Still obscure mechanisms, but maybe involving the Wnt signaling and Twist proteins, would allow pre-senescent hepatocytes to bypass senescence, acquire immortality by telomerase reactivation and get the last genetic/epigenetic hits necessary for cancerous transformation. Among some of the oncogenic pathways that might play key driving roles in hepatocarcinogenesis, c-myc and the Wnt/β-catenin signaling seem of particular interest. Finally, antiproliferative and apoptosis deficiencies involving TGF-β, Akt/PTEN, IGF2 pathways for instance are prerequisite for cancerous transformation. Of evidence, not only the transformed liver cell per se but the facilitating microenvironment is of fundamental importance for tumor bulk growth and metastasis.

  3. Mechanism of Generation of Oxidative Stress and Pathophysiology of Type 2 Diabetes Mellitus: How Are They Interlinked?

    Science.gov (United States)

    Rehman, Kanwal; Akash, Muhammad Sajid Hamid

    2017-11-01

    Oxidative stress has been considered as a major hallmark for the pathogenesis and development of type 2 diabetes mellitus (T2DM), but still it is debatable whether it is a mere aggregation of inflammatory-induced responses or clinical entity that underlies with various pathophysiological factors. In this regard, the latest studies have shown the increasing trends for the involvement of reactive oxygen species (ROS) and oxidative stress in the pathogenesis and development of T2DM. ROS are highly reactive species and almost all cellular components are chemically changed due to the influence of ROS that ultimately results in the production of lipid peroxidation. Lipid peroxidation is a major causative factor for the development of oxidative stress that leads to overt T2DM and its associated micro- and macro-vascular complications. In this article, we have briefly described the role of various causative factors, transcriptional and metabolic pathways which are responsible to increase the production of oxidative stress, a most pivotal factor for the pathogenesis and development of T2DM. Therefore, we conclude that measurement of oxidative stress biomarkers may be one of the optional tool for the diagnosis and prediction of T2DM. Moreover, the key findings described in this article also provides a new conceptual framework for forthcoming investigations on the role of oxidative stress in pathogenesis of T2DM and drug discovery. J. Cell. Biochem. 118: 3577-3585, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  4. Characterization of the mechanical behavior and pathophysiological state of abdominal aortic aneurysms based on 4D ultrasound strain imaging

    Science.gov (United States)

    Wittek, Andreas; Blase, Christopher; Derwich, Wojciech; Schmitz-Rixen, Thomas; Fritzen, Claus-Peter

    2017-06-01

    Abdominal aortic aneurysms (AAA) are a degenerative disease of the human aortic wall that may lead to weakening and eventually rupture of the wall with high mortality rates. Since the currently established criterion for surgical or endovascular treatment of the disease is imprecise in the individual case and treatment is not free of complications, the need for additional patient-individual biomarkers for short-term AAA rupture risk as basis for improved clinical decision making. Time resolved 3D ultrasound combined with speckle tracking algorithms is a novel non-invasive medical imaging technique that provides full-field displacement and strain measurements of aortic and aneurysmal wall motion. This is patient-individual information that has not been used so far to assess wall strength and rupture risk. The current study uses simple statistical indices of the heterogeneous spatial distribution of in-plane strain components as biomarkers for the pathological state of the aortic and aneurysmal wall. The pathophysiological rationale behind this approach are the known changes in microstructural composition of the aortic wall with progression of AAA development that results in increased stiffening and heterogeneity of the walls mechanical properties and in decreased wall strength. In a comparative analysis of the aortic wall motion of young volunteers without known cardiovascular diseases, aged arteriosclerotic patients without AAA, and AAA patients, mean values of all in-plane strain components were significantly reduced, and the heterogeneity of circumferential strain was significantly increased in the AAA group compared to both other groups. The capacity of the proposed method to differentiate between wall motion of aged, arteriosclerotic patients and AAA patients is a promising step towards a new method for in vivo assessment of AAA wall strength or stratification of AAA rupture risk as basis for improved clinical decision making on surgical or endovascular

  5. Deciphering the Cognitive and Neural Mechanisms Underlying ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Deciphering the Cognitive and Neural Mechanisms Underlying Auditory Learning. This project seeks to understand the brain mechanisms necessary for people to learn to perceive sounds. Neural circuits and learning. The research team will test people with and without musical training to evaluate their capacity to learn ...

  6. Activation and Inhibition of Sodium-Hydrogen Exchanger Is a Mechanism That Links the Pathophysiology and Treatment of Diabetes Mellitus With That of Heart Failure.

    Science.gov (United States)

    Packer, Milton

    2017-10-17

    The mechanisms underlying the progression of diabetes mellitus and heart failure are closely intertwined, such that worsening of one condition is frequently accompanied by worsening of the other; the degree of clinical acceleration is marked when the 2 coexist. Activation of the sodium-hydrogen exchanger in the heart and vasculature (NHE1 isoform) and the kidneys (NHE3 isoform) may serve as a common mechanism that links both disorders and may underlie their interplay. Insulin insensitivity and adipokine abnormalities (the hallmarks of type 2 diabetes mellitus) are characteristic features of heart failure; conversely, neurohormonal systems activated in heart failure (norepinephrine, angiotensin II, aldosterone, and neprilysin) impair insulin sensitivity and contribute to microvascular disease in diabetes mellitus. Each of these neurohormonal derangements may act through increased activity of both NHE1 and NHE3. Drugs used to treat diabetes mellitus may favorably affect the pathophysiological mechanisms of heart failure by inhibiting either or both NHE isoforms, and drugs used to treat heart failure may have beneficial effects on glucose tolerance and the complications of diabetes mellitus by interfering with the actions of NHE1 and NHE3. The efficacy of NHE inhibitors on the risk of cardiovascular events may be enhanced when heart failure and glucose intolerance coexist and may be attenuated when drugs with NHE inhibitory actions are given concomitantly. Therefore, the sodium-hydrogen exchanger may play a central role in the interplay of diabetes mellitus and heart failure, contribute to the physiological and clinical progression of both diseases, and explain certain drug-drug and drug-disease interactions that have been reported in large-scale randomized clinical trials. © 2017 American Heart Association, Inc.

  7. Special features of pathophysiological mechanisms of psychical disadaptation under influence of the Chernobyl NPP disaster

    International Nuclear Information System (INIS)

    Sinitskij, V.N.; Kovtun, T.V.; Kharchenko, N.K.; Stognij, N.A.; Duplenko, P.Yu.; Opanasenko, E.V.

    1994-01-01

    A complex clinical-laboratory examination of 110 patients with various phenomena of psychical disadaptation has been carried out.In the first group (5% of examined patients) the signs of psychical-organical syndrome characteristics for dismnestical dementia has been stated. In the second group (75% of examined patients) the neurological (vascular, vegetative, convulsive) disorders, developed due to systemic lesion of subcortical mezodiencephalular and limbic formation of the brain, have been revealed. For the third group of patients the neurotical and neurosis-like disorders have been typical. The most characteristic changes of electroencephalogram, higher neural activity, psychic-test data, indexes of vegetative-vascular tonus, exchange of biogenic amines (catecholamines and serotonin), the content of key metabolites in the blood, glomeruli filtration of kidneys have been investigated for the patients of each group

  8. Mechanical buckling of artery under pulsatile pressure.

    Science.gov (United States)

    Liu, Qin; Han, Hai-Chao

    2012-04-30

    Tortuosity that often occurs in carotid and other arteries has been shown to be associated with high blood pressure, atherosclerosis, and other diseases. However the mechanisms of tortuosity development are not clear. Our previous studies have suggested that arteries buckling could be a possible mechanism for the initiation of tortuous shape but artery buckling under pulsatile flow condition has not been fully studied. The objectives of this study were to determine the artery critical buckling pressure under pulsatile pressure both experimentally and theoretically, and to elucidate the relationship of critical pressures under pulsatile flow, steady flow, and static pressure. We first tested the buckling pressures of porcine carotid arteries under these loading conditions, and then proposed a nonlinear elastic artery model to examine the buckling pressures under pulsatile pressure conditions. Experimental results showed that under pulsatile pressure arteries buckled when the peak pressures were approximately equal to the critical buckling pressures under static pressure. This was also confirmed by model simulations at low pulse frequencies. Our results provide an effective tool to predict artery buckling pressure under pulsatile pressure. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Amorphization of ice under mechanical stresses

    Science.gov (United States)

    Bordonskii, G. S.; Krylov, S. D.

    2017-11-01

    The dielectric parameters of freshly produced freshwater ice in the microwave range are investigated. It is established that this kind of ice contains a noticeable amount of amorphous ice. Its production is associated with plastic deformation under mechanical stresses. An assessment of the dielectric-permeability change caused by amorphous ice in the state of a slowly flowing medium is given.

  10. Gas Bubble Dynamics under Mechanical Vibrations

    Science.gov (United States)

    Mohagheghian, Shahrouz; Elbing, Brian

    2017-11-01

    The scientific community has a limited understanding of the bubble dynamics under mechanical oscillations due to over simplification of Navier-Stockes equation by neglecting the shear stress tensor and not accounting for body forces when calculating the acoustic radiation force. The current work experimental investigates bubble dynamics under mechanical vibration and resulting acoustic field by measuring the bubble size and velocity using high-speed imaging. The experimental setup consists of a custom-designed shaker table, cast acrylic bubble column, compressed air injection manifold and an optical imaging system. The mechanical vibrations resulted in accelerations between 0.25 to 10 times gravitational acceleration corresponding to frequency and amplitude range of 8 - 22Hz and 1 - 10mm respectively. Throughout testing the void fraction was limited to definition of Bjerknes force in combination with Rayleigh-Plesset equation. Physical behavior of the system was capture and classified. Bubble size, velocity as well as size and spatial distribution will be presented.

  11. The Pathophysiology of Autism

    OpenAIRE

    Compart, Pamela J.

    2013-01-01

    Autism has been classically defined by its behavioral symptoms. Traditional medical research has focused on genetic or intrinsic brain-based causes of autism. While both of these are important, additional research has focused on the underlying disordered biochemistry seen in many individuals with autism. Many of these biomedical factors are amenable to treatment. This article will review the main pathophysiologic factors seen in individuals with autism spectrum disorders.

  12. DNA under Force: Mechanics, Electrostatics, and Hydration

    Directory of Open Access Journals (Sweden)

    Jingqiang Li

    2015-02-01

    Full Text Available Quantifying the basic intra- and inter-molecular forces of DNA has helped us to better understand and further predict the behavior of DNA. Single molecule technique elucidates the mechanics of DNA under applied external forces, sometimes under extreme forces. On the other hand, ensemble studies of DNA molecular force allow us to extend our understanding of DNA molecules under other forces such as electrostatic and hydration forces. Using a variety of techniques, we can have a comprehensive understanding of DNA molecular forces, which is crucial in unraveling the complex DNA functions in living cells as well as in designing a system that utilizes the unique properties of DNA in nanotechnology.

  13. [Pathophysiology of urticaria].

    Science.gov (United States)

    Nosbaum, A; Augey, F; Nicolas, J-F; Bérard, F

    2014-11-01

    Urticaria is a dermal edema resulting from vascular dilatation and leakage of fluid into the skin in response to molecules released from mast cells. The major mediator responsible for urticaria is histamine. However, the clinical spectrum and pattern of lesions indicate that other molecules, including prostaglandins, leukotrienes, cytokines, and chemokines, produced at different times after mast cell activation contribute to the polymorphism of this symptom and the variable evolution of this disease. It is a common practice to distinguish immunological and nonimmunological urticaria. Immunological urticaria is a hypersensitivity reaction mediated by antibodies and/or T-cells that results in mast cell activation. Although immunoglobulin (Ig) E-mediated type I hypersensitivity (HS) was long postulated to be the major immunological pathway associated with mast cell activation, interaction between IgEbound mast cells and allergens is unlikely to be the mechanism by which urticaria develops in most patients. It is now well established that urticaria may result from the binding of IgG auto-antibodies to IgE and/or to the receptor for IgE molecules on mast cells, thus corresponding to a type II HS reaction. These auto-immune urticarias represent up to 50 % of patients with chronic urticaria. Mast cell activation can also result from type III HS through the binding of circulating immune complexes to mast cell-expressing Fc receptors for IgG and IgM. Finally, under certain circumstances, T-cells can induce activation of mast cells, as well as histamine release (type IV HS). Nonimmunological urticarias result from mast cell activation through membrane receptors involved in innate immunity (e.g., complement, Toll-like, cytokine/chemokine, opioid) or by direct toxicity of xenobiotics (haptens, drugs). In conclusion, urticaria may result from different pathophysiological mechanisms that explain the great heterogeneity of clinical symptoms and the variable responses to treatment

  14. POSSIBLE MECHANISMS UNDERLYING THE THERAPEUTIC EFFECTS OF TRANSCRANIAL MAGNETIC STIMULATION

    Directory of Open Access Journals (Sweden)

    Alexander eChervyakov

    2015-06-01

    Full Text Available Transcranial magnetic stimulation (TMS is an effective method used to diagnose and treat many neurological disorders. Although repetitive TMS (rTMS has been used to treat a variety of serious pathological conditions including stroke, depression, Parkinson's disease, epilepsy, pain, and migraines, the pathophysiological mechanisms underlying the effects of long-term TMS remain unclear. In the present review, the effects of rTMS on neurotransmitters and synaptic plasticity are described, including the classic interpretations of TMS effects on synaptic plasticity via long-term potentiation (LTP and long-term depression (LTD. We also discuss the effects of rTMS on the genetic apparatus of neurons, glial cells and the prevention of neuronal death. The neurotrophic effects of rTMS on dendritic growth and sprouting and neurotrophic factors are described, including change in brain-derived neurotrophic factor (BDNF concentration under the influence of rTMS. Also, non-classical effects of TMS related to biophysical effects of magnetic fields are described, including the quantum effects, the magnetic spin effects, genetic magnetoreception, the macromolecular effects of TMS, and the electromagnetic theory of consciousness. Finally, we discuss possible interpretations of TMS effects according to dynamical systems theory. Evidence suggests that a rTMS-induced magnetic field should be considered a separate physical factor that can be impactful at the subatomic level and that rTMS is capable of significantly altering the reactivity of molecules (radicals. It is thought that these factors underlie the therapeutic benefits of therapy with TMS. Future research on these mechanisms will be instrumental to the development of more powerful and reliable TMS treatment protocols.

  15. Pathophysiology of Retinopathy of Prematurity

    Directory of Open Access Journals (Sweden)

    İmren Akkoyun

    2012-12-01

    Full Text Available Retinopathy of prematurity (ROP, an ocular disease characterized by onset of vascular abnormalities in the developing retina, is the major cause of visual impairment and blindness in premature neonates. ROP is a complex multifactorial disease that occurs with microvascular degeneration followed by neovascularization which passing through different stages can progress to retinal detachment. Currently used ablative therapies like cryocoagulation and laser photocoagulation for proliferative ROP have limitations, and patients can still have long-term complications despite a successful treatment. Based on the knowledge regarding ROP pathophysiology, new treatment modalities are being developed. First results of intravitreal anti-VEGF therapy using bevacizumab are promising. Furthermore, besides intravitreal anti-VEGF therapy, systemic therapy with mediators like insulin-like growth factor (IGF-1 and/or ω3-fatty acids outlines the pharmacological approach to treatment of ROP. One of the most destructive manifestations of ROP is preretinal neovascularization. As we continue to decipher the underlying pathophysiological cellular mechanisms governing proliferative retinopathy, fostering normal retinal revascularization will open new therapeutic possibilities. All efforts should be focused on developing preventive strategies for ROP in order to avoid the need for nondestructive therapy modalities. (Turk J Ophthalmol 2012; 42: Supplement 63-7

  16. Evolved Mechanisms Versus Underlying Conditional Relations

    Directory of Open Access Journals (Sweden)

    Astorga Miguel López

    2015-03-01

    Full Text Available The social contracts theory claims that, in social exchange circumstances, human reasoning is not necessarily led by logic, but by certain evolved mental mechanisms that are useful for catching offenders. An emblematic experiment carried out with the intention to prove this thesis is the first experiment described by Fiddick, Cosmides, and Tooby in their paper of 2000. Lopez Astorga has questioned that experiment claiming that its results depend on an underlying conditional logical form not taken into account by Fiddick, Cosmides, and Tooby. In this paper, I propose an explanation alternative to that of Lopez Astorga, which does not depend on logical forms and is based on the mental models theory. Thus, I conclude that this other alternative explanation is one more proof that the experiment in question does not demonstrate the fundamental thesis of the social contracts theory.

  17. Pathophysiological mechanisms of sino-atrial dysfunction and ventricular conduction disease associated with SCN5A deficiency: insights from mouse models

    Directory of Open Access Journals (Sweden)

    Christopher L-H Huang

    2012-07-01

    Full Text Available Genetically modified mice provide a number of models for studying cardiac channelopathies related to cardiac Na+ channel (SCN5A abnormalities. We review key pathophysiological features in these murine models that may underlie clinical features observed in sinus node dysfunction and progressive cardiac conduction disease, thereby providing insights into their pathophysiological mechanisms. We describe loss of Na+ channel function and fibrotic changes associated with both loss and gain-of-function Na+ channel mutations. Recent reports further relate the progressive fibrotic changes to upregulation of TGF-β1 production and the transcription factors, Atf3, a stress-inducible gene, and Egr1, to the presence of heterozygous Scn5a inactivation. Both changes are thus directly implicated in the clinically observed disruptions in sino-atrial node pacemaker function, and sino-atrial and ventricular conduction, and their progression with age. Murine systems with genetic modifications in Scn5a thus prove a useful tool to address questions concerning roles of genetic and environmental modifiers on human SCN5A disease phenotypes.

  18. Mechanisms underlying UV-induced immune suppression

    Energy Technology Data Exchange (ETDEWEB)

    Ullrich, Stephen E. [Department of Immunology, University of Texas, MD Anderson Cancer Center, South Campus Research Building 1, 7455 Fannin St., P.O. Box 301402, Houston, TX 77030-1903 (United States)]. E-mail: sullrich@mdanderson.org

    2005-04-01

    Skin cancer is the most prevalent form of human neoplasia. Estimates suggest that in excess of one million new cases of skin cancer will be diagnosed this year alone in the United States (www.cancer.org/statistics). Fortunately, because of their highly visible location, skin cancers are more rapidly diagnosed and more easily treated than other types of cancer. Be that as it may, approximately 10,000 Americans a year die from skin cancer. The cost of treating non-melanoma skin cancer is estimated to be in excess of US$ 650 million a year [J.G. Chen, A.B. Fleischer, E.D. Smith, C. Kancler, N.D. Goldman, P.M. Williford, S.R. Feldman, Cost of non-melanoma skin cancer treatment in the United States, Dermatol. Surg. 27 (2001) 1035-1038], and when melanoma is included, the estimated cost of treating skin cancer in the United States is estimated to rise to US$ 2.9 billion annually (www.cancer.org/statistics). Because the morbidity and mortality associated with skin cancer is a major public health problem, it is important to understand the mechanisms underlying skin cancer development. The primary cause of skin cancer is the ultraviolet (UV) radiation found in sunlight. In addition to its carcinogenic potential, UV radiation is also immune suppressive. In fact, data from studies with both experimental animals and biopsy proven skin cancer patients suggest that there is an association between the immune suppressive effects of UV radiation and its carcinogenic potential. The focus of this manuscript will be to review the mechanisms underlying the induction of immune suppression following UV exposure. Particular attention will be directed to the role of soluble mediators in activating immune suppression.

  19. Mechanisms underlying UV-induced immune suppression

    International Nuclear Information System (INIS)

    Ullrich, Stephen E.

    2005-01-01

    Skin cancer is the most prevalent form of human neoplasia. Estimates suggest that in excess of one million new cases of skin cancer will be diagnosed this year alone in the United States (www.cancer.org/statistics). Fortunately, because of their highly visible location, skin cancers are more rapidly diagnosed and more easily treated than other types of cancer. Be that as it may, approximately 10,000 Americans a year die from skin cancer. The cost of treating non-melanoma skin cancer is estimated to be in excess of US$ 650 million a year [J.G. Chen, A.B. Fleischer, E.D. Smith, C. Kancler, N.D. Goldman, P.M. Williford, S.R. Feldman, Cost of non-melanoma skin cancer treatment in the United States, Dermatol. Surg. 27 (2001) 1035-1038], and when melanoma is included, the estimated cost of treating skin cancer in the United States is estimated to rise to US$ 2.9 billion annually (www.cancer.org/statistics). Because the morbidity and mortality associated with skin cancer is a major public health problem, it is important to understand the mechanisms underlying skin cancer development. The primary cause of skin cancer is the ultraviolet (UV) radiation found in sunlight. In addition to its carcinogenic potential, UV radiation is also immune suppressive. In fact, data from studies with both experimental animals and biopsy proven skin cancer patients suggest that there is an association between the immune suppressive effects of UV radiation and its carcinogenic potential. The focus of this manuscript will be to review the mechanisms underlying the induction of immune suppression following UV exposure. Particular attention will be directed to the role of soluble mediators in activating immune suppression

  20. Two distinct neural mechanisms underlying indirect reciprocity.

    Science.gov (United States)

    Watanabe, Takamitsu; Takezawa, Masanori; Nakawake, Yo; Kunimatsu, Akira; Yamasue, Hidenori; Nakamura, Mitsuhiro; Miyashita, Yasushi; Masuda, Naoki

    2014-03-18

    Cooperation is a hallmark of human society. Humans often cooperate with strangers even if they will not meet each other again. This so-called indirect reciprocity enables large-scale cooperation among nonkin and can occur based on a reputation mechanism or as a succession of pay-it-forward behavior. Here, we provide the functional and anatomical neural evidence for two distinct mechanisms governing the two types of indirect reciprocity. Cooperation occurring as reputation-based reciprocity specifically recruited the precuneus, a region associated with self-centered cognition. During such cooperative behavior, the precuneus was functionally connected with the caudate, a region linking rewards to behavior. Furthermore, the precuneus of a cooperative subject had a strong resting-state functional connectivity (rsFC) with the caudate and a large gray matter volume. In contrast, pay-it-forward reciprocity recruited the anterior insula (AI), a brain region associated with affective empathy. The AI was functionally connected with the caudate during cooperation occurring as pay-it-forward reciprocity, and its gray matter volume and rsFC with the caudate predicted the tendency of such cooperation. The revealed difference is consistent with the existing results of evolutionary game theory: although reputation-based indirect reciprocity robustly evolves as a self-interested behavior in theory, pay-it-forward indirect reciprocity does not on its own. The present study provides neural mechanisms underlying indirect reciprocity and suggests that pay-it-forward reciprocity may not occur as myopic profit maximization but elicit emotional rewards.

  1. Dissociable cognitive mechanisms underlying human path integration.

    Science.gov (United States)

    Wiener, Jan M; Berthoz, Alain; Wolbers, Thomas

    2011-01-01

    Path integration is a fundamental mechanism of spatial navigation. In non-human species, it is assumed to be an online process in which a homing vector is updated continuously during an outward journey. In contrast, human path integration has been conceptualized as a configural process in which travelers store working memory representations of path segments, with the computation of a homing vector only occurring when required. To resolve this apparent discrepancy, we tested whether humans can employ different path integration strategies in the same task. Using a triangle completion paradigm, participants were instructed either to continuously update the start position during locomotion (continuous strategy) or to remember the shape of the outbound path and to calculate home vectors on basis of this representation (configural strategy). While overall homing accuracy was superior in the configural condition, participants were quicker to respond during continuous updating, strongly suggesting that homing vectors were computed online. Corroborating these findings, we observed reliable differences in head orientation during the outbound path: when participants applied the continuous updating strategy, the head deviated significantly from straight ahead in direction of the start place, which can be interpreted as a continuous motor expression of the homing vector. Head orientation-a novel online measure for path integration-can thus inform about the underlying updating mechanism already during locomotion. In addition to demonstrating that humans can employ different cognitive strategies during path integration, our two-systems view helps to resolve recent controversies regarding the role of the medial temporal lobe in human path integration.

  2. Mechanics of carbon nanotube scission under sonication.

    Science.gov (United States)

    Stegen, J

    2014-06-28

    As-produced carbon nanotubes come in bundles that must be exfoliated for practical applications in nanocomposites. Sonication not only causes the exfoliation of nanotube bundles but also unwanted scission. An understanding of how precisely sonication induces the scission and exfoliation of nanotubes will help maximising the degree of exfoliation while minimising scission. We present a theoretical study of the mechanics of carbon nanotube scission under sonicaton, based on the accepted view that it is caused by strong gradients in the fluid velocity near a transiently collapsing bubble. We calculate the length-dependent scission rate by taking the actual movement of the nanotube during the collapse of a bubble into account, allowing for the prediction of the temporal evolution of the length distribution of the nanotubes. We show that the dependence of the scission rate on the sonication settings and the nanotube properties results in non-universal, experiment-dependent scission kinetics potentially explaining the variety in experimentally observed scission kinetics. The non-universality arises from the dependence of the maximum strain rate of the fluid experienced by a nanotube on its length. The maximum strain rate that a nanotube experiences increases with decreasing distance to the bubble. As short nanotubes are dragged along more easily by the fluid flow they experience a higher maximum strain rate than longer nanotubes. This dependence of the maximum strain rate on nanotube length affects the scaling of tensile strength with terminal length. We find that the terminal length scales with tensile strength to the power of 1/1.16 instead of with an exponent of 1/2 as found when nanotube motion is neglected. Finally, we show that the mechanism we propose responsible for scission can also explain the exfoliation of carbon nanotube bundles.

  3. Changes in blood monocyte Toll-like receptor and serum surfactant protein A reveal a pathophysiological mechanism for community-acquired pneumonia in patients with type 2 diabetes.

    Science.gov (United States)

    Que, Y; Shen, X

    2016-02-01

    The lung is one of the target organs of microangiopathy in diabetes mellitus (DM); patients with type 2 diabetes mellitus (T2DM) are vulnerable to pneumonia, and a variety of pathophysiological mechanisms has been described. This study aimed to determine the pathophysiological mechanism of community-acquired pneumonia (CAP) in T2DM patients. A total of 90 individuals was included in this study comprised of three groups (n = 30): healthy control, T2DM and T2DM+ CAP groups. Toll-like receptor (TLR)2 and 4 protein and messenger RNA expression in peripheral blood monocytes(PBMC) was assessed by western blot and reverse transcription-polymerase chain reaction, respectively, and surfactant protein A (SP-A) levels were examined in serum samples by enzyme-linked immunosorbent assay. In T2DM and T2DM+CAP groups, levels of both TLR2/4 protein and mRNA in PBMC were decreased compared with controls (P <0.05), with lower levels observed in the T2DM+CAP group in comparison with T2DM patients (P <0.05). The serum SP-A levels in T2DM+CAP individuals were significantly higher than the values obtained for T2DM patients (P <0.05). It also showed apparent increases when compared with that in controls although no statistical significance was detected. In T2DM patients with pneumonia, TLR2/4 levels in PBMC and serum SP-A were altered, maybe playing an important role in the susceptibility to pneumonia in T2DM patients. © 2016 Royal Australasian College of Physicians.

  4. Vascular Adventitia Calcification and Its Underlying Mechanism.

    Directory of Open Access Journals (Sweden)

    Na Li

    Full Text Available Previous research on vascular calcification has mainly focused on the vascular intima and media. However, we show here that vascular calcification may also occur in the adventitia. The purpose of this work is to help elucidate the pathogenic mechanisms underlying vascular calcification. The calcified lesions were examined by Von Kossa staining in ApoE-/- mice which were fed high fat diets (HFD for 48 weeks and human subjects aged 60 years and older that had died of coronary heart disease, heart failure or acute renal failure. Explant cultured fibroblasts and smooth muscle cells (SMCswere obtained from rat adventitia and media, respectively. After calcification induction, cells were collected for Alizarin Red S staining. Calcified lesions were observed in the aorta adventitia and coronary artery adventitia of ApoE-/-mice, as well as in the aorta adventitia of human subjects examined. Explant culture of fibroblasts, the primary cell type comprising the adventitia, was successfully induced for calcification after incubation with TGF-β1 (20 ng/ml + mineralization media for 4 days, and the phenotype conversion vascular adventitia fibroblasts into myofibroblasts was identified. Culture of SMCs, which comprise only a small percentage of all cells in the adventitia, in calcifying medium for 14 days resulted in significant calcification.Vascular calcification can occur in the adventitia. Adventitia calcification may arise from the fibroblasts which were transformed into myofibroblasts or smooth muscle cells.

  5. Proteoglycans remodeling in cancer: Underlying molecular mechanisms.

    Science.gov (United States)

    Theocharis, Achilleas D; Karamanos, Nikos K

    2017-11-08

    Extracellular matrix is a highly dynamic macromolecular network. Proteoglycans are major components of extracellular matrix playing key roles in its structural organization and cell signaling contributing to the control of numerous normal and pathological processes. As multifunctional molecules, proteoglycans participate in various cell functions during morphogenesis, wound healing, inflammation and tumorigenesis. Their interactions with matrix effectors, cell surface receptors and enzymes enable them with unique properties. In malignancy, extensive remodeling of tumor stroma is associated with marked alterations in proteoglycans' expression and structural variability. Proteoglycans exert diverse functions in tumor stroma in a cell-specific and context-specific manner and they mainly contribute to the formation of a permissive provisional matrix for tumor growth affecting tissue organization, cell-cell and cell-matrix interactions and tumor cell signaling. Proteoglycans also modulate cancer cell phenotype and properties, the development of drug resistance and tumor stroma angiogenesis. This review summarizes the proteoglycans remodeling and their novel biological roles in malignancies with particular emphasis to the underlying molecular mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Are mechanically sensitive regulators involved in the function and (patho)physiology of cerebral palsy-related contractures?

    Science.gov (United States)

    Pingel, Jessica; Suhr, Frank

    2017-08-01

    Skeletal muscle tissue is mechanosensitive, as it is able to sense mechanical impacts and to translate these into biochemical signals making the tissue adapt. Among its mechanosensitive nature, skeletal muscle tissue is the largest metabolic organ of the human body. Disturbances in skeletal muscle mechanosensing and metabolism cause and contribute to many diseases, i.e. muscular dystrophies/myopathies, cardiovascular diseases, COPD or diabetes mellitus type 2. A less commonly focused muscle-related disorder is clinically known as muscle contractures that derive from cerebral palsy (CP) conditions in young and adults. Muscle contractures are characterized by gradually increasing passive muscle stiffness resulting in complete fixation of joints. Different mechanisms have been identified in CP-related contractures, i.e. altered calcium handling, altered metabolism or altered titin regulation. The muscle-related extracellular matrix (ECM), specifically collagens, plays a role in CP-related contractures. Herein, we focus on mechanically sensitive complexes, known as costameres (Cstms), and discuss their potential role in CP-related contractures. We extend our discussion to the ECM due to the limited knowledge of its role in CP-related contractures. The aims of this review are (1) to summarize CP-related contracture mechanisms, (2) to raise novel hypotheses on the genesis of contractures with a focus on Cstms, and (3) to stimulate novel approaches to study CP-related contractures.

  7. Mechanical behaviour of nuclear fuel under irradiation

    International Nuclear Information System (INIS)

    Guerin, Y.

    1985-01-01

    The main mechanical properties (fracture, thermal and irradiation creep) of oxide and carbide fuels are summarised and discussed. Some examples are given of the influence of these mechanical properties on the in-pile behaviour of fuel pins [fr

  8. Obesity and asthma: Pathophysiology and implications for diagnosis and management in primary care

    OpenAIRE

    Mohanan, Sveta; Tapp, Hazel; McWilliams, Andrew; Dulin, Michael

    2014-01-01

    The effects of obesity on asthma diagnosis, control, and exacerbation severity are increasingly recognized; however, the underlying pathophysiology of this association is poorly understood. Mainstream clinical practice has yet to adopt aggressive management of obesity as a modifiable risk factor in asthma care, as is the case with a risk factor like tobacco or allergen exposure. This review summarizes existing data that support the pathophysiologic mechanisms underlying the association betwee...

  9. Are mechanically sensitive regulators involved in the function and (patho)physiology of cerebral palsy-related contractures?

    DEFF Research Database (Denmark)

    Pingel, Jessica; Suhr, Frank

    2017-01-01

    mechanosensing and metabolism cause and contribute to many diseases, i.e. muscular dystrophies/myopathies, cardiovascular diseases, COPD or diabetes mellitus type 2. A less commonly focused muscle-related disorder is clinically known as muscle contractures that derive from cerebral palsy (CP) conditions in young...... and adults. Muscle contractures are characterized by gradually increasing passive muscle stiffness resulting in complete fixation of joints. Different mechanisms have been identified in CP-related contractures, i.e. altered calcium handling, altered metabolism or altered titin regulation. The muscle......Skeletal muscle tissue is mechanosensitive, as it is able to sense mechanical impacts and to translate these into biochemical signals making the tissue adapt. Among its mechanosensitive nature, skeletal muscle tissue is the largest metabolic organ of the human body. Disturbances in skeletal muscle...

  10. The Gut-Brain Axis, Including the Microbiome, Leaky Gut and Bacterial Translocation: Mechanisms and Pathophysiological Role in Alzheimer's Disease.

    Science.gov (United States)

    Köhler, Cristiano A; Maes, Michael; Slyepchenko, Anastasiya; Berk, Michael; Solmi, Marco; Lanctôt, Krista L; Carvalho, André F

    2016-01-01

    Alzheimer's disease (AD), the most common form of dementia, is a progressive disorder manifested by gradual memory loss and subsequent impairment in mental and behavioral functions. Though the primary risk factor for AD is advancing age, other factors such as diabetes mellitus, hyperlipidemia, obesity, vascular factors and depression play a role in its pathogenesis. The human gastrointestinal tract has a diverse commensal microbial population, which has bidirectional interactions with the human host that are symbiotic in health, and in addition to nutrition, digestion, plays major roles in inflammation and immunity. The most prevalent hypothesis for AD is the amyloid hypothesis, which states that changes in the proteolytic processing of the amyloid precursor protein leads to the accumulation of the amyloid beta (Aβ) peptide. Aβ then triggers an immune response that drives neuroinflammation and neurodegeneration in AD. The specific role of gut microbiota in modulating neuro-immune functions well beyond the gastrointestinal tract may constitute an important influence on the process of neurodegeneration. We first review the main mechanisms involved in AD physiopathology. Then, we review the alterations in gut microbiota and gut-brain axis that might be relevant to mediate or otherwise affect AD pathogenesis, especially those associated with aging. We finally summarize possible mechanisms that could mediate the involvement of gut-brain axis in AD physiopathology, and propose an integrative model.

  11. Unravelling Endogenous MicroRNA System Dysfunction as a New Pathophysiological Mechanism in Machado-Joseph Disease.

    Science.gov (United States)

    Carmona, Vitor; Cunha-Santos, Janete; Onofre, Isabel; Simões, Ana Teresa; Vijayakumar, Udaya; Davidson, Beverly L; Pereira de Almeida, Luís

    2017-04-05

    Machado-Joseph disease (MJD) is a genetic neurodegenerative disease caused by an expanded polyglutamine tract within the protein ataxin-3 (ATXN3). Despite current efforts, MJD's mechanism of pathogenesis remains unclear and no disease-modifying treatment is available. Therefore, in this study, we investigated (1) the role of the 3' UTR of ATXN3, a putative microRNA (miRNA) target, (2) whether miRNA biogenesis and machinery are dysfunctional in MJD, and (3) which specific miRNAs target ATXN3-3' UTR and whether they can alleviate MJD neuropathology in vivo. Our results demonstrate that endogenous miRNAs, by targeting sequences in the 3' UTR, robustly reduce ATXN3 expression and aggregation in vitro and neurodegeneration and neuroinflammation in vivo. Importantly, we found an abnormal MJD-associated downregulation of genes involved in miRNA biogenesis and silencing activity. Finally, we identified three miRNAs-mir-9, mir-181a, and mir-494-that interact with the ATXN3-3' UTR and whose expression is dysregulated in human MJD neurons and in other MJD cell and animal models. Furthermore, overexpression of these miRNAs in mice resulted in reduction of mutATXN3 levels, aggregate counts, and neuronal dysfunction. Altogether, these findings indicate that endogenous miRNAs and the 3' UTR of ATXN3 play a crucial role in MJD pathogenesis and provide a promising opportunity for MJD treatment. Copyright © 2017 The American Society of Gene and Cell Therapy. All rights reserved.

  12. Pathophysiology of nocturnal enuresis

    DEFF Research Database (Denmark)

    Rittig, Søren; Kamperis, Konstantinos

    2015-01-01

    overactivity, or a defect intrinsic circadian control of bladder function. The role of sleep is currently under scrutiny as recent evidence point towards poor sleep with increased sleep fragmentation, arousal index, and periodic limb movements as important factors. One unifying pathophysiologic theory suggests...... vasopressin levels and renal factors such as increased GFR and solute excretion (e.g. sodium) as well as increased prostaglandin PGE2 excretion. Furthermore, nocturnal polyuria has been associated with poor sleep (e.g. sleep fragmentation) and increased nocturnal arterial blood pressure levels. Another...... important part of enuresis pathogenesis is reduced bladder capacity, either during night-time only or present during daytime also (i.e. reduced MVV on a FV chart). The background behind the reduced nocturnal reservoir function is not fully clarified but may involve CNS regulatory centers, detrusor...

  13. An investigation into the mechanism underlying enhanced ...

    African Journals Online (AJOL)

    The solubilisation of primary sewage sludge under sulphate reducing conditions was conducted in controlled flask studies and previously reported findings of enhanced hydrolysis were confirmed. The maximum percentage solubilisation obtained in this study over a 10-day period was 31% and 64% for the methanogenic ...

  14. The lethality test used for estimating the potency of antivenoms against Bothrops asper snake venom: pathophysiological mechanisms, prophylactic analgesia, and a surrogate in vitro assay.

    Science.gov (United States)

    Chacón, Francisco; Oviedo, Andrea; Escalante, Teresa; Solano, Gabriela; Rucavado, Alexandra; Gutiérrez, José María

    2015-01-01

    The potency of antivenoms is assessed by analyzing the neutralization of venom-induced lethality, and is expressed as the Median Effective Dose (ED50). The present study was designed to investigate the pathophysiological mechanisms responsible for lethality induced by the venom of Bothrops asper, in the experimental conditions used for the evaluation of the neutralizing potency of antivenoms. Mice injected with 4 LD50s of venom by the intraperitoneal route died within ∼25 min with drastic alterations in the abdominal organs, characterized by hemorrhage, increment in plasma extravasation, and hemoconcentration, thus leading to hypovolemia and cardiovascular collapse. Snake venom metalloproteinases (SVMPs) play a predominat role in lethality, as judged by partial inhibition by the chelating agent CaNa2EDTA. When venom was mixed with antivenom, there was a venom/antivenom ratio at which hemorrhage was significantly reduced, but mice died at later time intervals with evident hemoconcentration, indicating that other components in addition to SVMPs also contribute to plasma extravasation and lethality. Pretreatment with the analgesic tramadol did not affect the outcome of the neutralization test, thus suggesting that prophylactic (precautionary) analgesia can be introduced in this assay. Neutralization of lethality in mice correlated with neutralization of in vitro coagulant activity in human plasma. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Supersymmetric quantum mechanics under point singularities

    International Nuclear Information System (INIS)

    Uchino, Takashi; Tsutsui, Izumi

    2003-01-01

    We provide a systematic study on the possibility of supersymmetry (SUSY) for one-dimensional quantum mechanical systems consisting of a pair of lines R or intervals [-l, l] each having a point singularity. We consider the most general singularities and walls (boundaries) at x = ±l admitted quantum mechanically, using a U(2) family of parameters to specify one singularity and similarly a U(1) family of parameters to specify one wall. With these parameter freedoms, we find that for a certain subfamily the line systems acquire an N = 1 SUSY which can be enhanced to N = 4 if the parameters are further tuned, and that these SUSY are generically broken except for a special case. The interval systems, on the other hand, can accommodate N = 2 or N = 4 SUSY, broken or unbroken, and exhibit a rich variety of (degenerate) spectra. Our SUSY systems include the familiar SUSY systems with the Dirac δ(x)-potential, and hence are extensions of the known SUSY quantum mechanics to those with general point singularities and walls. The self-adjointness of the supercharge in relation to the self-adjointness of the Hamiltonian is also discussed

  16. An update on oxidative stress-mediated organ pathophysiology.

    Science.gov (United States)

    Rashid, Kahkashan; Sinha, Krishnendu; Sil, Parames C

    2013-12-01

    Exposure to environmental pollutants and drugs can result in pathophysiological situations in the body. Research in this area is essential as the knowledge on cellular survival and death would help in designing effective therapeutic strategies that are needed for the maintenance of the normal physiological functions of the body. In this regard, naturally occurring bio-molecules can be considered as potential therapeutic targets as they are normally available in commonly consumed foodstuffs and are thought to have minimum side effects. This review article describes the detailed mechanisms of oxidative stress-mediated organ pathophysiology and the ultimate fate of the cells either to survive or to undergo necrotic or apoptotic death. The mechanisms underlying the beneficial role of a number of naturally occurring bioactive molecules in oxidative stress-mediated organ pathophysiology have also been included in the review. The review provides useful information about the recent progress in understanding the mechanism(s) of various types of organ pathophysiology, the complex cross-talk between these pathways, as well as their modulation in stressed conditions. Additionally, it suggests possible therapeutic applications of a number of naturally occurring bioactive molecules in conditions involving oxidative stress. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Pathophysiological mechanisms in antiphospholipid syndrome

    Science.gov (United States)

    Harper, Brock E; Wills, Rohan; Pierangeli, Silvia S

    2013-01-01

    Antiphospholipid syndrome is a systemic autoimmune disease associated with thrombosis and recurrent fetal loss in the setting of detectable antiphospholipid (aPL) antibodies. The major antigenic target has been identifed as β2-glycoprotein I (β2GPI), which mediates binding of aPL antibodies to target cells including endothelial cells, monocytes, platelets and trophoblasts, leading to prothrombotic and proinfammatory changes that ultimately result in thrombosis and fetal loss. This article summarizes recent insights into the role of β2GPI in normal hemostasis, interactions between aPL antibodies, β2GPI and cell-surface molecules, molecular prothrombotic and proinfammatory changes induced by aPL antibodies and pathogenic changes leading to fetal loss in antiphospholipid syndrome. New directions in therapy using these insights are examined. PMID:23487578

  18. Polymers under mechanical stress- an NMR investigation

    Energy Technology Data Exchange (ETDEWEB)

    Boehme, Ute; Scheler, Ulrich [Leibniz Institute of Polymer Research Dresden (Germany); Xu, Bo; Leisen, Johannes; Beckham, Haskell W. [Georgia Institute of Technology, Atlanta, Georgia (United States)

    2010-07-01

    Low-field NMR using permanent magnets in Halbach arrangements permit NMR investigation without the limits present in high-field NMR. The lower field in conjunction with confined stray field permit the application of NMR, in particular relaxation NMR in a stretching apparatus and a rheometer. Crystalline and amorphous fraction of semi-crystalline polymers are distinguished by their transverse relaxation times. Upon mechanical load the relaxation times of the amorphous fraction changes as seen in in-situ measurements on polypropylene rods. During the formation of a neck the crystalline fraction becomes more prominent.

  19. Mechanisms Underlying Sex Differences in Cannabis Use.

    Science.gov (United States)

    Calakos, Katina C; Bhatt, Shivani; Foster, Dawn W; Cosgrove, Kelly P

    2017-12-01

    Cannabis is the most commonly used illicit substance worldwide. In recent decades, highly concentrated products have flooded the market, and prevalence rates have increased. Gender differences exist in cannabis use, as men have higher prevalence of both cannabis use and cannabis use disorder (CUD), while women progress more rapidly from first use to CUD. This paper reviews findings from preclinical and human studies examining the sex-specific neurobiological underpinnings of cannabis use and CUD, and associations with psychiatric symptoms. Sex differences exist in the endocannabinoid system, in cannabis exposure effects on brain structure and function, and in the co-occurrence of cannabis use with symptoms of anxiety, depression and schizophrenia. In female cannabis users, anxiety symptoms correlate with larger amygdala volume and social anxiety disorder symptoms correlate with CUD symptoms. Female cannabis users are reported to be especially vulnerable to earlier onset of schizophrenia, and mixed trends emerge in the correlation of depressive symptoms with cannabis exposure in females and males. As prevalence of cannabis use may continue to increase given the shifting policy landscape regarding marijuana laws, understanding the neurobiological mechanisms of cannabis exposure in females and males is key. Examining these mechanisms may help inform future research on sex-specific pharmacological and behavioral interventions for women and men with high-risk cannabis use, comorbid psychiatric disease, and CUD.

  20. Habitats under Mechanical and Herbicide Management Regimes

    Directory of Open Access Journals (Sweden)

    Wendy-Ann P. Isaac

    2012-01-01

    Full Text Available Commelina diffusa is a colonising species of banana orchard habitats in St. Vincent in the Windward Islands of the Caribbean. In the present study, the population dynamics of C. diffusa were investigated in response to mechanical weed management with either a rotary string trimmer or glufosinate in ruderal and banana habitats. The study focused on density and size distribution of the weed over time and their response to two weed management strategies. The population dynamics of C. diffusa differed between the two habitats. Seedling establishment appeared to be an important factor influencing the dynamics of C. diffusa in banana orchards as there was little recruitment of seeds with less flower production compared with ruderal habitats where plants produced more flowers. Plants of C. diffusa in the banana orchard habitat had a longer growth cycle. In the banana orchard habitat, the C. diffusa population was greater and the plants were shorter with mechanical management than in areas treated with glufosinate. The results suggest that it is possible to manipulate the dynamics of C. diffusa in banana orchards as there is less chance of seed recruitment. Further research is necessary to refine an IPM approach for the management of C. diffusa.

  1. Physical and chemical mechanisms underlying hematoma evolution

    International Nuclear Information System (INIS)

    Cho, K.J.; Fanders, B.L.; Smid, A.R.; McLaughlin, P.

    1986-01-01

    Angiostat, a new collagen embolic material supplied at a concentration of 35 mg/ml (Target Therapeutics, Los Angeles) was used for flow-directed hepatic artery embolization in a series of rabbits to examine its acute effects on hepatic microcirculation. Arteriograms were obtained both before and after embolization. The aorta and portal vein were perfused with two different colors of Microfil after the animals were killed,. Cleared liver specimens were examined under a dissection microscope. Extent of dearterialization, status of portal sinusoidal perfusion, and collateral formation after embolization with Angiostat were evaluated. Results will be compared with results achieved using other liquid and particulate embolic agents

  2. Environmental genotoxicity: Probing the underlying mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Shugart, L. [Oak Ridge National Lab., TN (United States); Theodorakis, C. [Tennessee Univ., Knoxville, TN (United States)

    1993-12-31

    Environmental pollution is a complex issue because of the diversity of anthropogenic agents, both chemical and physical, that have been detected and catalogued. The consequences to biota from exposure to genotoxic agents present an additional problem because of the potential for these agents to produce adverse change at the cellular and organismal levels. Past studies in genetic toxicology at the Oak Ridge National Laboratory have focused on structural damage to the DNA of environmental species that may occur after exposure to genotoxic agents and the use of this information to document exposure and to monitor remediation. In an effort to predict effects at the population, community and ecosystem levels, current studies in genetic ecotoxicology are attempting to characterize the biological mechanisms at the gene level that regulate and limit the response of an individual organism to genotoxic factors in their environment.

  3. Physiological mechanisms underlying animal social behaviour.

    Science.gov (United States)

    Seebacher, Frank; Krause, Jens

    2017-08-19

    Many species of animal live in groups, and the group represents the organizational level within which ecological and evolutionary processes occur. Understanding these processes, therefore, relies on knowledge of the mechanisms that permit or constrain group formation. We suggest that physiological capacities and differences in physiology between individuals modify fission-fusion dynamics. Differences between individuals in locomotor capacity and metabolism may lead to fission of groups and sorting of individuals into groups with similar physiological phenotypes. Environmental impacts such as hypoxia can influence maximum group sizes and structure in fish schools by altering access to oxygenated water. The nutritional environment determines group cohesion, and the increase in information collected by the group means that individuals should rely more on social information and form more cohesive groups in uncertain environments. Changing environmental contexts require rapid responses by individuals to maintain group coordination, which are mediated by neuroendocrine signalling systems such as nonapeptides and steroid hormones. Brain processing capacity may constrain social complexity by limiting information processing. Failure to evaluate socially relevant information correctly limits social interactions, which is seen, for example, in autism. Hence, functioning of a group relies to a large extent on the perception and appropriate processing of signals from conspecifics. Many if not all physiological systems are mechanistically linked, and therefore have synergistic effects on social behaviour. A challenge for the future lies in understanding these interactive effects, which will improve understanding of group dynamics, particularly in changing environments.This article is part of the themed issue 'Physiological determinants of social behaviour in animals'. © 2017 The Author(s).

  4. The role of autoantibodies in the pathophysiology of rheumatoid arthritis.

    Science.gov (United States)

    Derksen, V F A M; Huizinga, T W J; van der Woude, D

    2017-06-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation. The presence of autoantibodies in the sera of RA patients has provided many clues to the underlying disease pathophysiology. Based on the presence of several autoantibodies like rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), anti-carbamylated protein antibodies (anti-CarP), and more recently anti-acetylated protein antibodies RA can be subdivided into seropositive and seronegative disease. The formation of these autoantibodies is associated with both genetic and environmental risk factors for RA, like specific human leukocyte antigen (HLA) alleles and smoking. Autoantibodies can be detected many years before disease onset in a subset of patients, suggesting a sequence of events in which the first autoantibodies develop in predisposed hosts, before an inflammatory response ensues leading to clinically apparent arthritis. Research on the characteristics and effector functions of these autoantibodies might provide more insight in pathophysiological processes underlying arthritis in RA. Recent data suggests that ACPA might play a role in perpetuating inflammation once it has developed. Furthermore, pathophysiological mechanisms have been discovered supporting a direct link between the presence of ACPA and both bone erosions and pain in RA patients. In conclusion, investigating the possible pathogenic potential of autoantibodies might lead to improved understanding of the underlying pathophysiological processes in rheumatoid arthritis.

  5. Saturation diving; physiology and pathophysiology.

    Science.gov (United States)

    Brubakk, Alf O; Ross, John A S; Thom, Stephen R

    2014-07-01

    . Furthermore, divers who are required to return to the surface quickly are under higher risk of serious injury as no adequate decompression procedures for such situations are available. Decompression also leads to the production of endothelial microparticles that may reduce endothelial function. As good endothelial function is a documented indicator of health that can be influenced by regular exercise, regular physical exercise is recommended for saturation divers. Nowadays, saturation diving is a reasonably safe and well controlled method for working under water. Until now, no long-term impact on health due to diving has been documented. However, we still have limited knowledge about the pathophysiologic mechanisms involved. In particular we know little about the effect of long exposure to hyperoxia and microparticles on the endothelium. © 2014 American Physiological Society.

  6. Modulation of MicroRNAs by Phytochemicals in Cancer: Underlying Mechanisms and Translational Significance

    Science.gov (United States)

    Srivastava, Sanjeev K.; Arora, Sumit; Averett, Courey; Singh, Ajay P.

    2015-01-01

    MicroRNAs (miRNAs) are small, endogenous noncoding RNAs that regulate a variety of biological processes such as differentiation, development, and survival. Recent studies suggest that miRNAs are dysregulated in cancer and play critical roles in cancer initiation, progression, and chemoresistance. Therefore, exploitation of miRNAs as targets for cancer prevention and therapy could be a promising approach. Extensive evidence suggests that many naturally occurring phytochemicals regulate the expression of numerous miRNAs involved in the pathobiology of cancer. Therefore, an understanding of the regulation of miRNAs by phytochemicals in cancer, their underlying molecular mechanisms, and functional consequences on tumor pathophysiology may be useful in formulating novel strategies to combat this devastating disease. These aspects are discussed in this review paper with an objective of highlighting the significance of these observations from the translational standpoint. PMID:25853141

  7. Cell volume regulation: physiology and pathophysiology

    DEFF Research Database (Denmark)

    Lambert, I H; Hoffmann, E K; Pedersen, Stine Helene Falsig

    2008-01-01

    not only under physiological conditions, e.g. following accumulation of nutrients, during epithelial absorption/secretion processes, following hormonal/autocrine stimulation, and during induction of apoptosis, but also under pathophysiological conditions, e.g. hypoxia, ischaemia and hyponatremia....../hypernatremia. On the other hand, it has recently become clear that an increase or reduction in cell volume can also serve as a specific signal in the regulation of physiological processes such as transepithelial transport, cell migration, proliferation and death. Although the mechanisms by which cell volume perturbations...... are sensed are still far from clear, significant progress has been made with respect to the nature of the sensors, transducers and effectors that convert a change in cell volume into a physiological response. In the present review, we summarize recent major developments in the field, and emphasize...

  8. A model-based approach to investigating the pathophysiological mechanisms of hypertension and response to antihypertensive therapies: extending the Guyton model.

    Science.gov (United States)

    Hallow, K Melissa; Lo, Arthur; Beh, Jeni; Rodrigo, Manoj; Ermakov, Sergey; Friedman, Stuart; de Leon, Hector; Sarkar, Anamika; Xiong, Yuan; Sarangapani, Ramesh; Schmidt, Henning; Webb, Randy; Kondic, Anna Georgieva

    2014-05-01

    Reproducibly differential responses to different classes of antihypertensive agents are observed among hypertensive patients and may be due to interindividual differences in hypertension pathology. Computational models provide a tool for investigating the impact of underlying disease mechanisms on the response to antihypertensive therapies with different mechanisms of action. We present the development, calibration, validation, and application of an extension of the Guyton/Karaaslan model of blood pressure regulation. The model incorporates a detailed submodel of the renin-angiotensin-aldosterone system (RAAS), allowing therapies that target different parts of this pathway to be distinguished. Literature data on RAAS biomarker and blood pressure responses to different classes of therapies were used to refine the physiological actions of ANG II and aldosterone on renin secretion, renal vascular resistance, and sodium reabsorption. The calibrated model was able to accurately reproduce the RAAS biomarker and blood pressure responses to combinations of dual-RAAS agents, as well as RAAS therapies in combination with diuretics or calcium channel blockers. The final model was used to explore the impact of underlying mechanisms of hypertension on the blood pressure response to different classes of antihypertensive agents. Simulations indicate that the underlying etiology of hypertension can impact the magnitude of response to a given class of therapy, making a patient more sensitive to one class and less sensitive others. Given that hypertension is usually the result of multiple mechanisms, rather than a single factor, these findings yield insight into why combination therapy is often required to adequately control blood pressure.

  9. Pathophysiology of overactive bladder.

    Science.gov (United States)

    Banakhar, Mai A; Al-Shaiji, Tariq F; Hassouna, Magdy M

    2012-08-01

    Overactive bladder (OAB) is a common disorder that negatively affects the quality of life of our patients and carries a large socioeconomic burden. According to the International Continence Society, it is characterized as urinary urgency, with or without urge incontinence, usually, with frequency and nocturia in the absence of causative infection. The pathophysiology of this disease entity varies between neurogenic, myogenic, or idiopathic factors. This paper provides a review of the contemporary theories behind the pathophysiology of OAB.

  10. [Pathophysiology of overuse tendon injury].

    Science.gov (United States)

    Kannus, P; Paavola, M; Paakkala, T; Parkkari, J; Järvinen, T; Järvinen, M

    2002-10-01

    Overuse tendon injury is one of the most common injuries in sports. The etiology as well as the pathophysiological mechanisms leading to tendinopathy are of crucial medical importance. At the moment intrinsic and extrinsic factors are assumed as mechanisms of overuse tendon injury. Except for the acute, extrinsic trauma, the chronic overuse tendon injury is a multifactorial process. There are many other factors, such as local hypoxia, less of nutrition, impaired metabolism and local inflammatory that may also contribute to the development of tissue damage. The exact interaction of these factors cannot be explained entirely at the moment. Further studies will be necessary in order to get more information.

  11. Mechanisms underlying epithelium-dependent relaxation in rat bronchioles

    DEFF Research Database (Denmark)

    Kroigaard, Christel; Dalsgaard, Thomas; Simonsen, Ulf

    2010-01-01

    This study investigated the mechanisms underlying epithelium-derived hyperpolarizing factor (EpDHF)-type relaxation in rat bronchioles. Immunohistochemistry was performed, and rat bronchioles and pulmonary arteries were mounted in microvascular myographs for functional studies. An opener of small...

  12. Underlying Mechanisms of Improving Physical Activity Behavior after Rehabilitation

    NARCIS (Netherlands)

    van der Ploeg, Hidde P.; Streppel, Kitty R.M.; van der Beek, Allard J.; Woude, Luc H.V.; van Harten, Willem H.; Vollenbroek-Hutten, Miriam Marie Rosé; van Mechelen, Willem

    2008-01-01

    Background: Regular physical activity is beneficial for the health and functioning of people with a disability. Effective components of successful physical activity promotion interventions should be identified and disseminated. Purpose: To study the underlying mechanisms of the combined sport

  13. Stress analysis in a functionally graded disc under mechanical loads ...

    Indian Academy of Sciences (India)

    Stress analysis in a functionally graded disc under mechanical loads and a steady state temperature distribution. HASAN ÇALLIO ˘GLU. Department of Mechanical Engineering, Pamukkale University, 20070,. Denizli, Turkey e-mail: hcallioglu@pau.edu.tr. MS received 25 November 2009; revised 12 August 2010; accepted.

  14. Obstructive sleep apnea and dyslipidemia: evidence and underlying mechanism.

    Science.gov (United States)

    Adedayo, Ajibola Monsur; Olafiranye, Oladipupo; Smith, David; Hill, Alethea; Zizi, Ferdinand; Brown, Clinton; Jean-Louis, Girardin

    2014-03-01

    Over the past half century, evidence has been accumulating on the emergence of obstructive sleep apnea (OSA), the most prevalent sleep-disordered breathing, as a major risk factor for cardiovascular disease. A significant body of research has been focused on elucidating the complex interplay between OSA and cardiovascular risk factors, including dyslipidemia, obesity, hypertension, and diabetes mellitus that portend increased morbidity and mortality in susceptible individuals. Although a clear causal relationship of OSA and dyslipidemia is yet to be demonstrated, there is increasing evidence that chronic intermittent hypoxia, a major component of OSA, is independently associated and possibly the root cause of the dyslipidemia via the generation of stearoyl-coenzyme A desaturase-1 and reactive oxygen species, peroxidation of lipids, and sympathetic system dysfunction. The aim of this review is to highlight the relationship between OSA and dyslipidemia in the development of atherosclerosis and present the pathophysiologic mechanisms linking its association to clinical disease. Issues relating to epidemiology, confounding factors, significant gaps in research and future directions are also discussed.

  15. Mechanisms underlying the nociceptive responses induced by platelet-activating factor (PAF) in the rat paw.

    Science.gov (United States)

    Marotta, Denise M; Costa, Robson; Motta, Emerson M; Fernandes, Elizabeth S; Medeiros, Rodrigo; Quintão, Nara L M; Campos, Maria M; Calixto, João B

    2009-04-01

    Platelet-activating factor (PAF) is an inflammatory mediator widely known to exert relevant pathophysiological functions. However, the relevance of PAF in nociception has received much less attention. Herein, we have investigated the mechanisms underlying PAF-induced spontaneous nociception and mechanical hypersensitivity in the rat paw. PAF injection (1- 30 nmol/paw) resulted in a dose-related overt nociception, whilst only the dose of 10 nmol/ paw produced a significant and time-related mechanical hypersensitivity. Local coinjection of PAF antagonist WEB2086 significantly inhibited both spontaneous nociception and mechanical hypersensitivity. Moreover, the coinjection of the natural IL-1beta receptor antagonist (IRA) notably prevented both PAF-induced nociceptive responses, whilst these responses were not altered by anti-TNFalpha coinjection. Interestingly, pretreatment with the ultrapotent vaniloid agonist resiniferotoxin, coinjection of the TRPV1 receptor antagonist SB366791, or mast cell depletion with compound 48/80 markedly prevented PAF-induced spontaneous nociception. Conversely, PAF-elicited mechanical hypersensitivity was strikingly susceptible to distinct antineutrophil-related strategies, namely the antineutrophil antibody, the selectin blocker fucoidin, the chemokine CXCR2 receptor antagonist SB225002, and the C5a receptor antibody anti-CD88. Notably, the same antineutrophil migration strategies significantly prevented the increase of myeloperoxidase activity induced by PAF. The mechanical hypersensitivity caused by PAF was also prevented by the cyclooxygenase inhibitors indomethacin or celecoxib, and by the selective beta(1) adrenergic receptor antagonist atenolol. Collectively, the present results provide consistent evidence indicating that distinct mechanisms are involved in the spontaneous nociception and mechanical hypersensitivity caused by PAF. They also support the concept that selective PAF receptor antagonists might constitute interesting

  16. The possible role of gastrointestinal endocrine cells in the pathophysiology of irritable bowel syndrome.

    Science.gov (United States)

    El-Salhy, Magdy; Hausken, Trygve; Gilja, Odd Helge; Hatlebakk, Jan Gunnar

    2017-02-01

    The etiology of irritable bowel syndrome (IBS) is unknown, but several factors appear to play a role in its pathophysiology, including abnormalities of the gastrointestinal endocrine cells. The present review illuminates the possible role of gastrointestinal hormones in the pathophysiology of IBS and the possibility of utilizing the current knowledge in treating the disease. Areas covered: Research into the intestinal endocrine cells and their possible role in the pathophysiology of IBS is discussed. Furthermore, the mechanisms underlying the abnormalities in the gastrointestinal endocrine cells in IBS patients are revealed. Expert commentary: The abnormalities observed in the gastrointestinal endocrine cells in IBS patients explains their visceral hypersensitivity, gastrointestinal dysmotility, and abnormal intestinal secretion, as well as the interchangeability of symptoms over time. Clarifying the role of the intestinal stem cells in the pathophysiology of IBS may lead to new treatment methods for IBS.

  17. [Etiology and pathophysiology of fibromyalgia syndrome].

    Science.gov (United States)

    Sommer, C; Häuser, W; Burgmer, M; Engelhardt, R; Gerhold, K; Petzke, F; Schmidt-Wilcke, T; Späth, M; Tölle, T; Uçeyler, N; Wang, H; Winkelmann, A; Thieme, K

    2012-06-01

    The scheduled update to the German S3 guidelines on fibromyalgia syndrome (FMS) by the Association of the Scientific Medical Societies ("Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften", AWMF; registration number 041/004) was planned starting in March 2011. The development of the guidelines was coordinated by the German Interdisciplinary Association for Pain Therapy ("Deutsche Interdisziplinären Vereinigung für Schmerztherapie", DIVS), 9 scientific medical societies and 2 patient self-help organizations. Eight working groups with a total of 50 members were evenly balanced in terms of gender, medical field, potential conflicts of interest and hierarchical position in the medical and scientific fields. Literature searches were performed using the Medline, PsycInfo, Scopus and Cochrane Library databases (until December 2010). The grading of the strength of the evidence followed the scheme of the Oxford Centre for Evidence-Based Medicine. Current data do not identify distinct etiologic or pathophysiological factors mediating development of FMS. The development of FMS is associated with inflammatory rheumatic diseases (EL2b), with gene polymorphisms of the 5-hydroxytryptamine (HT)(2) receptor (EL3a), lifestyle factors (smoking, obesity, lack of physical activity; EL2b), physical and sexual abuse in childhood and adulthood (EL3a). FMS is most likely the result of various pathogenetic factors and pathophysiological mechanisms. The English full-text version of this article is available at SpringerLink (under "Supplemental").

  18. Amount of fear extinction changes its underlying mechanisms.

    Science.gov (United States)

    An, Bobae; Kim, Jihye; Park, Kyungjoon; Lee, Sukwon; Song, Sukwoon; Choi, Sukwoo

    2017-07-03

    There has been a longstanding debate on whether original fear memory is inhibited or erased after extinction. One possibility that reconciles this uncertainty is that the inhibition and erasure mechanisms are engaged in different phases (early or late) of extinction. In this study, using single-session extinction training and its repetition (multiple-session extinction training), we investigated the inhibition and erasure mechanisms in the prefrontal cortex and amygdala of rats, where neural circuits underlying extinction reside. The inhibition mechanism was prevalent with single-session extinction training but faded when single-session extinction training was repeated. In contrast, the erasure mechanism became prevalent when single-session extinction training was repeated. Moreover, ablating the intercalated neurons of amygdala, which are responsible for maintaining extinction-induced inhibition, was no longer effective in multiple-session extinction training. We propose that the inhibition mechanism operates primarily in the early phase of extinction training, and the erasure mechanism takes over after that.

  19. Constipation: Pathophysiology and Current Therapeutic Approaches.

    Science.gov (United States)

    Sharma, Amol; Rao, Satish

    2017-01-01

    Chronic constipation is a common, persistent condition affecting many patients worldwide, presenting significant economic burden and resulting in substantial healthcare utilization. In addition to infrequent bowel movements, the definition of constipation includes excessive straining, a sense of incomplete evacuation, failed or lengthy attempts to defecate, use of digital manoeuvres for evacuation of stool, abdominal bloating, and hard consistency of stools. After excluding secondary causes of constipation, chronic idiopathic or primary constipation can be classified as functional defecation disorder, slow-transit constipation (STC), and constipation-predominant irritable bowel syndrome (IBS-C). These classifications are not mutually exclusive and significant overlap exists. Initial therapeutic approach to primary constipation, regardless of aetiology, consists of diet and lifestyle changes such as encouraging adequate fluid and fibre intake, regular exercise, and dietary modification. Laxatives are the mainstay of pharmacologic treatment for potential long-term therapy in patients who do not respond to lifestyle or dietary modification. After a failed empiric trial of laxatives, diagnostic testing is necessary to understand underlying anorectal and/or colonic pathophysiology. No single test provides a comprehensive assessment for primary constipation; therefore, multiple tests are used to provide complementary information to one another. Dyssynergic defecation, a functional defecation disorder, is an acquired behavioural disorder of defecation present in two-thirds of adult patients, where an inability to coordinate the abdominal, recto-anal, and pelvic floor muscles during attempted defecation exists. Biofeedback therapy is the mainstay treatment for dyssynergic defecation aimed at improving coordination of abdominal and anorectal muscles. A large percentage of patients with dyssynergic defecation also exhibit rectal hyposensitivity and may benefit from the

  20. Pathophysiology of migraine

    Directory of Open Access Journals (Sweden)

    Peter J Goadsby

    2012-01-01

    Full Text Available Migraine is a common disabling brain disorder whose pathophysiology is now being better understood. The study of anatomy and physiology of pain producing structures in the cranium and the central nervous system modulation of the input have led to the conclusion that migraine involves alterations in the sub-cortical aminergic sensory modulatory systems that influence the brain widely.

  1. Pathophysiology of Equine Neonatal Septicemia

    Directory of Open Access Journals (Sweden)

    Juan Carlos Ospina Chirivi

    2014-07-01

    Full Text Available Neonatal septicemia is a major cause of mortality and morbidity in horses in their first seven days of life and within their pathophysiology. It is important to consider the extrinsic and intrinsic predisposing factors which make foals susceptible to agents of primarily bacterial etiology. However, other types of infectious etiology (viruses and fungi should be considered too, as well as noninfectious etiologies. The paper mentions a wide variety of mechanisms that produce different injuries that must be addressed with measures of critical neonatal care, so it is imperative for the veterinarian to know the pathogenic mechanisms of the disease, its clinical presentation and anatomo-pathological lesions. Thus, systemic inflammatory response syndrome (SIRS, multiple organ dysfunction syndrome (MODS, and peripheral circulatory collapse or shock are some of the elements defined as the pillars of the pathophysiology of neonatal septicemia, extensively studied in equine medicine. This paper presents a short review of the triggering mechanisms of neonatal septicemia highlighting the importance of epidemiological investigations in Colombia. It shows the need for retrospective and prospective studies and for divulgation of some of the preventive measures of the disease in horses.

  2. Mechanical Property Analysis of Circular Polymer Membrane under Uniform Pressure

    OpenAIRE

    Jianbing, Sang; Xiang, Li; Sufang, Xing; Wenjia, Wang

    2017-01-01

    Mechanical property analysis of circular hyperelastic polymer membrane under uniform pressure has been researched in this work. The polymer membrane material is assumed to be homogeneous and isotropic and incompressibility of materials has been considered. Based on the modified stain energy function from Gao and nonmomental theory of axial symmetry thin shell, finite deformation analysis of polymer membrane under uniform pressure has been proposed in current configuration and governing equati...

  3. Emotional responses to music: the need to consider underlying mechanisms.

    Science.gov (United States)

    Juslin, Patrik N; Västfjäll, Daniel

    2008-10-01

    Research indicates that people value music primarily because of the emotions it evokes. Yet, the notion of musical emotions remains controversial, and researchers have so far been unable to offer a satisfactory account of such emotions. We argue that the study of musical emotions has suffered from a neglect of underlying mechanisms. Specifically, researchers have studied musical emotions without regard to how they were evoked, or have assumed that the emotions must be based on the "default" mechanism for emotion induction, a cognitive appraisal. Here, we present a novel theoretical framework featuring six additional mechanisms through which music listening may induce emotions: (1) brain stem reflexes, (2) evaluative conditioning, (3) emotional contagion, (4) visual imagery, (5) episodic memory, and (6) musical expectancy. We propose that these mechanisms differ regarding such characteristics as their information focus, ontogenetic development, key brain regions, cultural impact, induction speed, degree of volitional influence, modularity, and dependence on musical structure. By synthesizing theory and findings from different domains, we are able to provide the first set of hypotheses that can help researchers to distinguish among the mechanisms. We show that failure to control for the underlying mechanism may lead to inconsistent or non-interpretable findings. Thus, we argue that the new framework may guide future research and help to resolve previous disagreements in the field. We conclude that music evokes emotions through mechanisms that are not unique to music, and that the study of musical emotions could benefit the emotion field as a whole by providing novel paradigms for emotion induction.

  4. Preeclampsia: from Pathophysiology to Treatment

    Directory of Open Access Journals (Sweden)

    Kaculini Enton

    2016-12-01

    Full Text Available Preeclampsia is a multisystem disorder unique to human pregnancy and is its most common glomerular complication. It occurs in 2% to 8% of pregnancies and is a major contributor to maternal mortality worldwide. Although the pathophysiology of this syndrome is not fully understood, many pathogenetic mechanisms are involved in this disorder. The role of the placenta is crucial in the development of this disorder. Some pathogenetic mechanisms involved in this disease comprise defective deep placentation, autoantibodies to type-1 angiotensin II receptor, endothelial dysfunction, oxidative stress, platelet and thrombin activation, intravascular inflammation, and the imbalance between angiogenic and antiangiogenic factors which is thought to be one of the most crucial mechanisms. Further understanding of the full picture could enhance our current knowledge of the pathogenesis of preeclampsia and improve its treatment. Thus, based on specific biomarkers the diagnosis and subclassification of preeclampsia might be more accurate in identifying patients at risk, monitoring disease progression and providing effective interventions

  5. Neural mechanisms underlying cognitive inflexibility in Parkinson's disease.

    Science.gov (United States)

    Lange, Florian; Seer, Caroline; Loens, Sebastian; Wegner, Florian; Schrader, Christoph; Dressler, Dirk; Dengler, Reinhard; Kopp, Bruno

    2016-12-01

    Cognitive inflexibility is a hallmark of executive dysfunction in Parkinson's disease (PD). This deficit consistently manifests itself in a PD-related increase in the number of perseverative errors committed on the Wisconsin Card Sorting Test (WCST). However, the neural processes underlying perseverative WCST performance in PD are still largely unknown. The present study is the first to investigate the event-related potential (ERP) correlates of cognitive inflexibility on the WCST in PD patients. Thirty-two PD patients and 35 matched control participants completed a computerized version of the WCST while the electroencephalogram (EEG) was recorded. Behavioral results revealed the expected increase in perseverative errors in patients with PD. ERP analysis focused on two established indicators of executive processes: the fronto-central P3a as an index of attentional orienting and the sustained parietal positivity (SPP) as an index of set-shifting processes. In comparison to controls, P3a amplitudes were significantly attenuated in PD patients. Regression analysis further revealed that P3a and SPP amplitudes interactively contributed to the prediction of perseverative errors in PD patients: The number of perseverative errors was only increased when both ERP amplitudes were attenuated. Notably, the two ERP markers of executive processes accounted for more than 40% of the variance in perseverative errors in PD patients. We conclude that cognitive inflexibility in PD occurs when the neural bases of multiple executive processes are affected by the pathophysiology of PD. The combined measurement of P3a and SPP might yield an electrophysiological marker of cognitive inflexibility in PD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Study on Mechanical Properties of Barite Concrete under Impact Load

    Science.gov (United States)

    Chen, Z. F.; Cheng, K.; Wu, D.; Gan, Y. C.; Tao, Q. W.

    2018-03-01

    In order to research the mechanical properties of Barite concrete under impact load, a group of concrete compression tests was carried out under the impact load by using the drop test machine. A high-speed camera was used to record the failure process of the specimen during the impact process. The test results show that:with the increase of drop height, the loading rate, the peak load, the strain under peak load, the strain rate and the dynamic increase factor (DIF) all increase gradually. The ultimate tensile strain is close to each other, and the time of impact force decreases significantly, showing significant strain rate effect.

  7. Damage mechanisms in PBT-GF30 under thermo-mechanical cyclic loading

    International Nuclear Information System (INIS)

    Schaaf, A.; De Monte, M.; Hoffmann, C.; Vormwald, M.; Quaresimin, M.

    2014-01-01

    The scope of this paper is the investigation of damage mechanisms at microscopic scale on a short glass fiber reinforced polybutylene terephthalate (PBT-GF30) under thermo-mechanical cyclic loading. In addition the principal mechanisms are verified through micro mechanical FE models. In order to investigate the fatigue behavior of the material both isothermal strain controlled fatigue (ISCF) tests at three different temperatures and thermo-mechanical fatigue (TMF) tests were conducted on plain and notched specimens, manufactured by injection molding. The goal of the work is to determine the damage mechanisms occurring under TMF conditions and to compare them with the mechanisms occurring under ISCF. For this reason fracture surfaces of TMF and ISCF samples loaded at different temperature levels were analyzed using scanning electron microscopy. Furthermore, specimens that failed under TMF were examined on microsections revealing insight into both crack initiation and crack propagation. The findings of this investigation give valuable information about the main damage mechanisms of PBT-GF30 under TMF loading and serve as basis for the development of a TMF life estimation methodology

  8. Neural Circuitry and Plasticity Mechanisms Underlying Delay Eyeblink Conditioning

    Science.gov (United States)

    Freeman, John H.; Steinmetz, Adam B.

    2011-01-01

    Pavlovian eyeblink conditioning has been used extensively as a model system for examining the neural mechanisms underlying associative learning. Delay eyeblink conditioning depends on the intermediate cerebellum ipsilateral to the conditioned eye. Evidence favors a two-site plasticity model within the cerebellum with long-term depression of…

  9. New insights into pathophysiology of vestibular migraine

    Directory of Open Access Journals (Sweden)

    Juan Manuel Espinosa-Sanchez

    2015-02-01

    Full Text Available Vestibular migraine (VM is a common disorder in which genetic, epigenetic and environmental factors probably contribute to its development. The pathophysiology of VM is unknown; nevertheless in the last few years, several studies are contributing to understand the neurophysiological pathways involved in VM. The current hypotheses are mostly based on the knowledge of migraine itself. The evidence of trigeminal innervation of the labyrinth vessels and the localization of vasoactive neuropeptides in the perivascular afferent terminals of these trigeminal fibers support the involvement of the trigemino-vascular system. The neurogenic inflammation triggered by activation of the trigeminal-vestibulocochlear reflex, with the subsequent inner ear plasma protein extravasation and the release of inflammatory mediators, can contribute to a sustained activation and sensitization of the trigeminal primary afferent neurons explaining VM symptoms. The reciprocal connections between brainstem vestibular nuclei and the structures that modulate trigeminal nociceptive inputs (rostral ventromedial medulla, ventrolateral periaqueductal grey, locus coeruleus and nucleus raphe magnus are critical to understand the pathophysiology of VM. Although cortical spreading depression can affect cortical areas involved in processing vestibular information, functional neuroimaging techniques suggest a dysmodulation in the multimodal sensory integration and processing of vestibular and nociceptive information, resulting from a vestibulo-thalamo-cortical dysfunction, as the pathogenic mechanism underlying VM. The elevated prevalence of VM suggests that multiple functional variants may confer a genetic susceptibility leading to a dysregulation of excitatory-inhibitory balance in brain structures involved in the processing of sensory information, vestibular inputs and pain. The interactions among several functional and structural neural networks could explain the pathogenic

  10. The fibromyalgia syndrome: musculoskeletal pathophysiology.

    Science.gov (United States)

    Geel, S E

    1994-04-01

    Fibromyalgia (FM) is a chronic pain disorder that afflicts predominantly middle-aged women with cardinal symptoms of diffuse musculoskeletal pain, defined tender points, deprived sleep, and fatigue. The etiology and pathological mechanisms are poorly understood, and treatment approaches are largely ineffective. The clinical features of the syndrome are presented, and the relevance of muscle dysfunction in the etiopathogenesis of the disorder is explored. The evidence for involvement of muscle pathophysiology as a primary mechanism mediating the onset of symptoms is not compelling. Musculoskeletal dysfunction can be considered secondary to central abnormalities of pain modulation and altered sleep physiology precipitated by emotional stress in genetically predisposed individuals. Contemporary evidence favors treatment strategies that emphasize pain control, sleep enhancement, and a program of conditioning.

  11. A possible realization of Einstein's causal theory underlying quantum mechanics

    International Nuclear Information System (INIS)

    Yussouff, M.

    1979-06-01

    It is shown that a new microscopic mechanics formulated earlier can be looked upon as a possible causal theory underlying quantum mechanics, which removes Einstein's famous objections against quantum theory. This approach is free from objections raised against Bohm's hidden variable theory and leads to a clear physical picture in terms of familiar concepts, if self interactions are held responsible for deviations from classical behaviour. The new level of physics unfolded by this approach may reveal novel frontiers in high-energy physics. (author)

  12. Permeability and mechanical properties of cracked glass under pressure

    International Nuclear Information System (INIS)

    Ougier-Simonin, A.

    2010-01-01

    Crack initiation and growth in brittle solids under tension have been extensively studied by various experimental, theoretical and numerical approaches. If has been established that dynamic brittle fracture is related to fundamental physical parameters and processes, such as crack speed, crack branching, surface roughening, and dynamic instabilities. On the other hand, less studies have been done in the area of compressive fracture despite its vital importance in geology, material science and engineering applications (such as the improvement and the insurance of the nuclear wastes storage). The present work aims to investigate thermo-mechanical cracking effects on elastic wave velocities, mechanical strength and permeability und r pressure to evaluate damage evolution, brittle failure and transport properties on a synthetic glass (SON 68), and to highlight the very different behavior of the glass amorphous structure compared to any rock structure. The original glass, produced in ideal conditions of slow cooling that prevent from any crack formation, exhibits a linear and reversible mechanical behavior and isotropic elastic velocities, as expected. It also presents a high strength as it fails at about 700 MPa of deviatoric stress for a confining pressure of 15 MPa. We choose to apply to some original glass samples a reproducible method (thermal treatment with a thermal shock of T=100,200 and 300 C) which creates cracks with a homogeneous distribution. The impact of the thermal treatment is clearly visible through the elastic wave velocity measurements as we observe crack closure under hydrostatic conditions (at about 30 MPa). For T ≥ 200 C, the glass mechanical behavior becomes non linear and records an irreversible damage. The total damage observed with the acoustic emissions in these samples underlines the combination of the thermal and the mechanical cracks which drive to the sample failure. The results obtained with pore fluid pressure show a very small

  13. Frictional behaviour of polymer films under mechanical and electrostatic loads

    International Nuclear Information System (INIS)

    Ginés, R; Christen, R; Motavalli, M; Bergamini, A; Ermanni, P

    2013-01-01

    Different polymer foils, namely polyimide, FEP, PFA and PVDF were tested on a setup designed to measure the static coefficient of friction between them. The setup was designed according to the requirements of a damping device based on electrostatically tunable friction. The foils were tested under different mechanically applied forces and showed reproducible results for the static coefficient of friction. With the same setup the measurements were performed under an electric field as the source of the normal force. Up to a certain electric field the values were in good agreement. Beyond this field discrepancies were found. (paper)

  14. Reliability Issues and Solutions in Flexible Electronics Under Mechanical Fatigue

    Science.gov (United States)

    Yi, Seol-Min; Choi, In-Suk; Kim, Byoung-Joon; Joo, Young-Chang

    2018-03-01

    Flexible devices are of significant interest due to their potential expansion of the application of smart devices into various fields, such as energy harvesting, biological applications and consumer electronics. Due to the mechanically dynamic operations of flexible electronics, their mechanical reliability must be thoroughly investigated to understand their failure mechanisms and lifetimes. Reliability issue caused by bending fatigue, one of the typical operational limitations of flexible electronics, has been studied using various test methodologies; however, electromechanical evaluations which are essential to assess the reliability of electronic devices for flexible applications had not been investigated because the testing method was not established. By employing the in situ bending fatigue test, we has studied the failure mechanism for various conditions and parameters, such as bending strain, fatigue area, film thickness, and lateral dimensions. Moreover, various methods for improving the bending reliability have been developed based on the failure mechanism. Nanostructures such as holes, pores, wires and composites of nanoparticles and nanotubes have been suggested for better reliability. Flexible devices were also investigated to find the potential failures initiated by complex structures under bending fatigue strain. In this review, the recent advances in test methodology, mechanism studies, and practical applications are introduced. Additionally, perspectives including the future advance to stretchable electronics are discussed based on the current achievements in research.

  15. [PATHOPHYSIOLOGY OF THE CARDIORENAL SYNDROME].

    Science.gov (United States)

    Balint, I; Vučak, J; Bašić-Marković, N; Klarić, D; Šakić, V Amerl

    2016-12-01

    Cardiorenal syndrome, a complex pathophysiological disorder of both the heart and kidneys, is a condition in which acute or chronic damage to one organ can lead to acute or chronic dysfunction of the other organ. Depending on primary organ dysfunction and disease duration, there are five different types of cardiorenal syndrome. Type 1 cardiorenal syndrome (acute cardiorenal syndrome) is defined as acute kidney injury caused by sudden decrease in heart function. Type 2 cardiorenal syndrome (chronic cardiorenal syndrome) refers to chronic kidney disease linked to chronic heart failure. Type 3 cardiorenal syndrome (acute renocardial syndrome) is caused by acute kidney injury that leads to heart failure. Type 4 cardiorenal syndrome (chronic renocardial syndrome) includes chronic heart failure due to chronic kidney disease. Type 5 cardiorenal syndrome (secondary cardiorenal syndrome) is reversible or irreversible condition marked by simultaneous heart and kidney insufficiency, as a result of multiorgan disease such as sepsis, diabetes mellitus, sarcoidosis, amyloidosis, etc. The pathophysiological patterns of cardiorenal syndrome are extremely complicated. Despite numerous publications, perplexed physiological, biochemical and hormonal disturbances as parts of the main pathogenic mechanisms of cardiorenal syndrome remain obscure. Even though there are guidelines for the treatment of patients with heart failure and chronic kidney disease, similar guidelines for the treatment of cardiorenal syndrome are lacking. In everyday practice, it is crucial to diagnose cardiorenal syndrome and use all diagnostic and therapeutic procedures available to prevent or alleviate kidney and heart failure.

  16. Control of a perturbed under-actuated mechanical system

    KAUST Repository

    Zayane, Chadia

    2015-11-05

    In this work, the trajectory tracking problem for an under-actuated mechanical system in presence of unknown input disturbances is addressed. The studied inertia wheel inverted pendulum falls in the class of non minimum phase systems. The proposed high order sliding mode control architecture including a controller and differentiator allows to track accurately the predefined trajectory and to stabilize the internal dynamics. The robustness of the proposed approach is illustrated through different perturbation and output noise configurations.

  17. Neural mechanisms underlying morphine withdrawal in addicted patients: a review

    Directory of Open Access Journals (Sweden)

    Nima Babhadiashar

    2015-06-01

    Full Text Available Morphine is one of the most potent alkaloid in opium, which has substantial medical uses and needs and it is the first active principle purified from herbal source. Morphine has commonly been used for relief of moderate to severe pain as it acts directly on the central nervous system; nonetheless, its chronic abuse increases tolerance and physical dependence, which is commonly known as opiate addiction. Morphine withdrawal syndrome is physiological and behavioral symptoms that stem from prolonged exposure to morphine. A majority of brain regions are hypofunctional over prolonged abstinence and acute morphine withdrawal. Furthermore, several neural mechanisms are likely to contribute to morphine withdrawal. The present review summarizes the literature pertaining to neural mechanisms underlying morphine withdrawal. Despite the fact that morphine withdrawal is a complex process, it is suggested that neural mechanisms play key roles in morphine withdrawal.

  18. An NMDA Receptor-Dependent Mechanism Underlies Inhibitory Synapse Development

    Directory of Open Access Journals (Sweden)

    Xinglong Gu

    2016-01-01

    Full Text Available In the mammalian brain, GABAergic synaptic transmission provides inhibitory balance to glutamatergic excitatory drive and controls neuronal output. The molecular mechanisms underlying the development of GABAergic synapses remain largely unclear. Here, we report that NMDA-type ionotropic glutamate receptors (NMDARs in individual immature neurons are the upstream signaling molecules essential for GABAergic synapse development, which requires signaling via Calmodulin binding motif in the C0 domain of the NMDAR GluN1 subunit. Interestingly, in neurons lacking NMDARs, whereas GABAergic synaptic transmission is strongly reduced, the tonic inhibition mediated by extrasynaptic GABAA receptors is increased, suggesting a compensatory mechanism for the lack of synaptic inhibition. These results demonstrate a crucial role for NMDARs in specifying the development of inhibitory synapses, and suggest an important mechanism for controlling the establishment of the balance between synaptic excitation and inhibition in the developing brain.

  19. Pathophysiological response to hypoxia - from the molecular mechanisms of malady to drug discovery: epigenetic regulation of the hypoxic response via hypoxia-inducible factor and histone modifying enzymes.

    Science.gov (United States)

    Mimura, Imari; Tanaka, Tetsuhiro; Wada, Youichiro; Kodama, Tatsuhiko; Nangaku, Masaomi

    2011-01-01

    The hypoxia response regulated primarily by hypoxia-inducible factor (HIF) influences metabolism, cell survival, and angiogenesis to maintain biological homeostasis. In addition to the traditional transcriptional regulation by HIF, recent studies have shown that epigenetic modulation such as histone methylation, acetylation, and DNA methylation could change the regulation of the response to hypoxia. Eukaryotic chromatin is known to be modified by multiple post-translational histone methylation and demethylation, which result in the chromatin conformation change to adapt to hypoxic stimuli. Interestingly, some of the histone demethylase enzymes, which have the Jumonji domain-containing family, require oxygen to function and are induced by hypoxia in an HIF-1-dependent manner. Recent studies have demonstrated that histone modifiers play important roles in the hypoxic environment such as that in cancer cells and that they may become new therapeutic targets for cancer patients. It may lead to finding a new therapy for cancer to clarify a new epigenetic mechanism by HIF and histone demethylase such as JMJD1A (KDM3A) under hypoxia.

  20. Giant panda׳s tooth enamel: Structure, mechanical behavior and toughening mechanisms under indentation.

    Science.gov (United States)

    Weng, Z Y; Liu, Z Q; Ritchie, R O; Jiao, D; Li, D S; Wu, H L; Deng, L H; Zhang, Z F

    2016-12-01

    The giant panda׳s teeth possess remarkable load-bearing capacity and damage resistance for masticating bamboos. In this study, the hierarchical structure and mechanical behavior of the giant panda׳s tooth enamel were investigated under indentation. The effects of loading orientation and location on mechanical properties of the enamel were clarified and the evolution of damage in the enamel under increasing load evaluated. The nature of the damage, both at and beneath the indentation surfaces, and the underlying toughening mechanisms were explored. Indentation cracks invariably were seen to propagate along the internal interfaces, specifically the sheaths between enamel rods, and multiple extrinsic toughening mechanisms, e.g., crack deflection/twisting and uncracked-ligament bridging, were active to shield the tips of cracks from the applied stress. The giant panda׳s tooth enamel is analogous to human enamel in its mechanical properties, yet it has superior hardness and Young׳s modulus but inferior toughness as compared to the bamboo that pandas primarily feed on, highlighting the critical roles of the integration of underlying tissues in the entire tooth and the highly hydrated state of bamboo foods. Our objective is that this study can aid the understanding of the structure-mechanical property relations in the tooth enamel of mammals and further provide some insight on the food habits of the giant pandas. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. The Pathophysiology of Eosinophilic Esophagitis

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    Daniel Avi Lemberg

    2014-05-01

    Full Text Available Eosinophilic Esophagitis (EoE is an emerging disease characterised by esophageal eosinophilia (>15eos/hpf, lack of responsiveness to acid-suppressive medication and is managed by allergen elimination and anti-allergy therapy. Although the pathophysiology of EoE is currently unsubstantiated, evidence implicates food and aeroallergen hypersensitivity in genetically predisposed individuals as contributory factors. Genome-wide expression analyses have isolated a remarkably conserved gene-expression profile irrespective of age and gender, suggesting a genetic contribution. EoE has characteristics of mainly TH2 type immune responses but also some TH1 cytokines, which appear to strongly contribute to tissue fibrosis, with esophageal epithelial cells providing a hospitable environment for this inflammatory process. Eosinophil-degranulation products appear to play a central role in tissue remodeling in EoE. This remodeling and dysregulation predisposes to fibrosis. Mast cell-derived molecules such as histamine may have an effect on enteric nerves and may also act in concert with TGF-β to interfere with esophageal musculature. Additionally, the esophageal epithelium may facilitate the inflammatory process under pathogenic contexts such as in EoE. This article aims to discuss the contributory factors in the pathophysiology of EoE.

  2. Mechanical properties of graphene nanoribbons under uniaxial tensile strain

    Science.gov (United States)

    Yoneyama, Kazufumi; Yamanaka, Ayaka; Okada, Susumu

    2018-03-01

    Based on the density functional theory with the generalized gradient approximation, we investigated the mechanical properties of graphene nanoribbons in terms of their edge shape under a uniaxial tensile strain. The nanoribbons with armchair and zigzag edges retain their structure under a large tensile strain, while the nanoribbons with chiral edges are fragile against the tensile strain compared with those with armchair and zigzag edges. The fracture started at the cove region, which corresponds to the border between the zigzag and armchair edges for the nanoribbons with chiral edges. For the nanoribbons with armchair edges, the fracture started at one of the cove regions at the edges. In contrast, the fracture started at the inner region of the nanoribbons with zigzag edges. The bond elongation under the tensile strain depends on the mutual arrangement of covalent bonds with respect to the strain direction.

  3. Peripheral Receptor Mechanisms Underlying Orofacial Muscle Pain and Hyperalgesia

    Science.gov (United States)

    Saloman, Jami L.

    Musculoskeletal pain conditions, particularly those associated with temporomandibular joint and muscle disorders (TMD) are severely debilitating and affect approximately 12% of the population. Identifying peripheral nociceptive mechanisms underlying mechanical hyperalgesia, a prominent feature of persistent muscle pain, could contribute to the development of new treatment strategies for the management of TMD and other muscle pain conditions. This study provides evidence of functional interactions between ligand-gated channels, P2X3 and TRPV1/TRPA1, in trigeminal sensory neurons, and proposes that these interactions underlie the development of mechanical hyperalgesia. In the masseter muscle, direct P2X3 activation, via the selective agonist αβmeATP, induced a dose- and time-dependent hyperalgesia. Importantly, the αβmeATP-induced hyperalgesia was prevented by pretreatment of the muscle with a TRPV1 antagonist, AMG9810, or the TRPA1 antagonist, AP18. P2X3 was co-expressed with both TRPV1 and TRPA1 in masseter muscle afferents confirming the possibility for intracellular interactions. Moreover, in a subpopulation of P2X3 /TRPV1 positive neurons, capsaicin-induced Ca2+ transients were significantly potentiated following P2X3 activation. Inhibition of Ca2+-dependent kinases, PKC and CaMKII, prevented P2X3-mechanical hyperalgesia whereas blockade of Ca2+-independent PKA did not. Finally, activation of P2X3 induced phosphorylation of serine, but not threonine, residues in TRPV1 in trigeminal sensory neurons. Significant phosphorylation was observed at 15 minutes, the time point at which behavioral hyperalgesia was prominent. Similar data were obtained regarding another nonselective cation channel, the NMDA receptor (NMDAR). Our data propose P2X3 and NMDARs interact with TRPV1 in a facilitatory manner, which could contribute to the peripheral sensitization underlying masseter hyperalgesia. This study offers novel mechanisms by which individual pro-nociceptive ligand

  4. Mechanical properties of a collagen fibril under simulated degradation.

    Science.gov (United States)

    Malaspina, David C; Szleifer, Igal; Dhaher, Yasin

    2017-11-01

    Collagen fibrils are a very important component in most of the connective tissue in humans. An important process associated with several physiological and pathological states is the degradation of collagen. Collagen degradation is usually mediated by enzymatic and non-enzymatic processes. In this work we use molecular dynamics simulations to study the influence of simulated degradation on the mechanical properties of the collagen fibril. We applied tensile stress to the collagen fiber at different stages of degradation. We compared the difference in the fibril mechanical priorities due the removal of enzymatic crosslink, surface degradation and volumetric degradation. As anticipated, our results indicated that, regardless of the degradation scenario, fibril mechanical properties is reduced. The type of degradation mechanism (crosslink, surface or volumetric) expressed differential effect on the change in the fibril stiffness. Our simulation results showed dramatic change in the fibril stiffness with a small amount of degradation. This suggests that the hierarchical structure of the fibril is a key component for the toughness and is very sensitive to changes in the organization of the fibril. The overall results are intended to provide a theoretical framework for the understanding the mechanical behavior of collagen fibrils under degradation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. The pathophysiology of bronchiectasis

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    Paul T King

    2009-10-01

    Full Text Available Paul T KingDepartment of Medicine, Department of Respiratory and Sleep Medicine, Monash University, Monash Medical Centre, Melbourne, Victoria, AustraliaAbstract: Bronchiectasis is defined by permanent and abnormal widening of the bronchi. This process occurs in the context of chronic airway infection and inflammation. It is usually diagnosed using computed tomography scanning to visualize the larger bronchi. Bronchiectasis is also characterized by mild to moderate airflow obstruction. This review will describe the pathophysiology of noncystic fibrosis bronchiectasis. Studies have demonstrated that the small airways in bronchiectasis are obstructed from an inflammatory infiltrate in the wall. As most of the bronchial tree is composed of small airways, the net effect is obstruction. The bronchial wall is typically thickened by an inflammatory infiltrate of lymphocytes and macrophages which may form lymphoid follicles. It has recently been demonstrated that patients with bronchiectasis have a progressive decline in lung function. There are a large number of etiologic risk factors associated with bronchiectasis. As there is generally a long-term retrospective history, it may be difficult to determine the exact role of such factors in the pathogenesis. Extremes of age and smoking/chronic obstructive pulmonary disease may be important considerations. There are a variety of different pathogens involved in bronchiectasis, but a common finding despite the presence of purulent sputum is failure to identify any pathogenic microorganisms. The bacterial flora appears to change with progression of disease. Keywords: bronchiectasis, inflammation, obstructive lung disease, pathophysiology, pathology

  6. Current concepts in the pathophysiology of glaucoma

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    Agarwal Renu

    2009-01-01

    Full Text Available Glaucoma, the second leading cause of blindness, is characterized by changes in the optic disc and visual field defects. The elevated intraocular pressure was considered the prime factor responsible for the glaucomatous optic neuropathy involving death of retinal ganglion cells and their axons. Extensive investigations into the pathophysiology of glaucoma now reveal the role of multiple factors in the development of retinal ganglion cell death. A better understanding of the pathophysiological mechanisms involved in the onset and progression of glaucomatous optic neuropathy is crucial in the development of better therapeutic options. This review is an effort to summarize the current concepts in the pathophysiology of glaucoma so that newer therapeutic targets can be recognized. The literature available in the National Medical Library and online Pubmed search engine was used for literature review.

  7. Temporomandibular disorders and painful comorbidities: clinical association and underlying mechanisms.

    Science.gov (United States)

    Costa, Yuri Martins; Conti, Paulo César Rodrigues; de Faria, Flavio Augusto Cardoso; Bonjardim, Leonardo Rigoldi

    2017-03-01

    The association between temporomandibular disorders (TMDs) and headaches, cervical spine dysfunction, and fibromyalgia is not artefactual. The aim of this review is to describe the comorbid relationship between TMD and these three major painful conditions and to discuss the clinical implications and the underlying pain mechanisms involved in these relationships. Common neuronal pathways and central sensitization processes are acknowledged as the main factors for the association between TMD and primary headaches, although the establishment of cause-effect mechanisms requires further clarification and characterization. The biomechanical aspects are not the main factors involved in the comorbid relationship between TMD and cervical spine dysfunction, which can be better explained by the neuronal convergence of the trigeminal and cervical spine sensory pathways as well as by central sensitization processes. The association between TMD and fibromyalgia also has supporting evidence in the literature, and the proposed main mechanism underlying this relationship is the impairment of the descending pain inhibitory system. In this particular scenario, a cause-effect relationship is more likely to occur in one direction, that is, fibromyalgia as a risk factor for TMD. Therefore, clinical awareness of the association between TMD and painful comorbidities and the support of multidisciplinary approaches are required to recognize these related conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Central voice production and pathophysiology of spasmodic dysphonia.

    Science.gov (United States)

    Mor, Niv; Simonyan, Kristina; Blitzer, Andrew

    2018-01-01

    Our ability to speak is complex, and the role of the central nervous system in controlling speech production is often overlooked in the field of otolaryngology. In this brief review, we present an integrated overview of speech production with a focus on the role of central nervous system. The role of central control of voice production is then further discussed in relation to the potential pathophysiology of spasmodic dysphonia (SD). Peer-review articles on central laryngeal control and SD were identified from PUBMED search. Selected articles were augmented with designated relevant publications. Publications that discussed central and peripheral nervous system control of voice production and the central pathophysiology of laryngeal dystonia were chosen. Our ability to speak is regulated by specialized complex mechanisms coordinated by high-level cortical signaling, brainstem reflexes, peripheral nerves, muscles, and mucosal actions. Recent studies suggest that SD results from a primary central disturbance associated with dysfunction at our highest levels of central voice control. The efficacy of botulinum toxin in treating SD may not be limited solely to its local effect on laryngeal muscles and also may modulate the disorder at the level of the central nervous system. Future therapeutic options that target the central nervous system may help modulate the underlying disorder in SD and allow clinicians to better understand the principal pathophysiology. NA.Laryngoscope, 128:177-183, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  9. Failure Mechanisms of Brittle Rocks under Uniaxial Compression

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    Liu Taoying

    2017-09-01

    Full Text Available The behaviour of a rock mass is determined not only by the properties of the rock matrix, but mostly by the presence and properties of discontinuities or fractures within the mass. The compression test on rock-like specimens with two prefabricated transfixion fissures, made by pulling out the embedded metal inserts in the pre-cured period was carried out on the servo control uniaxial loading tester. The influence of the geometry of pre-existing cracks on the cracking processes was analysed with reference to the experimental observation of crack initiation and propagation from pre-existing flaws. Based on the rock fracture mechanics and the stress-strain curves, the evolution failure mechanism of the fissure body was also analyzed on the basis of exploring the law of the compression-shear crack initiation, wing crack growth and rock bridge connection. Meanwhile, damage fracture mechanical models of a compression-shear rock mass are established when the rock bridge axial transfixion failure, tension-shear combined failure, or wing crack shear connection failure occurs on the specimen under axial compression. This research was of significance in studying the failure mechanism of fractured rock mass.

  10. The mechanism underlying fast germination of tomato cultivar LA2711.

    Science.gov (United States)

    Yang, Rongchao; Chu, Zhuannan; Zhang, Haijun; Li, Ying; Wang, Jinfang; Li, Dianbo; Weeda, Sarah; Ren, Shuxin; Ouyang, Bo; Guo, Yang-Dong

    2015-09-01

    Seed germination is important for early plant morphogenesis as well as abiotic stress tolerance, and is mainly controlled by the phytohormones abscisic acid (ABA) and gibberellic acid (GA). Our previous studies identified a salt-tolerant tomato cultivar, LA2711, which is also a fast-germinating genotype, compared to its salt-sensitive counterpart, ZS-5. In an effort to further clarify the mechanism underlying this phenomenon, we compared the dynamic levels of ABA and GA4, the transcript abundance of genes involved in their biosynthesis and catabolism as well as signal transduction between the two cultivars. In addition, we tested seed germination sensitivity to ABA and GAs. Our results revealed that insensitivity of seed germination to exogenous ABA and low ABA content in seeds are the physiological mechanisms conferring faster germination rates of LA2711 seeds. SlCYP707A2, which encodes an ABA catabolic enzyme, may play a decisive role in the fast germination rate of LA2711, as it showed a significantly higher level of expression in LA2711 than ZS-5 at most time points tested during germination. The current results will enable us to gain insight into the mechanism(s) regarding seed germination of tomato and the role of fast germination in stress tolerance. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Mechanisms underlying HIV-1 Vpu-mediated viral egress

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    Nicolas eRoy

    2014-05-01

    Full Text Available Viruses such as lentiviruses that are responsible for long lasting infections, have to evade several level of cellular immune mechanisms to persist and efficiently disseminate in the host. Over the past decades, many evidences have emerged regarding the major role of accessory proteins of primate lentiviruses (Human (HIV and simian immunodeficiency viruses (SIV in viral evasion from the host immune defense. This short review will provide an overview of the mechanism whereby the accessory protein Vpu contributes to this escape. Vpu is a multifunctional protein that was shown to contribute to viral egress by down-regulating several mediators of the immune system such as CD4, CD1d, NTB-A and the restriction factor BST2. The mechanisms underlying its activity are not fully characterized but rely on its ability to interfere with the host machinery regulating proteins turnover and vesicular trafficking. This review will focus on our current understanding of the mechanisms whereby Vpu down-regulates CD4 and BST2 expression level to favour viral egress.

  12. Mechanical Design of AM Fabricated Prismatic Rods under Torsion

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    Manzhirov Alexander V.

    2017-01-01

    Full Text Available We study the stress-strain state of viscoelastic prismatic rods fabricated or repaired by additive manufacturing technologies under torsion. An adequate description of the processes involved is given by methods of a new scientific field, mechanics of growing solids. Three main stages of the deformation process (before the beginning of growth, in the course of growth, and after the termination of growth are studied. Two versions of statement of two problems are given: (i given the torque, find the stresses, displacements, and torsion; (ii given the torsion, find the stresses, displacements, and torque. Solution methods using techniques of complex analysis are presented. The results can be used in mechanical and instrument engineering.

  13. Nanomaterials modulate stem cell differentiation: biological interaction and underlying mechanisms.

    Science.gov (United States)

    Wei, Min; Li, Song; Le, Weidong

    2017-10-25

    Stem cells are unspecialized cells that have the potential for self-renewal and differentiation into more specialized cell types. The chemical and physical properties of surrounding microenvironment contribute to the growth and differentiation of stem cells and consequently play crucial roles in the regulation of stem cells' fate. Nanomaterials hold great promise in biological and biomedical fields owing to their unique properties, such as controllable particle size, facile synthesis, large surface-to-volume ratio, tunable surface chemistry, and biocompatibility. Over the recent years, accumulating evidence has shown that nanomaterials can facilitate stem cell proliferation and differentiation, and great effort is undertaken to explore their possible modulating manners and mechanisms on stem cell differentiation. In present review, we summarize recent progress in the regulating potential of various nanomaterials on stem cell differentiation and discuss the possible cell uptake, biological interaction and underlying mechanisms.

  14. Pathophysiology of MDS: genomic aberrations.

    Science.gov (United States)

    Ichikawa, Motoshi

    2016-01-01

    Myelodysplastic syndromes (MDS) are characterized by clonal proliferation of hematopoietic stem/progenitor cells and their apoptosis, and show a propensity to progress to acute myelogenous leukemia (AML). Although MDS are recognized as neoplastic diseases caused by genomic aberrations of hematopoietic cells, the details of the genetic abnormalities underlying disease development have not as yet been fully elucidated due to difficulties in analyzing chromosomal abnormalities. Recent advances in comprehensive analyses of disease genomes including whole-genome sequencing technologies have revealed the genomic abnormalities in MDS. Surprisingly, gene mutations were found in approximately 80-90% of cases with MDS, and the novel mutations discovered with these technologies included previously unknown, MDS-specific, mutations such as those of the genes in the RNA-splicing machinery. It is anticipated that these recent studies will shed new light on the pathophysiology of MDS due to genomic aberrations.

  15. Age differences in the underlying mechanisms of stereotype threat effects.

    Science.gov (United States)

    Popham, Lauren E; Hess, Thomas M

    2015-03-01

    The goals of the present study were to (a) examine whether age differences exist in the mechanisms underlying stereotype threat effects on cognitive performance and (b) examine whether emotion regulation abilities may buffer against threat effects on performance. Older and younger adults were exposed to positive or negative age-relevant stereotypes, allowing us to examine the impact of threat on regulatory focus and working memory. Self-reported emotion regulation measures were completed prior to the session. Older adults' performance under threat suggested a prevention-focused approach to the task, indexed by increased accuracy and reduced speed. The same pattern was observed in younger adults, but the effects were not as strong. Age differences emerged when examining the availability of working memory resources under threat, with young adults showing decrements, whereas older adults did not. Emotion regulation abilities moderated threat effects in young adults but not in older adults. The results provide support for the notion that stereotype threat may lead to underperformance through somewhat different pathways in older and younger adults. Future research should further examine whether the underlying reason for this age difference is rooted in age-related improvements in emotion regulation. © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Pathophysiology of glucagon secretion

    International Nuclear Information System (INIS)

    Boettger, J.; Pabst, H.W.

    1980-01-01

    Pathophysiology of glucagon secretion is reviewed in brief separating hyperglucagonemic from hypoclucagonemic states. Many questions concerning the role of glucagon in diabetes mellitus and in other diseases are still unresolved. The clucagon RIA is of clinical significance in a few diseases like glucagonoma, which may present without symptoms of the 'glucagonoma syndrome', the probably very rare hyperglucagonemia and some of the spontaneous hypoglycemias. Glucagon secretion may be evaluated by the determination of fasting immunoreactive glucagon (IRG) and by appropriate function tests as stimulation with i.v. arginine and suppression with oral glucose. However, the glucagon RIA at present is not a routine method, although commercial kits are available. Many pitfalls of radioimmunological glucagon determination still exist. (orig.) [de

  17. Mecanismos básicos da encefalopatia urêmica Mechanisms underlying uremic encephalopathy

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    Giselli Scaini

    2010-06-01

    Full Text Available Em pacientes com insuficiência renal, a encefalopatia é um problema comum que pode ser provocado pela uremia, deficiência de tiamina, diálise, rejeição de transplante, hipertensão, desequilíbrios hidroeletrolíticos e toxicidades medicamentosas. Em geral a encefalopatia se apresenta como um complexo de sintomas que progride de uma leve obnubilação sensitiva até delírio e coma. Esta revisão discute questões importantes com relação aos mecanismos de base da fisiopatologia da encefalopatia urêmica. A fisiopatologia da encefalopatia urêmica é até hoje incerta, mas postula-se o envolvimento de diversos fatores; trata-se de um processo complexo e provavelmente multifatorial. Distúrbios hormonais, estresse oxidativo, acúmulo de metabólitos, desequilíbrio entre os neurotransmissores excitatórios e inibitórios, e distúrbio do metabolismo intermediário foram identificados como fatores contribuintes. A despeito do progresso continuado na terapêutica, a maior parte das complicações neurológicas da uremia, como a encefalopatia urêmica, não respondem plenamente à diálise e muitas delas são desencadeadas ou agravadas pela diálise ou transplante renal. Por outro lado, estudos prévios demonstraram que a terapia antioxidante pode ser utilizada como terapia coadjuvante para o tratamento destas complicações neurológicas.In patients with renal failure, encephalopathy is a common problem that may be caused by uremia, thiamine deficiency, dialysis, transplant rejection, hypertension, fluid and electrolyte disturbances or drug toxicity. In general, encephalopathy presents with a symptom complex progressing from mild sensorial clouding to delirium and coma. This review discusses important issues regarding the mechanisms underlying the pathophysiology of uremic encephalopathy. The pathophysiology of uremic encephalopathy up to now is uncertain, but several factors have been postulated to be involved; it is a complex and probably

  18. Electrochemical mechanism of tin membrane electrodeposition under ultrasonic waves.

    Science.gov (United States)

    Nan, Tianxiang; Yang, Jianguang; Chen, Bing

    2018-04-01

    Tin was electrodeposited from chloride solutions using a membrane cell under ultrasonic waves. Cyclic voltammetry (CV), linear sweep voltammetry (LSV), chronoamperometry (CHR), and chronopotentiometry were applied to investigate the electrochemical mechanism of tin electrodeposition under ultrasonic field. Chronoamperometry curves showed that the initial process of tin electrodeposition followed the diffusion controlled three-dimensional nucleation and grain growth mechanism. The analysis of the cyclic voltammetry and linear sweep voltammetry diagrams showed that the application of ultrasound can change the tin membrane electro-deposition reaction from diffusion to electrochemical control, and the optimum parameters for tin electrodeposition were H + concentration 3.5 mol·L -1 , temperature 35 °C and ultrasonic power 100 W. The coupling ultrasonic field played a role in refining the grain in this process. The growth of tin crystals showed no orientation preferential, and the tin deposition showed a tendency to form a regular network structure after ultrasonic coupling. While in the absence of ultrasonic coupling, the growth of tin crystals has a high preferential orientation, and the tin deposition showed a tendency to form tin whiskers. Ultrasonic coupling was more favorable for obtaining a more compact and smoother cathode tin layer. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Mechanisms Underlying the Antidepressant Response and Treatment Resistance

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    Marjorie Rose Levinstein

    2014-06-01

    Full Text Available Depression is a complex and heterogeneous disorder affecting millions of Americans. There are several different medications and other treatments that are available and effective for many patients with depression. However, a substantial percentage of patients fail to achieve remission with these currently available interventions, and relapse rates are high. Therefore, it is necessary to determine both the mechanisms underlying the antidepressant response and the differences between responders and non-responders to treatment. Delineation of these mechanisms largely relies on experiments that utilize animal models. Therefore, this review provides an overview of the various mouse models that are currently used to assess the antidepressant response, such as chronic mild stress, social defeat, and chronic corticosterone. We discuss how these mouse models can be used to advance our understanding of the differences between responders and non-responders to antidepressant treatment. We also provide an overview of experimental treatment modalities that are used for treatment-resistant depression, such as deep brain stimulation and ketamine administration. We will then review the various genetic polymorphisms and transgenic mice that display resistance to antidepressant treatment. Finally, we synthesize the published data to describe a potential neural circuit underlying the antidepressant response and treatment resistance.

  20. Autophagy as a Possible Underlying Mechanism of Nanomaterial Toxicity

    Directory of Open Access Journals (Sweden)

    Vanessa Cohignac

    2014-07-01

    Full Text Available The rapid development of nanotechnologies is raising safety concerns because of the potential effects of engineered nanomaterials on human health, particularly at the respiratory level. Since the last decades, many in vivo studies have been interested in the pulmonary effects of different classes of nanomaterials. It has been shown that some of them can induce toxic effects, essentially depending on their physico-chemical characteristics, but other studies did not identify such effects. Inflammation and oxidative stress are currently the two main mechanisms described to explain the observed toxicity. However, the exact underlying mechanism(s still remain(s unknown and autophagy could represent an interesting candidate. Autophagy is a physiological process in which cytoplasmic components are digested via a lysosomal pathway. It has been shown that autophagy is involved in the pathogenesis and the progression of human diseases, and is able to modulate the oxidative stress and pro-inflammatory responses. A growing amount of literature suggests that a link between nanomaterial toxicity and autophagy impairment could exist. In this review, we will first summarize what is known about the respiratory effects of nanomaterials and we will then discuss the possible involvement of autophagy in this toxicity. This review should help understand why autophagy impairment could be taken as a promising candidate to fully understand nanomaterials toxicity.

  1. Effects of manual hyperinflation in preterm newborns under mechanical ventilation.

    Science.gov (United States)

    Viana, Camila Chaves; Nicolau, Carla Marques; Juliani, Regina Celia Turola Passos; Carvalho, Werther Brunow de; Krebs, Vera Lucia Jornada

    2016-09-01

    To assess the effects of manual hyperinflation, performed with a manual resuscitator with and without the positive end-expiratory pressure valve, on the respiratory function of preterm newborns under mechanical ventilation. Cross-sectional study of hemodynamically stable preterm newborns with gestational age of less than 32 weeks, under mechanical ventilation and dependent on it at 28 days of life. Manual hyperinflation was applied randomly, alternating the use or not of the positive end-expiratory pressure valve, followed by tracheal aspiration for ending the maneuver. For nominal data, the two-tailed Wilcoxon test was applied at the 5% significance level and 80% power. Twenty-eight preterm newborns, with an average birth weight of 1,005.71 ± 372.16g, an average gestational age of 28.90 ± 1.79 weeks, an average corrected age of 33.26 ± 1.78 weeks, and an average mechanical ventilation time of 29.5 (15 - 53) days, were studied. Increases in inspiratory and expiratory volumes occurred between time-points A5 (before the maneuver) and C1 (immediately after tracheal aspiration) in both the maneuver with the valve (p = 0.001 and p = 0.009) and without the valve (p = 0.026 and p = 0.001), respectively. There was also an increase in expiratory resistance between time-points A5 and C1 (p = 0.044). Lung volumes increased when performing the maneuver with and without the valve, with a significant difference in the first minute after aspiration. There was a significant difference in expiratory resistance between the time-points A5 (before the maneuver) and C1 (immediately after tracheal aspiration) in the first minute after aspiration within each maneuver.

  2. Exploration of mechanisms underlying the strain-rate-dependent mechanical property of single chondrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Trung Dung; Gu, YuanTong, E-mail: yuantong.gu@qut.edu.au [School of Chemistry, Physics and Mechanical Engineering, Queensland University of Technology, Brisbane, Queensland (Australia)

    2014-05-05

    Based on the characterization by Atomic Force Microscopy, we report that the mechanical property of single chondrocytes has dependency on the strain-rates. By comparing the mechanical deformation responses and the Young's moduli of living and fixed chondrocytes at four different strain-rates, we explore the deformation mechanisms underlying this dependency property. We found that the strain-rate-dependent mechanical property of living cells is governed by both of the cellular cytoskeleton and the intracellular fluid when the fixed chondrocytes are mainly governed by their intracellular fluid, which is called the consolidation-dependent deformation behavior. Finally, we report that the porohyperelastic constitutive material model which can capture the consolidation-dependent behavior of both living and fixed chondrocytes is a potential candidature to study living cell biomechanics.

  3. Transcranial magnetic stimulation and sleep disorders: pathophysiologic insights.

    Science.gov (United States)

    Nardone, Raffaele; Höller, Yvonne; Brigo, Francesco; Tezzon, Frediano; Golaszewski, Stefan; Trinka, Eugen

    2013-11-01

    The neural mechanisms underlying the development of the most common intrinsic sleep disorders are not completely known. Therefore, there is a great need for noninvasive tools which can be used to better understand the pathophysiology of these diseases. Transcranial magnetic stimulation (TMS) offers a method to noninvasively investigate the functional integrity of the motor cortex and its corticospinal projections in neurologic and psychiatric diseases. To date, TMS studies have revealed cortical and corticospinal dysfunction in several sleep disorders, with cortical hyperexcitability being a characteristic feature in some disorders (i.e., the restless legs syndrome) and cortical hypoexcitability being a well-established finding in others (i.e., obstructive sleep apnea syndrome narcolepsy). Several research groups also have applied TMS to evaluate the effects of pharmacologic agents, such as dopaminergic agent or wake-promoting substances. Our review will focus on the mechanisms underlying the generation of abnormal TMS measures in the different types of sleep disorders, the contribution of TMS in enhancing the understanding of their pathophysiology, and the potential diagnostic utility of TMS techniques. We also briefly discussed the possible future implications for improving therapeutic approaches. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. The mechanisms underlying fructose-induced hypertension: a review

    Science.gov (United States)

    Klein, Alice Victoria; Kiat, Hosen

    2015-01-01

    We are currently in the midst of an epidemic of metabolic disorders, which may, in part, be explained by excess fructose intake. This theory is supported by epidemiological observations as well as experimental studies in animals and humans. Rising consumption of fructose has been matched with growing rates of hypertension, leading to concern from public health experts. At this stage, the mechanisms underlying fructose-induced hypertension have not been fully characterized and the bulk of our knowledge is derived from animal models. Animal studies have shown that high-fructose diets up-regulate sodium and chloride transporters, resulting in a state of salt overload that increases blood pressure. Excess fructose has also been found to activate vasoconstrictors, inactivate vasodilators, and over-stimulate the sympathetic nervous system. Further work is required to determine the relevance of these findings to humans and to establish the level at which dietary fructose increases the risk of developing hypertension PMID:25715094

  5. Degradation Mechanisms of Transparent Polyurethane Interlayer under UV Irradiation

    Directory of Open Access Journals (Sweden)

    OU Yingchun

    2017-01-01

    Full Text Available According to the ageing problem of laminated transparency, the trasparent polyurethane film used as interlayer had been irradiated by fluorescent ultraviolet lamp for 0 h, 200 h, 300 h, and 500 h respectively. With the aid of ultraviolet/visible spectrophotometer, FTIR and SEM etc., the color, structure and morphology of the materials were studied. SEM shows that when the irradiation time is increased to 500 h, the film surface cracks. The UV degradation mechanisms are that -CH2- of the position connecting the O and N from hard segment and the soft segment are easy to oxidize and produce hydrogen peroxide under UV and oxygen, which is furtherly oxidized to CO, and some part of the C-O and C-N bonds is cracked through β scission, and then the materials are fractured.

  6. Nonlinear mechanical response of supercooled melts under applied forces

    Science.gov (United States)

    Cárdenas, Heliana; Frahsa, Fabian; Fritschi, Sebastian; Nicolas, Alexandre; Papenkort, Simon; Voigtmann, Thomas; Fuchs, Matthias

    2017-08-01

    We review recent progress on a microscopic theoretical approach to describe the nonlinear response of glass-forming colloidal dispersions under strong external forcing leading to homogeneous and inhomogeneous flow. Using mode-coupling theory (MCT), constitutive equations for the rheology of viscoelastic shear-thinning fluids are obtained. These are, in suitably simplified form, employed in continuum fluid dynamics, solved by a hybrid-Lattice Boltzmann (LB) algorithm that was developed to deal with long-lasting memory effects. The combined microscopic theoretical and mesoscopic numerical approach captures a number of phenomena far from equilibrium, including the yielding of metastable states, process-dependent mechanical properties, and inhomogeneous pressure-driven channel flow.

  7. Epidemiological and pathophysiological aspects of abdominal pain predominant functional gastrointestinal disorders in children and adolescents: a Sri Lankan perspective

    NARCIS (Netherlands)

    Devanarayana, N.M.

    2015-01-01

    Abdominal pain-predominant functional gastrointestinal disorders (AP-FGIDs) are a worldwide pediatric problem with uncertain pathology. Main objectives of this thesis were to assess epidemiology, risk factors and underlying pathophysiological mechanisms of AP-FGIDs. A systematic review and

  8. Simulated airplane headache: a proxy towards identification of underlying mechanisms.

    Science.gov (United States)

    Bui, Sebastian Bao Dinh; Petersen, Torben; Poulsen, Jeppe Nørgaard; Gazerani, Parisa

    2017-12-01

    Airplane Headache (AH) occurs during flights and often appears as an intense, short lasting headache during take-off or landing. Reports are limited on pathological mechanisms underlying the occurrence of this headache. Proper diagnosis and treatments would benefit from identification of potential pathways involved in AH pathogenesis. This study aimed at providing a simulated airplane headache condition as a proxy towards identification of its underlying mechanisms. Fourteen participants including 7 volunteers suffering from AH and 7 healthy matched controls were recruited after meeting the diagnostic and safety criteria based on an approved study protocol. Simulation of AH was achieved by entering a pressure chamber with similar characteristics of an airplane flight. Selected potential biomarkers including salivary prostaglandin E 2 (PGE 2 ), cortisol, facial thermo-images, blood pressure, pulse, and saturation pulse oxygen (SPO) were defined and values were collected before, during and after flight simulation in the pressure chamber. Salivary samples were analyzed with ELISA techniques, while data analysis and statistical tests were handled with SPSS version 22.0. All participants in the AH-group experienced a headache attack similar to AH experience during flight. The non-AH-group did not experience any headaches. Our data showed that the values for PGE 2 , cortisol and SPO were significantly different in the AH-group in comparison with the non-AH-group during the flight simulation in the pressure chamber. The pressure chamber proved useful not only to provoke AH-like attack but also to study potential biomarkers for AH in this study. PGE 2 , and cortisol levels together with SPO presented dysregulation during the simulated AH-attack in affected individuals compared with healthy controls. Based on these findings we propose to use pressure chamber as a model to induce AH, and thus assess new potential biomarkers for AH in future studies.

  9. Nonlinear Mechanics of MEMS Rectangular Microplates under Electrostatic Actuation

    KAUST Repository

    Saghir, Shahid

    2016-12-01

    The first objective of the dissertation is to develop a suitable reduced order model capable of investigating the nonlinear mechanical behavior of von-Karman plates under electrostatic actuation. The second objective is to investigate the nonlinear static and dynamic behavior of rectangular microplates under small and large actuating forces. In the first part, we present and compare various approaches to develop reduced order models for the nonlinear von-Karman rectangular microplates actuated by nonlinear electrostatic forces. The reduced-order models aim to investigate the static and dynamic behavior of the plate under small and large actuation forces. A fully clamped microplate is considered. Different types of basis functions are used in conjunction with the Galerkin method to discretize the governing equations. First we investigate the convergence with the number of modes retained in the model. Then for validation purpose, a comparison of the static results is made with the results calculated by a nonlinear finite element model. The linear eigenvalue problem for the plate under the electrostatic force is solved for a wide range of voltages up to pull-in. In the second part, we present an investigation of the static and dynamic behavior of a fully clamped microplate. We investigate the effect of different non-dimensional design parameters on the static response. The forced-vibration response of the plate is then investigated when the plate is excited by a harmonic AC load superimposed to a DC load. The dynamic behavior is examined near the primary and secondary (superharmonic and subharmonic) resonances. The microplate shows a strong hardening behavior due to the cubic nonlinearity of midplane stretching. However, the behavior switches to softening as the DC load is increased. Next, near-square plates are studied to understand the effect of geometric imperfections of microplates. In the final part of the dissertation, we investigate the mechanical behavior of

  10. Mechanisms underlying the social enhancement of vocal learning in songbirds.

    Science.gov (United States)

    Chen, Yining; Matheson, Laura E; Sakata, Jon T

    2016-06-14

    Social processes profoundly influence speech and language acquisition. Despite the importance of social influences, little is known about how social interactions modulate vocal learning. Like humans, songbirds learn their vocalizations during development, and they provide an excellent opportunity to reveal mechanisms of social influences on vocal learning. Using yoked experimental designs, we demonstrate that social interactions with adult tutors for as little as 1 d significantly enhanced vocal learning. Social influences on attention to song seemed central to the social enhancement of learning because socially tutored birds were more attentive to the tutor's songs than passively tutored birds, and because variation in attentiveness and in the social modulation of attention significantly predicted variation in vocal learning. Attention to song was influenced by both the nature and amount of tutor song: Pupils paid more attention to songs that tutors directed at them and to tutors that produced fewer songs. Tutors altered their song structure when directing songs at pupils in a manner that resembled how humans alter their vocalizations when speaking to infants, that was distinct from how tutors changed their songs when singing to females, and that could influence attention and learning. Furthermore, social interactions that rapidly enhanced learning increased the activity of noradrenergic and dopaminergic midbrain neurons. These data highlight striking parallels between humans and songbirds in the social modulation of vocal learning and suggest that social influences on attention and midbrain circuitry could represent shared mechanisms underlying the social modulation of vocal learning.

  11. Neurodevelopmental Disorders and Environmental Toxicants: Epigenetics as an Underlying Mechanism

    Directory of Open Access Journals (Sweden)

    Nguyen Quoc Vuong Tran

    2017-01-01

    Full Text Available The increasing prevalence of neurodevelopmental disorders, especially autism spectrum disorders (ASD and attention deficit hyperactivity disorder (ADHD, calls for more research into the identification of etiologic and risk factors. The Developmental Origin of Health and Disease (DOHaD hypothesizes that the environment during fetal and childhood development affects the risk for many chronic diseases in later stages of life, including neurodevelopmental disorders. Epigenetics, a term describing mechanisms that cause changes in the chromosome state without affecting DNA sequences, is suggested to be the underlying mechanism, according to the DOHaD hypothesis. Moreover, many neurodevelopmental disorders are also related to epigenetic abnormalities. Experimental and epidemiological studies suggest that exposure to prenatal environmental toxicants is associated with neurodevelopmental disorders. In addition, there is also evidence that environmental toxicants can result in epigenetic alterations, notably DNA methylation. In this review, we first focus on the relationship between neurodevelopmental disorders and environmental toxicants, in particular maternal smoking, plastic-derived chemicals (bisphenol A and phthalates, persistent organic pollutants, and heavy metals. We then review studies showing the epigenetic effects of those environmental factors in humans that may affect normal neurodevelopment.

  12. Thermal stability of nafion membranes under mechanical stress

    Energy Technology Data Exchange (ETDEWEB)

    Quintilii, M.; Struis, R. [Paul Scherrer Inst. (PSI), Villigen (Switzerland)

    1997-06-01

    The feasibility of adequately modified fluoro-ionomer membranes (NAFION{sup R}) is demonstrated for the selective separation of methanol synthesis products from the raw reactor gas at temperatures around 200{sup o}C. For an economically relevant application of this concept on a technical scale the Nafion membranes should be thin ({approx_equal}10 {mu}m) and thermally stable over a long period of time (1-2 years). In cooperation with industry (Methanol Casale SA, Lugano (CH)), we test the thermal stability of Nafion hollow fibers and supported Nafion thin sheet membranes at temperatures between 160 and 200{sup o}C under mechanical stress by applying a gas pressure difference over the membrane surface ({Delta}P{<=} 40 bar). Tests with the hollow fibers revealed that Nafion has visco-elastic properties. Tests with 50 {mu}m thin Nafion sheets supported by a porous metal carrier at 200{sup o}C and {Delta}P=39 bar showed no mechanical defects over a period of 92 days. (author) 5 figs., 4 refs.

  13. Using Drosophila to discover mechanisms underlying type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Ronald W. Alfa

    2016-04-01

    Full Text Available Mechanisms of glucose homeostasis are remarkably well conserved between the fruit fly Drosophila melanogaster and mammals. From the initial characterization of insulin signaling in the fly came the identification of downstream metabolic pathways for nutrient storage and utilization. Defects in these pathways lead to phenotypes that are analogous to diabetic states in mammals. These discoveries have stimulated interest in leveraging the fly to better understand the genetics of type 2 diabetes mellitus in humans. Type 2 diabetes results from insulin insufficiency in the context of ongoing insulin resistance. Although genetic susceptibility is thought to govern the propensity of individuals to develop type 2 diabetes mellitus under appropriate environmental conditions, many of the human genes associated with the disease in genome-wide association studies have not been functionally studied. Recent advances in the phenotyping of metabolic defects have positioned Drosophila as an excellent model for the functional characterization of large numbers of genes associated with type 2 diabetes mellitus. Here, we examine results from studies modeling metabolic disease in the fruit fly and compare findings to proposed mechanisms for diabetic phenotypes in mammals. We provide a systematic framework for assessing the contribution of gene candidates to insulin-secretion or insulin-resistance pathways relevant to diabetes pathogenesis.

  14. Mechanisms underlying temperature extremes in Iberia: a Lagrangian perspective

    Directory of Open Access Journals (Sweden)

    João A. Santos

    2015-04-01

    Full Text Available The mechanisms underlying the occurrence of temperature extremes in Iberia are analysed considering a Lagrangian perspective of the atmospheric flow, using 6-hourly ERA-Interim reanalysis data for the years 1979–2012. Daily 2-m minimum temperatures below the 1st percentile and 2-m maximum temperatures above the 99th percentile at each grid point over Iberia are selected separately for winter and summer. Four categories of extremes are analysed using 10-d backward trajectories initialized at the extreme temperature grid points close to the surface: winter cold (WCE and warm extremes (WWE, and summer cold (SCE and warm extremes (SWE. Air masses leading to temperature extremes are first transported from the North Atlantic towards Europe for all categories. While there is a clear relation to large-scale circulation patterns in winter, the Iberian thermal low is important in summer. Along the trajectories, air mass characteristics are significantly modified through adiabatic warming (air parcel descent, upper-air radiative cooling and near-surface warming (surface heat fluxes and radiation. High residence times over continental areas, such as over northern-central Europe for WCE and, to a lesser extent, over Iberia for SWE, significantly enhance these air mass modifications. Near-surface diabatic warming is particularly striking for SWE. WCE and SWE are responsible for the most extreme conditions in a given year. For WWE and SCE, strong temperature advection associated with important meridional air mass transports are the main driving mechanisms, accompanied by comparatively minor changes in the air mass properties. These results permit a better understanding of mechanisms leading to temperature extremes in Iberia.

  15. Different neurophysiological mechanisms underlying word and rule extraction from speech.

    Directory of Open Access Journals (Sweden)

    Ruth De Diego Balaguer

    Full Text Available The initial process of identifying words from spoken language and the detection of more subtle regularities underlying their structure are mandatory processes for language acquisition. Little is known about the cognitive mechanisms that allow us to extract these two types of information and their specific time-course of acquisition following initial contact with a new language. We report time-related electrophysiological changes that occurred while participants learned an artificial language. These changes strongly correlated with the discovery of the structural rules embedded in the words. These changes were clearly different from those related to word learning and occurred during the first minutes of exposition. There is a functional distinction in the nature of the electrophysiological signals during acquisition: an increase in negativity (N400 in the central electrodes is related to word-learning and development of a frontal positivity (P2 is related to rule-learning. In addition, the results of an online implicit and a post-learning test indicate that, once the rules of the language have been acquired, new words following the rule are processed as words of the language. By contrast, new words violating the rule induce syntax-related electrophysiological responses when inserted online in the stream (an early frontal negativity followed by a late posterior positivity and clear lexical effects when presented in isolation (N400 modulation. The present study provides direct evidence suggesting that the mechanisms to extract words and structural dependencies from continuous speech are functionally segregated. When these mechanisms are engaged, the electrophysiological marker associated with rule-learning appears very quickly, during the earliest phases of exposition to a new language.

  16. Understanding and imitating unfamiliar actions: distinct underlying mechanisms.

    Directory of Open Access Journals (Sweden)

    Joana C Carmo

    Full Text Available The human "mirror neuron system" has been proposed to be the neural substrate that underlies understanding and, possibly, imitating actions. However, since the brain activity with mirror properties seems insufficient to provide a good description for imitation of actions outside one's own repertoire, the existence of supplementary processes has been proposed. Moreover, it is unclear whether action observation requires the same neural mechanisms as the explicit access to their meaning. The aim of this study was two-fold as we investigated whether action observation requires different processes depending on 1 whether the ultimate goal is to imitate or understand the presented actions and 2 whether the to-be-imitated actions are familiar or unfamiliar to the subject. Participants were presented with both meaningful familiar actions and meaningless unfamiliar actions that they had to either imitate or discriminate later. Event-related Potentials were used as differences in brain activity could have been masked by the use of other techniques with lower temporal resolution. In the imitation task, a sustained left frontal negativity was more pronounced for meaningless actions than for meaningful ones, starting from an early time-window. Conversely, observing unfamiliar versus familiar actions with the intention of discriminating them led to marked differences over right centro-posterior scalp regions, in both middle and latest time-windows. These findings suggest that action imitation and action understanding may be sustained by dissociable mechanisms: while imitation of unfamiliar actions activates left frontal processes, that are likely to be related to learning mechanisms, action understanding involves dedicated operations which probably require right posterior regions, consistent with their involvement in social interactions.

  17. Mechanical properties and failure mechanisms of graphene under a central load.

    Science.gov (United States)

    Wang, Shuaiwei; Yang, Baocheng; Zhang, Shouren; Yuan, Jinyun; Si, Yubing; Chen, Houyang

    2014-09-15

    By employing molecular dynamics simulations, the evolution of deformation of a monolayer graphene sheet under a central transverse loading are investigated. Dependence of mechanical responses on the symmetry (shape) of the loading domain, on the size of the graphene sheet, and on temperature, is determined. It is found that the symmetry of the loading domain plays a central role in fracture strength and strain. By increasing the size of the graphene sheet or increasing temperature, the tensile strength and fracture strain decrease. The results have demonstrated that the breaking force and breaking displacement are sensitive to both temperature and the symmetry of the loading domain. In addition, we find that the intrinsic strength of graphene under a central load is much smaller than that of graphene under a uniaxial load. By examining the deformation processes, two failure mechanisms are identified namely, brittle bond breaking and plastic relaxation. In the second mechanism, the Stone-Wales transformation occurs. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Microcracking in composite laminates under thermal and mechanical loading. Thesis

    Science.gov (United States)

    Maddocks, Jason R.

    1995-01-01

    Composites used in space structures are exposed to both extremes in temperature and applied mechanical loads. Cracks in the matrix form, changing the laminate thermoelastic properties. The goal of the present investigation is to develop a predictive methodology to quantify microcracking in general composite laminates under both thermal and mechanical loading. This objective is successfully met through a combination of analytical modeling and experimental investigation. In the analysis, the stress and displacement distributions in the vicinity of a crack are determined using a shear lag model. These are incorporated into an energy based cracking criterion to determine the favorability of crack formation. A progressive damage algorithm allows the inclusion of material softening effects and temperature-dependent material properties. The analysis is implemented by a computer code which gives predicted crack density and degraded laminate properties as functions of any thermomechanical load history. Extensive experimentation provides verification of the analysis. AS4/3501-6 graphite/epoxy laminates are manufactured with three different layups to investigate ply thickness and orientation effects. Thermal specimens are cooled to progressively lower temperatures down to -184 C. After conditioning the specimens to each temperature, cracks are counted on their edges using optical microscopy and in their interiors by sanding to incremental depths. Tensile coupons are loaded monotonically to progressively higher loads until failure. Cracks are counted on the coupon edges after each loading. A data fit to all available results provides input parameters for the analysis and shows them to be material properties, independent of geometry and loading. Correlation between experiment and analysis is generally very good under both thermal and mechanical loading, showing the methodology to be a powerful, unified tool. Delayed crack initiation observed in a few cases is attributed to a

  19. Pathophysiology of shunt dysfunction in shunt treated hydrocephalus

    DEFF Research Database (Denmark)

    Blegvad, C.; Skjolding, A D; Broholm, H

    2013-01-01

    We hypothesized that shunt dysfunction in the ventricular catheter and the shunt valve is caused by different cellular responses. We also hypothesized that the cellular responses depend on different pathophysiological mechanisms....

  20. Mechanical Modeling of a WIPP Drum Under Pressure

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Jeffrey A. [Sandia National Laboratories, Albuquerque, NM (United States)

    2014-11-25

    Mechanical modeling was undertaken to support the Waste Isolation Pilot Plant (WIPP) technical assessment team (TAT) investigating the February 14th 2014 event where there was a radiological release at the WIPP. The initial goal of the modeling was to examine if a mechanical model could inform the team about the event. The intention was to have a model that could test scenarios with respect to the rate of pressurization. It was expected that the deformation and failure (inability of the drum to contain any pressure) would vary according to the pressurization rate. As the work progressed there was also interest in using the mechanical analysis of the drum to investigate what would happen if a drum pressurized when it was located under a standard waste package. Specifically, would the deformation be detectable from camera views within the room. A finite element model of a WIPP 55-gallon drum was developed that used all hex elements. Analyses were conducted using the explicit transient dynamics module of Sierra/SM to explore potential pressurization scenarios of the drum. Theses analysis show similar deformation patterns to documented pressurization tests of drums in the literature. The calculated failure pressures from previous tests documented in the literature vary from as little as 16 psi to 320 psi. In addition, previous testing documented in the literature shows drums bulging but not failing at pressures ranging from 69 to 138 psi. The analyses performed for this study found the drums failing at pressures ranging from 35 psi to 75 psi. When the drums are pressurized quickly (in 0.01 seconds) there is significant deformation to the lid. At lower pressurization rates the deformation of the lid is considerably less, yet the lids will still open from the pressure. The analyses demonstrate the influence of pressurization rate on deformation and opening pressure of the drums. Analyses conducted with a substantial mass on top of the closed drum demonstrate that the

  1. Pathophysiology of acute small bowel disease with CT correlation

    Energy Technology Data Exchange (ETDEWEB)

    Sarwani, N., E-mail: nsarwani@hmc.psu.ed [Department of Radiology, Section of Abdominal Imaging, Penn State Milton Hershey Medical Center, Hershey, PA (United States); Tappouni, R.; Tice, J. [Department of Radiology, Section of Abdominal Imaging, Penn State Milton Hershey Medical Center, Hershey, PA (United States)

    2011-01-15

    The objective of this article is to review the pathophysiology of acute small bowel diseases, and to correlate the mechanisms of disease with computed tomography (CT) findings. Disease entities will be classified into the following: immune mediated and infectious causes, vascular causes, mechanical causes, trauma, and others. Having an understanding of acute small bowel pathophysiology is a useful teaching tool, and can lead to imaging clues to the most likely diagnosis of acute small bowel disorders.

  2. Metabolic acidosis as an underlying mechanism of respiratory distress in children with severe acute asthma.

    Science.gov (United States)

    Meert, Kathleen L; Clark, Jeff; Sarnaik, Ashok P

    2007-11-01

    1) To alert the clinician that increasing rate and depth of breathing during treatment of acute asthma may be a manifestation of metabolic acidosis with hyperventilation rather than worsening airway obstruction; and 2) to describe the frequency of metabolic acidosis with hyperventilation in children with severe acute asthma admitted to our pediatric intensive care unit. Retrospective medical record review. University-affiliated children's hospital. All patients admitted to the pediatric intensive care unit with a diagnosis of asthma between January 1, 2005, and December 31, 2005. None. Fifty-three patients with asthma (median age 7.8 yrs, range 0.7-17.9 yrs; 35 [66%] male; 46 [87%] black and 7 [13%] white) were admitted to the pediatric intensive care unit during the study period. Fifteen (28%) patients developed metabolic acidosis with hyperventilation (pH 120 mg/dL [6.7 mmol/L]). Patients who developed metabolic acidosis with hyperventilation received asthma therapy similar to that received by patients who did not develop the disorder. Metabolic acidosis resolved contemporaneously with tapering of beta2-adrenergic agonists and administration of supportive care. All patients survived. Metabolic acidosis with hyperventilation manifesting as respiratory distress can occur in children with severe acute asthma. A pathophysiologic rationale exists for the contribution of beta2-adrenergic agents to the development of this acid-base disorder. Failure to recognize metabolic acidosis as the underlying mechanism of respiratory distress may lead to inappropriate intensification of bronchodilator therapy. Supportive care and tapering of beta2-adrenergic agents are recommended to resolve this condition.

  3. Pathophysiology of constipation in the older adult

    OpenAIRE

    McCrea, G Lindsay; Miaskowski, Christine; Stotts, Nancy A; Macera, Liz; Varma, Madhulika G

    2008-01-01

    This review provides information on the definition of constipation, normal continence and defecation and a description of the pathophysiologic mechanisms of constipation. In addition, changes in the anatomy and physiology of the lower gastrointestinal tract associated with aging that may contribute to constipation are described. MEDLINE (1966-2007) and CINAHL (1980-2007) were searched. The following MeSH terms were used: constipation/etiology OR constipation/physiology OR constipation/physiop...

  4. Video analysis of concussion injury mechanism in under-18 rugby

    Science.gov (United States)

    Hendricks, Sharief; O'Connor, Sam; Lambert, Michael; Brown, James C; Burger, Nicholas; Mc Fie, Sarah; Readhead, Clint; Viljoen, Wayne

    2016-01-01

    Background Understanding the mechanism of injury is necessary for the development of effective injury prevention strategies. Video analysis of injuries provides valuable information on the playing situation and athlete-movement patterns, which can be used to formulate these strategies. Therefore, we conducted a video analysis of the mechanism of concussion injury in junior-level rugby union and compared it with a representative and matched non-injury sample. Methods Injury reports for 18 concussion events were collected from the 2011 to 2013 under-18 Craven Week tournaments. Also, video footage was recorded for all 3 years. On the basis of the injury events, a representative ‘control’ sample of matched non-injury events in the same players was identified. The video footage, which had been recorded at each tournament, was then retrospectively analysed and coded. 10 injury events (5 tackle, 4 ruck, 1 aerial collision) and 83 non-injury events were analysed. Results All concussions were a result of contact with an opponent and 60% of players were unaware of the impending contact. For the measurement of head position on contact, 43% had a ‘down’ position, 29% the ‘up and forward’ and 29% the ‘away’ position (n=7). The speed of the injured tackler was observed as ‘slow’ in 60% of injurious tackles (n=5). In 3 of the 4 rucks in which injury occurred (75%), the concussed player was acting defensively either in the capacity of ‘support’ (n=2) or as the ‘jackal’ (n=1). Conclusions Training interventions aimed at improving peripheral vision, strengthening of the cervical muscles, targeted conditioning programmes to reduce the effects of fatigue, and emphasising safe and effective playing techniques have the potential to reduce the risk of sustaining a concussion injury. PMID:27900149

  5. Video analysis of concussion injury mechanism in under-18 rugby.

    Science.gov (United States)

    Hendricks, Sharief; O'Connor, Sam; Lambert, Michael; Brown, James C; Burger, Nicholas; Mc Fie, Sarah; Readhead, Clint; Viljoen, Wayne

    2016-01-01

    Understanding the mechanism of injury is necessary for the development of effective injury prevention strategies. Video analysis of injuries provides valuable information on the playing situation and athlete-movement patterns, which can be used to formulate these strategies. Therefore, we conducted a video analysis of the mechanism of concussion injury in junior-level rugby union and compared it with a representative and matched non-injury sample. Injury reports for 18 concussion events were collected from the 2011 to 2013 under-18 Craven Week tournaments. Also, video footage was recorded for all 3 years. On the basis of the injury events, a representative 'control' sample of matched non-injury events in the same players was identified. The video footage, which had been recorded at each tournament, was then retrospectively analysed and coded. 10 injury events (5 tackle, 4 ruck, 1 aerial collision) and 83 non-injury events were analysed. All concussions were a result of contact with an opponent and 60% of players were unaware of the impending contact. For the measurement of head position on contact , 43% had a 'down' position, 29% the 'up and forward' and 29% the 'away' position (n=7). The speed of the injured tackler was observed as 'slow' in 60% of injurious tackles (n=5). In 3 of the 4 rucks in which injury occurred (75%), the concussed player was acting defensively either in the capacity of 'support' (n=2) or as the 'jackal' (n=1). Training interventions aimed at improving peripheral vision, strengthening of the cervical muscles, targeted conditioning programmes to reduce the effects of fatigue, and emphasising safe and effective playing techniques have the potential to reduce the risk of sustaining a concussion injury.

  6. Underlying Mechanisms of Tinnitus: Review and Clinical Implications

    Science.gov (United States)

    Henry, James A.; Roberts, Larry E.; Caspary, Donald M.; Theodoroff, Sarah M.; Salvi, Richard J.

    2016-01-01

    Background The study of tinnitus mechanisms has increased tenfold in the last decade. The common denominator for all of these studies is the goal of elucidating the underlying neural mechanisms of tinnitus with the ultimate purpose of finding a cure. While these basic science findings may not be immediately applicable to the clinician who works directly with patients to assist them in managing their reactions to tinnitus, a clear understanding of these findings is needed to develop the most effective procedures for alleviating tinnitus. Purpose The goal of this review is to provide audiologists and other health-care professionals with a basic understanding of the neurophysiological changes in the auditory system likely to be responsible for tinnitus. Results It is increasingly clear that tinnitus is a pathology involving neuroplastic changes in central auditory structures that take place when the brain is deprived of its normal input by pathology in the cochlea. Cochlear pathology is not always expressed in the audiogram but may be detected by more sensitive measures. Neural changes can occur at the level of synapses between inner hair cells and the auditory nerve and within multiple levels of the central auditory pathway. Long-term maintenance of tinnitus is likely a function of a complex network of structures involving central auditory and nonauditory systems. Conclusions Patients often have expectations that a treatment exists to cure their tinnitus. They should be made aware that research is increasing to discover such a cure and that their reactions to tinnitus can be mitigated through the use of evidence-based behavioral interventions. PMID:24622858

  7. Mechanisms underlying recovery of zooplankton in Lake Orta after liming

    Directory of Open Access Journals (Sweden)

    Roberta Piscia

    2016-04-01

    Full Text Available The goal of this study was to improve the understanding of the large-scale mechanisms underlying the recovery of the zooplankton of Lake Orta from historical contamination, following reduced input of ammonia and metals and the subsequent 1989/90 liming intervention. The industrial pollution had been severe and long-lasting (1929-1990. Zooplankton biodiversity has improved, but most of the new taxa appearing in our counts are rotifers, while many calanoids and the large cladoceran predators (Bythotrephes and Leptodora that are common in the nearby Lake Maggiore, were still absent from Lake Orta 17 years after liming. To aid understanding of the large-scale mechanisms controlling changes in annual richness, we assessed the annual persistence (P of Crustacea and Rotifera taxa as an estimator of whether propagules that survived introduction, as result of the natural recolonization process, also thrived. We found that the rate of introduction of zooplankton colonists and their persistence in the water column of Lake Orta changed from 1971 to 2007. New rotifer taxa appeared in the lake after the mid-1980s, when discharge of toxic substances decreased, but their annual persistence was low (P<0.5 until the turn of the century. The numerical values of rotifer and crustacean persistence in Lake Orta were unexpectedly high in 2001 and 2007 (0.55 and 0.72 for rotifers, 0.85 and 0.86 for crustacean, respectively, much higher than in limed lakes in Sudbury, Canada, and in adjacent Lake Maggiore. We hypothesize this could be related to the lack of Cladoceran predators and zooplanktivorous fish in the pelagic waters of Lake Orta.

  8. Mechanisms underlying stage-1 TRPL channel translocation in Drosophila photoreceptors.

    Directory of Open Access Journals (Sweden)

    Minh-Ha Lieu

    Full Text Available TRP channels function as key mediators of sensory transduction and other cellular signaling pathways. In Drosophila, TRP and TRPL are the light-activated channels in photoreceptors. While TRP is statically localized in the signaling compartment of the cell (the rhabdomere, TRPL localization is regulated by light. TRPL channels translocate out of the rhabdomere in two distinct stages, returning to the rhabdomere with dark-incubation. Translocation of TRPL channels regulates their availability, and thereby the gain of the signal. Little, however, is known about the mechanisms underlying this trafficking of TRPL channels.We first examine the involvement of de novo protein synthesis in TRPL translocation. We feed flies cycloheximide, verify inhibition of protein synthesis, and test for TRPL translocation in photoreceptors. We find that protein synthesis is not involved in either stage of TRPL translocation out of the rhabdomere, but that re-localization to the rhabdomere from stage-1, but not stage-2, depends on protein synthesis. We also characterize an ex vivo eye preparation that is amenable to biochemical and genetic manipulation. We use this preparation to examine mechanisms of stage-1 TRPL translocation. We find that stage-1 translocation is: induced with ATP depletion, unaltered with perturbation of the actin cytoskeleton or inhibition of endocytosis, and slowed with increased membrane sterol content.Our results indicate that translocation of TRPL out of the rhabdomere is likely due to protein transport, and not degradation/re-synthesis. Re-localization from each stage to the rhabdomere likely involves different strategies. Since TRPL channels can translocate to stage-1 in the absence of ATP, with no major requirement of the cytoskeleton, we suggest that stage-1 translocation involves simple diffusion through the apical membrane, which may be regulated by release of a light-dependent anchor in the rhabdomere.

  9. The behavior of the planetary rings under the Kozai Mechanism

    Science.gov (United States)

    Sucerquia, M. A.; Ramírez, C. V.; Zuluaga, J. I.

    2017-07-01

    Rings are one of the main feature of almost all giant planets in the Solar System. Even though thousands of exoplanets have been discovered to date, no evidence of exoplanetary rings have been found despite the effort made in the development and enhancing of techniques and methods for direct or indirect detection. In the transit of a ringed planet, the dynamic of the ring itself could play a meaningful role due to the so called Kozai Mechanism (KM) acting on each particle of it. When some specific initial conditions of the ring are fulfilled (as a ring inclination greater than ˜ 39°), KM generates short periodic changes in the inclination and eccentricity of each particle, leading to a meaningful characteristic collective behavior of the ring: it changes its width, inclination and optical depth. These changes induce periodic variations on the eclipsed area of the parent star, generating slight changes in the observed transit signal. Under this mechanism, light curves depths and shapes oscillate according to the fluctuations of the ring. To show this effect we have performed numerical simulations of the dynamic of a system of particles to asses the ring inclination and width variations over time. We have calculated the expected variations in the transit depth and finally, we have estimated the effect on the light curve of a hypothetical ringed exoplanet affected by the KM. The detection of this effect could be used as an alternative method to detect/confirm exoplanetary rings, and also it could be considered as a way to explain anomalous light curves patterns of exoplanets, as the case of KIC 8462852 star.

  10. Neural Mechanisms Underlying Hyperphagia in Prader-Willi Syndrome

    Science.gov (United States)

    Holsen, Laura M.; Zarcone, Jennifer R.; Brooks, William M.; Butler, Merlin G.; Thompson, Travis I.; Ahluwalia, Jasjit S.; Nollen, Nicole L.; Savage, Cary R.

    2006-01-01

    Objective Prader-Willi syndrome (PWS) is a genetic disorder associated with developmental delay, obesity, and obsessive behavior related to food consumption. The most striking symptom of PWS is hyperphagia; as such, PWS may provide important insights into factors leading to overeating and obesity in the general population. We used functional magnetic resonance imaging to study the neural mechanisms underlying responses to visual food stimuli, before and after eating, in individuals with PWS and a healthy weight control (HWC) group. Research Methods and Procedures Participants were scanned once before (pre-meal) and once after (post-meal) eating a standardized meal. Pictures of food, animals, and blurred control images were presented in a block design format during acquisition of functional magnetic resonance imaging data. Results Statistical contrasts in the HWC group showed greater activation to food pictures in the pre-meal condition compared with the post-meal condition in the amygdala, orbitofrontal cortex, medial prefrontal cortex (medial PFC), and frontal operculum. In comparison, the PWS group exhibited greater activation to food pictures in the post-meal condition compared with the pre-meal condition in the orbitofrontal cortex, medial PFC, insula, hippocampus, and parahippocampal gyrus. Between-group contrasts in the pre- and post-meal conditions confirmed group differences, with the PWS group showing greater activation than the HWC group after the meal in food motivation networks. Discussion Results point to distinct neural mechanisms associated with hyperphagia in PWS. After eating a meal, the PWS group showed hyperfunction in limbic and para-limbic regions that drive eating behavior (e.g., the amygdala) and in regions that suppress food intake (e.g., the medial PFC). PMID:16861608

  11. Neural mechanisms underlying hyperphagia in Prader-Willi syndrome.

    Science.gov (United States)

    Holsen, Laura M; Zarcone, Jennifer R; Brooks, William M; Butler, Merlin G; Thompson, Travis I; Ahluwalia, Jasjit S; Nollen, Nicole L; Savage, Cary R

    2006-06-01

    Prader-Willi syndrome (PWS) is a genetic disorder associated with developmental delay, obesity, and obsessive behavior related to food consumption. The most striking symptom of PWS is hyperphagia; as such, PWS may provide important insights into factors leading to overeating and obesity in the general population. We used functional magnetic resonance imaging to study the neural mechanisms underlying responses to visual food stimuli, before and after eating, in individuals with PWS and a healthy weight control (HWC) group. Participants were scanned once before (pre-meal) and once after (post-meal) eating a standardized meal. Pictures of food, animals, and blurred control images were presented in a block design format during acquisition of functional magnetic resonance imaging data. Statistical contrasts in the HWC group showed greater activation to food pictures in the pre-meal condition compared with the post-meal condition in the amygdala, orbitofrontal cortex, medial prefrontal cortex (medial PFC), and frontal operculum. In comparison, the PWS group exhibited greater activation to food pictures in the post-meal condition compared with the pre-meal condition in the orbitofrontal cortex, medial PFC, insula, hippocampus, and parahippocampal gyrus. Between-group contrasts in the pre- and post-meal conditions confirmed group differences, with the PWS group showing greater activation than the HWC group after the meal in food motivation networks. Results point to distinct neural mechanisms associated with hyperphagia in PWS. After eating a meal, the PWS group showed hyperfunction in limbic and paralimbic regions that drive eating behavior (e.g., the amygdala) and in regions that suppress food intake (e.g., the medial PFC).

  12. TFOS DEWS II pathophysiology report.

    Science.gov (United States)

    Bron, Anthony J; de Paiva, Cintia S; Chauhan, Sunil K; Bonini, Stefano; Gabison, Eric E; Jain, Sandeep; Knop, Erich; Markoulli, Maria; Ogawa, Yoko; Perez, Victor; Uchino, Yuichi; Yokoi, Norihiko; Zoukhri, Driss; Sullivan, David A

    2017-07-01

    The TFOS DEWS II Pathophysiology Subcommittee reviewed the mechanisms involved in the initiation and perpetuation of dry eye disease. Its central mechanism is evaporative water loss leading to hyperosmolar tissue damage. Research in human disease and in animal models has shown that this, either directly or by inducing inflammation, causes a loss of both epithelial and goblet cells. The consequent decrease in surface wettability leads to early tear film breakup and amplifies hyperosmolarity via a Vicious Circle. Pain in dry eye is caused by tear hyperosmolarity, loss of lubrication, inflammatory mediators and neurosensory factors, while visual symptoms arise from tear and ocular surface irregularity. Increased friction targets damage to the lids and ocular surface, resulting in characteristic punctate epithelial keratitis, superior limbic keratoconjunctivitis, filamentary keratitis, lid parallel conjunctival folds, and lid wiper epitheliopathy. Hybrid dry eye disease, with features of both aqueous deficiency and increased evaporation, is common and efforts should be made to determine the relative contribution of each form to the total picture. To this end, practical methods are needed to measure tear evaporation in the clinic, and similarly, methods are needed to measure osmolarity at the tissue level across the ocular surface, to better determine the severity of dry eye. Areas for future research include the role of genetic mechanisms in non-Sjögren syndrome dry eye, the targeting of the terminal duct in meibomian gland disease and the influence of gaze dynamics and the closed eye state on tear stability and ocular surface inflammation. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Mechanisms Underlying HIV-Associated Noninfectious Lung Disease.

    Science.gov (United States)

    Presti, Rachel M; Flores, Sonia C; Palmer, Brent E; Atkinson, Jeffrey J; Lesko, Catherine R; Lau, Bryan; Fontenot, Andrew P; Roman, Jesse; McDyer, John F; Twigg, Homer L

    2017-11-01

    Pulmonary disease remains a primary source of morbidity and mortality in persons living with HIV (PLWH), although the advent of potent combination antiretroviral therapy has resulted in a shift from predominantly infectious to noninfectious pulmonary complications. PLWH are at high risk for COPD, pulmonary hypertension, and lung cancer even in the era of combination antiretroviral therapy. The underlying mechanisms of this are incompletely understood, but recent research in both human and animal models suggests that oxidative stress, expression of matrix metalloproteinases, and genetic instability may result in lung damage, which predisposes PLWH to these conditions. Some of the factors that drive these processes include tobacco and other substance use, direct HIV infection and expression of specific HIV proteins, inflammation, and shifts in the microbiome toward pathogenic and opportunistic organisms. Further studies are needed to understand the relative importance of these factors to the development of lung disease in PLWH. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  14. [Neurophysiologic mechanisms of arterial hypertension under experimental chronic emotional stress].

    Science.gov (United States)

    Baumann, H; Martin, G; Urmantscheeva, T G; Degen, G; Wolter, F; Chasabova, W A; Gurk, C; Hinays, I; Läuter, J

    1976-01-01

    Neurophysiological studies were conducted with subhuman primates (macaca mulatta) in order to obtain an estimate of central nervous effects of socio-emotional stress. This was combined with continuously aggravated conditioning procedures in view of the possible significance of chronic environmental stress escalation for etiology and pathogenesis of an arterial hypertension model. Our conclusions are based on evoked potentials (EP) as integrative characteristics of cerebral information processing. The EPs were recorded by means of electrodes chronically implanted in brain structures of emotional and cardio-vascular relevance. Multivariate mathematico-statistical analyses of average EPs (AEP) provide an objective measure of stress sensibility of the individual, particularly of the effects of acute and chronic environmental stress factors upon the functional organization of the CNS. By means of a quantitative approach to AEP we were able to demonstrate a disjunction between distinct limbic and hypothalamic structures starting under stress conditions of subchronic character. We assume that the constancy of functionally antagonistic hyperactive excitation foci at diencephalic and supradiencephalic levels and their specific interaction with the equally stress related neocortical functional insufficiency constitutes a decisive pathogenetic central mechanism of neurotic behaviour. Long-term changes of amplification of external and internal afferences could be demonstrated on the basis of hypo- and hyperreactive neuroelectric functional patterns. These processes cause cerebro-visceral regulatory diseases as, e. g., a primary arterial hypertension by restriction of neocortical control and the corresponding efferent reactions for re-establishment of the dynamic homeostasis.

  15. Deciphering Molecular Mechanism Underlying Hypolipidemic Activity of Echinocystic Acid

    Directory of Open Access Journals (Sweden)

    Li Han

    2014-01-01

    Full Text Available Our previous study showed that a triterpene mixture, consisting of echinocystic acid (EA and oleanolic acid (OA at a ratio of 4 : 1, dose-dependently ameliorated the hyperlipidemia and atherosclerosis in rabbits fed with high fat/high cholesterol diets. This study was aimed at exploring the mechanisms underlying antihyperlipidemic effect of EA. Molecular docking simulation of EA was performed using Molegro Virtual Docker (version: 4.3.0 to investigate the potential targets related to lipid metabolism. Based on the molecular docking information, isotope labeling method or spectrophotometry was applied to examine the effect of EA on the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase, acyl-CoA:cholesterol acyltransferase (ACAT, and diacylglycerol acyltransferase (DGAT in rat liver microsomes. Our results revealed a strong affinity of EA towards ACAT and DGAT in molecular docking analysis, while low binding affinity existed between EA and HMG-CoA reductase as well as between EA and cholesteryl ester transfer protein. Consistent with the results of molecular docking, in vitro enzyme activity assays showed that EA inhibited ACAT and DGAT, with IC50 values of 103 and 139 μM, respectively, and exhibited no significant effect on HMG-CoA reductase activity. The present findings suggest that EA may exert hypolipidemic effect by inhibiting the activity of ACAT and DGAT.

  16. Molecular mechanisms underlying phosphate sensing, signaling, and adaptation in plants.

    Science.gov (United States)

    Zhang, Zhaoliang; Liao, Hong; Lucas, William J

    2014-03-01

    As an essential plant macronutrient, the low availability of phosphorus (P) in most soils imposes serious limitation on crop production. Plants have evolved complex responsive and adaptive mechanisms for acquisition, remobilization and recycling of phosphate (Pi) to maintain P homeostasis. Spatio-temporal molecular, physiological, and biochemical Pi deficiency responses developed by plants are the consequence of local and systemic sensing and signaling pathways. Pi deficiency is sensed locally by the root system where hormones serve as important signaling components in terms of developmental reprogramming, leading to changes in root system architecture. Root-to-shoot and shoot-to-root signals, delivered through the xylem and phloem, respectively, involving Pi itself, hormones, miRNAs, mRNAs, and sucrose, serve to coordinate Pi deficiency responses at the whole-plant level. A combination of chromatin remodeling, transcriptional and posttranslational events contribute to globally regulating a wide range of Pi deficiency responses. In this review, recent advances are evaluated in terms of progress toward developing a comprehensive understanding of the molecular events underlying control over P homeostasis. Application of this knowledge, in terms of developing crop plants having enhanced attributes for P use efficiency, is discussed from the perspective of agricultural sustainability in the face of diminishing global P supplies. © 2014 Institute of Botany, Chinese Academy of Sciences.

  17. Fatigue life prediction of mechanical structures under stochastic loading

    Directory of Open Access Journals (Sweden)

    Leitner Bohuš

    2018-01-01

    Full Text Available Problems of fatigue life prediction of materials and structures are discussed in the paper. Service loading is assumed as a continuous loading process with possible discontinuous events, which are caused by various operating conditions. The damage in a material is due to a cumulative degradation process. The damaging process is then represented either by rain-flow matrices or by a fatigue damage function which is derived using some hypothesis of a fatigue failure criterion. Presented theoretical procedure enables a very effective estimation of a service life and/or reliable evaluation of residual life of any structures under various types of loading and environmental conditions. This approach creates a good basis for powerful expert systems in structural and mechanical engineering. The aim of the paper is to present briefly some results of analysis of load-bearing steel structure loads of special railway crane PKP 25/20i which was utilized in some specific ad relatively hard operating conditions. Virtual models of the structure were being used in an analysis of acting working dynamics loads influence to be able to forecast fatigue life of load-bearing of the crane jib.

  18. Neural mechanisms underlying the induction and relief of perceptual curiosity

    Directory of Open Access Journals (Sweden)

    Marieke eJepma

    2012-02-01

    Full Text Available Curiosity is one of the most basic biological drives in both animals and humans, and has been identified as a key motive for learning and discovery. Despite the importance of curiosity and related behaviors, the topic has been largely neglected in human neuroscience; hence little is known about the neurobiological mechanisms underlying curiosity. We used functional magnetic resonance imaging (fMRI to investigate what happens in our brain during the induction and subsequent relief of perceptual curiosity. Our core findings were that (i the induction of perceptual curiosity, through the presentation of ambiguous visual input, activated the anterior insula and anterior cingulate cortex, brain regions sensitive to conflict and arousal; (ii the relief of perceptual curiosity, through visual disambiguation, activated regions of the striatum that have been related to reward processing; and (iii the relief of perceptual curiosity was associated with hippocampal activation and enhanced incidental memory. These findings provide the first demonstration of the neural basis of human perceptual curiosity. Our results provide neurobiological support for a classic psychological theory of curiosity, which holds that curiosity is an aversive condition of increased arousal whose termination is rewarding and facilitates memory.

  19. Spread of Epidemic on Complex Networks Under Voluntary Vaccination Mechanism

    Science.gov (United States)

    Xue, Shengjun; Ruan, Feng; Yin, Chuanyang; Zhang, Haifeng; Wang, Binghong

    Under the assumption that the decision of vaccination is a voluntary behavior, in this paper, we use two forms of risk functions to characterize how susceptible individuals estimate the perceived risk of infection. One is uniform case, where each susceptible individual estimates the perceived risk of infection only based on the density of infection at each time step, so the risk function is only a function of the density of infection; another is preferential case, where each susceptible individual estimates the perceived risk of infection not only based on the density of infection but only related to its own activities/immediate neighbors (in network terminology, the activity or the number of immediate neighbors is the degree of node), so the risk function is a function of the density of infection and the degree of individuals. By investigating two different ways of estimating the risk of infection for susceptible individuals on complex network, we find that, for the preferential case, the spread of epidemic can be effectively controlled; yet, for the uniform case, voluntary vaccination mechanism is almost invalid in controlling the spread of epidemic on networks. Furthermore, given the temporality of some vaccines, the waves of epidemic for two cases are also different. Therefore, our work insight that the way of estimating the perceived risk of infection determines the decision on vaccination options, and then determines the success or failure of control strategy.

  20. Mechanisms underlying the antihypertensive effects of garlic bioactives.

    Science.gov (United States)

    Shouk, Reem; Abdou, Aya; Shetty, Kalidas; Sarkar, Dipayan; Eid, Ali H

    2014-02-01

    Cardiovascular disease remains the leading cause of death worldwide with hypertension being a major contributing factor to cardiovascular disease-associated mortality. On a population level, non-pharmacological approaches, such as alternative/complementary medicine, including phytochemicals, have the potential to ameliorate cardiovascular risk factors, including high blood pressure. Several epidemiological studies suggest an antihypertensive effect of garlic (Allium sativum) and of many its bioactive components. The aim of this review is to present an in-depth discussion regarding the molecular, biochemical and cellular rationale underlying the antihypertensive properties of garlic and its bioactive constituents with a primary focus on S-allyl cysteine and allicin. Key studies, largely from PubMed, were selected and screened to develop a comprehensive understanding of the specific role of garlic and its bioactive constituents in the management of hypertension. We also reviewed recent advances focusing on the role of garlic bioactives, S-allyl cysteine and allicin, in modulating various parameters implicated in the pathogenesis of hypertension. These parameters include oxidative stress, nitric oxide bioavailability, hydrogen sulfide production, angiotensin converting enzyme activity, expression of nuclear factor-κB and the proliferation of vascular smooth muscle cells. This review suggests that garlic and garlic derived bioactives have significant medicinal properties with the potential for ameliorating hypertension and associated morbidity; however, further clinical and epidemiological studies are required to determine completely the specific physiological and biochemical mechanisms involved in disease prevention and management. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Role of Adenosine A2A Receptors in Modulating Synaptic Functions and Brain Levels of BDNF: a Possible Key Mechanism in the Pathophysiology of Huntington's Disease

    Directory of Open Access Journals (Sweden)

    Maria Teresa Tebano

    2010-01-01

    Full Text Available In the last few years, accumulating evidence has shown the existence of an important cross-talk between adenosine A2A receptors (A2ARs and brain-derived neurotrophic factor (BDNF. Not only are A2ARs involved in the mechanism of transactivation of BDNF receptor TrkB, they also modulate the effect of BDNF on synaptic transmission, playing a facilitatory and permissive role. The cAMP-PKA pathway, the main transduction system operated by A2ARs, is involved in such effects. Furthermore, a basal tonus of A2ARs is required to allow the regulation of BDNF physiological levels in the brain, as demonstrated by the reduced protein levels measured in A2ARs KO mice. The crucial role of adenosine A2ARs in the maintenance of synaptic functions and BDNF levels will be reviewed here and discussed in the light of possible implications for Huntington's disease therapy, in which a joint impairment of BDNF and A2ARs seems to play a pathogenetic role.

  2. [Pathophysiology and genetics of obesity].

    Science.gov (United States)

    Oberkofler, Hannes; Krempler, Franz; Patsch, Wolfgang

    2002-01-01

    Obesity has become the most prevalent nutritional disorder in post-industrialised societies and it is associated with the development of severe and costly complications such as type 2 diabetes mellitus and coronary heart disease or cancer. A large proportion of the risk of obesity is determined by the genetic susceptibility of an individual, but environmental factors conducive for the disorder play an important role in its phenotypic expression. Several candidate genes emerged from studies in animal models of obesity, but human pathophysiology is likely to be more complex. Thus, most cases of human obesity probably result from subtle interactions of susceptibility genes with environmental factors favouring deposition of excess calories as fat. The recent surge of obesity may relate to past evolutionary pressure which favoured selection of mechanisms defending body-weight against caloric restriction rather than against caloric excess. Rapidly developing new techniques in quantitative genetics and growing information from functional genomics will help to understand the interaction of environmental factors with signalling networks that regulate energy metabolism. The role of previously unknown pathways in the aetiology of obesity will be uncovered. The typing of numerous genetic variants will become possible and allow individual risk assessment for obesity and/or its associated disorders. Thus, rational and individually tailored therapies may be developed to combat obesity and its associated disorders.

  3. Extracellular Vesicles in Renal Pathophysiology.

    Science.gov (United States)

    Pomatto, Margherita A C; Gai, Chiara; Bussolati, Benedetta; Camussi, Giovanni

    2017-01-01

    Extracellular vesicles are a heterogeneous population of microparticles released by virtually all living cells which have been recently widely investigated in different biological fields. They are typically composed of two primary types (exosomes and microvesicles) and are recently commanding increasing attention as mediators of cellular signaling. Indeed, these vesicles can affect recipient cells by carrying and delivering complex cargos of biomolecules (including proteins, lipids and nucleic acids), protected from enzymatic degradation in the environment. Their importance has been demonstrated in the pathophysiology of several organs, in particular in kidney, where different cell types secrete extracellular vesicles that mediate their communication with downstream urinary tract cells. Over the past few years, evidence has been shown that vesicles participate in kidney development and normal physiology. Moreover, EVs are widely demonstrated to be implicated in cellular signaling during renal regenerative and pathological processes. Although many EV mechanisms are still poorly understood, in particular in kidney, the discovery of their role could help to shed light on renal biological processes which are so far elusive. Lastly, extracellular vesicles secreted by renal cells gather in urine, thus becoming a great resource for disease or recovery markers and a promising non-invasive diagnostic instrument for renal disease. In the present review, we discuss the most recent findings on the role of extracellular vesicles in renal physiopathology and their potential implication in diagnosis and therapy.

  4. Mechanism of crack initiation and crack growth under thermal and mechanical fatigue loading

    International Nuclear Information System (INIS)

    Utz, S.; Soppa, E.; Silcher, H.; Kohler, C.

    2013-01-01

    The present contribution is focused on the experimental investigations and numerical simulations of the deformation behaviour and crack development in the austenitic stainless steel X6CrNiNb18-10 under thermal and mechanical cyclic loading in HCF and LCF regimes. The main objective of this research is the understanding of the basic mechanisms of fatigue damage and the development of simulation methods, which can be applied further in safety evaluations of nuclear power plant components. In this context the modelling of crack initiation and crack growth inside the material structure induced by varying thermal or mechanical loads are of particular interest. The mechanisms of crack initiation depend among other things on the type of loading, microstructure, material properties and temperature. The Nb-stabilized austenitic stainless steel in the solution-annealed condition was chosen for the investigations. Experiments with two kinds of cyclic loading - pure thermal and pure mechanical - were carried out and simulated. The fatigue behaviour of the steel X6CrNiNb18-10 under thermal loading was studied within the framework of the joint research project [4]. Interrupted thermal cyclic tests in the temperature range of 150 C to 300 C combined with non-destructive residual stress measurements (XRD) and various microscopic investigations, e.g. in SEM (Scanning Electron Microscope), were used to study the effects of thermal cyclic loading on the material. This thermal cyclic loading leads to thermal induced stresses and strains. As a result intrusions and extrusions appear inside the grains (at the surface), at which microcracks arise and evolve to a dominant crack. Finally, these microcracks cause a continuous and significant decrease of residual stresses. The fatigue behaviour of the steel X6CrNiNb18-10 under mechanical loading at room temperature was studied within the framework of the research project [5], [8]. With a combination of interrupted LCF tests and EBSD

  5. Mechanism of crack initiation and crack growth under thermal and mechanical fatigue loading

    Energy Technology Data Exchange (ETDEWEB)

    Utz, S.; Soppa, E.; Silcher, H.; Kohler, C. [Stuttgart Univ. (Germany). Materials Testing Inst.

    2013-07-01

    The present contribution is focused on the experimental investigations and numerical simulations of the deformation behaviour and crack development in the austenitic stainless steel X6CrNiNb18-10 under thermal and mechanical cyclic loading in HCF and LCF regimes. The main objective of this research is the understanding of the basic mechanisms of fatigue damage and the development of simulation methods, which can be applied further in safety evaluations of nuclear power plant components. In this context the modelling of crack initiation and crack growth inside the material structure induced by varying thermal or mechanical loads are of particular interest. The mechanisms of crack initiation depend among other things on the type of loading, microstructure, material properties and temperature. The Nb-stabilized austenitic stainless steel in the solution-annealed condition was chosen for the investigations. Experiments with two kinds of cyclic loading - pure thermal and pure mechanical - were carried out and simulated. The fatigue behaviour of the steel X6CrNiNb18-10 under thermal loading was studied within the framework of the joint research project [4]. Interrupted thermal cyclic tests in the temperature range of 150 C to 300 C combined with non-destructive residual stress measurements (XRD) and various microscopic investigations, e.g. in SEM (Scanning Electron Microscope), were used to study the effects of thermal cyclic loading on the material. This thermal cyclic loading leads to thermal induced stresses and strains. As a result intrusions and extrusions appear inside the grains (at the surface), at which microcracks arise and evolve to a dominant crack. Finally, these microcracks cause a continuous and significant decrease of residual stresses. The fatigue behaviour of the steel X6CrNiNb18-10 under mechanical loading at room temperature was studied within the framework of the research project [5], [8]. With a combination of interrupted LCF tests and EBSD

  6. Mechanisms underlying the antihypertensive properties of Urtica dioica.

    Science.gov (United States)

    Qayyum, Rahila; Qamar, Hafiz Misbah-Ud-Din; Khan, Shamim; Salma, Umme; Khan, Taous; Shah, Abdul Jabbar

    2016-09-01

    Urtica dioica has traditionally been used in the management of cardiovascular disorders especially hypertension. The aim of this study was to explore pharmacological base of its use in hypertension. Crude methanolic extract of U. dioica (Ud.Cr) and its fractions (Ud.EtAc, Ud.nHex, Ud.Chl and Ud.Aq) were tested in vivo on normotensive and hypertensive rats under anesthesia for blood pressure lowering effect. In-vitro experiments on rat and rabbit aortae were employed to probe the vasorelaxation mechanism(s). The responses were measured using pressure and force transducers connected to PowerLab Data Acquisition System. Ud.Cr and fractions were found more effective antihypertensive in hypertensive rats than normotensive with remarkable potency exhibited by the ethyl acetate fraction. The effect was same in the presence of atropine. In isolated rat aortic rings, Ud.Cr and all its fractions exhibited L-NAME sensitive endothelium-dependent vasodilator effect and also inhibit K(+) (80 mM)-induced pre-contractions. In isolated rabbit thoracic aortic rings Ud.Cr and its fractions induced relaxation with more potency against K(+) (80 mM) than phenylephrine (1 µM) like verapamil, showing Ud.EtAc fraction the most potent one. Pre-incubation of aortic rings with Ud.Cr and its fractions exhibited Ca(2+) channel blocking activity comparable with verapamil by shifting Ca(2+) concentration response curves to the right. Ud.Cr and its fractions also ablated the intracellular Ca(2+) release by suppressing PE peak formation in Ca(2+) free medium. When tested on basal tension, the crude extract and all fractions were devoid of any vasoconstrictor effect. These data indicate that crude methanolic extract and its fractions possess antihypertensive effect. Identification of NO-mediated vasorelaxation and calcium channel blocking effects explain the antihypertensive potential of U. dioica and provide a potential pharmacological base to its medicinal use in the management of hypertension.

  7. Antioxidant Property of Jobelyn as the Possible Mechanism Underlying

    Directory of Open Access Journals (Sweden)

    Solomon Umukoro

    2013-01-01

    Full Text Available   Introduction: Amnesia or loss of memory is the cardinal hallmark of Alzheimer’s disease (AD, a progressive neurodegenerative disorder associated with ageing process. Although, AD had been discovered over a century ago, drugs which could cure or halt the progression of the disease are yet to see the light of the day. However, there has been a growing interest in the use of phytomedicines with multipronged mechanisms of action that could target various aspects of the pathologies of AD. Jobelyn (JB is a potent antioxidant African polyherbal formulation with active components that have been acclaimed to show neuroprotection. T his investigation was carried out to evaluate whether JB has anti-amnesic and antioxidant activities.   Methods: The alteration of alternation behavior in the Y-maze paradigm was utilized as the test for memory function in mice. The effect of JB on a cetylcholinesterase (AChE activity, malondialdehyde (MDA level and the concentrations of glutathione (GSH in the frontal cortex and hippocampus were assessed in rats as means of providing insight into the mechanism underlying its anti-amnesic activity. The animals were given JB (1, 2.5 or 5mg/kg, i.p. daily for 7 days before the biochemical assays or test for memory functions were carried out.   Results: JB was found to produce a significant increase in the level of alternation behavior compared with the control, suggesting anti-amnesic activity. Also, JB reversed the memory impairment induced by scopolamine, which further indicates anti-amnesic property. Furthermore, JB demonstrated a significant inhibition of MDA formation in the frontal cortex and hippocampus of rats, indicating antioxidant property. In addition, it increased the defense armory of the brain tissues, as it significantly increased the concentrations of GSH in the frontal cortex and hippocampus of rats. However, JB did not demonstrate any inhibitory effect against AChE activity in the frontal cortex and

  8. Bronchopulmonary dysplasia: understanding of the underlying pathological mechanisms

    Directory of Open Access Journals (Sweden)

    Daniela Fanni

    2014-06-01

    better understanding of the underlying pathological mechanisms of BPD might provide insight into development of new therapeutic and preventive strategies.  Proceedings of the International Course on Perinatal Pathology (part of the 10th International Workshop on Neonatology · October 22nd-25th, 2014 · Cagliari (Italy · October 25th, 2014 · The role of the clinical pathological dialogue in problem solving Guest Editors: Gavino Faa, Vassilios Fanos, Peter Van Eyken

  9. Alteration mechanisms of UOX spent fuel under water

    International Nuclear Information System (INIS)

    Muzeau, B.

    2008-06-01

    The mechanisms of spent fuel alteration in aqueous media need to be understood on the assumption of a direct disposal of the assemblies in a geological formation or for long duration storage in pool. This work is a contribution to the study of the effects of the alpha and/or beta/gamma radiolysis of water on the oxidation and the dissolution of the UO 2 matrix of UOX spent fuel. The effects of the alpha radiolysis, predominant in geological disposal conditions, were quantified by using samples of UO 2 doped with plutonium. The leaching experiments highlighted two types of control for the matrix alteration according to the alpha activity. The first is based on the radiolytic oxidation of the surface and leads to a continuous release of uranium in solution whereas the second is based on a control by the solubility of uranium. An activity threshold, between 18 MBq.g -1 and 33 MBq.g -1 , was defined in a carbonated water. The value of this threshold is dependent on the experimental conditions and the presence or not of electro-active species such as hydrogen in the system. The effects of the alpha/beta/gamma radiolysis in relation with the storage conditions were also quantified. The experimental data obtained on spent fuel indicate that the alteration rate of the matrix based on the behaviour of tracer elements (caesium and strontium) reached a maximum value of some mg.m -2 .d -1 , even under very oxidizing conditions. The solubility of uranium and the nature of the secondary phases depend however on the extent of the oxidizing conditions. (author)

  10. Unraveling the Molecular Mechanisms Underlying the Nasopharyngeal Bacterial Community Structure

    Directory of Open Access Journals (Sweden)

    Wouter A. A. de Steenhuijsen Piters

    2016-03-01

    Full Text Available The upper respiratory tract is colonized by a diverse array of commensal bacteria that harbor potential pathogens, such as Streptococcus pneumoniae. As long as the local microbial ecosystem—also called “microbiome”—is in balance, these potentially pathogenic bacterial residents cause no harm to the host. However, similar to macrobiological ecosystems, when the bacterial community structure gets perturbed, potential pathogens can overtake the niche and cause mild to severe infections. Recent studies using next-generation sequencing show that S. pneumoniae, as well as other potential pathogens, might be kept at bay by certain commensal bacteria, including Corynebacterium and Dolosigranulum spp. Bomar and colleagues are the first to explore a specific biological mechanism contributing to the antagonistic interaction between Corynebacterium accolens and S. pneumoniae in vitro [L. Bomar, S. D. Brugger, B. H. Yost, S. S. Davies, K. P. Lemon, mBio 7(1:e01725-15, 2016, doi:10.1128/mBio.01725-15]. The authors comprehensively show that C. accolens is capable of hydrolyzing host triacylglycerols into free fatty acids, which display antipneumococcal properties, suggesting that these bacteria might contribute to the containment of pneumococcus. This work exemplifies how molecular epidemiological findings can lay the foundation for mechanistic studies to elucidate the host-microbe and microbial interspecies interactions underlying the bacterial community structure. Next, translation of these results to an in vivo setting seems necessary to unveil the magnitude and importance of the observed effect in its natural, polymicrobial setting.

  11. Cognitive mechanisms underlying instructed choice exploration of small city maps

    Directory of Open Access Journals (Sweden)

    Sofia eSakellaridi

    2015-03-01

    Full Text Available We investigated the cognitive mechanisms underlying the exploration and decision-making in realistic and novel environments. Twelve human subjects were shown small circular U.S. city maps with two locations highlighted on the circumference, as possible choices for a post office (targets. At the beginning of a trial, subjects fixated a spot at the center of the map and ultimately chose one of the two locations. A space syntax analysis of the map paths (from the center to each target revealed that the chosen location was associated with the less convoluted path, as if subjects navigated mentally the paths in an ant’s way, i.e. by staying within street boundaries, and ultimately choosing the target that could be reached from the center in the shortest way, and the fewest turns and intersections. The subjects’ strategy for map exploration and decision making was investigated by monitoring eye position during the task. This revealed a restricted exploration of the map delimited by the location of the two alternative options and the center of the map. Specifically, subjects explored the areas around the two target options by repeatedly looking at them before deciding which one to choose, presumably implementing an evaluation and decision-making process. The ultimate selection of a specific target was significantly associated with the time spent exploring the area around that target. Finally, an analysis of the sequence of eye fixations revealed that subjects tended to look systematically towards the target ultimately chosen even from the beginning of the trial. This finding indicates an early cognitive selection bias for the ensuing decision process.

  12. Pathophysiology of Hyperhidrosis.

    Science.gov (United States)

    Schick, Christoph H

    2016-11-01

    Studies and case reports on excessive sweating frequently state that hyperhidrosis is a disease whose origin and mechanism are unknown. However, the term excessive is rarely based on systematic diagnostic measurements, instead being a description of the symptoms from patient histories, which suggests that hyperhidrosis is purely a problem involving the quantity of sweat, whereas it is a change in the control mechanism of sweating in which the need for and production of sweat are strongly disproportionate. This lack of proportion is perceived by those affected to be a limitation of activities of daily living and is thus pathologic. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Plant-insect interactions under bacterial influence: ecological implications and underlying mechanisms.

    Science.gov (United States)

    Sugio, Akiko; Dubreuil, Géraldine; Giron, David; Simon, Jean-Christophe

    2015-02-01

    Plants and insects have been co-existing for more than 400 million years, leading to intimate and complex relationships. Throughout their own evolutionary history, plants and insects have also established intricate and very diverse relationships with microbial associates. Studies in recent years have revealed plant- or insect-associated microbes to be instrumental in plant-insect interactions, with important implications for plant defences and plant utilization by insects. Microbial communities associated with plants are rich in diversity, and their structure greatly differs between below- and above-ground levels. Microbial communities associated with insect herbivores generally present a lower diversity and can reside in different body parts of their hosts including bacteriocytes, haemolymph, gut, and salivary glands. Acquisition of microbial communities by vertical or horizontal transmission and possible genetic exchanges through lateral transfer could strongly impact on the host insect or plant fitness by conferring adaptations to new habitats. Recent developments in sequencing technologies and molecular tools have dramatically enhanced opportunities to characterize the microbial diversity associated with plants and insects and have unveiled some of the mechanisms by which symbionts modulate plant-insect interactions. Here, we focus on the diversity and ecological consequences of bacterial communities associated with plants and herbivorous insects. We also highlight the known mechanisms by which these microbes interfere with plant-insect interactions. Revealing such mechanisms in model systems under controlled environments but also in more natural ecological settings will help us to understand the evolution of complex multitrophic interactions in which plants, herbivorous insects, and micro-organisms are inserted. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions

  14. Pathophysiology of osteoporosis: new mechanistic insights.

    Science.gov (United States)

    Armas, Laura A G; Recker, Robert R

    2012-09-01

    Understanding of the pathophysiology of osteoporosis has evolved to include compromised bone strength and skeletal fragility caused by several factors: (1) defects in microarchitecture of trabeculae, (2) defective intrinsic material properties of bone tissue, (3) defective repair of microdamage from normal daily activities, and (4) excessive bone remodeling rates. These factors occur in the context of age-related bone loss. Clinical studies of estrogen deprivation, antiresorptives, mechanical loading, and disuse have helped further knowledge of the factors affecting bone quality and the mechanisms that underlie them. This progress has led to several new drug targets in the treatment of osteoporosis. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Molecular Mechanics: The Method and Its Underlying Philosophy.

    Science.gov (United States)

    Boyd, Donald B.; Lipkowitz, Kenny B.

    1982-01-01

    Molecular mechanics is a nonquantum mechanical method for solving problems concerning molecular geometries and energy. Methodology based on: the principle of combining potential energy functions of all structural features of a particular molecule into a total force field; derivation of basic equations; and use of available computer programs is…

  16. Potential Mechanisms Underlying Centralized Pain and Emerging Therapeutic Interventions

    Directory of Open Access Journals (Sweden)

    Olivia C. Eller-Smith

    2018-02-01

    Full Text Available Centralized pain syndromes are associated with changes within the central nervous system that amplify peripheral input and/or generate the perception of pain in the absence of a noxious stimulus. Examples of idiopathic functional disorders that are often categorized as centralized pain syndromes include fibromyalgia, chronic pelvic pain syndromes, migraine, and temporomandibular disorder. Patients often suffer from widespread pain, associated with more than one specific syndrome, and report fatigue, mood and sleep disturbances, and poor quality of life. The high degree of symptom comorbidity and a lack of definitive underlying etiology make these syndromes notoriously difficult to treat. The main purpose of this review article is to discuss potential mechanisms of centrally-driven pain amplification and how they may contribute to increased comorbidity, poorer pain outcomes, and decreased quality of life in patients diagnosed with centralized pain syndromes, as well as discuss emerging non-pharmacological therapies that improve symptomology associated with these syndromes. Abnormal regulation and output of the hypothalamic-pituitary-adrenal (HPA axis is commonly associated with centralized pain disorders. The HPA axis is the primary stress response system and its activation results in downstream production of cortisol and a dampening of the immune response. Patients with centralized pain syndromes often present with hyper- or hypocortisolism and evidence of altered downstream signaling from the HPA axis including increased Mast cell (MC infiltration and activation, which can lead to sensitization of nearby nociceptive afferents. Increased peripheral input via nociceptor activation can lead to “hyperalgesic priming” and/or “wind-up” and eventually to central sensitization through long term potentiation in the central nervous system. Other evidence of central modifications has been observed through brain imaging studies of functional

  17. [Study on main pharmacodynamics and underlying mechanisms of 999 Ganmaoling].

    Science.gov (United States)

    Xu, Qi-Hua; He, Rong; Peng, Bo; Ye, Zu-Guang; Li, Jian-Rong; Zhang, Yue-Fei; Dai, Zhi

    2016-04-01

    To observe synergistic effects of 999 Ganmaoling (GML) and its Chinese/Western materia medica (CMM and WMM) on pharmacodynamic action and to study underlying mechanisms, their anti-inflammatory, antipyretic effects were compared by assaying the increased capillary permeability induced by glacial acetic acid in mice, ear swelling induced by Xylene in mice, non-specific pleurisy induced by carrageenan in rats, and yeast induced fever in rats. Crystal violet (CV) and microbial activity (XTT) assay were used to evaluate the inhibition of GML and its CMM and WMM on KPN biofilm formation, and scanning electron microscopy (SEM) was applied for observing KPN biofilm morphology changes. The results showed that compared with control group, GML could reduce exudation amount of Evans-Blue and the degree of Ear swelling significantly, and CMM and WMM have no significant effects. The concentration of TNF-α and IL-1β of rat pleural effusion in GML, CMM and WMM group decreased significantly. The concentration of TNF-α, IL-1β and IL-8 in GML group, TNF-α, IL-8 in WMM group and IL-8 in CMM in rats serum decreased significantly. The body temperature in rats decreased significantly in GML and WMM group after 4-8 h of administration. CMM group showed no significant difference in rat body temperature compare with control. Compared with control group, GML (55-13.75 g•L⁻¹) could inhibit KPN biofilm formation and reduce number of viable cells in the KPN biofilm. CMM (45-22.5 g•L⁻¹) and WMM (10 g•L⁻¹) could also inhibit KPN biofilm formation and reduce number of viable cells (P<0.01). Result of SEM also showed that GML (55 g•L⁻¹) and its CMM (45 g•L⁻¹) and WMM (10 g•L⁻¹) could interfere the bacterial arrangement of KPN biofilm and extracellular matrix. GML and its CMM & WMM could inhibit the formation of KPN biofilm, CMM & WMM in GML showed synergism and complementation in inhibit KPN biofilm. Results showed that GML had obvious anti-inflammatory and

  18. Mechanisms and pharmacogenetic signals underlying thiazide diuretics blood pressure response.

    Science.gov (United States)

    Shahin, Mohamed H; Johnson, Julie A

    2016-04-01

    Thiazide (TZD) diuretics are among the most commonly prescribed antihypertensives globally; however their chronic blood pressure (BP) lowering mechanism remains unclear. Herein we discuss the current evidence regarding specific mechanisms regulating the antihypertensive effects of TZDs, suggesting that TZDs act via multiple complex and interacting mechanisms, including natriuresis with short term use and direct vasodilatory effects chronically. Additionally, we review pharmacogenomics signals that have been associated with TZDs BP-response in several cohorts (i.e. NEDD4L, PRKCA, EDNRA-GNAS, and YEATS4) and discuss how these genes might be related to TZD BP-response mechanism. Understanding the association between these genes and TZD BP mechanism might facilitate the development of new drugs and therapeutic approaches based on a deeper understanding of the determinants of BP-response. Copyright © 2016. Published by Elsevier Ltd.

  19. Pathophysiological mechanisms of urbanisation-related ...

    African Journals Online (AJOL)

    Twenty-seven urban hypertensive patients and the same number of normotensive controls were studied on baseline diet, after 5 days of sodium restriction and after 5 days of sodium loading. Mean arterial blood pressure, plasma and ET values, PRA, TXA2/PGI2 and ALDO were assessed on each diet. The results showed ...

  20. Obesity-related hypertension: possible pathophysiological mechanisms

    Czech Academy of Sciences Publication Activity Database

    Vaněčková, Ivana; Maletínská, Lenka; Behuliak, Michal; Nagelová, Veronika; Zicha, Josef; Kuneš, Jaroslav

    2014-01-01

    Roč. 223, č. 3 (2014), R63-R78 ISSN 0022-0795 R&D Projects: GA ČR(CZ) GAP304/12/0259 Institutional support: RVO:67985823 ; RVO:61388963 Keywords : obesity * hypertension * sympathetic nervous system * renin-angiotensin system * critical developmental periods * epigenetics * rat Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 3.718, year: 2014

  1. Mechanical response of collagen molecule under hydrostatic compression

    International Nuclear Information System (INIS)

    Saini, Karanvir; Kumar, Navin

    2015-01-01

    Proteins like collagen are the basic building blocks of various body tissues (soft and hard). Collagen molecules find their presence in the skeletal system of the body where they bear mechanical loads from different directions, either individually or along with hydroxy-apatite crystals. Therefore, it is very important to understand the mechanical behavior of the collagen molecule which is subjected to multi-axial state of loading. The estimation of strains of collagen molecule along different directions resulting from the changes in hydrostatic pressure magnitude, can provide us new insights into its mechanical behavior. In the present work, full atomistic simulations have been used to study global (volumetric) as well as local (along different directions) mechanical properties of the hydrated collagen molecule which is subjected to different hydrostatic pressure magnitudes. To estimate the local mechanical properties, the strains of collagen molecule along its longitudinal and transverse directions have been acquired at different hydrostatic pressure magnitudes. In spite of non-homogeneous distribution of atoms within the collagen molecule, the calculated values of local mechanical properties have been found to carry the same order of magnitude along the longitudinal and transverse directions. It has been demonstrated that the values of global mechanical properties like compressibility, bulk modulus, etc. as well as local mechanical properties like linear compressibility, linear elastic modulus, etc. are functions of magnitudes of applied hydrostatic pressures. The mechanical characteristics of collagen molecule based on the atomistic model have also been compared with that of the continuum model in the present work. The comparison showed up orthotropic material behavior for the collagen molecule. The information on collagen molecule provided in the present study can be very helpful in designing the future bio-materials.

  2. Sepsis: Current Definition, Pathophysiology, Diagnosis, and Management.

    Science.gov (United States)

    Taeb, Abdalsamih M; Hooper, Michael H; Marik, Paul E

    2017-06-01

    Sepsis is a clinical syndrome that results from the dysregulated inflammatory response to infection that leads to organ dysfunction. The resulting losses to society in terms of financial burden, morbidity, and mortality are enormous. We provide a review of sepsis, its underlying pathophysiology, and guidance for diagnosis and management of this common disease. Current established treatments include appropriate antimicrobial agents to target the underlying infection, optimization of intravascular volume to improve stroke volume, vasopressors to counteract vasoplegic shock, and high-quality supportive care. Appropriate implementation of established treatments combined with novel therapeutic approaches promises to continue to decrease the impact of this disease.

  3. Mechanical Characterization of Anion Exchange Membranes Under Controlled Environmental Conditions

    Science.gov (United States)

    2015-05-11

    supporting textiles and test the mechanical properties. Even though their films were only 10 microns, the SER fixture was used by applying double stick tape...aramid and stainless steel. The authors conclude that supporting textile has a large impact on mechanical properties due to the difference in...Elongation) are depicted. 2.2 Conductivity Ionic conductivity was measured by electrochemical impedance spectroscopy using a four- electrode in-plane

  4. Features wear nodes mechanization wing aircraft operating under dynamic loads

    Directory of Open Access Journals (Sweden)

    А.М. Хімко

    2009-03-01

    Full Text Available  The conducted researches of titanic alloy ВТ-22 at dynamic loading with cycled sliding and dynamic loading in conditions of rolling with slipping. It is established that roller jamming in the carriage increases wear of rod of mechanization of a wing to twenty times. The optimum covering for strengthening wearied sites and restoration of working surfaces of wing’s mechanization rod is defined.

  5. Synthetic oligorotaxanes exert high forces when folding under mechanical load

    Science.gov (United States)

    Sluysmans, Damien; Hubert, Sandrine; Bruns, Carson J.; Zhu, Zhixue; Stoddart, J. Fraser; Duwez, Anne-Sophie

    2018-01-01

    Folding is a ubiquitous process that nature uses to control the conformations of its molecular machines, allowing them to perform chemical and mechanical tasks. Over the years, chemists have synthesized foldamers that adopt well-defined and stable folded architectures, mimicking the control expressed by natural systems1,2. Mechanically interlocked molecules, such as rotaxanes and catenanes, are prototypical molecular machines that enable the controlled movement and positioning of their component parts3-5. Recently, combining the exquisite complexity of these two classes of molecules, donor-acceptor oligorotaxane foldamers have been synthesized, in which interactions between the mechanically interlocked component parts dictate the single-molecule assembly into a folded secondary structure6-8. Here we report on the mechanochemical properties of these molecules. We use atomic force microscopy-based single-molecule force spectroscopy to mechanically unfold oligorotaxanes, made of oligomeric dumbbells incorporating 1,5-dioxynaphthalene units encircled by cyclobis(paraquat-p-phenylene) rings. Real-time capture of fluctuations between unfolded and folded states reveals that the molecules exert forces of up to 50 pN against a mechanical load of up to 150 pN, and displays transition times of less than 10 μs. While the folding is at least as fast as that observed in proteins, it is remarkably more robust, thanks to the mechanically interlocked structure. Our results show that synthetic oligorotaxanes have the potential to exceed the performance of natural folding proteins.

  6. Pathophysiology of hantavirus pulmonary syndrome in rhesus macaques

    Science.gov (United States)

    Safronetz, David; Prescott, Joseph; Feldmann, Friederike; Haddock, Elaine; Rosenke, Rebecca; Okumura, Atsushi; Brining, Douglas; Dahlstrom, Eric; Porcella, Stephen F.; Ebihara, Hideki; Scott, Dana P.; Hjelle, Brian; Feldmann, Heinz

    2014-01-01

    The pathophysiology of hantavirus pulmonary syndrome (HPS) remains unclear because of a lack of surrogate disease models with which to perform pathogenesis studies. Nonhuman primates (NHP) are considered the gold standard model for studying the underlying immune activation/suppression associated with immunopathogenic viruses such as hantaviruses; however, to date an NHP model for HPS has not been described. Here we show that rhesus macaques infected with Sin Nombre virus (SNV), the primary etiological agent of HPS in North America, propagated in deer mice develop HPS, which is characterized by thrombocytopenia, leukocytosis, and rapid onset of respiratory distress caused by severe interstitial pneumonia. Despite establishing a systemic infection, SNV differentially activated host responses exclusively in the pulmonary endothelium, potentially the mechanism leading to acute severe respiratory distress. This study presents a unique chronological characterization of SNV infection and provides mechanistic data into the pathophysiology of HPS in a closely related surrogate animal model. We anticipate this model will advance our understanding of HPS pathogenesis and will greatly facilitate research toward the development of effective therapeutics and vaccines against hantaviral diseases. PMID:24778254

  7. Mechanisms underlying p53 regulation of PIK3CA transcription in ovarian surface epithelium and in ovarian cancer.

    Science.gov (United States)

    Astanehe, Arezoo; Arenillas, David; Wasserman, Wyeth W; Leung, Peter C K; Dunn, Sandra E; Davies, Barry R; Mills, Gordon B; Auersperg, Nelly

    2008-03-01

    Inactivation of the transcription factor and tumor suppressor p53, and overexpression or mutational activation of PIK3CA, which encodes the p110alpha catalytic subunit of phosphatidylinositol-3-kinase (PI3K), are two of the most common deleterious genomic changes in cancer, including in ovarian carcinomas. We investigated molecular mechanisms underlying interactions between these two mediators and their possible roles in ovarian tumorigenesis. We identified two alternate PIK3CA promoters and showed direct binding of and transcriptional inhibition by p53 to one of these promoters. Conditional suppression of functional p53 increased p110alpha transcripts, protein levels and PI3K activity in immortalized, non-tumorigenic ovarian surface epithelial (OSE) cells, the precursors of ovarian carcinoma. Conversely, overexpression of p53 by adenoviral infection and activation of p53 by gamma-irradiation both diminished p110alpha protein levels in normal OSE and ovarian cancer cells. The demonstration that p53 binds directly to the PIK3CA promoter and inhibits its activity identifies a novel mechanism whereby these two mediators regulate cellular functions, and whereby inactivation of p53 and subsequent upregulation of PIK3CA might contribute to the pathophysiology of ovarian cancer.

  8. Pathophysiology diabetic foot ulcer

    Science.gov (United States)

    Syafril, S.

    2018-03-01

    Diabetes Mellitus (DM) is known to have many complications. Diabetes and its complications are rapidly becoming the world’s most significant cause of morbidity and mortality, and one of the most distressing is Diabetic Foot Ulcer (DFU). Chronic wound complications are a growing concern worldwide, and the effect is a warning to public health and the economy. The etiology of a DFU is multifaceted, and several components cause added together create a sufficient impact on ulceration: neuropathy, vasculopathy, immunopathy, mechanical stress, and neuroarthropathy. There are many classifications of the diabetic foot. About 50% of patients with foot ulcers due to DM present clinical signs of infection. It is essential to manage multifactorial etiology of DFU to get a good outcome.

  9. OCT monitoring of pathophysiological processes

    Science.gov (United States)

    Gladkova, Natalia D.; Shakhova, Natalia M.; Shakhov, Andrei; Petrova, Galina P.; Zagainova, Elena; Snopova, Ludmila; Kuznetzova, Irina N.; Chumakov, Yuri; Feldchtein, Felix I.; Gelikonov, Valentin M.; Gelikonov, Grigory V.; Kamensky, Vladislav A.; Kuranov, Roman V.; Sergeev, Alexander M.

    1999-04-01

    Based on results of clinical examination of about 200 patients we discuss capabilities of the optical coherence tomography (OCT) in monitoring and diagnosing of various pathophysiological processes. Performed in several clinical areas including dermatology, urology, laryngology, gynecology, and dentistry, our study shows the existence of common optical features in manifestation of a pathophysiological process in different organs. In this paper we focus at such universal tomographic optical signs for processes of inflammation, necrosis and tumor growth. We also present data on dynamical OCT monitoring of evolution of pathophysiological processes, both at the stage of disease development and following-up results of different treatments such as drug application, radiation therapy, cryodestruction, and laser vaporization. The discovered peculiarities of OCT images for structural and functional imaging of biological tissues can be put as a basis for application of this method for diagnosing of pathology, guidance of treatment, estimation of its adequacy and assessing of the healing process.

  10. Pathophysiology of the underactive bladder

    Directory of Open Access Journals (Sweden)

    Naoki Aizawa

    2017-12-01

    Full Text Available Underactive bladder (UAB, which has been described as a symptom complex suggestive of detrusor underactivity, is usually characterized by prolonged urination time with or without a sensation of incomplete bladder emptying, usually with hesitancy, reduced sensation on filling, and slow stream often with storage symptoms. Several causes such as aging, bladder outlet obstruction, diabetes mellitus, neurologic disorders, and nervous injury to the spinal cord, cauda equine, and peripheral pelvic nerve have been assumed to be responsible for the development of UAB. Several contributing factors have been suggested in the pathophysiology of UAB, including myogenic failure, efferent and/or afferent dysfunctions, and central nervous system dysfunction. In this review article, we have described relationships between individual contributing factors and the pathophysiology of UAB based on previous reports. However, many pathophysiological uncertainties still remain, which require more investigations using appropriate animal models.

  11. Mechanism and kinetics of mineral weathering under acid conditions

    NARCIS (Netherlands)

    Anbeek, C.

    1994-01-01

    This study deals with the relationships between crystal structure, grain diameter, surface morphology and dissolution kinetics for feldspar and quartz under acid conditions.

    Intensively ground samples from large, naturally weathered mineral fragments are frequently used in

  12. Performance of multifilamentary Nb3Sn under mechanical load

    International Nuclear Information System (INIS)

    Easton, D.S.; Schwall, R.E.

    1976-01-01

    The critical current of a commercial multifilamentary Nb 3 Sn conductor has been measured under the application of uniaxial tension at 4.2 K and following bending at room temperature. Significant reductions in J/subc/ are observed under uniaxial loading. Results are presented for a monolithic conductor manufactured by the bronze diffusion technique and for cable conductors formed by the tin-dip technique

  13. Decentralized control mechanism underlying interlimb coordination of millipedes.

    Science.gov (United States)

    Kano, Takeshi; Sakai, Kazuhiko; Yasui, Kotaro; Owaki, Dai; Ishiguro, Akio

    2017-04-04

    Legged animals exhibit adaptive and resilient locomotion through interlimb coordination. The long-term goal of this study is to clarify the relationship between the number of legs and the inherent decentralized control mechanism for interlimb coordination. As a preliminary step, the study focuses on millipedes as they represent the species with the greatest number of legs among various animal species. A decentralized control mechanism involving local force feedback was proposed based on the qualitative findings of behavioural experiments in which responses to the removal of part of the terrain and leg amputation were observed. The proposed mechanism was implemented in a developed millipede-like robot to demonstrate that the robot can adapt to the removal of the part of the terrain and leg amputation in a manner similar to that in behavioural experiments.

  14. Advanced waterflooding in chalk reservoirs: Understanding of underlying mechanisms

    DEFF Research Database (Denmark)

    Zahid, Adeel; Sandersen, Sara Bülow; Stenby, Erling Halfdan

    2011-01-01

    Over the last decade, a number of studies have shown SO42−, Ca2+ and Mg2+ to be potential determining ions, which may be added to the injected brine for improving oil recovery during waterflooding in chalk reservoirs. However the understanding of the mechanism leading to an increase in oil recove...... of a microemulsion phase could be the possible reasons for the observed increase in oil recovery with sulfate ions at high temperature in chalk reservoirs besides the mechanism of the rock wettability alteration, which has been reported in most previous studies.......Over the last decade, a number of studies have shown SO42−, Ca2+ and Mg2+ to be potential determining ions, which may be added to the injected brine for improving oil recovery during waterflooding in chalk reservoirs. However the understanding of the mechanism leading to an increase in oil recovery...

  15. Epigenetic mechanisms underlying the pathogenesis of neurogenetic diseases.

    Science.gov (United States)

    Qureshi, Irfan A; Mehler, Mark F

    2014-10-01

    There have been considerable advances in uncovering the complex genetic mechanisms that underlie nervous system disease pathogenesis, particularly with the advent of exome and whole genome sequencing techniques. The emerging field of epigenetics is also providing further insights into these mechanisms. Here, we discuss our understanding of the interplay that exists between genetic and epigenetic mechanisms in these disorders, highlighting the nascent field of epigenetic epidemiology-which focuses on analyzing relationships between the epigenome and environmental exposures, development and aging, other health-related phenotypes, and disease states-and next-generation research tools (i.e., those leveraging synthetic and chemical biology and optogenetics) for examining precisely how epigenetic modifications at specific genomic sites affect disease processes.

  16. Pathophysiology, evaluation, and management of sleep disorders in the mucopolysaccharidoses.

    Science.gov (United States)

    Rapoport, David M; Mitchell, John J

    2017-12-01

    The mucopolysaccharidoses (MPS) represent a heterogeneous group of lysosomal storage disorders, each one associated with a deficiency in one of the enzymes involved in glycosaminoglycan degradation. Sleep disorders are a frequent manifestation of all types of MPS. Underlying causes are diverse and comprised of both respiratory and central nervous system (CNS) abnormalities. Sleep disordered breathing such as obstructive sleep apnea and nocturnal hypoventilation can arise in patients with upper airway obstruction and/or with alterations in respiratory mechanics, causing restrictive pulmonary disease. MPS patients with CNS disease can also develop sleep disturbances unrelated to ventilatory impairments, often associated with severe behavioral problems or night-time epileptic seizures. The present review discusses the pathophysiology, evaluation, and management of sleep disorders in MPS based on information from a meeting on the brain in MPS, attended by an international group of experts (April 28-30, 2016, Stockholm, Sweden), and additional literature searches. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Pathophysiology of Resistant Hypertension: The Role of Sympathetic Nervous System

    Directory of Open Access Journals (Sweden)

    Costas Tsioufis

    2011-01-01

    Full Text Available Resistant hypertension (RH is a powerful risk factor for cardiovascular morbidity and mortality. Among the characteristics of patients with RH, obesity, obstructive sleep apnea, and aldosterone excess are covering a great area of the mosaic of RH phenotype. Increased sympathetic nervous system (SNS activity is present in all these underlying conditions, supporting its crucial role in the pathophysiology of antihypertensive treatment resistance. Current clinical and experimental knowledge points towards an impact of several factors on SNS activation, namely, insulin resistance, adipokines, endothelial dysfunction, cyclic intermittent hypoxaemia, aldosterone effects on central nervous system, chemoreceptors, and baroreceptors dysregulation. The further investigation and understanding of the mechanisms leading to SNS activation could reveal novel therapeutic targets and expand our treatment options in the challenging management of RH.

  18. Pathology and pathophysiology of pulmonary manifestations in leptospirosis

    Directory of Open Access Journals (Sweden)

    Marisa Dolhnikoff

    Full Text Available Leptospirosis is a re-emerging zoonosis occurring as large outbreaks throughout the world caused by Leptospira interrogans. The incidence of pulmonary involvement in leptospirosis has been reported to be increasing in the last years, affecting up to 70% of the patients. Alveolar hemorrhage presented as dyspnea and hemoptysis is the main pulmonary manifestation. The emergence of massive hemoptysis and acute respiratory distress syndrome has characterized the recent changes reported in the clinical patterns of leptospirosis. The pulmonary involvement has been emerged as a serious life threat, becoming the main cause of death due to leptospirosis in some countries. In this review we present the main clinical and pathological manifestations of pulmonary involvement in leptospirosis, with special focus on recent data concerning the pathophysiological mechanisms underlying lung injury.

  19. Pathophysiological dilemmas of lipedema.

    Science.gov (United States)

    Szél, E; Kemény, L; Groma, G; Szolnoky, G

    2014-11-01

    Lipedema is a common, but often underdiagnosed masquerading disease of obesity, which almost exclusively affects females. There are many debates regarding the diagnosis as well as the treatment strategies of the disease. The clinical diagnosis is relatively simple, however, knowledge regarding the pathomechanism is less than limited and curative therapy does not exist at all demanding an urgent need for extensive research. According to our hypothesis, lipedema is an estrogen-regulated polygenetic disease, which manifests in parallel with feminine hormonal changes and leads to vasculo- and lymphangiopathy. Inflammation of the peripheral nerves and sympathetic innervation abnormalities of the subcutaneous adipose tissue also involving estrogen may be responsible for neuropathy. Adipocyte hyperproliferation is likely to be a secondary phenomenon maintaining a vicious cycle. Herein, the relevant articles are reviewed from 1913 until now and discussed in context of the most likely mechanisms leading to the disease, which could serve as a starting point for further research. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Pathophysiology of Hemophilic Arthropathy.

    Science.gov (United States)

    Melchiorre, Daniela; Manetti, Mirko; Matucci-Cerinic, Marco

    2017-06-25

    Spontaneous joint bleeding and repeated hemarthroses lead to hemophilic arthropathy-a debilitating disease with a significant negative impact on mobility and quality of life. Iron, cytokines, and angiogenic growth factors play a pivotal role in the onset of the inflammatory process that involves the synovial tissue, articular cartilage, and subchondral bone, with early damages and molecular changes determining the perpetuation of a chronic inflammatory condition. Synovitis is one of the earliest complications of hemarthrosis, and is characterized by synovial hypertrophy, migration of inflammatory cells, and a high degree of neo-angiogenesis with subsequent bleeding. The pathogenic mechanisms and molecular pathways by which blood in the joint cavity causes articular cartilage and subchondral bone destruction have yet to be fully elucidated. Both cytokines and matrix metalloproteinases and hydroxyl radicals may induce chondrocyte apoptosis. Members of the tumor necrosis factor receptor superfamily (such as the molecular triad: osteoprotegerin-OPG; receptor activator of nuclear factor κB-RANK; RANK ligand-RANKL) seem instead to play a major role in the inflammatory process. These pathogenic processes interact with each other and ultimately lead to a fibrotic joint and the disabling condition characteristic of hemophilic arthropathy.

  1. Chemical sensitivity: pathophysiology or pathopsychology?

    Science.gov (United States)

    Genuis, Stephen J

    2013-05-01

    symptoms in some cases. Sustained resolution of the CS state occurs after successful elimination of the accrued body burden of toxicants through natural mechanisms of toxicant bioelimination and/or interventions of clinical detoxification. Despite extensive clinical evidence to support the veracity of this clinical state, many members of the medical community are reluctant to accept this condition as a pathophysiologic disorder. The emerging problem of ubiquitous adverse toxicant exposures in modern society has resulted in escalating numbers of individuals developing a CS disorder. As usual in medical history, iconoclastic ideas and emerging evidence regarding novel disease mechanisms, such as the pathogenesis of CS, have been met with controversy, resistance, and sluggish knowledge translation. Copyright © 2013 Elsevier HS Journals, Inc. All rights reserved.

  2. A review of mechanisms underlying anticarcinogenicity by brassica vegetables

    NARCIS (Netherlands)

    Verhoeven, D.T.H.; Verhagen, H.; Goldbohm, R.A.; Brandt, P.A. van den; Poppel, G. van

    1997-01-01

    The mechanisms by which brassica vegetables might decrease the risk of cancer are reviewed in this paper. Brassicas, including all types of cabbages, broccoli, cauliflower and Brussels sprouts, may be protective against cancer due to their relatively high glucosinolate content. Glucosinolates are

  3. Peer influence: neural mechanisms underlying in-group conformity

    NARCIS (Netherlands)

    Stallen, M.; Smidts, A.; Sanfey, A.G.

    2013-01-01

    People often conform to the behavior of others with whom they identify. However, it is unclear what fundamental mechanisms underlie this type of conformity. Here, we investigate the processes mediating in-group conformity by using functional magnetic resonance imaging (fMRI). Participants completed

  4. Peer influence: Neural mechanisms underlying in-group conformity

    NARCIS (Netherlands)

    M. Stallen (Mirre); A. Smidts (Ale); A.G. Sanfey (Alan)

    2013-01-01

    textabstractPeople often conform to the behavior of others with whom they identify. However, it is unclear what fundamental mechanisms underlie this type of conformity. Here, we investigate the processes mediating in-group conformity by using functional magnetic resonance imaging (fMRI).

  5. Survival under stress: molecular mechanisms of metabolic rate ...

    African Journals Online (AJOL)

    Studies in my laboratory are analysing the molecular mechanisms and regulatory events that underlie transitions to and from hypometabolic states In systems including anoxia-tolerant turtles and molluscs, estivating snails and toads, hibernating small mammals, and freeze tolerant frogs and insects. Our newest research ...

  6. Underlying mechanisms of transient luminous events: a review

    Directory of Open Access Journals (Sweden)

    V. V. Surkov

    2012-08-01

    Full Text Available Transient luminous events (TLEs occasionally observed above a strong thunderstorm system have been the subject of a great deal of research during recent years. The main goal of this review is to introduce readers to recent theories of electrodynamics processes associated with TLEs. We examine the simplest versions of these theories in order to make their physics as transparent as possible. The study is begun with the conventional mechanism for air breakdown at stratospheric and mesospheric altitudes. An electron impact ionization and dissociative attachment to neutrals are discussed. A streamer size and mobility of electrons as a function of altitude in the atmosphere are estimated on the basis of similarity law. An alternative mechanism of air breakdown, runaway electron mechanism, is discussed. In this section we focus on a runaway breakdown field, characteristic length to increase avalanche of runaway electrons and on the role played by fast seed electrons in generation of the runaway breakdown. An effect of thunderclouds charge distribution on initiation of blue jets and gigantic jets is examined. A model in which the blue jet is treated as upward-propagating positive leader with a streamer zone/corona on the top is discussed. Sprite models based on streamer-like mechanism of air breakdown in the presence of atmospheric conductivity are reviewed. To analyze conditions for sprite generation, thunderstorm electric field arising just after positive cloud-to-ground stroke is compared with the thresholds for propagation of positively/negatively charged streamers and with runway breakdown. Our own estimate of tendril's length at the bottom of sprite is obtained to demonstrate that the runaway breakdown can trigger the streamer formation. In conclusion we discuss physical mechanisms of VLF (very low frequency and ELF (extremely low frequency phenomena associated with sprites.

  7. Mechanisms underlying social inequality in post-menopausal breast cancer.

    Science.gov (United States)

    Hvidtfeldt, Ulla Arthur

    2014-10-01

    This thesis is based on studies conducted in the period 2010-2014 at Department of Public Health, University of Copenhagen and at Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York. The results are presented in three scientific papers and a synopsis. The main objective of the thesis was to determine mechanisms underlying social inequality (defined by educational level) in postmenopausal breast cancer (BC) by addressing mediating effects through hormone therapy (HT) use, BMI, lifestyle and reproductive factors. The results of previous studies suggest that the higher risk of postmenopausal BC among women of high socioeconomic position (SEP) may be explained by reproductive factors and health behaviors. Women of higher SEP generally have fewer children and give birth at older ages than women of low SEP, and these factors have been found to affect the risk of BC - probably through altered hormone levels. Adverse effects on BC risk have also been documented for modifiable health behaviors that may affect hormone levels, such as alcohol consumption, high BMI, physical inactivity, and HT use. Alcohol consumption and HT use are likewise more common among women of higher SEP. The analyses were based on the Social Inequality in Cancer (SIC) cohort and a subsample of the Women's Health Initiative Observational Study (WHI-OS). The SIC cohort was derived by pooling 6 individual studies from the Copenhagen area including 33,562 women (1,733 BC cases) aged 50-70 years at baseline. The subsample of WHI-OS consisted of two case-cohort studies with measurements of endogenous estradiol (N = 1,601) and insulin (N = 791). Assessment of mediation often relies on comparing multiplicative models with and without the potential mediator. Such approaches provide potentially biased results, because they do not account for mediator-outcome confounding, exposure-dependent mediator-outcome confounding, exposure-mediator interaction and interactions

  8. Pathophysiology of epileptic encephalopathies.

    Science.gov (United States)

    Lado, Fred A; Rubboli, Guido; Capovilla, Giuseppe; Capovilla, Pippo; Avanzini, Giuliano; Moshé, Solomon L

    2013-11-01

    The application of metabolic imaging and genetic analysis, and now the development of appropriate animal models, has generated critical insights into the pathogenesis of epileptic encephalopathies. In this article we present ideas intended to move from the lesions associated with epileptic encephalopathies toward understanding the effects of these lesions on the functioning of the brain, specifically of the cortex. We argue that the effects of focal lesions may be magnified through the interaction between cortical and subcortical structures, and that disruption of subcortical arousal centers that regulate cortex early in life may lead to alterations of intracortical synapses that affect a critical period of cognitive development. Impairment of interneuronal function globally through the action of a genetic lesion similarly causes widespread cortical dysfunction manifesting as increased delta slow waves on electroencephalography (EEG) and as developmental delay or arrest clinically. Finally, prolonged focal epileptic activity during sleep (as occurring in the syndrome of continuous spike-wave in slow sleep, or CSWSS) might interfere with local slow wave activity at the site of the epileptic focus, thereby impairing the neural processes and, possibly, the local plastic changes associated with learning and other cognitive functions. Seizures may certainly add to these pathologic processes, but they are likely not necessary for the development of the cognitive pathology. Nevertheless, although seizures may be either a consequence or symptom of the underlying lesion, their effective treatment can improve outcomes as both clinical and experimental studies may suggest. Understanding their substrates may lead to novel, effective treatments for all aspects of the epileptic encephalopathy phenotype. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

  9. Contrast medium-induced nephropathy: the pathophysiology

    DEFF Research Database (Denmark)

    Persson, P B; Tepel, Martin

    2006-01-01

    A widespread, rather general, definition of contrast-induced nephropathy (CIN) is an impairment in renal function occurring within 3 days following the intravascular administration of contrast media (CM) and the absence of an alternative aetiology. In spite of the vast clinical importance of CIN...... the current knowledge of the mechanisms causing CIN, it is not possible to recommend a certain class of contrast media, except to avoid large doses of CM of the first generation. From a pathophysiological perspective, volume expansion is effective in avoiding CIN, since water permeability of the collecting...

  10. Pathophysiology of the anorexia of aging.

    Science.gov (United States)

    Morley, John E

    2013-01-01

    Anorexia represents a major problem for older persons leading to weight loss, sarcopenia, functional decline, and mortality. There is increasing information on the pathophysiological mechanisms that lead to anorexia. Increasing evidence has shown the importance of gastrointestinal hormones (ghrelin, cholecystokinin, and glucagon-like peptide) and adipokines in producing the anorexia of aging. Numerous neurotransmitters have been shown to be involved in this aging anorexia, but evidence in humans is lacking. The early recognition of anorexia of aging is important to allow intervention and prevent functional deterioration in older persons. Screening tests for anorexia have been developed. New approaches to managing anorexia are being tested.

  11. Evidence from pharmacology and pathophysiology suggests that chemicals with dissimilar mechanisms of action could be of bigger concern in the toxicological risk assessment of chemical mixtures than chemicals with a similar mechanism of action

    DEFF Research Database (Denmark)

    Hadrup, Niels

    2014-01-01

    such as cancer or HIV, it is generally recognised that pharmacological combination therapy targeting different mechanisms of action is more effective than a strategy where only one mechanism is targeted. Moreover, in diseases such as acute myocardial infarction and congestive heart failure, several organ systems...

  12. Mechanical response of human female breast skin under uniaxial stretching.

    Science.gov (United States)

    Kumaraswamy, N; Khatam, Hamed; Reece, Gregory P; Fingeret, Michelle C; Markey, Mia K; Ravi-Chandar, Krishnaswamy

    2017-10-01

    Skin is a complex material covering the entire surface of the human body. Studying the mechanical properties of skin to calibrate a constitutive model is of great importance to many applications such as plastic or cosmetic surgery and treatment of skin-based diseases like decubitus ulcers. The main objective of the present study was to identify and calibrate an appropriate material constitutive model for skin and establish certain universal properties that are independent of patient-specific variability. We performed uniaxial tests performed on breast skin specimens freshly harvested during mastectomy. Two different constitutive models - one phenomenological and another microstructurally inspired - were used to interpret the mechanical responses observed in the experiments. Remarkably, we found that the model parameters that characterize dependence on previous maximum stretch (or preconditioning) exhibited specimen-independent universal behavior. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Peer influence: Neural mechanisms underlying in-group conformity

    Directory of Open Access Journals (Sweden)

    Mirre eStallen

    2013-03-01

    Full Text Available People often conform to the behavior of others with whom they identify. However, it is unclear what fundamental mechanisms underlie this type of conformity. Here, we investigate the processes mediating in-group conformity by using functional magnetic resonance imaging (fMRI. Participants completed a perceptual decision-making task while undergoing fMRI, during which they were exposed to the judgments of both in-group and out-group members. Our data suggest that conformity to the in-group is mediated by both positive affect as well as the cognitive capacity of perspective taking. Examining the processes that drive in-group conformity by utilizing a basic decision-making paradigm combined with neuroimaging methods provides important insights into the potential mechanisms of conformity. These results may provide an integral step in developing more effective campaigns using group conformity as a tool for behavioral change.

  14. Peer influence: neural mechanisms underlying in-group conformity.

    Science.gov (United States)

    Stallen, Mirre; Smidts, Ale; Sanfey, Alan G

    2013-01-01

    People often conform to the behavior of others with whom they identify. However, it is unclear what fundamental mechanisms underlie this type of conformity. Here, we investigate the processes mediating in-group conformity by using functional magnetic resonance imaging (fMRI). Participants completed a perceptual decision-making task while undergoing fMRI, during which they were exposed to the judgments of both in-group and out-group members. Our data suggest that conformity to the in-group is mediated by both positive affect as well as the cognitive capacity of perspective taking. Examining the processes that drive in-group conformity by utilizing a basic decision-making paradigm combined with neuroimaging methods provides important insights into the potential mechanisms of conformity. These results may provide an integral step in developing more effective campaigns using group conformity as a tool for behavioral change.

  15. Molecular Mechanism Underlying Lymphatic Metastasis in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Zhiwen Xiao

    2014-01-01

    Full Text Available As the most challenging human malignancies, pancreatic cancer is characterized by its insidious symptoms, low rate of surgical resection, high risk of local invasion, metastasis and recurrence, and overall dismal prognosis. Lymphatic metastasis, above all, is recognized as an early adverse event in progression of pancreatic cancer and has been described to be an independent poor prognostic factor. It should be noted that the occurrence of lymphatic metastasis is not a casual or stochastic but an ineluctable and designed event. Increasing evidences suggest that metastasis-initiating cells (MICs and the microenvironments may act as a double-reed style in this crime. However, the exact mechanisms on how they function synergistically for this dismal clinical course remain largely elusive. Therefore, a better understanding of its molecular and cellular mechanisms involved in pancreatic lymphatic metastasis is urgently required. In this review, we will summarize the latest advances on lymphatic metastasis in pancreatic cancer.

  16. Mental imagery in music performance: underlying mechanisms and potential benefits.

    Science.gov (United States)

    Keller, Peter E

    2012-04-01

    This paper examines the role of mental imagery in music performance. Self-reports by musicians, and various other sources of anecdotal evidence, suggest that covert auditory, motor, and/or visual imagery facilitate multiple aspects of music performance. The cognitive and motor mechanisms that underlie such imagery include working memory, action simulation, and internal models. Together these mechanisms support the generation of anticipatory images that enable thorough action planning and movement execution that is characterized by efficiency, temporal precision, and biomechanical economy. In ensemble performance, anticipatory imagery may facilitate interpersonal coordination by enhancing online predictions about others' action timing. Overlap in brain regions subserving auditory imagery and temporal prediction is consistent with this view. It is concluded that individual differences in anticipatory imagery may be a source of variation in expressive performance excellence and the quality of ensemble cohesion. Engaging in effortful musical imagery is therefore justified when artistic perfection is the goal. © 2012 New York Academy of Sciences.

  17. Neural mechanisms underlying context-dependent shifts in risk preferences

    NARCIS (Netherlands)

    Losecaat Vermeer, A.B.; Boksem, M.A.S.; Sanfey, A.G.

    2014-01-01

    Studies of risky decision-making have demonstrated that humans typically prefer risky options after incurring a financial loss, while generally preferring safer options after a monetary gain. Here, we examined the neural processes underlying these inconsistent risk preferences by investigating the

  18. [Mechanisms underlying glucocorticoid resistance in chronic rhinosinusitis with nasal polyps].

    Science.gov (United States)

    Zhang, Y Y; Lou, H F; Wang, C S; Zhang, L

    2018-02-07

    Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease that occurs in the nasal and sinus mucosa, which is a common disease in otorhinolaryngology. At present, CRSwNP can be effectively treated by glucocorticoids (GC). GC binds to GC receptors in the nasal mucosa, affects the expression of inflammatory genes, inhibits the activation and action of eosinophils, T cell-associated inflammatory responses in nasal polyps, as well as tissue remodeling. However, there are some patients fall reponse to GC, so called GC resistance. The study suggests that the possible mechanism of CRSwNP GC resistance is mainly related to GC receptor abnormal, the role of cytokines and transcription factors, such as Th cells and IL-8. In addition, MAPK-related kinases and histone deacetylase in the GC signaling pathway also play important roles in the GC resistance process. This paper reviews the mechanism of GC treatment of CRSwNP, the mechanism of GC resistance and alternative treatment of GC.

  19. The Survival Advantage: Underlying Mechanisms and Extant Limitations

    Directory of Open Access Journals (Sweden)

    Stephanie A. Kazanas

    2015-04-01

    Full Text Available Recently, researchers have begun to investigate the function of memory in our evolutionary history. According to Nairne and colleagues (e.g., Nairne, Pandeirada, and Thompson, 2008; Nairne, Thompson, and Pandeirada, 2007, the best mnemonic strategy for learning lists of unrelated words may be one that addresses the same problems that our Pleistocene ancestors faced: fitness-relevant problems including securing food and water, as well as protecting themselves from predators. Survival processing has been shown to promote better recall and recognition memory than many well-known mnemonic strategies (e.g., pleasantness ratings, imagery, generation, etc.. However, the survival advantage does not extend to all types of stimuli and tasks. The current review presents research that has replicated Nairne et al.'s (2007 original findings, in addition to the research designs that fail to replicate the survival advantage. In other words, there are specific manipulations in which survival processing does not appear to benefit memory any more than other strategies. Potential mechanisms for the survival advantage are described, with an emphasis on those that are the most plausible. These proximate mechanisms outline the memory processes that may contribute to the advantage, although the ultimate mechanism may be the congruity between the survival scenario and Pleistocene problem-solving.

  20. Passive and active response of bacteria under mechanical compression

    Science.gov (United States)

    Garces, Renata; Miller, Samantha; Schmidt, Christoph F.; Byophysics Team; Institute of Medical Sciences Collaboration

    Bacteria display simple but fascinating cellular structures and geometries. Their shapes are the result of the interplay between osmotic pressure and cell wall construction. Typically, bacteria maintain a high difference of osmotic pressure (on the order of 1 atm) to the environment. This pressure difference (turgor pressure) is supported by the cell envelope, a composite of lipid membranes and a rigid cell wall. The response of the cell envelope to mechanical perturbations such as geometrical confinements is important for the cells survival. Another key property of bacteria is the ability to regulate turgor pressure after abrupt changes of external osmotic conditions. This response relies on the activity of mechanosensitive (MS) channels: membrane proteins that release solutes in response to excessive stress in the cell envelope. We here present experimental data on the mechanical response of the cell envelope and on turgor regulation of bacteria subjected to compressive forces. We indent living cells with micron-sized beads attached to the cantilever of an atomic force microscope (AFM). This approach ensures global deformation of the cell. We show that such mechanical loading is sufficient to gate mechanosensitive channels in isosmotic conditions.

  1. Phosphorene under strain:electronic, mechanical and piezoelectric responses

    Science.gov (United States)

    Drissi, L. B.; Sadki, S.; Sadki, K.

    2018-01-01

    Structural, electronic, elastic and piezoelectric properties of pure phosphorene under in-plane strain are investigated using first-principles calculations based on density functional theory. The two critical yielding points are determined along armchair and zigzag directions. It is shown that the buckling, the band gap and the charge transfer can be controlled under strains. A semiconductor to metallic transition is observed in metastable region. Polar plots of Young's modulus, Poisson ratio, sound velocities and Debye temperature exhibit evident anisotropic feature of phosphorene and indicate auxetic behavior for some angles θ. Our calculations show also that phosphorene has both in-plane and out-of-plane piezoelectric responses comparable to known 2D materials. The findings of this work reveal the great potential of pure phosphorene in nanomechanical applications.

  2. Electronic, mechanical and dielectric properties of silicane under tensile strain

    Energy Technology Data Exchange (ETDEWEB)

    Jamdagni, Pooja, E-mail: j.poojaa1228@gmail.com; Sharma, Munish; Ahluwalia, P. K. [Physics Department, Himachal Pradesh University, Shimla, Himachal Pradesh, India 171005 (India); Kumar, Ashok [Physics Department, Panjab University, Chandigarh, India, 160014 (India); Thakur, Anil [Physics Department, Govt. Collage Solan, Himachal Pradesh, India,173212 (India)

    2015-05-15

    The electronic, mechanical and dielectric properties of fully hydrogenated silicene i.e. silicane in stable configuration are studied by means of density functional theory based calculations. The band gap of silicane monolayer can be flexibly reduced to zero when subjected to bi-axial tensile strain, leading to semi-conducting to metallic transition, whereas the static dielectric constant for in-plane polarization increases monotonically with increasing strain. Also the EEL function show the red shift in resonance peak with tensile strain. Our results offer useful insight for the application of silicane monolayer in nano-optical and electronics devices.

  3. Electronic, mechanical and dielectric properties of silicane under tensile strain

    International Nuclear Information System (INIS)

    Jamdagni, Pooja; Sharma, Munish; Ahluwalia, P. K.; Kumar, Ashok; Thakur, Anil

    2015-01-01

    The electronic, mechanical and dielectric properties of fully hydrogenated silicene i.e. silicane in stable configuration are studied by means of density functional theory based calculations. The band gap of silicane monolayer can be flexibly reduced to zero when subjected to bi-axial tensile strain, leading to semi-conducting to metallic transition, whereas the static dielectric constant for in-plane polarization increases monotonically with increasing strain. Also the EEL function show the red shift in resonance peak with tensile strain. Our results offer useful insight for the application of silicane monolayer in nano-optical and electronics devices

  4. Studies on Molecular Mechanisms Underlying Spinocerebellar Ataxia Type 3

    DEFF Research Database (Denmark)

    Kristensen, Line Vildbrad

    The polyglutamine (polyQ) disorders comprise nine diseases characterized by an expanded polyQ tract within the respective proteins. These disorders are rare but include the well-known Huntington’s disease, and several spinocerebellar ataxias (SCAs). The diseases usually strike midlife and progress....... Even though a range of mechanisms contributing to polyQ diseases have been uncovered, there is still no treatment available. One of the more common polyQ diseases is SCA3, which is caused by a polyQ expansion in the ataxin-3 protein that normally functions as a deubiquitinating enzyme involved...

  5. Ethanol Neurotoxicity in the Developing Cerebellum: Underlying Mechanisms and Implications

    Directory of Open Access Journals (Sweden)

    Ambrish Kumar

    2013-06-01

    Full Text Available Ethanol is the main constituent of alcoholic beverages that exerts toxicity to neuronal development. Ethanol affects synaptogenesis and prevents proper brain development. In humans, synaptogenesis takes place during the third trimester of pregnancy, and in rodents this period corresponds to the initial few weeks of postnatal development. In this period neuronal maturation and differentiation begin and neuronal cells start migrating to their ultimate destinations. Although the neuronal development of all areas of the brain is affected, the cerebellum and cerebellar neurons are more susceptible to the damaging effects of ethanol. Ethanol’s harmful effects include neuronal cell death, impaired differentiation, reduction of neuronal numbers, and weakening of neuronal plasticity. Neuronal development requires many hormones and growth factors such as retinoic acid, nerve growth factors, and cytokines. These factors regulate development and differentiation of neurons by acting through various receptors and their signaling pathways. Ethanol exposure during development impairs neuronal signaling mechanisms mediated by the N-methyl-d-aspartate (NMDA receptors, the retinoic acid receptors, and by growth factors such as brain-derived neurotrophic factor (BDNF, insulin-like growth factor 1 (IGF-I, and basic fibroblast growth factor (bFGF. In combination, these ethanol effects disrupt cellular homeostasis, reduce the survival and migration of neurons, and lead to various developmental defects in the brain. Here we review the signaling mechanisms that are required for proper neuronal development, and how these processes are impaired by ethanol resulting in harmful consequences to brain development.

  6. Brainstem mechanisms underlying the cough reflex and its regulation.

    Science.gov (United States)

    Mutolo, Donatella

    2017-09-01

    Cough is a very important airway protective reflex. Cough-related inputs are conveyed to the caudal nucleus tractus solitarii (cNTS) that projects to the brainstem respiratory network. The latter is reconfigured to generate the cough motor pattern. A high degree of modulation is exerted on second-order neurons and the brainstem respiratory network by sensory inputs and higher brain areas. Two medullary structures proved to have key functions in cough production and to be strategic sites of action for centrally active drugs: the cNTS and the caudal ventral respiratory group (cVRG). Drugs microinjected into these medullary structures caused downregulation or upregulation of the cough reflex. The results suggest that inhibition and disinhibition are prominent regulatory mechanisms of this reflex and that both the cNTS and the cVRG are essential in the generation of the entire cough motor pattern. Studies on the basic neural mechanisms subserving the cough reflex may provide hints for novel therapeutic approaches. Different proposals for further investigations are advanced. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Internal insulation failure mechanisms of HV equipment under service conditions

    Energy Technology Data Exchange (ETDEWEB)

    Lokhanin, A.K.; Morozova, T.I. [All-Russian Electrochemical Inst. (Russian Federation); Shneider, G.Y. [Electrozavod Holding Company (Russian Federation); Sokolov, V.V. [Scientific and Engineering Centre, ZTZ Service Research Inst. (Russian Federation); Chornogotsky, V.M. [Ukrainian Transformer Research Inst. (Ukraine)

    2005-09-01

    Failure mechanisms in oil-barrier transformer insulation and oil-paper condenser type insulation of transformers and HV bushing were discussed with reference to typical defects and failure modes of oil-barrier insulation of transformers, shunt reactor, condenser type bushing and instrument current transformers. It was noted that insulation problems predominantly involve the impairment of insulation, and that the relative rate of major failures in shunt reactors is about 1 per cent. It was suggested that bushings can cause about 45 per cent of major transformer failures, with aged mode failure occurring most frequently. The failure rate of 220-500 kV CTs accounts for more than 60 per cent of total instrument transformer failures. Two failure modes were observed: ionisation-mode and aging-mode failures. The reduction of switching surge breakdown voltage due to deposit of insoluble aging products was discussed. A long-term dielectric strength test revealed the following 2 mechanisms of insulation breakdown: accidental breakdown during the first period of aging and wearing mode breakdown due to degradation of materials at the last stage of the calculated terms of aging. Issues concerning the mechanism of the incipient irreversible failure in oil-barrier insulation were discussed, as well as issues concerning creeping discharge and large failures during normal operating conditions. It was suggested that the occurrence of surface discharge is associated with increased voltage due to oil breakdown progressing into insulation destruction and surface discharge as a self-firing phenomenon. Failure modes induced by peculiar oil and staining of internal porcelain were reviewed. It was noted that the discharges across the inner part of the transformer and porcelain were the out-come of a typical aging-mode phenomenon in the bushing. In addition, failure modes induced by staining the outer surface of bottom porcelain were discussed, as well as failure of oil-filled paper

  8. Parametric study of control mechanism of cortical bone remodeling under mechanical stimulus

    Science.gov (United States)

    Wang, Yanan; Qin, Qing-Hua

    2010-03-01

    The control mechanism of mechanical bone remodeling at cellular level was investigated by means of an extensive parametric study on a theoretical model described in this paper. From a perspective of control mechanism, it was found that there are several control mechanisms working simultaneously in bone remodeling which is a complex process. Typically, an extensive parametric study was carried out for investigating model parameter space related to cell differentiation and apoptosis which can describe the fundamental cell lineage behaviors. After analyzing all the combinations of 728 permutations in six model parameters, we have identified a small number of parameter combinations that can lead to physiologically realistic responses which are similar to theoretically idealized physiological responses. The results presented in the work enhanced our understanding on mechanical bone remodeling and the identified control mechanisms can help researchers to develop combined pharmacological-mechanical therapies to treat bone loss diseases such as osteoporosis.

  9. Mechanisms Underlying Profibrotic Epithelial Phenotype and Epithelial-Mesenchymal Crosstalk

    DEFF Research Database (Denmark)

    Bialik, Janne Folke

    , their roles in epithelial reprogramming are unclear. The aim of this thesis was to elucidate (i) the mechanism of TGFβ-induced TAZ expression in kidney fibrosis, (ii) the roles of MRTF and TAZ in PEP, (iii) how MRTF and TAZ regulate the oxidative state of the epithelium, and (iv) if the ensuing ROS production...... and TAZ prevented this, linking the cytoskeleton to the oxidative state of the cell. In Paper II TGFβ-induced increase in TAZ expression was investigated. Using pharmacological inhibition we show that non-canonical signaling via p38 and its downstream target MK2 mediates this upregulation. Furthermore......, MRTF regulates TAZ expression in a translocation-independent manner. Pharmacological inhibition of Nox4, a known activator of p38, resulted in decreased TAZ, suggesting a feedback loop in which Nox4 regulates TAZ and MRTF, which in turn regulates Nox4. In Paper III we investigated cytokine expression...

  10. Mechanisms underlying rapid aldosterone effects in the kidney.

    LENUS (Irish Health Repository)

    Thomas, Warren

    2012-02-01

    The steroid hormone aldosterone is a key regulator of electrolyte transport in the kidney and contributes to both homeostatic whole-body electrolyte balance and the development of renal and cardiovascular pathologies. Aldosterone exerts its action principally through the mineralocorticoid receptor (MR), which acts as a ligand-dependent transcription factor in target tissues. Aldosterone also stimulates the activation of protein kinases and secondary messenger signaling cascades that act independently on specific molecular targets in the cell membrane and also modulate the transcriptional action of aldosterone through MR. This review describes current knowledge regarding the mechanisms and targets of rapid aldosterone action in the nephron and how aldosterone integrates these responses into the regulation of renal physiology.

  11. Mechanisms underlying rapid aldosterone effects in the kidney.

    LENUS (Irish Health Repository)

    Thomas, Warren

    2011-03-17

    The steroid hormone aldosterone is a key regulator of electrolyte transport in the kidney and contributes to both homeostatic whole-body electrolyte balance and the development of renal and cardiovascular pathologies. Aldosterone exerts its action principally through the mineralocorticoid receptor (MR), which acts as a ligand-dependent transcription factor in target tissues. Aldosterone also stimulates the activation of protein kinases and secondary messenger signaling cascades that act independently on specific molecular targets in the cell membrane and also modulate the transcriptional action of aldosterone through MR. This review describes current knowledge regarding the mechanisms and targets of rapid aldosterone action in the nephron and how aldosterone integrates these responses into the regulation of renal physiology.

  12. Molecular mechanisms underlying the development of hepatocellular carcinoma.

    Science.gov (United States)

    Bergsland, E K

    2001-10-01

    Hepatocellular carcinoma (HCC) is a disease that is extremely difficult to manage and is markedly increasing in incidence. Malignant transformation generally occurs in the setting of liver dysfunction related to a number of different diseases, including viral hepatitis, alcoholic liver disease, and aflatoxin exposure. Short of surgical or ablative approaches, no standard therapy exists for HCC and the prognosis is poor. Perhaps our best hope is that further elucidation of the specific molecular features underlying the disease will translate into innovative, and potentially disease-specific strategies to manage this difficult cancer. Exposure to aflatoxin is associated with a specific mutation in the tumor-suppressor gene p53. The exact molecular events underlying hepatocarcinogenesis in the setting of viral infection have yet to be elucidated, although there is evidence to suggest that virus-encoded proteins contribute to malignant transformation. Both hepatitis B X antigen and hepatitis C core protein appear to interact with a variety of cellular proteins leading to alterations in signal transduction and transcriptional activity. These events presumably cooperate to facilitate malignant progression by promoting extended hepatocyte survival, evasion of the immune response, and acquisition of mutations through genomic instability. Copyright 2001 by W.B. Saunders Company.

  13. Neural mechanisms underlying neurooptometric rehabilitation following traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Hudac CM

    2012-01-01

    Full Text Available Caitlin M Hudac1, Srinivas Kota1, James L Nedrow2, Dennis L Molfese1,31Department of Psychology, University of Nebraska-Lincoln, 2Oculi Vision Rehabilitation, 3Center for Brain, Biology, and Behavior, University of Nebraska-Lincoln, Lincoln, NEAbstract: Mild to severe traumatic brain injuries have lasting effects on everyday functioning. Issues relating to sensory problems are often overlooked or not addressed until well after the onset of the injury. In particular, vision problems related to ambient vision and the magnocellular pathway often result in posttrauma vision syndrome or visual midline shift syndrome. Symptoms from these syndromes are not restricted to the visual domain. Patients commonly experience proprioceptive, kinesthetic, vestibular, cognitive, and language problems. Neurooptometric rehabilitation often entails the use of corrective lenses, prisms, and binasal occlusion to accommodate the unstable magnocellular system. However, little is known regarding the neural mechanisms engaged during neurooptometric rehabilitation, nor how these mechanisms impact other domains. Event-related potentials from noninvasive electrophysiological recordings can be used to assess rehabilitation progress in patients. In this case report, high-density visual event-related potentials were recorded from one patient with posttrauma vision syndrome and secondary visual midline shift syndrome during a pattern reversal task, both with and without prisms. Results indicate that two factors occurring during the end portion of the P148 component (168–256 milliseconds poststimulus onset map onto two separate neural systems that were engaged with and without neurooptometric rehabilitation. Without prisms, neural sources within somatosensory, language, and executive brain regions engage inefficient magnocellular system processing. However, when corrective prisms were worn, primary visual areas were appropriately engaged. The impact of using early

  14. Mechanical characterization of stomach tissue under uniaxial tensile action.

    Science.gov (United States)

    Jia, Z G; Li, W; Zhou, Z R

    2015-02-26

    In this article, the tensile properties of gastric wall were investigated by using biomechanical test and theoretical analysis. The samples of porcine stomach strips from smaller and greater curvature of the stomach were cut in longitudinal and circumferential direction, respectively. The loading-unloading, stress relaxation, strain creep, tensile fracture tests were performed at mucosa-submucosa, serosa-muscle and intact layer, respectively. Results showed that the biomechanical properties of the porcine stomach depended on the layers, orientations and locations of the gastric wall and presented typical viscoelastic, nonlinear and anisotropic mechanical properties. During loading-unloading test, the stress of serosa-muscle layer in the longitudinal direction was 15-20% more than that in the circumferential direction at 12% stretch ratio, while it could reach about 40% for the intact layer and 50% for the mucosa-submucosa layer. The results of stress relaxation and strain creep showed that the variation degree was obviously faster in the circumferential direction than that in the longitudinal direction, and the ultimate residual values were also different for the different layers, orientations and locations. In the process of fracture test, the serosa-muscle layer fractured firstly followed by the mucosa-submucosa layer when the intact layer was tested, the longitudinal strips firstly began to fracture and the required stress value was about twice as much as that in the circumferential strips. The anisotropy and heterogeneity of mechanical characterization of the porcine stomach were related to its complicated geometry, structure and functions. The results would help us to understand the biomechanics of soft organ tissue. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Mechanisms underlying probucol-induced hERG-channel deficiency

    Directory of Open Access Journals (Sweden)

    Shi YQ

    2015-07-01

    Full Text Available Yuan-Qi Shi,1,* Cai-Chuan Yan,1,* Xiao Zhang,1 Meng Yan,1 Li-Rong Liu,1 Huai-Ze Geng,1 Lin Lv,1 Bao-Xin Li1,21Department of Pharmacology, Harbin Medical University, 2State-Province Key Laboratory of Biopharmaceutical Engineering, Harbin, Heilongjiang, People’s Republic of China*These authors contributed equally to this workAbstract: The hERG gene encodes the pore-forming α-subunit of the rapidly activating delayed rectifier potassium channel (IKr, which is important for cardiac repolarization. Reduction of IhERG due to genetic mutations or drug interferences causes long QT syndrome, leading to life-threatening cardiac arrhythmias (torsades de pointes or sudden death. Probucol is a cholesterol-lowering drug that could reduce hERG current by decreasing plasma membrane hERG protein expression and eventually cause long QT syndrome. Here, we investigated the mechanisms of probucol effects on IhERG and hERG-channel expression. Our data demonstrated that probucol reduces SGK1 expression, known as SGK isoform, in a concentration-dependent manner, resulting in downregulation of phosphorylated E3 ubiquitin ligase Nedd4-2 expression, but not the total level of Nedd4-2. As a result, the hERG protein reduces, due to the enhanced ubiquitination level. On the contrary, carbachol could enhance the phosphorylation level of Nedd4-2 as an alternative to SGK1, and thus rescue the ubiquitin-mediated degradation of hERG channels caused by probucol. These discoveries provide a novel mechanism of probucol-induced hERG-channel deficiency, and imply that carbachol or its analog may serve as potential therapeutic compounds for the handling of probucol cardiotoxicity.Keywords: long QT, hERG potassium channels, probucol, SGK1, Nedd4-2

  16. Algorithmic mechanisms for reliable crowdsourcing computation under collusion.

    Science.gov (United States)

    Fernández Anta, Antonio; Georgiou, Chryssis; Mosteiro, Miguel A; Pareja, Daniel

    2015-01-01

    We consider a computing system where a master processor assigns a task for execution to worker processors that may collude. We model the workers' decision of whether to comply (compute the task) or not (return a bogus result to save the computation cost) as a game among workers. That is, we assume that workers are rational in a game-theoretic sense. We identify analytically the parameter conditions for a unique Nash Equilibrium where the master obtains the correct result. We also evaluate experimentally mixed equilibria aiming to attain better reliability-profit trade-offs. For a wide range of parameter values that may be used in practice, our simulations show that, in fact, both master and workers are better off using a pure equilibrium where no worker cheats, even under collusion, and even for colluding behaviors that involve deviating from the game.

  17. Mechanisms of microstructural changes of fuel under irradiation

    International Nuclear Information System (INIS)

    Garcia, P.; Carlot, G.; Dorado, B.; Maillard, S.; Sabathier, C.; Martin, G.; Oh, J.Y.; Welland, M.J.

    2015-01-01

    Nuclear fuels are subjected to high levels of radiation damage mainly due to the slowing of fission fragments, which results in substantial modifications of the initial fuel microstructure. Microstructure changes alter practically all engineering fuel properties such as atomic transport or thermomechanical properties so understanding these changes is essential to predicting the performance of fuel elements. Also, with increasing burn-up, the fuel drifts away from its initial composition as the fission process produces new chemical elements. Because nuclear fuels operate at high temperature and usually under high-temperature gradients, damage annealing, foreign atom or defect clustering and migration occur on multiple time and length scales, which make long-term predictions difficult. The end result is a fuel microstructure which may show extensive differences on the scale of a single fuel pellet. The main challenge we are faced with is, therefore, to identify the phenomena occurring on the atom scale that are liable to have macroscopic effects that will determine the microstructure changes and ultimately the life-span of a fuel element. One step towards meeting this challenge is to develop and apply experimental or modelling methods capable of connecting events that occur over very short length and timescales to changes in the fuel microstructure over engineering length and timescales. In the first part of this chapter, we provide an overview of some of the more important microstructure modifications observed in nuclear fuels. The emphasis is placed on oxide fuels because of the extensive amount of data available in relation to these materials under neutron or ion irradiation. When possible and relevant, the specifics of other types of fuels such as metallic or carbide fuels are alluded to. Throughout this chapter but more specifically in the latter part, we attempt to give examples of how modelling and experimentation at various scales can provide us with

  18. Separable mechanisms underlying global feature-based attention.

    Science.gov (United States)

    Bondarenko, Rowena; Boehler, Carsten N; Stoppel, Christian M; Heinze, Hans-Jochen; Schoenfeld, Mircea A; Hopf, Jens-Max

    2012-10-31

    Feature-based attention is known to operate in a spatially global manner, in that the selection of attended features is not bound to the spatial focus of attention. Here we used electromagnetic recordings in human observers to characterize the spatiotemporal signature of such global selection of an orientation feature. Observers performed a simple orientation-discrimination task while ignoring task-irrelevant orientation probes outside the focus of attention. We observed that global feature-based selection, indexed by the brain response to unattended orientation probes, is composed of separable functional components. One such component reflects global selection based on the similarity of the probe with task-relevant orientation values ("template matching"), which is followed by a component reflecting selection based on the similarity of the probe with the orientation value under discrimination in the focus of attention ("discrimination matching"). Importantly, template matching occurs at ∼150 ms after stimulus onset, ∼80 ms before the onset of discrimination matching. Moreover, source activity underlying template matching and discrimination matching was found to originate from ventral extrastriate cortex, with the former being generated in more anterolateral and the latter in more posteromedial parts, suggesting template matching to occur in visual cortex higher up in the visual processing hierarchy than discrimination matching. We take these observations to indicate that the population-level signature of global feature-based selection reflects a sequence of hierarchically ordered operations in extrastriate visual cortex, in which the selection based on task relevance has temporal priority over the selection based on the sensory similarity between input representations.

  19. Neural mechanisms underlying melodic perception and memory for pitch.

    Science.gov (United States)

    Zatorre, R J; Evans, A C; Meyer, E

    1994-04-01

    The neural correlates of music perception were studied by measuring cerebral blood flow (CBF) changes with positron emission tomography (PET). Twelve volunteers were scanned using the bolus water method under four separate conditions: (1) listening to a sequence of noise bursts, (2) listening to unfamiliar tonal melodies, (3) comparing the pitch of the first two notes of the same set of melodies, and (4) comparing the pitch of the first and last notes of the melodies. The latter two conditions were designed to investigate short-term pitch retention under low or high memory load, respectively. Subtraction of the obtained PET images, superimposed on matched MRI scans, provides anatomical localization of CBF changes associated with specific cognitive functions. Listening to melodies, relative to acoustically matched noise sequences, resulted in CBF increases in the right superior temporal and right occipital cortices. Pitch judgments of the first two notes of each melody, relative to passive listening to the same stimuli, resulted in right frontal-lobe activation. Analysis of the high memory load condition relative to passive listening revealed the participation of a number of cortical and subcortical regions, notably in the right frontal and right temporal lobes, as well as in parietal and insular cortex. Both pitch judgment conditions also revealed CBF decreases within the left primary auditory cortex. We conclude that specialized neural systems in the right superior temporal cortex participate in perceptual analysis of melodies; pitch comparisons are effected via a neural network that includes right prefrontal cortex, but active retention of pitch involves the interaction of right temporal and frontal cortices.

  20. Comparative analysis reveals the underlying mechanism of vertebrate seasonal reproduction.

    Science.gov (United States)

    Ikegami, Keisuke; Yoshimura, Takashi

    2016-02-01

    Animals utilize photoperiodic changes as a calendar to regulate seasonal reproduction. Birds have highly sophisticated photoperiodic mechanisms and functional genomics analysis in quail uncovered the signal transduction pathway regulating avian seasonal reproduction. Birds detect light with deep brain photoreceptors. Long day (LD) stimulus induces secretion of thyroid-stimulating hormone (TSH) from the pars tuberalis (PT) of the pituitary gland. PT-derived TSH locally activates thyroid hormone (TH) in the hypothalamus, which induces gonadotropin-releasing hormone (GnRH) and hence gonadotropin secretion. However, during winter, low temperatures increase serum TH for adaptive thermogenesis, which accelerates germ cell apoptosis by activating the genes involved in metamorphosis. Therefore, TH has a dual role in the regulation of seasonal reproduction. Studies using TSH receptor knockout mice confirmed the involvement of PT-derived TSH in mammalian seasonal reproduction. In addition, studies in mice revealed that the tissue-specific glycosylation of TSH diversifies its function in the circulation to avoid crosstalk. In contrast to birds and mammals, one of the molecular machineries necessary for the seasonal reproduction of fish are localized in the saccus vasculosus from the photoreceptor to the neuroendocrine output. Thus, comparative analysis is a powerful tool to uncover the universality and diversity of fundamental properties in various organisms. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Mechanisms underlying the formation of induced pluripotent stem cells

    Science.gov (United States)

    González, Federico; Huangfu, Danwei

    2015-01-01

    Human pluripotent stem cells (hPSCs) offer unique opportunities for studying human biology, modeling diseases and for therapeutic applications. The simplest approach so far to generate human PSCs lines is through reprogramming of somatic cells from an individual by defined factors, referred to simply as reprogramming. Reprogramming circumvents the ethical issues associated with human embryonic stem cells (hESCs) and nuclear transfer hESCs (nt-hESCs), and the resulting induced pluripotent stem cells (hiPSCs) retain the same basic genetic makeup as the somatic cell used for reprogramming. Since the first report of iPSCs by Takahashi and Yamanaka, the molecular mechanisms of reprogramming have been extensively investigated. A better mechanistic understanding of reprogramming is fundamental not only to iPSC biology and improving the quality of iPSCs for therapeutic use, but also to our understanding of the molecular basis of cell identity, pluripotency and plasticity. Here we summarize the genetic, epigenetic and cellular events during reprogramming, and the roles of various factors identified thus far in the reprogramming process. PMID:26383234

  2. The neural sociometer: brain mechanisms underlying state self-esteem.

    Science.gov (United States)

    Eisenberger, Naomi I; Inagaki, Tristen K; Muscatell, Keely A; Byrne Haltom, Kate E; Leary, Mark R

    2011-11-01

    On the basis of the importance of social connection for survival, humans may have evolved a "sociometer"-a mechanism that translates perceptions of rejection or acceptance into state self-esteem. Here, we explored the neural underpinnings of the sociometer by examining whether neural regions responsive to rejection or acceptance were associated with state self-esteem. Participants underwent fMRI while viewing feedback words ("interesting," "boring") ostensibly chosen by another individual (confederate) to describe the participant's previously recorded interview. Participants rated their state self-esteem in response to each feedback word. Results demonstrated that greater activity in rejection-related neural regions (dorsal ACC, anterior insula) and mentalizing regions was associated with lower-state self-esteem. Additionally, participants whose self-esteem decreased from prescan to postscan versus those whose self-esteem did not showed greater medial prefrontal cortical activity, previously associated with self-referential processing, in response to negative feedback. Together, the results inform our understanding of the origin and nature of our feelings about ourselves.

  3. Raynaud's Phenomenon: A Brief Review of the Underlying Mechanisms.

    Science.gov (United States)

    Fardoun, Manal M; Nassif, Joseph; Issa, Khodr; Baydoun, Elias; Eid, Ali H

    2016-01-01

    Raynaud's phenomenon (RP) is characterized by exaggerated cold-induced vasoconstriction. This augmented vasoconstriction occurs by virtue of a reflex response to cooling via the sympathetic nervous system as well as by local activation of α 2C adrenoceptors (α 2C -AR). In a cold-initiated, mitochondrion-mediated mechanism involving reactive oxygen species and the Rho/ROCK pathway, cytoskeletal rearrangement in vascular smooth muscle cells orchestrates the translocation of α 2C -AR to the cell membrane, where this receptor readily interacts with its ligand. Different parameters are involved in this spatial and functional rescue of α 2C -AR. Of notable relevance is the female hormone, 17β-estradiol, or estrogen. This is consistent with the high prevalence of RP in premenopausal women compared to age-matched males. In addition to dissecting the role of these various players, the contribution of pollution as well as genetic background to the onset and prevalence of RP are also discussed. Different therapeutic approaches employed as treatment modalities for this disease are also highlighted and analyzed. The lack of an appropriate animal model for RP mandates that more efforts be undertaken in order to better understand and eventually treat this disease. Although several lines of treatment are utilized, it is important to note that precaution is often effective in reducing severity or frequency of RP attacks.

  4. Neural mechanisms underlying social conformity in an ultimatum game

    Directory of Open Access Journals (Sweden)

    Zhenyu eWei

    2013-12-01

    Full Text Available When individuals’ actions are incongruent with those of the group they belong to, they may change their initial behavior in order to conform to the group norm. This phenomenon is known as social conformity. In the present study, we used event-related functional magnetic resonance imaging (fMRI to investigate brain activity in response to group opinion during an ultimatum game. Results showed that participants changed their choices when these choices conflicted with the normative opinion of the group they were members of, especially in conditions of unfair treatment. The fMRI data revealed that a conflict with group norms activated the brain regions involved in norm violations and behavioral adjustment. Furthermore, in the reject-unfair condition, we observed that a conflict with group norms activated the medial frontal gyrus. These findings contribute to recent research examining neural mechanisms involved in detecting violations of social norms, and provide information regarding the neural representation of conformity behavior in an economic game.

  5. Adhesive wear mechanism under combined electric diamond grinding

    Directory of Open Access Journals (Sweden)

    Popov Vyacheslav

    2017-01-01

    Full Text Available The article provides a scientific substantiation of loading of metal-bond diamond grinding wheels and describes the mechanism of contact interaction (interlocking of wheels with tool steel as well as its general properties having an influence on combined electric diamond grinding efficiency. The study concluded that a loaded layer can be formed in a few stages different by nature. It is known, that one of the causes of grinding degradation is a continuous loading of active grits (abrasive grinding tool by workpiece chips. It all affects the diamond grinding wheels efficiency and grinding ability with a result in increase of tool pressure, contact temperature and wheels specific removal rate. Science has partially identified some various methods to minimize grinding wheel loading, however, as to loading of metal-bond diamond grinding wheels the search is still in progress. Therefore, research people have to state, that in spite of the fact that the wheels made of cubic boron nitride are of little use as applied to ceramic, ultrahard, hard-alloyed hard-to-machine and nano-materials of the time, but manufactures have to apply cubic boron nitride wheels wherein diamond ones preferable.

  6. Linking Pesticide Exposure with Pediatric Leukemia: Potential Underlying Mechanisms.

    Science.gov (United States)

    Hernández, Antonio F; Menéndez, Pablo

    2016-03-29

    Leukemia is the most common cancer in children, representing 30% of all childhood cancers. The disease arises from recurrent genetic insults that block differentiation of hematopoietic stem and/or progenitor cells (HSPCs) and drives uncontrolled proliferation and survival of the differentiation-blocked clone. Pediatric leukemia is phenotypically and genetically heterogeneous with an obscure etiology. The interaction between genetic factors and environmental agents represents a potential etiological driver. Although information is limited, the principal toxic mechanisms of potential leukemogenic agents (e.g., etoposide, benzene metabolites, bioflavonoids and some pesticides) include topoisomerase II inhibition and/or excessive generation of free radicals, which may induce DNA single- and double-strand breaks (DNA-DSBs) in early HSPCs. Chromosomal rearrangements (duplications, deletions and translocations) may occur if these lesions are not properly repaired. The initiating hit usually occurs in utero and commonly leads to the expression of oncogenic fusion proteins. Subsequent cooperating hits define the disease latency and occur after birth and may be of a genetic, epigenetic or immune nature (i.e., delayed infection-mediated immune deregulation). Here, we review the available experimental and epidemiological evidence linking pesticide exposure to infant and childhood leukemia and provide a mechanistic basis to support the association, focusing on early initiating molecular events.

  7. Raynaud's Phenomenon: a Brief Review of the Underlying Mechanisms

    Directory of Open Access Journals (Sweden)

    Manal Fardoun

    2016-11-01

    Full Text Available Raynaud's phenomenon (RP is characterized by exaggerated cold-induced vasoconstriction. This augmented vasoconstriction occurs by virtue of a reflex response to cooling via the sympathetic nervous system as well as by local activation of α2C adrenoceptors (α2C-AR. In a cold-initiated, mitochondrion-mediated mechanism involving reactive oxygen species and the Rho/ROCK pathway, cytoskeletal rearrangement in vascular smooth muscle cells (VSMCs orchestrates the translocation of α2C-AR to the cell membrane, where this receptor readily interacts with its ligand. Different parameters are involved in this spatial and functional rescue of α2C-AR. Of notable relevance is the female hormone, 17β-estradiol, or estrogen. This is consistent with the high prevalence of RP in pre-menopausal women compared to age-matched males. In addition to dissecting the role of these various players, the contribution of pollution as well as genetic background to the onset and prevalence of RP are also discussed. Different therapeutic approaches employed as treatment modalities for this disease are also highlighted and analyzed. The lack of an appropriate animal model for RP mandates that more efforts be undertaken in order to better understand and eventually treat this disease. Although several lines of treatment are utilized, it is important to note that precaution is often effective in reducing severity or frequency of RP attacks.

  8. Assessing mechanical vulnerability in water distribution networks under multiple failures

    Science.gov (United States)

    Berardi, Luigi; Ugarelli, Rita; Røstum, Jon; Giustolisi, Orazio

    2014-03-01

    Understanding mechanical vulnerability of water distribution networks (WDN) is of direct relevance for water utilities since it entails two different purposes. On the one hand, it might support the identification of severe failure scenarios due to external causes (e.g., natural or intentional events) which result into the most critical consequences on WDN supply capacity. On the other hand, it aims at figure out the WDN portions which are more prone to be affected by asset disruptions. The complexity of such analysis stems from the number of possible scenarios with single and multiple simultaneous shutdowns of asset elements leading to modifications of network topology and insufficient water supply to customers. In this work, the search for the most disruptive combinations of multiple asset failure events is formulated and solved as a multiobjective optimization problem. The higher vulnerability failure scenarios are detected as those causing the lower supplied demand due to the lower number of simultaneous failures. The automatic detection of WDN topology, subsequent to the detachments of failed elements, is combined with pressure-driven analysis. The methodology is demonstrated on a real water distribution network. Results show that, besides the failures causing the detachment of reservoirs, tanks, or pumps, there are other different topological modifications which may cause severe WDN service disruptions. Such information is of direct relevance to support planning asset enhancement works and improve the preparedness to extreme events.

  9. Neural mechanism underlying autobiographical memory modulated by remoteness and emotion

    Science.gov (United States)

    Ge, Ruiyang; Fu, Yan; Wang, DaHua; Yao, Li; Long, Zhiying

    2012-03-01

    Autobiographical memory is the ability to recollect past events from one's own life. Both emotional tone and memory remoteness can influence autobiographical memory retrieval along the time axis of one's life. Although numerous studies have been performed to investigate brain regions involved in retrieving processes of autobiographical memory, the effect of emotional tone and memory age on autobiographical memory retrieval remains to be clarified. Moreover, whether the involvement of hippocampus in consolidation of autobiographical events is time dependent or independent has been controversial. In this study, we investigated the effect of memory remoteness (factor1: recent and remote) and emotional valence (factor2: positive and negative) on neural correlates underlying autobiographical memory by using functional magnetic resonance imaging (fMRI) technique. Although all four conditions activated some common regions known as "core" regions in autobiographical memory retrieval, there are some other regions showing significantly different activation for recent versus remote and positive versus negative memories. In particular, we found that bilateral hippocampal regions were activated in the four conditions regardless of memory remoteness and emotional valence. Thus, our study confirmed some findings of previous studies and provided further evidence to support the multi-trace theory which believes that the role of hippocampus involved in autobiographical memory retrieval is time-independent and permanent in memory consolidation.

  10. [Pathophysiology and treatment of ARMD].

    Science.gov (United States)

    Musat, O; Ochinciuc, Uliana; Gutu, Tatiana; Cristescu, T R; Coman, Corina

    2012-01-01

    A review regarding the pathophysiology of AMD as shown in the literature Targets in AMD treatment include: 1. Protection against oxidative stress; 2. Prevention of the accumulation of lipofuscin; 3. Reduction or elimination of chronic inflammation; 4. Changes involving the participation of complement inflammatory phenomena; 5. Changes in the phenomena of chronic inflammation which do not involve the participation of complement (eg. Mitochondria and extracellular matrix). The Neovascularization process includes: 1. Production of angiogenic factor; 2. Release of angiogenic factor; 3. The binding of factors to extracellular receptors and activation of intracellular signaling; 4. Activation of endothelial cells with basement membrane degradation; 5. Endothelial cell proliferation; 6. Endothelial cell migration; 7. Remodeling of extracellular matrix; 8. Tube formation; 9. Vascular stabilization. Therapy inAMD, based on physiological characteristics of early and late stages, is possible nowadays. It is possible to apply a specific treatment for each stage of AMD, but effective treatment requires combinations of specific therapeutic remedies involving different pathophysiological pathways.

  11. [Immune pathophysiology of refractory anemias].

    Science.gov (United States)

    Nakao, Shinji

    2008-03-01

    Among different immune pathophysiologies of anemia, those of bone marrow failure syndromes such as aplastic anemia and myelodysplastic syndrome are most difficult to understand. An increase in the proportion of glycosylphosphatidyl-inositol anchored protein-deficient cells has been identified as the best marker for the presence of immune pathophysiology in this elusive syndrome. The significance of detecting small populations of such paroxysmal nocturnal hemoglobinuria (PNH)-type cells was substantiated by a recent observation that PNH-type cells arose from a donor-derived hematopoietic stem cell with a PIG-A mutation in an aplastic anemia patient with late graft failure which responded well to immunosuppressive therapy. Identification of auto-antigens capable of inducing cytotoxic T cells against hematopoietic stem cells is necessary to prove the escape of PIG-A mutant clone from the immune system attack using animal models.

  12. Molecular Mechanisms Underlying Origin and Diversification of the Angiosperm Flower

    Science.gov (United States)

    Theissen, Guenter; Melzer, Rainer

    2007-01-01

    Background Understanding the mode and mechanisms of the evolution of the angiosperm flower is a long-standing and central problem of evolutionary biology and botany. It has essentially remained unsolved, however. In contrast, considerable progress has recently been made in our understanding of the genetic basis of flower development in some extant model species. The knowledge that accumulated this way has been pulled together in two major hypotheses, termed the ‘ABC model’ and the ‘floral quartet model’. These models explain how the identity of the different types of floral organs is specified during flower development by homeotic selector genes encoding transcription factors. Scope We intend to explain how the ‘ABC model’ and the ‘floral quartet model’ are now guiding investigations that help to understand the origin and diversification of the angiosperm flower. Conclusions Investigation of orthologues of class B and class C floral homeotic genes in gymnosperms suggest that bisexuality was one of the first innovations during the origin of the flower. The transition from dimer to tetramer formation of floral homeotic proteins after establishment of class E proteins may have increased cooperativity of DNA binding of the transcription factors controlling reproductive growth. That way, we hypothesize, better ‘developmental switches’ originated that facilitated the early evolution of the flower. Expression studies of ABC genes in basally diverging angiosperm lineages, monocots and basal eudicots suggest that the ‘classical’ ABC system known from core eudicots originated from a more fuzzy system with fading borders of gene expression and gradual transitions in organ identity, by sharpening of ABC gene expression domains and organ borders. Shifting boundaries of ABC gene expression may have contributed to the diversification of the angiosperm flower many times independently, as may have changes in interactions between ABC genes and their target

  13. Enhancement of sleep slow waves: underlying mechanisms and practical consequences.

    Directory of Open Access Journals (Sweden)

    Michele eBellesi

    2014-10-01

    Full Text Available Even modest sleep restriction, especially the loss of sleep slow wave activity, is invariably associated with slower EEG activity during wake, the occurrence of local sleep in an otherwise awake brain, and impaired performance due to cognitive and memory deficits. Recent studies not only confirm the beneficial role of sleep in memory consolidation, but also point to a specific role for sleep slow waves. Thus, the implementation of methods to enhance sleep slow waves without unwanted arousals or lightening of sleep could have significant practical implications. Here we first review the evidence that it is possible to enhance sleep slow waves in humans using transcranial direct-current stimulation and transcranial magnetic stimulation. Since these methods are currently impractical and their safety is questionable, especially for chronic long-term exposure, we then discuss novel data suggesting that it is possible to enhance slow waves using sensory stimuli. We consider the physiology of the K-complex, a peripheral evoked slow wave, and show that, among different sensory modalities, acoustic stimulation is the most effective in increasing the magnitude of slow waves, likely through the activation of non-lemniscal ascending pathways to the thalamo-cortical system. In addition, we discuss how intensity and frequency of the acoustic stimuli, as well as exact timing and pattern of stimulation, affect sleep enhancement. Finally, we discuss automated algorithms that read the EEG and, in real-time, adjust the stimulation parameters in a closed-loop manner to obtain an increase in sleep slow waves and avoid undesirable arousals. In conclusion, while discussing the mechanisms that underlie the generation of sleep slow waves, we review the converging evidence showing that acoustic stimulation is safe and represents an ideal tool for slow wave sleep enhancement.

  14. Thin circular cylinder under axisymmetrical thermal and mechanical loading

    International Nuclear Information System (INIS)

    Arnaudeau, F.; Zarka, J.; Gerij, J.

    1977-01-01

    To assess structural integrity of components subjected to cyclic thermal loadings one must look at thermal ratchetting as a possible failure mode. Considering a thin circular cylinder subjected to constant internal pressure and cyclically varying thermal gradient through the thickness Bree, J. Strain Analysis 2 (1967) No.3, obtained a diagram that serves as a foundation for many design rules (e.g.: ASME code). The upper part of the french LMFBR main vessel is subjected to an axisymmetrical axial thermal loading and an axial load (own weight). Operation of the reactor leads to cyclic variations of the axial thermal loading. The question that arises is whether or not the Bree diagram is realistic for such loading conditions. A special purpose computer code (Ratch) was developed to analyse a thin circular cylinder subjected to axisymmetrical mechanical and thermal loadings. The Mendelson's approach of this problem is followed. Classical Kirchoff-Love hypothesis of thin shells is used and a state of plane stress is assumed. Space integrations are performed by Gaussian quadrature in the axial direction and by Simpson's one third rule throughout the thickness. Thermoelastic-plastic constitutive equations are solved with an implicit scheme (Nguyen). Thermovisco-plastic constitutive equations are solved with an explicit time integration scheme (Treanor's algorithm especially fitted). A Bree type diagram is obtained for an axial step of temperature which varies cyclically and a sustained constant axial load. The material behavior is assumed perfectly plastic and creep effect is not considered. Results show that the domain where no ratchetting occurs is reduced when compared with the domain predicted by the Bree diagram

  15. Compression under a mechanical counter pressure space suit glove

    Science.gov (United States)

    Waldie, James M A.; Tanaka, Kunihiko; Tourbier, Dietmar; Webb, Paul; Jarvis, Christine W.; Hargens, Alan R.

    2002-01-01

    Background: Current gas-pressurized space suits are bulky stiff shells severely limiting astronaut function and capability. A mechanical counter pressure (MCP) space suit in the form of a tight elastic garment could dramatically improve extravehicular activity (EVA) dexterity, but also be advantageous in safety, cost, mass and volume. The purpose of this study was to verify that a prototype MCP glove exerts the design compression of 200 mmHg, a pressure similar to the current NASA EVA suit. Methods: Seven male subjects donned a pressure measurement array and MCP glove on the right hand, which was placed into a partial vacuum chamber. Average compression was recorded on the palm, the bottom of the middle finger, the top of the middle finger and the dorsum of the hand at pressures of 760 (ambient), 660 and 580 mmHg. The vacuum chamber was used to simulate the pressure difference between the low breathing pressure of the current NASA space suits (approximately 200 mmHg) and an unprotected hand in space. Results: At ambient conditions, the MCP glove compressed the dorsum of the hand at 203.5 +/- 22.7 mmHg, the bottom of the middle finger at 179.4 +/- 16.0 mmHg, and the top of the middle finger at 183.8 +/- 22.6 mmHg. The palm compression was significantly lower (59.6 +/- 18.8 mmHg, pglove compression with the chamber pressure reductions. Conclusions: The MCP glove compressed the dorsum of the hand and middle finger at the design pressure.

  16. Maternal syphilis: pathophysiology and treatment.

    OpenAIRE

    Berman, Stuart M.

    2004-01-01

    Despite the long history of medical interest in syphilis and its effects on pregnancy outcome, many fundamental questions about the pathophysiology and treatment of syphilis during pregnancy remain unanswered. However, understanding has been advanced by recent scientific reports such as those which delineate the complete sequence of the genome of the syphilis spirochaete, provide a more precise description of fetal and neonate infection by use of rabbit infectivity tests and describe the gest...

  17. Pathophysiological approach to chronic diarrhoea.

    Science.gov (United States)

    Corazziari, Enrico Stefano

    2012-10-01

    Chronic diarrhoea disrupts everyday life because of urgency, incontinence and frequent bowel movements. Non-inflammatory diarrhoea may be secondary to altered process of absorption, secretion or digestion. The most prevalent functional diarrhoea is due to altered gut-brain interaction and often after an acute gastroenteritis. Microscopic colitis, rare cases of eosinophilic colitis, congenital diarrhoeal disorders and bile acid malabsorption have been more frequently reported and their pathophysiology elucidated.

  18. Design principles and developmental mechanisms underlying retinal mosaics.

    Science.gov (United States)

    Reese, Benjamin E; Keeley, Patrick W

    2015-08-01

    Most structures within the central nervous system (CNS) are composed of different types of neuron that vary in both number and morphology, but relatively little is known about the interplay between these two features, i.e. about the population dynamics of a given cell type. How such arrays of neurons are distributed within a structure, and how they differentiate their dendrites relative to each other, are issues that have recently drawn attention in the invertebrate nervous system, where the genetic and molecular underpinnings of these organizing principles are being revealed in exquisite detail. The retina is one of the few locations where these principles have been extensively studied in the vertebrate CNS, indeed, where the design principles of 'mosaic regularity' and 'uniformity of coverage' were first explicitly defined, quantified, and related to each other. Recent studies have revealed a number of genes that influence the formation of these histotypical features in the retina, including homologues of those invertebrate genes, although close inspection reveals that they do not always mediate comparable developmental processes nor elucidate fundamental design principles. The present review considers just how pervasive these features of 'mosaic regularity' and 'uniform dendritic coverage' are within the mammalian retina, discussing the means by which such features can be assessed in the mature and developing nervous system and examining the limitations associated with those assessments. We then address the extent to which these two design principles co-exist within different populations of neurons, and how they are achieved during development. Finally, we consider the neural phenotypes obtained in mutant nervous systems, to address whether a prospective gene of interest underlies those very design principles. © 2014 The Authors. Biological Reviews © 2014 Cambridge Philosophical Society.

  19. Mechanism of attenuation of leptin signaling under chronic ligand stimulation

    Directory of Open Access Journals (Sweden)

    Bamberg-Lemper Simone

    2010-01-01

    Full Text Available Abstract Background Leptin is an adipocyte-derived hormone that acts via its hypothalamic receptor (LEPRb to regulate energy balance. A downstream effect essential for the weight-regulatory action of leptin is the phosphorylation and activation of the latent transcription factor STAT3 by LEPRb-associated Janus kinases (JAKs. Obesity is typically associated with chronically elevated leptin levels and a decreased ability of LEPRb to activate intracellular signal transduction pathways (leptin resistance. Here we have studied the roles of the intracellular tyrosine residues in the negative feedback regulation of LEPRb-signaling under chronic leptin stimulation. Results Mutational analysis showed that the presence of either Tyr985 and Tyr1077 in the intracellular domain of LEPRb was sufficient for the attenuation of STAT3 phosphorylation, whereas mutation of both tyrosines rendered LEPRb resistant to feedback regulation. Overexpression and RNA interference-mediated downregulation of suppressor of cytokine signaling 3 (SOCS3 revealed that both Tyr985 and Tyr1077 were capable of supporting the negative modulatory effect of SOCS3 in reporter gene assays. In contrast, the inhibitory effect of SOCS1 was enhanced by the presence of Tyr985 but not Tyr1077. Finally, the reduction of the STAT-phosphorylating activity of the LEPRb complex after 2 h of leptin stimulation was not accompanied by the dephosphorylation or degradation of LEPRb or the receptor-associated JAK molecule, but depended on Tyr985 and/or Tyr1077. Conclusions Both Tyr985 and Tyr1077 contribute to the negative regulation of LEPRb signaling. The inhibitory effects of SOCS1 and SOCS3 differ in the dependence on the tyrosine residues in the intracellular domain of LEPRb.

  20. Photodegradation kinetics, products and mechanism of timolol under simulated sunlight

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yong, E-mail: ychen@hust.edu.cn [School of Environmental Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074 (China); Liang, Qi; Zhou, Danna [College of Material Science and Chemical Engineering, China University of Geosciences, Wuhan 430074 (China); Wang, Zongping, E-mail: zongpingw@hust.edu.cn [School of Environmental Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074 (China); Tao, Tao [School of Environmental Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074 (China); Zuo, Yuegang [Department of Chemistry and Biochemistry, University of Massachusetts Dartmouth, 285 Old Westport Road, North Dartmouth, MA 02747 (United States)

    2013-05-15

    Highlights: ► The indirect degradation of timolol is first investigated in fulvic acid solution. ► {sup 3}FA{sup *} and {sup 1}O{sub 2} accounted for the degradation of timolol in the aerated FA solutions. ► The presence of halides inhibited the degradation in the order of Cl{sup −} < Br{sup −} < I{sup −}. ► The role of I{sup −} in the degradation was first found to be concentration-dependent. ► The photoproducts of timolol were identified by LC-DAD/ESI-MS/MS analysis. -- Abstract: The photodegradation of β-blocker timolol in fulvic acid (FA) solution was investigated under simulated sunlight. The triplet excited state of FA ({sup 3}FA{sup *}) and singlet oxygen ({sup 1}O{sub 2}) were the main reactive species responsible for the degradation of timolol in the aerated FA solutions. Both dissolved oxygen and iodide ions (I{sup −}) are the efficient quenchers of {sup 3}FA{sup *}. The photodegradation was drastically accelerated after removing the dissolved oxygen. The presence of I{sup −} inhibited the photosensitized degradation of timolol in the deoxygenated FA solutions, whereas the role of I{sup −} in the reaction was concentration-dependent in the aerated solutions. The other halide ions such as chloride (Cl{sup −}) and bromide (Br{sup −}) exhibited less effect on the photodegradation of timolol in both aerated and deoxygenated solutions. By LC-DAD/ESI-MS/MS analysis, the photoproducts of timolol in both aerated and deoxygenated FA solutions were identified. Electron transfer interaction occurred between {sup 3}FA{sup *} and amine moiety of timolol, leading to the cleavage of C–O bond in the side chain and oxidation of the hexatomic ring. These findings suggest the photosensitized degradation was a significant pathway for the elimination of timolol in natural waters.

  1. A review on Alzheimer's disease pathophysiology and its management: an update.

    Science.gov (United States)

    Kumar, Anil; Singh, Arti; Ekavali

    2015-04-01

    Alzheimer's disease acknowledged as progressive multifarious neurodegenerative disorder, is the leading cause of dementia in late adult life. Pathologically it is characterized by intracellular neurofibrillary tangles and extracellular amyloidal protein deposits contributing to senile plaques. Over the last two decades, advances in the field of pathogenesis have inspired the researchers for the investigation of novel pharmacological therapeutics centered more towards the pathophysiological events of the disease. Currently available treatments i.e. acetylcholinesterase inhibitors (rivastigmine, galantamine, donepezil) and N-methyl d-aspartate receptor antagonist (memantine) contribute minimal impact on the disease and target late aspects of the disease. These drugs decelerate the progression of the disease, provide symptomatic relief but fail to achieve a definite cure. While the neuropathological features of Alzheimer's disease are recognized but the intricacies of the mechanism have not been clearly defined. This lack of understanding regarding the pathogenic process may be the likely reason for the non-availability of effective treatment which can prevent onset and progression of the disease. Owing to the important progress in the field of pathophysiology in the last couple of years, new therapeutic targets are available that should render the underlying disease process to be tackled directly. In this review, authors will discusses the different aspects of pathophysiological mechanisms behind Alzheimer's disease and its management through conventional drug therapy, including modern investigational therapeutic strategies, recently completed and ongoing. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  2. Pathophysiologic response to severe burn injury.

    Science.gov (United States)

    Jeschke, Marc G; Chinkes, David L; Finnerty, Celeste C; Kulp, Gabriela; Suman, Oscar E; Norbury, William B; Branski, Ludwik K; Gauglitz, Gerd G; Mlcak, Ronald P; Herndon, David N

    2008-09-01

    To improve clinical outcome and to determine new treatment options, we studied the pathophysiologic response postburn in a large prospective, single center, clinical trial. A severe burn injury leads to marked hypermetabolism and catabolism, which are associated with morbidity and mortality. The underlying pathophysiology and the correlations between humoral changes and organ function have not been well delineated. Two hundred forty-two severely burned pediatric patients [>30% total body surface area (TBSA)], who received no anabolic drugs, were enrolled in this study. Demographics, clinical data, serum hormones, serum cytokine expression profile, organ function, hypermetabolism, muscle protein synthesis, incidence of wound infection sepsis, and body composition were obtained throughout acute hospital course. Average age was 8 +/- 0.2 years, and average burn size was 56 +/- 1% TBSA with 43 +/- 1% third-degree TBSA. All patients were markedly hypermetabolic throughout acute hospital stay and had significant muscle protein loss as demonstrated by a negative muscle protein net balance (-0.05% +/- 0.007 nmol/100 mL leg/min) and loss of lean body mass (LBM) (-4.1% +/- 1.9%); P < 0.05. Patients lost 3% +/- 1% of their bone mineral content (BMC) and 2 +/- 1% of their bone mineral density (BMD). Serum proteome analysis demonstrated profound alterations immediately postburn, which remained abnormal throughout acute hospital stay; P < 0.05. Cardiac function was compromised immediately after burn and remained abnormal up to discharge; P < 0.05. Insulin resistance appeared during the first week postburn and persisted until discharge. Patients were hyperinflammatory with marked changes in IL-8, MCP-1, and IL-6, which were associated with 2.5 +/- 0.2 infections and 17% sepsis. In this large prospective clinical trial, we delineated the complexity of the postburn pathophysiologic response and conclude that the postburn response is profound, occurring in a timely manner, with

  3. Quantitative Phase Imaging Techniques for the Study of Cell Pathophysiology: From Principles to Applications

    Directory of Open Access Journals (Sweden)

    Hyunjoo Park

    2013-03-01

    Full Text Available A cellular-level study of the pathophysiology is crucial for understanding the mechanisms behind human diseases. Recent advances in quantitative phase imaging (QPI techniques show promises for the cellular-level understanding of the pathophysiology of diseases. To provide important insight on how the QPI techniques potentially improve the study of cell pathophysiology, here we present the principles of QPI and highlight some of the recent applications of QPI ranging from cell homeostasis to infectious diseases and cancer.

  4. Adropin – physiological and pathophysiological role

    Directory of Open Access Journals (Sweden)

    Natalia Marczuk

    2016-09-01

    Full Text Available Adropin is a peptide hormone that was discovered in 2008 by Kumar et al. This protein consists of 76 amino acids, and it was originally described as a secreted peptide, with residues 1-33 encoding a secretory signal peptide sequence. The amino acid sequence of this protein in humans, mice and rats is identical. While our knowledge of the exact physiological roles of this poorly understood peptide continues to evolve, recent data suggest a role in energy homeostasis and the control of glucose and fatty acid metabolism. This protein is encoded by the Enho gene, which is expressed primarily in the liver and the central nervous system. The regulation of adropin secretion is controversial. Adropin immunoreactivity has been reported by several laboratories in the circulation of humans, non-human primates and rodents. However, more recently it has been suggested that adropin is a membrane-bound protein that modulates cell-cell communication. Moreover, adropin has been detected in various tissues and body fluids, such as brain, cerebellum, liver, kidney, heart, pancreas, small intestine, endothelial cells, colostrum, cheese whey and milk. The protein level, as shown by previous research, changes in various physiological and pathophysiological conditions. Adropin is involved in carbohydrate-lipid metabolism, metabolic diseases, central nervous system function, endothelial function and cardiovascular disease. The knowledge of this interesting protein, its exact role and mechanism of action is insufficient. This article provides an overview of the existing literature about the role of adropin, both in physiological and pathophysiological conditions.

  5. Fracture mechanics in new designed power module under thermo-mechanical loads

    Directory of Open Access Journals (Sweden)

    Durand Camille

    2014-06-01

    Full Text Available Thermo-mechanically induced failure is a major reliability issue in the microelectronic industry. On this account, a new type of Assembly Interconnected Technology used to connect MOSFETs in power modules has been developed. The reliability is increased by using a copper clip soldered on the top side of the chip, avoiding the use of aluminium wire bonds, often responsible for the failure of the device. Thus the new designed MOSFET package does not follow the same failure mechanisms as standard modules. Thermal and power cycling tests were performed on these new packages and resulting failures were analyzed. Thermo-mechanical simulations including cracks in the aluminium metallization and intermetallics (IMC were performed using Finite Element Analysis in order to better understand crack propagation and module behaviour.

  6. Effects of Warm versus Cold Ischemic Donor Lung Preservation on the Underlying Mechanisms of Injuries during Ischemia and Reperfusion.

    Science.gov (United States)

    Iskender, Ilker; Cypel, Marcelo; Martinu, Tereza; Chen, Manyin; Sakamoto, Jin; Kim, Hyunhee; Yu, Keke; Lin, Huiqing; Guan, Zehong; Hashimoto, Kohei; Waddell, Thomas K; Liu, Mingyao; Keshavjee, Shaf

    2018-02-20

    Ischemia-reperfusion injury related to lung transplantation is a major contributor to early postoperative morbidity and mortality. We hypothesized that donation after cardiac death donor lungs experience warm ischemic conditions that activate different injurious mechanisms compared with donor lungs that undergo prolonged cold ischemic conditions. Rat donor lungs were preserved under different cold ischemic times (CIT: 12 hours or 18 hours), or under warm ischemia time (WIT: 3 hours) after cardiac death, followed by single left lung transplantation. Lung function was analyzed during the 2-hours reperfusion period. Microscopic injury, cell death, energy status and inflammatory responses were assessed. Pulmonary oxygenation function was significantly worse in both 18hCIT and WIT groups, accompanied by higher peak airway pressure, acute lung injury scores and expression of cell death markers compared to the 12hCIT control group. In lung tissue, reperfusion induced increased expression levels of interleukin (IL)-1α, IL-1β, IL-6, and chemokines CCL2, CCL3, CXCL1, and CXCL2 in CIT lungs. Notably, these changes were much lower in the WIT group. Additionally, plasma levels of IL-6, IL-18, CCL2 and VEGF were significantly higher, and ATP levels were significantly reduced in warm versus cold ischemic lungs. Compared to 12hCIT, posttransplant pathophysiology deteriorated similarly in both 18hCIT and WIT groups. However, tissue ATP levels and inflammatory profiling differed between warm versus cold ischemic donor lungs. These differences should be carefully considered when developing specific therapeutic strategies to reduce ischemia reperfusion injury in lung transplantation.

  7. Molecular pathophysiology of cerebral edema.

    Science.gov (United States)

    Stokum, Jesse A; Gerzanich, Volodymyr; Simard, J Marc

    2016-03-01

    Advancements in molecular biology have led to a greater understanding of the individual proteins responsible for generating cerebral edema. In large part, the study of cerebral edema is the study of maladaptive ion transport. Following acute CNS injury, cells of the neurovascular unit, particularly brain endothelial cells and astrocytes, undergo a program of pre- and post-transcriptional changes in the activity of ion channels and transporters. These changes can result in maladaptive ion transport and the generation of abnormal osmotic forces that, ultimately, manifest as cerebral edema. This review discusses past models and current knowledge regarding the molecular and cellular pathophysiology of cerebral edema. © The Author(s) 2015.

  8. Narcolepsy: Pathophysiology and Neuropsychological Changes

    Directory of Open Access Journals (Sweden)

    Angela Naumann

    2003-01-01

    Full Text Available Narcolepsy is now recognized as a distinctive disorder with specific pathophysiology and neurochemical abnormalities. Findings on the role of the neuropeptide hypocretin are opening new avenues of research and new strategies for therapy. Recently, neuropsychological and electrophysiological studies have provided evidence for reduced memory performance on standard memory tests in addition to subjective complaints of forgetfulness which may be related to changes in attentional processing. Further studies are, however, necessary to clarify the neuropsychological profile in narcolepsy. This review focuses on the recent advances in understanding narcolepsy.

  9. Epigenetic regulation in the pathophysiology of Alzheimer's disease

    NARCIS (Netherlands)

    Chouliaras, L.; Rutten, B.P.F.; Kenis, G.; Peerbooms, O.; Visser, P.J.; Verhey, F.; van Os, J; Steinbusch, H.W.M.; van der Hove, D.L.A.

    2010-01-01

    With the aging of the population, the growing incidence and prevalence of Alzheimer's disease (AD) increases the burden on individuals and society as a whole. To date, the pathophysiology of AD is not yet fully understood. Recent studies have suggested that epigenetic mechanisms may play a pivotal

  10. Molecular Mechanisms Underlying Curcumin-Mediated Therapeutic Effects in Type 2 Diabetes and Cancer

    Directory of Open Access Journals (Sweden)

    Marzena Wojcik

    2018-01-01

    Full Text Available The growing prevalence of age-related diseases, especially type 2 diabetes mellitus (T2DM and cancer, has become global health and economic problems. Due to multifactorial nature of both diseases, their pathophysiology is not completely understood so far. Compelling evidence indicates that increased oxidative stress, resulting from an imbalance between production of reactive oxygen species (ROS and their clearance by antioxidant defense mechanisms, as well as the proinflammatory state contributes to the development and progression of the diseases. Curcumin (CUR; diferuloylmethane, a well-known polyphenol derived from the rhizomes of turmeric Curcuma longa, has attracted a great deal of attention as a natural compound with beneficial antidiabetic and anticancer properties, partly due to its antioxidative and anti-inflammatory actions. Although this polyphenolic compound is increasingly being recognized for its growing number of protective health effects, the precise molecular mechanisms through which it reduces diabetes- and cancer-related pathological events have not been fully unraveled. Hence, CUR is the subject of intensive research in the fields Diabetology and Oncology as a potential candidate in the treatment of both T2DM and cancer, particularly since current therapeutic options for their treatment are not satisfactory in clinics. In this review, we summarize the recent progress made on the molecular targets and pathways involved in antidiabetic and anticancer activities of CUR that are responsible for its beneficial health effects.

  11. Cannabinoid Hyperemesis Syndrome: Diagnosis, Pathophysiology, and Treatment-a Systematic Review.

    Science.gov (United States)

    Sorensen, Cecilia J; DeSanto, Kristen; Borgelt, Laura; Phillips, Kristina T; Monte, Andrew A

    2017-03-01

    Cannabinoid hyperemesis syndrome (CHS) is a syndrome of cyclic vomiting associated with cannabis use. Our objective is to summarize the available evidence on CHS diagnosis, pathophysiology, and treatment. We performed a systematic review using MEDLINE, Ovid MEDLINE, Embase, Web of Science, and the Cochrane Library from January 2000 through September 24, 2015. Articles eligible for inclusion were evaluated using the Grading and Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Data were abstracted from the articles and case reports and were combined in a cumulative synthesis. The frequency of identified diagnostic characteristics was calculated from the cumulative synthesis and evidence for pathophysiologic hypothesis as well as treatment options were evaluated using the GRADE criteria. The systematic search returned 2178 articles. After duplicates were removed, 1253 abstracts were reviewed and 183 were included. Fourteen diagnostic characteristics were identified, and the frequency of major characteristics was as follows: history of regular cannabis for any duration of time (100%), cyclic nausea and vomiting (100%), resolution of symptoms after stopping cannabis (96.8%), compulsive hot baths with symptom relief (92.3%), male predominance (72.9%), abdominal pain (85.1%), and at least weekly cannabis use (97.4%). The pathophysiology of CHS remains unclear with a dearth of research dedicated to investigating its underlying mechanism. Supportive care with intravenous fluids, dopamine antagonists, topical capsaicin cream, and avoidance of narcotic medications has shown some benefit in the acute setting. Cannabis cessation appears to be the best treatment. CHS is a cyclic vomiting syndrome, preceded by daily to weekly cannabis use, usually accompanied by symptom improvement with hot bathing, and resolution with cessation of cannabis. The pathophysiology underlying CHS is unclear. Cannabis cessation appears to be the best treatment.

  12. Pathophysiology of Radiation-Induced Dysphagia in Head and Neck Cancer.

    Science.gov (United States)

    King, Suzanne N; Dunlap, Neal E; Tennant, Paul A; Pitts, Teresa

    2016-06-01

    Oncologic treatments, such as curative radiotherapy and chemoradiation, for head and neck cancer can cause long-term swallowing impairments (dysphagia) that negatively impact quality of life. Radiation-induced dysphagia comprised a broad spectrum of structural, mechanical, and neurologic deficits. An understanding of the biomolecular effects of radiation on the time course of wound healing and underlying morphological tissue responses that precede radiation damage will improve options available for dysphagia treatment. The goal of this review is to discuss the pathophysiology of radiation-induced injury and elucidate areas that need further exploration.

  13. Pathophysiology of the Belgrade Rat

    Directory of Open Access Journals (Sweden)

    Tania eVeuthey

    2014-04-01

    Full Text Available The Belgrade rat is an animal model of Divalent Metal Transporter-1 (DMT1 deficiency. This strain originates from an X-irradiation experiment first reported in 1966. Since then, the Belgrade rat’s pathophysiology has helped to reveal the importance of iron balance and the role of DMT1. This review discusses our current understanding of iron transport homeostasis and summarizes molecular details of DMT1 function. We describe how studies of the Belgrade rat have revealed key roles for DMT1 in iron distribution to red blood cells as well as duodenal iron absorption. The Belgrade rat’s pathology has extended our knowledge of hepatic iron handling, pulmonary and olfactory iron transport as well as brain iron uptake and renal iron handling. For example, relationships between iron and manganese metabolism have been discerned since both are essential metals transported by DMT1. Pathophysiologic features of the Belgrade rat provide us with a unique and interesting animal model to understand iron homeostasis.

  14. Interactivity effects in social media marketing on brand engagement: an investigation of underlying mechanisms

    NARCIS (Netherlands)

    Antheunis, M.L.; van Noort, G.; Eisend, M.; Langner, T.

    2011-01-01

    Although, SNS advertising spending increases, research on SNS campaigning is still underexposed. First, this study aims to investigate the effect of SNS campaign interactivity on the receivers brand engagement, taking four underlying mechanisms into account (brand identification, campaign

  15. Pathophysiology of acute heart failure: a world to know.

    Science.gov (United States)

    Sánchez-Marteles, M; Rubio Gracia, J; Giménez López, I

    2016-01-01

    Our understanding of the pathophysiological mechanisms of heart failure (HF) has changed considerably in recent years, progressing from a merely haemodynamic viewpoint to a concept of systemic and multifactorial involvement in which numerous mechanisms interact and concatenate. The effects of these mechanisms go beyond the heart itself, to other organs of vital importance such as the kidneys, liver and lungs. Despite this, the pathophysiology of acute HF still has aspects that elude our deeper understanding. Haemodynamic overload, venous congestion, neurohormonal systems, natriuretic peptides, inflammation, oxidative stress and its repercussion on cardiac and vascular remodelling are currently considered the main players in acute HF. Starting with the concept of acute HF, this review provides updates on the various mechanisms involved in this disease. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  16. micro-mechanical experimental investigation and modelling of strain and damage of argillaceous rocks under combined hydric and mechanical loads

    International Nuclear Information System (INIS)

    Wang, L.

    2012-01-01

    The hydro-mechanical behavior of argillaceous rocks, which are possible host rocks for underground radioactive nuclear waste storage, is investigated by means of micro-mechanical experimental investigations and modellings. Strain fields at the micrometric scale of the composite structure of this rock, are measured by the combination of environmental scanning electron microscopy, in situ testing and digital image correlation technique. The evolution of argillaceous rocks under pure hydric loading is first investigated. The strain field is strongly heterogeneous and manifests anisotropy. The observed nonlinear deformation at high relative humidity (RH) is related not only to damage, but also to the nonlinear swelling of the clay mineral itself, controlled by different local mechanisms depending on RH. Irreversible deformations are observed during hydric cycles, as well as a network of microcracks located in the bulk of the clay matrix and/or at the inclusion-matrix interface. Second, the local deformation field of the material under combined hydric and mechanical loadings is quantified. Three types of deformation bands are evidenced under mechanical loading, either normal to stress direction (compaction), parallel (microcracking) or inclined (shear). Moreover, they are strongly controlled by the water content of the material: shear bands are in particular prone to appear at high RH states. In view of understanding the mechanical interactions a local scale, the material is modeled as a composite made of non-swelling elastic inclusions embedded in an elastic swelling clay matrix. The internal stress field induced by swelling strain incompatibilities between inclusions and matrix, as well as the overall deformation, is numerically computed at equilibrium but also during the transient stage associated with a moisture gradient. An analytical micro-mechanical model based on Eshelby's solution is proposed. In addition, 2D finite element computations are performed. Results

  17. Pathophysiology of salt sensitivity hypertension.

    Science.gov (United States)

    Ando, Katsuyuki; Fujita, Toshiro

    2012-06-01

    Dietary salt intake is the most important factor contributing to hypertension, but the salt susceptibility of blood pressure (BP) is different in individual subjects. Although the pathogenesis of salt-sensitive hypertension is heterogeneous, it is mainly attributable to an impaired renal capacity to excrete sodium (Na(+) ). We recently identified two novel mechanisms that impair renal Na(+) -excreting function and result in an increase in BP. First, mineralocorticoid receptor (MR) activation in the kidney, which facilitates distal Na(+) reabsorption through epithelial Na(+) channel activation, causes salt-sensitive hypertension. This mechanism exists not only in models of high-aldosterone hypertension as seen in conditions of obesity or metabolic syndrome, but also in normal- or low-aldosterone type of salt-sensitive hypertension. In the latter, Rac1 activation by salt excess causes MR stimulation. Second, renospecific sympathoactivation may cause an increase in BP under conditions of salt excess. Renal beta2 adrenoceptor stimulation in the kidney leads to decreased transcription of the gene encoding WNK4, a negative regulator of Na(+) reabsorption through Na(+) -Cl (-) cotransporter in the distal convoluted tubules, resulting in salt-dependent hypertension. Abnormalities identified in these two pathways of Na(+) reabsorption in the distal nephron may present therapeutic targets for the treatment of salt-sensitive hypertension.

  18. Microbial Mechanisms Underlying Acidity-induced Reduction in Soil Respiration Under Nitrogen Fertilization

    Science.gov (United States)

    Niu, S.; Li, Y.

    2016-12-01

    Terrestrial ecosystems are receiving increasing amounts of reactive nitrogen (N) due to anthropogenic activities, which largely changes soil respiration and its feedback to climate change. N enrichment can not only increase N availability but also induce soil acidification, both may affect soil microbial activity and root growth with a consequent impact on soil respiration. However, it remains unclear whether elevated N availability or soil acidity has greater impact on soil respiration (Rs). We conducted a manipulative experiment to simulate N enrichment (10 g m-2 yr-1 NH4NO3) and soil acidity (0.552 mol H+ m-2 yr-1 sulfuric acid) and studied their effects on Rs and its components in a temperate forest. Our results showed that soil pH was reduced by 0.2 under N addition or acid addition treatment. Acid addition significantly decreased autotrophic respiration (Ra) and heterotrophic respiration (Rh) by 21.5% and 22.7% in 2014, 34.8% and 21.9% in 2015, respectively, resulting in a reduction of Rs by 22.2% in 2014 and 26.1% in 2015. Nitrogen enrichment reduced Ra, Rh, Rs by 21.9%, 16.2%, 18.6% in 2014 and 22.1%, 5.9%, 11.7% in 2015, respectively. The reductions of Rs and its components were attributable to decrease of fine root biomass, microbial biomass, and cellulose degrading enzymes. N addition did not change microbial community but acid addition increased both fungal and arbuscular mycorrhiza fungi PLFAs, and N plus acid addition significantly enhanced fungal to bacterial ratio. All the hydrolase enzymes were reduced more by soil acidity (43-50%) than nitrogen addition (30-39%). Structural equation model showed that soil acidity played more important role than N availability in reducing soil respiration mainly by changing microbial extracellular enzymes. We therefore suggest that N deposition induced indirect effect of soil acidification on microbial properties is critical and should be taken into account to better understand and predict ecosystem C cycling in

  19. Cognitive mechanisms underlying disorganization of thought in a genetic syndrome (47,XXY)

    NARCIS (Netherlands)

    Van Rijn, Sophie; Aleman, Andre; De Sonneville, Leo; Swaab, Hanna

    Because of the risk for development of psychopathology such as psychotic symptoms, it has been suggested that studying men with the XXY karyotype may help in the search for underlying cognitive, neural and genetic mechanisms. The aim of this study was to identify cognitive mechanisms that may

  20. STATIC AND DYNAMIC ANALYSIS UNDER MECHANICAL AND THERMAL LOADS OF THE DOUBLE SCARA ROBOT

    Directory of Open Access Journals (Sweden)

    Iosif TEMPEA

    2016-05-01

    Full Text Available The paper presents a synthesis of the Double SCARA Robot modelling, leading to an optimal solution, from workspace point of view, as well as precision and stability of the endeffector in performing the planned trajectory. For the design of the final mechanism CATIA software has been used, as well as NASTRAN/PATRAN software, for the mechanism analysis under mechanical and thermal loads.

  1. Pathophysiology of Headaches with a Prominent Vascular Component

    Directory of Open Access Journals (Sweden)

    Juan A Pareja

    1996-01-01

    Full Text Available Vascular changes, whether preliminary or secondary, seem to accompany most headaches. The literature concerning pathophysiological mechanisms in headaches where vascular phenomena are a major, integral part, ie, migraine and cluster headache syndrome, is reviewed and the most common forms of headache associated with cerebrovascular disease are discussed. Emphasis is placed on the vascular phenomena and on the abundant hypotheses and theories regarding headache mechanisms. This review also presents alternative explanatory models, and compares the available anatomical, physiological and biochemical results.

  2. The effects of different size gold nanoparticles on mechanical properties of vascular smooth muscle cells under mechanical stretching

    Science.gov (United States)

    Kieu, Tri Minh

    Nanotechnology is an emerging and promising frontier for medicine and biomedical research due to its potential for applications such as drug delivery, imaging enhancement, and cancer treatment. While these materials may possess significant possibilities, the effects of these particles in the body and how the particles affect the cells is not fully understood. In this study, vascular smooth muscle cells (VSMCs) will be exposed to 5 and 20 nm diameter citrate AuNPs under mechanical conditions. The cytotoxicity properties of these particles will be investigated using LDH and MTT assays. Atomic force microscopy will be used to study how the size of the nanoparticles affect the mechanical properties of the VSMCs. Immunofluorescence staining for alpha actin will also be performed to enhance understanding of the phenotypic shift. The LDH and MTT cytotoxicity assay results demonstrated that neither 5 nor 20 nm diameter nanoparticles are cytotoxic to the cells. However, the mechanical properties and cell morphology of the VSMCs was altered. Under static conditions, both AuNP treatments decreased the mechanical properties of the cells. The size of the nanoparticles had a softening effect on elastic modulus of the cell and sign of a synthetic phenotype was observed. The VSMCs subjected to mechanical stretching exhibited higher elastic modulus compared to the static experimental groups. Again, both AuNPs treatments decreased the mechanical properties of the cells and signs of more synthetic phenotype was seen. However, the size of the nanoparticles did not have any influence on cell's elastic modulus unlike the static treated cells. The mechanical testing condition provided a better look at how these particles would affect the cells in vivo. While the nanoparticles are not cytotoxic to the VSMCs, they are altering the mechanical properties and phenotype of the cell.

  3. Maternal syphilis: pathophysiology and treatment.

    Science.gov (United States)

    Berman, Stuart M

    2004-06-01

    Despite the long history of medical interest in syphilis and its effects on pregnancy outcome, many fundamental questions about the pathophysiology and treatment of syphilis during pregnancy remain unanswered. However, understanding has been advanced by recent scientific reports such as those which delineate the complete sequence of the genome of the syphilis spirochaete, provide a more precise description of fetal and neonate infection by use of rabbit infectivity tests and describe the gestational age distribution of fetal death secondary to syphilis. It appears that fetal syphilitic involvement progresses in a rather predictable fashion, and although there is disagreement about the optimal prenatal treatment regimen, programmatic efforts to prevent fetal death must provide seropositive pregnant women with a recommended treatment early in pregnancy, and certainly before the third trimester.

  4. Molecular Mechanisms Underlying the Anti-depressant Effects of Resveratrol: a Review.

    Science.gov (United States)

    de Oliveira, Marcos Roberto; Chenet, Aline Lukasievicz; Duarte, Adriane Ribeiro; Scaini, Giselli; Quevedo, João

    2017-07-10

    Major depression is a public health problem, affecting 121 million people worldwide. Patients suffering from depression present high rates of morbidity, causing profound economic and social impacts. Furthermore, patients with depression present cognitive impairments, which could influence on treatment adherence and long-term outcomes. The pathophysiology of major depression is not completely understood yet but involves reduced levels of monoamine neurotransmitters, bioenergetics, and redox disturbances, as well as inflammation and neuronal loss. Treatment with anti-depressants provides a complete remission of symptoms in approximately 50% of patients with major depression. However, these drugs may cause side effects, as sedation and weight gain. In this context, there is increasing interest in studies focusing on the anti-depressant effects of natural compounds found in the diet. Resveratrol is a polyphenolic phytoalexin (3,4',5-trihydroxystilbene; C 14 H 12 O 3 ; MW 228.247 g/mol) and has been found in peanuts, berries, grapes, and wine and induces anti-oxidant, anti-inflammatory, and anti-apoptotic effects in several mammalian cell types. Resveratrol also elicits anti-depressant effects, as observed in experimental models using animals. Therefore, resveratrol may be viewed as a potential anti-depressant agent, as well as may serve as a model of molecule to be modified aiming to ameliorate depressive symptoms in humans. In the present review, we describe and discuss the anti-depressant effects of resveratrol focusing on the mechanism of action of this phytoalexin in different experimental models.

  5. Comparison of mechanical and thermodynamic properties of fcc and bcc titanium under high pressure

    Science.gov (United States)

    Zhang, Yongmei; Zhao, Yuhong; Hou, Hua; Wen, Zhiqin; Duan, Meiling

    2018-02-01

    The mechanical and thermodynamic properties of fcc and bcc Ti have been discussed based on the first-principles calculation combined with the quasi-harmonic Debye model. We find that the bulk modulus B, shear modulus G, Young’s modulus E of fcc Ti are larger, while Poisson’s ratio σ is smaller than that of bcc Ti under the same pressure, which indicates the better mechanical performance of fcc Ti compared with bcc Ti. The values of B/G and σ indicate that mechanically stable fcc structure is much less ductile than the bcc structure, while mechanically metastable fcc structure has better ductility than stable bcc structure under high pressure. The normalized volume, isothermal bulk modulus, heat capacity, volume thermal expansion coefficient and Debye temperature under pressure and temperature for fcc and bcc Ti are predicted.

  6. Mechanical behaviour and microstructural evolution of alloy 800H under biaxial cyclic loading

    International Nuclear Information System (INIS)

    Dolabella Portella, P.; Feng Jiao; Oesterle, W.; Ziebs, J.

    1999-01-01

    The mechanical behaviour of alloy 800H under biaxial cyclic loading was investigated at room temperature and at 800 C. The low-cycle fatigue experiments were carried out using tubular specimens under axial and torsional loading with constant total equivalent strain amplitude following either proportional or nonproportional loading paths. The cyclic hardening observed under nonproportional loading was clearly higher than that under proportional loading. The extra hardening due to the nonproportional loading path was more pronounced at room temperature. The evolution of the dislocation structure was characterized by transmission electron microscopy of specimens after interrupted fatigue tests. The changes in the dislocation structure and the precipitation phenomena are in accordance with the observed mechanical behaviour of the specimens. Twinning was observed in very few grains of some specimens and does not influence the extra hardening under nonproportional loading, martensite was not detected in any specimen. (orig.)

  7. An investigation of the mechanism underlying teacher aggression : Testing I3 theory and the General Aggression Model

    NARCIS (Netherlands)

    Montuoro, Paul; Mainhard, Tim

    2017-01-01

    Background: Considerable research has investigated the deleterious effects of teachers responding aggressively to students who misbehave, but the mechanism underlying this dysfunctional behaviour remains unknown. Aims: This study investigated whether the mechanism underlying teacher aggression

  8. Tensile mechanical behavior of hollow and filled carbon nanotubes under tension or combined tension-torsion

    Science.gov (United States)

    Jeong, Byeong-Woo; Lim, Jang-Keun; Sinnott, Susan B.

    2007-01-01

    The tensile mechanical behavior of hollow and filled single-walled carbon nanotubes under tension or combined tension-torsion is examined using classical molecular dynamics simulations. These simulations indicate that the tensile strength under combined tension-torsion can be increased by filling the carbon nanotubes, and the amount of this increase depends on the kind of filling material. They also predict that the tensile strength under combined tension-torsion decreases linearly under applied torsion. The tensile strength can be modified by adjusting the system temperature and through chemical functionalization to the carbon nanotube walls.

  9. Tuberculosis 2: Pathophysiology and microbiology of pulmonary ...

    African Journals Online (AJOL)

    2005-08-01

    Aug 1, 2005 ... February 2013 Downloaded from www.southsudanmedicaljournal.com. MaIN arTIClES. 10. Tuberculosis 2: Pathophysiology and microbiology of pulmonary tuberculosis. Robert L. Serafino Wania MBBS, MrCP, MSc (Trop Med). Pathophysiology. Inhalation of Mycobacterium tuberculosis leads to one of.

  10. Pathophysiology of enteric infections with Giardia duodenalis

    Directory of Open Access Journals (Sweden)

    Buret A.G.

    2008-09-01

    Full Text Available Giardia is the most prevalent human intestinal parasitic protist in the world, and one of the most common parasite of companion animals and young livestock. Giardia is a major cause of diarrhea in children and in travelers. The host-microbial interactions that govern the outcome of infection remain incompletely understood. Findings available to date indicate that the infection causes diarrhea via a combination of intestinal malabsorption and hypersecretion. Malabsorption and maldigestion mainly result from a diffuse shortening of epithelial microvilli. This enterocytic injury is mediated by activated host T lymphocytes. Pathophysiological activation of lymphocytes is secondary to Giardia-induced disruption of epithelial tight junctions, which in turn increases intestinal permeability. Loss of epithelial barrier function is a result of Giardia-induced enterocyte apoptosis. Recent findings suggest that these effects may facilitate the development of chronic enteric disorders, including inflammatory bowel disease, irritable bowel syndrome, and allergies, via mechanisms that remain poorly understood. A newly discovered SGLT-1 glucose uptake-mediated host cytoprotective mechanism may represent an effective modulator of the epithelial apoptosis induced by this parasite, and, possibly, by other enteropathogens. A better understanding of the pathogenesis of giardiasis will shed light on new potential therapeutic targets.

  11. How diagnostic tests help to disentangle the mechanisms underlying neuropathic pain symptoms in painful neuropathies.

    Science.gov (United States)

    Truini, Andrea; Cruccu, Giorgio

    2016-02-01

    Neuropathic pain, ie, pain arising directly from a lesion or disease affecting the somatosensory afferent pathway, manifests with various symptoms, the commonest being ongoing burning pain, electrical shock-like sensations, and dynamic mechanical allodynia. Reliable insights into the mechanisms underlying neuropathic pain symptoms come from diagnostic tests documenting and quantifying somatosensory afferent pathway damage in patients with painful neuropathies. Neurophysiological investigation and skin biopsy studies suggest that ongoing burning pain primarily reflects spontaneous activity in nociceptive-fiber pathways. Electrical shock-like sensations presumably arise from high-frequency ectopic bursts generated in demyelinated, nonnociceptive, Aβ fibers. Although the mechanisms underlying dynamic mechanical allodynia remain debatable, normally innocuous stimuli might cause pain by activating spared and sensitized nociceptive afferents. Extending the mechanistic approach to neuropathic pain symptoms might advance targeted therapy for the individual patient and improve testing for new drugs.

  12. Visualization of hot spot formation in energetic materials under periodic mechanical excitation using phosphor thermography

    Science.gov (United States)

    Casey, Alex; Fenoglio, Gabriel; Detrinidad, Humberto

    2017-06-01

    Under mechanical excitation, energy is known to localize within an energetic material resulting in `hot spot' formation. While many formation mechanisms have been proposed, additional insight to heat generation mechanisms, the effect of binder/crystal interfaces, and predication capabilities can be gained by quantifying the initiation and growth of the hot spots. Phosphor thermography is a well established temperature sensing technique wherein an object's temperature is obtained by collecting the temperature dependent luminescence of an optically excited phosphor. Herein, the phosphor thermography technique has been applied to Dow Corning Sylgard® 184/octahydro 1,3,5,7 tetranitro 1,3,5,7 tetrazocine (HMX) composite materials under mechanical excitation in order to visualize the evolution of the temperature field, and thus hot spot formation, within the binder. Funded by AFOSR. Supported by the Department of Defense (DoD) through the National Defense Science & Engineering Graduate Fellowship (NDSEG) Program.

  13. [Dysphagia in Parkinson's Disease: Pathophysiology, Diagnosis and Therapy].

    Science.gov (United States)

    Suttrup, I; Warnecke, T

    2016-07-01

    Oropharyngeal and esophageal dysphagia are a frequent, but seldom diagnosed symptom of Parkinson's disease (PD). More than 80 % of patients with PD develop dysphagia during the course of their disease leading to a reduced quality of life, complicated medication intake, malnutrition and aspiration pneumonia, which is a major cause of death in PD. The underlying pathophysiology is poorly understood. Impaired dopaminergic and non-dopaminergic mechanisms of the cortical swallowing network as well as peripheral neuromuscular involvement have been suggested to contribute to its multifactorial genesis. Diagnostic screening methods include PD-specific questionnaires and a modified water test. Fiber optic endoscopic evaluation of swallowing (FEES) and videofluoroscopic swallowing study (VFSS), which complement each other, are the gold standard for evaluation of PD-related dysphagia. For evaluation of esophageal dysphagia, the high-resolution manometry (HRM) may be a helpful tool. In addition to dysphagia-specific treatment by speech and language therapists (SLTs), optimized dopaminergic medication is a meaningful therapeutic option. A promising novel method is intensive training of expiratory muscle strength (EMST). Deep brain stimulation does not seem to have a clinically relevant effect on swallowing function in PD. © Georg Thieme Verlag KG Stuttgart · New York.

  14. A Cross-Cultural Approach to Psychological Mechanisms Underlying Emotional Reactions to Music

    OpenAIRE

    Barradas, Gonçalo

    2017-01-01

    Music plays a crucial role in everyday life by enabling listeners to seek individual emotional experiences. To explain why such emotions occur, we must understand the underlying process that mediates between surface-level features of the music and aroused emotions. This thesis aimed to investigate how musical emotions are mediated by psychological mechanisms from a cross-cultural perspective. Study I manipulated four mechanisms by selecting ecologically valid pieces of music that featured inf...

  15. Elucidation of the molecular mechanisms underlying adverse reactions associated with a kinase inhibitor using systems toxicology.

    Science.gov (United States)

    Amemiya, Takahiro; Honma, Masashi; Kariya, Yoshiaki; Ghosh, Samik; Kitano, Hiroaki; Kurachi, Yoshihisa; Fujita, Ken-Ichi; Sasaki, Yasutsuna; Homma, Yukio; Abernethy, Darrel R; Kume, Haruki; Suzuki, Hiroshi

    2015-01-01

    Targeted kinase inhibitors are an important class of agents in anticancer therapeutics, but their limited tolerability hampers their clinical performance. Identification of the molecular mechanisms underlying the development of adverse reactions will be helpful in establishing a rational method for the management of clinically adverse reactions. Here, we selected sunitinib as a model and demonstrated that the molecular mechanisms underlying the adverse reactions associated with kinase inhibitors can efficiently be identified using a systems toxicological approach. First, toxicological target candidates were short-listed by comparing the human kinase occupancy profiles of sunitinib and sorafenib, and the molecular mechanisms underlying adverse reactions were predicted by sequential simulations using publicly available mathematical models. Next, to evaluate the probability of these predictions, a clinical observation study was conducted in six patients treated with sunitinib. Finally, mouse experiments were performed for detailed confirmation of the hypothesized molecular mechanisms and to evaluate the efficacy of a proposed countermeasure against adverse reactions to sunitinib. In silico simulations indicated the possibility that sunitinib-mediated off-target inhibition of phosphorylase kinase leads to the generation of oxidative stress in various tissues. Clinical observations of patients and mouse experiments confirmed the validity of this prediction. The simulation further suggested that concomitant use of an antioxidant may prevent sunitinib-mediated adverse reactions, which was confirmed in mouse experiments. A systems toxicological approach successfully predicted the molecular mechanisms underlying clinically adverse reactions associated with sunitinib and was used to plan a rational method for the management of these adverse reactions.

  16. Mechanisms Underlying Stress Fracture and the Influence of Sex and Race/Ethnicity

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-1-0652 TITLE: Mechanisms Underlying Stress Fracture and the Influence of Sex and Race/Ethnicity PRINCIPAL INVESTIGATOR...5a. CONTRACT NUMBER W81XWH-16-1-0652 Mechanisms Underlying Stress Fracture and the Influence of Sex and Race/Ethnicity 5b. GRANT NUMBER W81XWH...Email addresses: mbouxsei@bidmc.harvard.edu; scaksa@mgh.harvard.edu; serudolph@mgh.harvard.edu ; kpopp@mgh.harvard.edu E-Mail: 5f. WORK UNIT NUMBER 7

  17. Comparative proteomics of peanut gynophore development under dark and mechanical stimulation.

    Science.gov (United States)

    Sun, Yong; Wang, Qingguo; Li, Zhen; Hou, Lei; Dai, Shaojun; Liu, Wei

    2013-12-06

    Peanut (Arachis hypogaea. L) is an important leguminous crop and source of proteins and lipids. It has attracted widespread attention of researchers due to its unique growth habit of geocarpy, which is regulated by geotropism, negative phototropism, and haptotropism. However, the protein expression pattern and molecular regulatory mechanism underlying the physiological processes of peanut remain unknown. In this study, the peanut gynophores under five treatment conditions were used for proteomic analysis, including aerial growth of the gynophores, the gynophores penetrated into the soil, as well as aerial growth of the gynophores under mechanical stimulation, dark, and mechanical stimulation combined with dark. The analysis of protein abundances in peanut gynophores under these conditions were conducted using comparative proteomic approaches. A total of 27 differentially expressed proteins were identified and further classified into nine biological functional groups of stress and defense, carbohydrate and energy metabolism, metabolism, photosynthesis, cell structure, signaling, transcription, protein folding and degradation, and function unknown. By searching gene functions against peanut database, 10 genes with similar annotations were selected as corresponding changed proteins, and their variation trends in gynophores under such growth conditions were further verified using quantitative real-time PCR. Overall, the investigation will benefit to enrich our understanding of the internal mechanisms of peanut gynophore development and lay a foundation for breeding and improving crop varieties and qualities.

  18. Model test study of evaporation mechanism of sand under constant atmospheric condition

    OpenAIRE

    CUI, Yu Jun; DING, Wenqi; SONG, Weikang

    2014-01-01

    The evaporation mechanism of Fontainebleau sand using a large-scale model chamber is studied. First, the evaporation test on a layer of water above sand surface is performed under various atmospheric conditions, validating the performance of the chamber and the calculation method of actual evaporation rate by comparing the calculated and measured cumulative evaporations. Second,the evaporation test on sand without water layer is conducted under constant atmospheric condition. Both the evoluti...

  19. Mechanical behavior of confined self-compacting reinforced concrete circular columns under concentric axial loading

    OpenAIRE

    Khairallah, Fouad

    2013-01-01

    While there is abundant research information on ordinary confined concrete, there are little data on the behavior of Self-Compacting Concrete (SCC) under such condition. Due to higher shrinkage and lower coarse aggregate content of SCC compared to that of Normal Concrete (NC), its composite performance under confined conditions needs more investigation. This paper has been devoted to investigate and compare the mechanical behavior of confined concrete circular columns cast with SCC and NC und...

  20. Exploring the genetics and non-cell autonomous mechanisms underlying ALS/FTLD.

    Science.gov (United States)

    Chen, Hongbo; Kankel, Mark W; Su, Susan C; Han, Steve W S; Ofengeim, Dimitry

    2018-03-01

    Although amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, was first described in 1874, a flurry of genetic discoveries in the last 10 years has markedly increased our understanding of this disease. These findings have not only enhanced our knowledge of mechanisms leading to ALS, but also have revealed that ALS shares many genetic causes with another neurodegenerative disease, frontotemporal lobar dementia (FTLD). In this review, we survey how recent genetic studies have bridged our mechanistic understanding of these two related diseases and how the genetics behind ALS and FTLD point to complex disorders, implicating non-neuronal cell types in disease pathophysiology. The involvement of non-neuronal cell types is consistent with a non-cell autonomous component in these diseases. This is further supported by studies that identified a critical role of immune-associated genes within ALS/FTLD and other neurodegenerative disorders. The molecular functions of these genes support an emerging concept that various non-autonomous functions are involved in neurodegeneration. Further insights into such a mechanism(s) will ultimately lead to a better understanding of potential routes of therapeutic intervention. Facts ALS and FTLD are severe neurodegenerative disorders on the same disease spectrum. Multiple cellular processes including dysregulation of RNA homeostasis, imbalance of proteostasis, contribute to ALS/FTLD pathogenesis. Aberrant function in non-neuronal cell types, including microglia, contributes to ALS/FTLD. Strong neuroimmune and neuroinflammatory components are associated with ALS/FTLD patients. Open Questions Why can patients with similar mutations have different disease manifestations, i.e., why do C9ORF72 mutations lead to motor neuron loss in some patients while others exhibit loss of neurons in the frontotemporal lobe? Do ALS causal mutations result in microglial dysfunction and contribute to ALS/FTLD pathology? How do microglia

  1. Ultrastructural changes of cell walls under intense mechanical treatment of selective plant raw material

    International Nuclear Information System (INIS)

    Bychkov, Aleksey L.; Ryabchikova, E.I.; Korolev, K.G.; Lomovsky, O.I.

    2012-01-01

    Structural changes of cell walls under intense mechanical treatment of corn straw and oil-palm fibers were studied by electron and light microscopy. Differences in the character of destruction of plant biomass were revealed, and the dependence of destruction mechanisms on the structure of cell walls and lignin content was demonstrated. We suggest that the high reactivity of the particles of corn straw (about 18% of lignin) after intense mechanical treatment is related to disordering of cell walls and an increase of the surface area, while in the case of oil palm (10% of lignin) the major contribution into an increase in the reactivity is made by an increase of surface area. -- Highlights: ► Structure of cell walls determines the processes of plant materials' destruction. ► Ultrastructure of highly lignified materials strongly disordering by mechanical action. ► Ultrastructure of low-lignified materials is not disordering by mechanical action.

  2. Major pathophysiological correlations of rosacea: a complete clinical appraisal.

    Science.gov (United States)

    Vemuri, Ravi Chandra; Gundamaraju, Rohit; Sekaran, Shamala Devi; Manikam, Rishya

    2015-01-01

    Rosacea is a characteristic cutaneous disorder with a diverse clinical manifestations ranging from facial vascular hyper-reactivity to sebaceous gland hyperplasia. Many theories on pathophysiology of rosacea were proposed over the past decade, however the pathogenicity is poorly understood. To review the evidence on different pathophysiological correlations of rosacea. A literature search was conducted for studies published between 1990 to March 2014. The inclusion criteria was pathophysiology, randomized controlled trials, controlled trials on rosacea. Out of 5141 articles, 14 high quality studies met all the selection criteria. Of 14 articles, 5 are randomized control trials (RCTs), 2 are controlled trial, 3 comparative trials, 2 observational trials, 1 prospective and 1 diagnostic trial. The studies were categorized into two groups: the trigger factors and sub-types & symptoms. Of 7 high quality studies, 4 provided strong evidence that immune responses causing disease triggered by external/internal factors such as sunlight, food and chemical agents, 3 trials provided significant evidence of microorganisms as causative agents. The remaining trials did not provide significant evidences on pathophysiology. Vasculature, chronic inflammatory responses, environmental triggers, food and chemicals ingested and microorganisms either alone or in combination are responsible for rosacea. Many promising drugs are under various phases of clinical trials and interestingly, probiotics could also possibly be used as one of the treatment option.

  3. Evolving evidence in adult idiopathic intracranial hypertension: pathophysiology and management

    OpenAIRE

    Mollan, Susan P; Ali, Fizzah; Hassan-Smith, Ghaniah; Botfield, Hannah; Friedman, Deborah I; Sinclair, Alexandra J

    2016-01-01

    Idiopathic intracranial hypertension (IIH) is a rare but important disease associated with significant morbidity. There is an expected rise in prevalence in line with the escalating global burden of obesity. Modern revisions in the terminology and diagnostic criteria for IIH help guide clinicians in investigations and researchers in standardising recruitment criteria for clinical trials. The pathophysiology of IIH is incompletely characterised; suggested underpinning mechanisms include the ro...

  4. Structural and Mechanical Properties of Intermediate Filaments under Extreme Conditions and Disease

    Science.gov (United States)

    Qin, Zhao

    Intermediate filaments are one of the three major components of the cytoskeleton in eukaryotic cells. It was discovered during the recent decades that intermediate filament proteins play key roles to reinforce cells subjected to large-deformation as well as participate in signal transduction. However, it is still poorly understood how the nanoscopic structure, as well as the biochemical properties of these protein molecules contribute to their biomechanical functions. In this research we investigate the material function of intermediate filaments under various extreme mechanical conditions as well as disease states. We use a full atomistic model and study its response to mechanical stresses. Learning from the mechanical response obtained from atomistic simulations, we build mesoscopic models following the finer-trains-coarser principles. By using this multiple-scale model, we present a detailed analysis of the mechanical properties and associated deformation mechanisms of intermediate filament network. We reveal the mechanism of a transition from alpha-helices to beta-sheets with subsequent intermolecular sliding under mechanical force, which has been inferred previously from experimental results. This nanoscale mechanism results in a characteristic nonlinear force-extension curve, which leads to a delocalization of mechanical energy and prevents catastrophic fracture. This explains how intermediate filament can withstand extreme mechanical deformation of > 1 00% strain despite the presence of structural defects. We combine computational and experimental techniques to investigate the molecular mechanism of Hutchinson-Gilford progeria syndrome, a premature aging disease. We find that the mutated lamin tail .domain is more compact and stable than the normal one. This altered structure and stability may enhance the association of intermediate filaments with the nuclear membrane, providing a molecular mechanism of the disease. We study the nuclear membrane association

  5. Nonlinear Dynamic Analysis of Telescopic Mechanism for Truss Structure Bridge Inspection Vehicle Under Pedestrian Excitation

    Directory of Open Access Journals (Sweden)

    Wenwen Sui

    Full Text Available Abstract Nonlinear dynamic analysis of an axially moving telescopic mechanism for truss structure bridge inspection vehicle under pedestrian excitation is carried out. A biomechanically inspired inverted-pendulum model is utilized to simplify the pedestrian. The nonlinear equations of motion for the beam-pedestrian system are derived using the Hamilton's principle. The equations are transformed into two ordinary differential equations by applying the Galerkin's method at the first two orders. The solutions to the equations are acquired by using the Newmark-β method associated with the Newton-Raphson method. The time-dependent feature of the eigenfunctions for the two beams are taken into consideration in the solutions. Accordingly, the equations of motion for a simplified system, in which the pedestrian is regarded as moving cart, are given. In the numerical examples, dynamic responses of the telescopic mechanism in eight conditions of different beam-telescoping and pedestrian-moving directions are simulated. Comparisons between the vibrations of the beams under pedestrian excitation and corresponding moving cart are carried out to investigate the influence of the pedestrian excitation on the telescopic mechanism. The results show that the displacement of the telescopic mechanism under pedestrian excitation is smaller than that under moving cart especially when the pedestrian approaches the beams end. Additionally, compared with moving cart, the pedestrian excitation can effectively strengthen the vibration when the beam extension is small or when the pedestrian is close to the beams end.

  6. Mechanisms underlying prorenin actions on hypothalamic neurons implicated in cardiometabolic control

    Directory of Open Access Journals (Sweden)

    Soledad Pitra

    2016-10-01

    Conclusions: We identified novel neuronal targets and cellular mechanisms underlying PR/PRR actions in critical hypothalamic neurons involved in cardiometabolic regulation. This fundamental mechanistic information regarding central PR/PRR actions is essential for the development of novel RAS-based therapeutic targets for the treatment of cardiometabolic disorders in obesity and hypertension.

  7. Unraveling the mechanisms underlying postural instability in Parkinson's disease using dynamic posturography

    NARCIS (Netherlands)

    Nonnekes, J.H.; Kam, D. de; Geurts, A.C.; Weerdesteijn, V.G.M.; Bloem, B.R.

    2013-01-01

    Postural instability, one of the cardinal symptoms of Parkinson's disease (PD), has devastating consequences for affected patients. Better strategies to prevent falls are needed, but this calls for an improved understanding of the complex mechanisms underlying postural instability. We must also

  8. The Mediated MIMIC Model for Understanding the Underlying Mechanism of DIF

    Science.gov (United States)

    Cheng, Ying; Shao, Can; Lathrop, Quinn N.

    2016-01-01

    Due to its flexibility, the multiple-indicator, multiple-causes (MIMIC) model has become an increasingly popular method for the detection of differential item functioning (DIF). In this article, we propose the mediated MIMIC model method to uncover the underlying mechanism of DIF. This method extends the usual MIMIC model by including one variable…

  9. Deformation Microstructures and Creep Mechanisms in Advanced ZR-Based Cladding Under Biazal Loading

    Energy Technology Data Exchange (ETDEWEB)

    K. Linga (KL) Murty

    2008-08-11

    Investigate creep behavior of Zr-based cladding tubes with attention to basic creep mechanisms and transitions in them at low stresses and/or temperatures and study the dislocation microstructures of deformed samples for correlation with the underlying micromechanism of creep

  10. Cementogenesis is inhibited under a mechanical static compressive force via Piezo1.

    Science.gov (United States)

    Zhang, Ying-Ying; Huang, Yi-Ping; Zhao, Hua-Xiang; Zhang, Ting; Chen, Feng; Liu, Yan

    2017-07-01

    To investigate whether Piezo1, a mechanotransduction gene mediates the cementogenic activity of cementoblasts under a static mechanical compressive force. Murine cementoblasts (OCCM-30) were exposed to a 2.0 g/cm 2 static compressive force for 3, 6, 12, and 24 hours. Then the expression profile of Piezo1 and the cementogenic activity markers osteoprotegerin (Opg), osteopontin (Opn), osteocalcin (Oc), and protein tyrosine phosphataselike member A (Ptpla) were analyzed. Opg, Opn, Oc, and Ptpla expression was further measured after using siRNA to knock down Piezo1. Real-time PCR, Western blot, and cell proliferation assays were performed according to standard procedures. After mechanical stimulation, cell morphology and proliferation did not change significantly. The expression of Piezo1, Opg, Opn, Oc, and Ptpla was significantly decreased, with a high positive correlation between Opg and Piezo1 expression. After Piezo1 knockdown, the expression of Opg, Opn, Oc, and Ptpla was further decreased under mechanical stimulation. Cementogenic activity was inhibited in OCCM-30 cells under static mechanical force, a process that was partially mediated by the decrease of Piezo1. This study provides a new viewpoint of the pathogenesis mechanism of orthodontically induced root resorption and repair.

  11. Large Deflections Mechanical Analysis of a Suspended Single-Wall Carbon Nanotube under Thermoelectrical Loading

    Directory of Open Access Journals (Sweden)

    Assaf Ya'akobovitz

    2011-01-01

    Full Text Available Following the recent progress in integrating single-wall carbon nanotubes (SWCNTs into silicon-based micro-electromechanical systems (MEMS, new modeling tools are needed to predict their behavior under different loads, including thermal, electrical and mechanical. In the present study, the mechanical behavior of SWCNTs under thermoelectrical loading is analyzed using a large deflection geometrically nonlinear string model. The effect of the resistive heating was found to have a substantial influence on the SWCNTs behavior, including significant enhancement of the strain (up to the millistrains range and buckling due to the thermal expansion. The effect of local buckling sites was also studied and was found to enhance the local strain. The theoretical and numerical results obtained in the present study demonstrate the importance of resistive heating in the analysis of SWCNTs and provide an additional insight into the unique mechanics of suspended SWCNTs.

  12. Intercomparison of chemical mechanisms for air quality policy formulation and assessment under North American conditions.

    Science.gov (United States)

    Derwent, Richard

    2017-07-01

    The intercomparison of seven chemical mechanisms for their suitability for air quality policy formulation and assessment is described. Box modeling techniques were employed using 44 sets of background environmental conditions covering North America to constrain the chemical development of the longer lived species. The selected mechanisms were modified to enable an unbiased assessment of the adequacy of the parameterizations of photochemical ozone production from volatile organic compound (VOC) oxidation in the presence of NO x . Photochemical ozone production rates responded differently to 30% NO x and VOC reductions with the different mechanisms, despite the striking similarities between the base-case ozone production rates. The 30% reductions in NO x and VOCs also produced changes in OH. The responses in OH to 30% reductions in NO x and VOCs appeared to be more sensitive to mechanism choice, compared with the responses in the photochemical ozone production rates. Although 30% NO x reductions generally led to decreases in OH, 30% reductions in VOCs led to increases in OH, irrespective of mechanism choice and background environmental conditions. The different mechanisms therefore gave different OH responses to NO x and VOC reductions and so would give different responses in terms of changes in the fate and behavior of air toxics, acidification and eutrophication, and fine particle formation compared with others, in response to ozone control strategies. Policymakers need to understand that there are likely to be inherent differences in the responses to ozone control strategies between different mechanisms, depending on background environmental conditions and the extents of NO x and VOC reductions under consideration. The purpose of this paper is to compare predicted ozone responses to NO x and VOC reductions with seven chemical mechanisms under North American conditions. The good agreement found between the tested mechanisms should provide some support for their

  13. Pathophysiology and Immune Dysfunction in Endometriosis

    Directory of Open Access Journals (Sweden)

    Soo Hyun Ahn

    2015-01-01

    Full Text Available Endometriosis is an estrogen-dependent, chronic, proinflammatory disease prevalent in 10% of women of reproductive age worldwide. Characterized by the growth of endometrium-like tissue in aberrant locations outside of the uterus, it is responsible for symptoms including chronic pelvic pain, dysmenorrhea, and subfertility that degrade quality of life of women significantly. In Canada, direct and indirect economic cost of endometriosis amounts to 1.8 billion dollars, and this is elevated to 20 billion dollars in the United States. Despite decades of research, the etiology and pathophysiology of endometriosis still remain to be elucidated. This review aims to bring together the current understanding regarding the pathogenesis of endometriosis with specific focus on mechanisms behind vascularization of the lesions and the contribution of immune factors in facilitating lesion establishment and development. The role of hormones, immune cells, and cytokine signaling is highlighted, in addition to discussing the current pharmaceutical options available for management of pain symptoms in women with endometriosis.

  14. Pathophysiology and Immune Dysfunction in Endometriosis

    Science.gov (United States)

    Ahn, Soo Hyun; Monsanto, Stephany P.; Miller, Caragh; Singh, Sukhbir S.; Thomas, Richard; Tayade, Chandrakant

    2015-01-01

    Endometriosis is an estrogen-dependent, chronic, proinflammatory disease prevalent in 10% of women of reproductive age worldwide. Characterized by the growth of endometrium-like tissue in aberrant locations outside of the uterus, it is responsible for symptoms including chronic pelvic pain, dysmenorrhea, and subfertility that degrade quality of life of women significantly. In Canada, direct and indirect economic cost of endometriosis amounts to 1.8 billion dollars, and this is elevated to 20 billion dollars in the United States. Despite decades of research, the etiology and pathophysiology of endometriosis still remain to be elucidated. This review aims to bring together the current understanding regarding the pathogenesis of endometriosis with specific focus on mechanisms behind vascularization of the lesions and the contribution of immune factors in facilitating lesion establishment and development. The role of hormones, immune cells, and cytokine signaling is highlighted, in addition to discussing the current pharmaceutical options available for management of pain symptoms in women with endometriosis. PMID:26247027

  15. Angioedema: etiology, pathophysiology, current and emerging therapies.

    Science.gov (United States)

    Lewis, Lawrence M

    2013-11-01

    Angioedema (AE) is characterized by nonpitting edema of the dermis and subcutaneous layers. The most common sites of involvement are the tongue, lips, face, and throat; however, swelling can also occur in the extremities, genitalia, and viscera. Life-threatening airway swelling can also occur. AE may be allergic or nonallergic. The overall lifetime incidence of AE is reported to be as high as 15%. This article summarizes the etiology, pathophysiology, and current treatment of several forms of nonallergic AE (including hereditary, acquired, and idiopathic AE) and focuses on angiotensin-converting enzyme inhibitor-induced angioedema (ACEi-AE), which is responsible for 30%-40% of all AE seen in United States emergency departments. Although the triggers, which are primary biologic mechanisms, and treatments for ACEi-AE may differ from those of the hereditary and acquired forms of AE, the clinical effects of ACEi-AE are mediated through a shared pathway, the kallikrein-kinin system. Thus, although current therapeutic options for ACEi-AE are limited, recent advances in the treatment of hereditary AE (HAE) appear promising for improving the outcomes of patients with ACEi-AE. New HAE medications that correct imbalances in the kallikrein-kinin system may prove safe and efficacious in the treatment of ACEi-AE. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Pathophysiology and Contributing Factors in Postprostatectomy Incontinence: A Review.

    Science.gov (United States)

    Heesakkers, John; Farag, Fawzy; Bauer, Ricarda M; Sandhu, Jaspreet; De Ridder, Dirk; Stenzl, Arnulf

    2017-06-01

    The incidence and awareness of postprostatectomy incontinence (PPI) has increased during the past few years, probably because of an increase in prostate cancer surgery. Many theories have been postulated to explain the pathophysiology of PPI. The current review scrutinizes various pathophysiologic mechanisms underlying the occurrence of PPI. A search was conducted on PubMed and EMBASE for publications on PPI. The primary search returned 2518 publications. Animal and basic research studies, letters, publications on prostatectomy for benign reasons, pathology of prostatic carcinoma, radiotherapy and hormone therapy of prostatic carcinoma, and review articles were all used as criteria for exclusion from the study. A total of 128 publications were selected for final analysis. Neuromuscular anatomic elements and pelvic support are known to influence PPI as evidenced by multiple publications. A number of non-anatomic and surgical elements have been postulated as contributing factors to PPI. Biological factors and preoperative parameters include: functional bladder changes, age, body mass index (BMI), pre-existing lower urinary tract symptoms (LUTS), prostate size, and oncologic factors. Multiple studies reported the impact of specific anatomic/surgical factors, including fibrosis, shorter membranous urethral length (MUL), anastomotic stricture, damage to the neurovascular bundle, and extensive dissection, all of which have a negative impact on the continence status of patients following radical prostatectomy (RP). Investigation of the impact of techniques to spare the bladder neck and additional procedures to reconstruct the posterior or anterior support structures (eg, the Rocco stitch) on continence status is ongoing. Anatomic support and pelvic innervation appear to be important factors in the etiology of PPI. Biological/preoperative factors including greater age at time of surgery, pre-existing LUTS, high BMI, shorter MUL, and functional bladder changes have a

  17. Cardiomyocyte Remodeling in Atrial Fibrillation and Hibernating Myocardium: Shared Pathophysiologic Traits Identify Novel Treatment Strategies?

    Directory of Open Access Journals (Sweden)

    Brian R. Weil

    2015-01-01

    Full Text Available Atrial fibrillation (AF is the most common arrhythmia and is associated with a high risk of morbidity and mortality. However, there are limited treatment strategies for prevention of disease onset and progression. Development of novel therapies for primary and secondary prevention of AF is critical and requires improved understanding of the cellular and molecular mechanisms underlying the AF disease process. Translational and clinical studies conducted over the past twenty years have revealed that atrial remodeling in AF shares several important pathophysiologic traits with the remodeling processes exhibited by hibernating myocardium that develop in response to chronic ischemia. These shared features, which include an array of structural, metabolic, and electrophysiologic changes, appear to represent a conserved adaptive myocyte response to chronic stress that involves dedifferentiation towards a fetal phenotype to promote survival. In this review, we discuss the pathophysiology of AF, summarize studies supporting a common remodeling program in AF and hibernating myocardium, and propose future therapeutic implications of this emerging paradigm. Ultimately, better understanding of the molecular mechanisms of atrial myocyte remodeling during the onset of AF and the transition from paroxysmal to persistent stages of the disease may facilitate discovery of new therapeutic targets.

  18. Migraine aura pathophysiology: the role of blood vessels and microembolisation

    OpenAIRE

    Dalkara, Turgay; Nozari, Ala; Moskowitz, Michael A

    2010-01-01

    Migraine attacks with auras are sometimes associated with underlying hereditary or acquired cerebrovascular disorders. A unifying pathophysiological explanation linking migraine to these conditions has been diffcult to identify. On the basis of genetic and epidemiological evidence, we suggest that changes in blood vessels, hypoperfusion disorders, and microembolisation can cause neurovascular dysfunction and evoke cortical spreading depression, an event that is widely thought to underlie aura...

  19. Pathophysiology of Resistant Hypertension: The Role of Sympathetic Nervous System

    OpenAIRE

    Tsioufis, Costas; Kordalis, Athanasios; Flessas, Dimitris; Anastasopoulos, Ioannis; Tsiachris, Dimitris; Papademetriou, Vasilios; Stefanadis, Christodoulos

    2011-01-01

    Resistant hypertension (RH) is a powerful risk factor for cardiovascular morbidity and mortality. Among the characteristics of patients with RH, obesity, obstructive sleep apnea, and aldosterone excess are covering a great area of the mosaic of RH phenotype. Increased sympathetic nervous system (SNS) activity is present in all these underlying conditions, supporting its crucial role in the pathophysiology of antihypertensive treatment resistance. Current clinical and experimental knowledge po...

  20. Pathophysiology and imaging in inflammatory and blastomatous synovial diseases

    Energy Technology Data Exchange (ETDEWEB)

    Imhof, H.; Noebauer-Huhmann, I.-M.; Gahleitner, A.; Kainberger, F.; Krestan, C.; Trattnig, S. [Osteology, Universitaets Klinik fuer Radiodiagnostik, AKH Vienna (Austria); Sulzbacher, I. [Klinisches Institut fuer klinische Pathologie, AKH Vienna (Austria)

    2002-06-01

    Variable pathologies are subsumed under the term ''synovial disease'', including common pathologies such as rheumatoid arthritis. While formerly radiologists had to rely on conventional radiographs and bone scintigraphy with their inherent problems in visualizing soft tissue, noninvasive imaging of the synovium has recently improved substantially with the technical development of MRI and (Doppler) ultrasound. These imaging modalities allow differentiation of characteristic pathologic features based on a profound knowledge of normal anatomy and pathophysiology. (orig.)

  1. Review of the damage mechanism in wind turbine gearbox bearings under rolling contact fatigue

    Science.gov (United States)

    Su, Yun-Shuai; Yu, Shu-Rong; Li, Shu-Xin; He, Yan-Ni

    2017-12-01

    Wind turbine gearbox bearings fail with the service life is much shorter than the designed life. Gearbox bearings are subjected to rolling contact fatigue (RCF) and they are observed to fail due to axial cracking, surface flaking, and the formation of white etching areas (WEAs). The current study reviewed these three typical failure modes. The underlying dominant mechanisms were discussed with emphasis on the formation mechanism of WEAs. Although numerous studies have been carried out, the formation of WEAs remains unclear. The prevailing mechanism of the rubbing of crack faces that generates WEAs was questioned by the authors. WEAs were compared with adiabatic shear bands (ASBs) generated in the high strain rate deformation in terms of microstructural compositions, grain refinement, and formation mechanism. Results indicate that a number of similarities exist between them. However, substantial evidence is required to verify whether or not WEAs and ASBs are the same matters.

  2. Transformational Leadership and Organizational Citizenship Behavior: A Meta-Analytic Test of Underlying Mechanisms.

    Science.gov (United States)

    Nohe, Christoph; Hertel, Guido

    2017-01-01

    Based on social exchange theory, we examined and contrasted attitudinal mediators (affective organizational commitment, job satisfaction) and relational mediators (trust in leader, leader-member exchange; LMX) of the positive relationship between transformational leadership and organizational citizenship behavior (OCB). Hypotheses were tested using meta-analytic path models with correlations from published meta-analyses (761 samples with 227,419 individuals overall). When testing single-mediator models, results supported our expectations that each of the mediators explained the relationship between transformational leadership and OCB. When testing a multi-mediator model, LMX was the strongest mediator. When testing a model with a latent attitudinal mechanism and a latent relational mechanism, the relational mechanism was the stronger mediator of the relationship between transformational leadership and OCB. Our findings help to better understand the underlying mechanisms of the relationship between transformational leadership and OCB.

  3. Effects of delaying transplanting on agronomic traits and grain yield of rice under mechanical transplantation pattern.

    Directory of Open Access Journals (Sweden)

    Qihua Liu

    Full Text Available A delay in the mechanical transplantation (MT of rice seedlings frequently occurs in Huanghuai wheat-rice rotation cropping districts of China, due to the late harvest of wheat, the poor weather conditions and the insufficiency of transplanters, missing the optimum transplanting time and causing seedlings to age. To identify how delaying transplanting rice affects the agronomic characteristics including the growth duration, photosynthetic productivity and dry matter remobilization efficiency and the grain yield under mechanical transplanting pattern, an experiment with a split-plot design was conducted over two consecutive years. The main plot includes two types of cultivation: mechanical transplanting and artificial transplanting (AT. The subplot comprises four japonica rice cultivars. The results indicate that the rice jointing, booting, heading and maturity stages were postponed under MT when using AT as a control. The tiller occurrence number, dry matter weight per tiller, accumulative dry matter for the population, leaf area index, crop growth rate, photosynthetic potential, and dry matter remobilization efficiency of the leaf under MT significantly decreased compared to those under AT. In contrast, the reduction rate of the leaf area during the heading-maturity stage was markedly enhanced under MT. The numbers of effective panicles and filled grains per panicle and the grain yield significantly decreased under MT. A significant correlation was observed between the dry matter production, remobilization and distribution characteristics and the grain yield. We infer that, as with rice from old seedlings, the decrease in the tiller occurrence, the photosynthetic productivity and the assimilate remobilization efficiency may be important agronomic traits that are responsible for the reduced grain yield under MT.

  4. Tinnitus: Network pathophysiology-network pharmacology

    Directory of Open Access Journals (Sweden)

    Ana Belen eElgoyhen

    2012-01-01

    Full Text Available Tinnitus, the phantom perception of sound, is a prevalent disorder. One in 10 adults has clinically significant subjective tinnitus, and for 1 in 100, tinnitus severely affects their quality of life. Despite the significant unmet clinical need for a safe and effective drug targeting tinnitus relief, there is currently not a single FDA-approved drug on the market. The search for drugs that target tinnitus is hampered by the lack of a deep knowledge of the underlying neural substrates of this pathology. Recent studies are increasingly demonstrating that, as described for other central nervous system disorders, tinnitus is a pathology of brain networks. The application of graph theoretical analysis to brain networks has recently provided new information concerning their topology, their robustness and their vulnerability to attacks. Moreover, the philosophy behind drug design and pharmacotherapy in central nervous system pathologies is changing from that of magic bullets that target individual chemoreceptors or disease-causing genes into that of magic shotguns, promiscuous or dirty drugs that target disease-causing networks, also known as network pharmacology. In the present work we provide some insight into how this knowledge could be applied to tinnitus pathophysiology and pharmacotherapy.

  5. Tinnitus: network pathophysiology-network pharmacology.

    Science.gov (United States)

    Elgoyhen, Ana B; Langguth, Berthold; Vanneste, Sven; De Ridder, Dirk

    2012-01-01

    Tinnitus, the phantom perception of sound, is a prevalent disorder. One in 10 adults has clinically significant subjective tinnitus, and for one in 100, tinnitus severely affects their quality of life. Despite the significant unmet clinical need for a safe and effective drug targeting tinnitus relief, there is currently not a single Food and Drug Administration (FDA)-approved drug on the market. The search for drugs that target tinnitus is hampered by the lack of a deep knowledge of the underlying neural substrates of this pathology. Recent studies are increasingly demonstrating that, as described for other central nervous system (CNS) disorders, tinnitus is a pathology of brain networks. The application of graph theoretical analysis to brain networks has recently provided new information concerning their topology, their robustness and their vulnerability to attacks. Moreover, the philosophy behind drug design and pharmacotherapy in CNS pathologies is changing from that of "magic bullets" that target individual chemoreceptors or "disease-causing genes" into that of "magic shotguns," "promiscuous" or "dirty drugs" that target "disease-causing networks," also known as network pharmacology. In the present work we provide some insight into how this knowledge could be applied to tinnitus pathophysiology and pharmacotherapy.

  6. Thalassemia: Pathophysiology and management. Part A

    International Nuclear Information System (INIS)

    Fucharoen, S.; Rowley, P.T.; Paul, N.W.

    1988-01-01

    This book contains papers divided among the following sections: molecular biology and pathogenesis; pathophysiology - molecular and cellular; clinical manifestations and hematologic changes; cardiopulmonary defects and platelet function; hormones and minerals; and infection and immunology

  7. Unraveling Molecular Mechanisms Underlying Alzheimer’s disease and its Related Endophenotypes

    NARCIS (Netherlands)

    S.J. van der Lee (Sven)

    2017-01-01

    markdownabstractDementia and its most common type, Alzheimer’s disease (AD) is a devastating disease that afflicts millions worldwide. Still, there are no targeted preventive interventions or pharmacological treatments for AD available. This makes further unraveling the pathophysiology of AD to find

  8. Dynamic Response and Failure Mechanism of Brittle Rocks Under Combined Compression-Shear Loading Experiments

    Science.gov (United States)

    Xu, Yuan; Dai, Feng

    2018-03-01

    A novel method is developed for characterizing the mechanical response and failure mechanism of brittle rocks under dynamic compression-shear loading: an inclined cylinder specimen using a modified split Hopkinson pressure bar (SHPB) system. With the specimen axis inclining to the loading direction of SHPB, a shear component can be introduced into the specimen. Both static and dynamic experiments are conducted on sandstone specimens. Given carefully pulse shaping, the dynamic equilibrium of the inclined specimens can be satisfied, and thus the quasi-static data reduction is employed. The normal and shear stress-strain relationships of specimens are subsequently established. The progressive failure process of the specimen illustrated via high-speed photographs manifests a mixed failure mode accommodating both the shear-dominated failure and the localized tensile damage. The elastic and shear moduli exhibit certain loading-path dependence under quasi-static loading but loading-path insensitivity under high loading rates. Loading rate dependence is evidently demonstrated through the failure characteristics involving fragmentation, compression and shear strength and failure surfaces based on Drucker-Prager criterion. Our proposed method is convenient and reliable to study the dynamic response and failure mechanism of rocks under combined compression-shear loading.

  9. Inspection Mechanism and Experimental Study of Prestressed Reverse Tension Method under PC Beam Bridge Anchorage

    Science.gov (United States)

    Peng, Zhang

    2018-03-01

    the prestress under anchorage is directly related to the structural security and performance of PC beam bridge. The reverse tension method is a kind of inspection which confirms the prestress by exerting reversed tension load on the exposed prestressing tendon of beam bridge anchoring system. The thesis elaborately expounds the inspection mechanism and mechanical effect of reverse tension method, theoretically analyzes the influential elements of inspection like tool anchorage deformation, compression of conjuncture, device glide, friction of anchorage loop mouth and elastic compression of concrete, and then presents the following formula to calculate prestress under anchorage. On the basis of model experiment, the thesis systematically studies some key issues during the reverse tension process of PC beam bridge anchorage system like the formation of stress-elongation curve, influential factors, judgment method of prestress under anchorage, variation trend and compensation scale, verifies the accuracy of mechanism analysis and demonstrates: the prestress under anchorage is less than or equal to 75% of the ultimate strength of prestressing tendon, the error of inspect result is less than 1%, which can meet with the demands of construction. The research result has provided theoretical basis and technical foundation for the promotion and application of reverse tension in bridge construction.

  10. Mechanical and electronic properties of monolayer and bilayer phosphorene under uniaxial and isotropic strains.

    Science.gov (United States)

    Hu, Ting; Han, Yang; Dong, Jinming

    2014-11-14

    The mechanical and electronic properties of both the monolayer and bilayer phosphorenes under either isotropic or uniaxial strain have been systematically investigated using first-principles calculations. It is interesting to find that: 1) Under a large enough isotropic tensile strain, the monolayer phosphorene would lose its pucker structure and transform into a flat hexagonal plane, while two inner sublayers of the bilayer phosphorene could be bonded due to its interlayer distance contraction. 2) Under the uniaxial tensile strain along a zigzag direction, the pucker distance of each layer in the bilayer phosphorene can exhibit a specific negative Poisson's ratio. 3) The electronic properties of both the monolayer and bilayer phosphorenes are sensitive to the magnitude and direction of the applied strains. Their band gaps decrease more rapidly under isotropic compressive strain than under uniaxial strain. Also, their direct-indirect band gap transitions happen at the larger isotropic tensile strains compared with that under uniaxial strain. 4) Under the isotropic compressive strain, the bilayer phosphorene exhibits a transition from a direct-gap semiconductor to a metal. In contrast, the monolayer phosphorene initially has the direct-indirect transition and then transitions to a metal. However, under isotropic tensile strain, both the bilayer and monolayer phosphorene show the direct-indirect transition and, finally, the transition to a metal. Our numerical results may open new potential applications of phosphorene in nanoelectronics and nanomechanical devices by external isotropic strain or uniaxial strain along different directions.

  11. A vicious circle in chronic lymphoedema pathophysiology?

    DEFF Research Database (Denmark)

    Cucchi, F; Rossmeislova, L; Simonsen, L

    2017-01-01

    Chronic lymphoedema is a disease caused by a congenital or acquired damage to the lymphatic system and characterized by complex chains of pathophysiologic events such as lymphatic fluid stasis, chronic inflammation, lymphatic vessels impairment, adipose tissue deposition and fibrosis. These event....... Together, these observations indicate strong reciprocal relationship between lymphatics and adipose tissue and suggest a possible key role of the adipocyte in the pathophysiology of chronic lymphoedema's vicious circle....

  12. Asymmetric flexural behavior from bamboo's functionally graded hierarchical structure: underlying mechanisms.

    Science.gov (United States)

    Habibi, Meisam K; Samaei, Arash T; Gheshlaghi, Behnam; Lu, Jian; Lu, Yang

    2015-04-01

    As one of the most renewable resources on Earth, bamboo has recently attracted increasing interest for its promising applications in sustainable structural purposes. Its superior mechanical properties arising from the unique functionally-graded (FG) hierarchical structure also make bamboo an excellent candidate for bio-mimicking purposes in advanced material design. However, despite its well-documented, impressive mechanical characteristics, the intriguing asymmetry in flexural behavior of bamboo, alongside its underlying mechanisms, has not yet been fully understood. Here, we used multi-scale mechanical characterizations assisted with advanced environmental scanning electron microscopy (ESEM) to investigate the asymmetric flexural responses of natural bamboo (Phyllostachys edulis) strips under different loading configurations, during "elastic bending" and "fracture failure" stages, with their respective deformation mechanisms at microstructural level. Results showed that the gradient distribution of the vascular bundles along the thickness direction is mainly responsible for the exhibited asymmetry, whereas the hierarchical fiber/parenchyma cellular structure plays a critical role in alternating the dominant factors for determining the distinctly different failure mechanisms. A numerical model has been likewise adopted to validate the effective flexural moduli of bamboo strips as a function of their FG parameters, while additional experiments on uniaxial loading of bamboo specimens were performed to assess the tension-compression asymmetry, for further understanding of the microstructure evolution of bamboo's outer and innermost layers under different bending states. This work could provide insights to help the processing of novel bamboo-based composites and enable the bio-inspired design of advanced structural materials with desired flexural behavior. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  13. Oxidative Stress and Mitochondrial Activation as the Main Mechanisms Underlying Graphene Toxicity against Human Cancer Cells

    Directory of Open Access Journals (Sweden)

    Anna Jarosz

    2016-01-01

    Full Text Available Due to the development of nanotechnology graphene and graphene-based nanomaterials have attracted the most attention owing to their unique physical, chemical, and mechanical properties. Graphene can be applied in many fields among which biomedical applications especially diagnostics, cancer therapy, and drug delivery have been arousing a lot of interest. Therefore it is essential to understand better the graphene-cell interactions, especially toxicity and underlying mechanisms for proper use and development. This review presents the recent knowledge concerning graphene cytotoxicity and influence on different cancer cell lines.

  14. Mechanical failure of zigzag graphene nanoribbons under tensile strain induced by edge reconstruction

    KAUST Repository

    Cheng, Yingchun

    2012-10-01

    The structural and mechanical properties of graphene nanoribbons (GNRs) under uniaxial tensile strain are studied by density functional theory. The ideal strength of a zigzag GNR (120 GPa) is close to that of pristine graphene. However, for a GNR with both edges reconstructed to pentagon–heptagon pairs (from hexagon–hexagon pairs) it decreases to 94 GPa and the maximum tensile strain is reduced to 15%. Our results constitute a comprehensive picture of the edge structure effect on the mechanical properties of GNRs.

  15. Different Pathophysiological Phenotypes among Newly Diagnosed Type 2 Diabetes Patients

    DEFF Research Database (Denmark)

    Stidsen, Jacob

    2013-01-01

    Type 2 diabetes (T2D) can be considered a syndrome with several different pathophysiological mechanisms leading to hyperglycemia. Nonetheless, T2D is treated according to algorithms as if it was one disease entity. Methods: We investigated the prevalence of different pathophysiological phenotypes...... autoimmune diabetes (LADA) (GAD antibody titer >= 20 IE/ml and not T1D), secondary diabetes (recent history of pancreatitis, pancreatectomy or pancreas amylase > 65U/l, and GAD negativity), steroid-induced diabetes (oral glucocorticoid-treated subjects), insulinopenic (f-P-C-peptide ... or secondary diabetes), classic obesity-associated insulin resistant diabetes ( f-P-C-peptide >= 568 pmol/l) and a normoinsulinopenic group (333

  16. Hypertension in women--pathophysiological and clinical aspects.

    Science.gov (United States)

    Erdine, Serap; Arslan, Eren; Olszanecka, Agnieszka

    2012-01-01

    Hypertension is the most important risk factor, responsible for cardiovascular morbidity and mortality worldwide, both in men and women. Cardiovascular disorders in women are still underestimated, due to lower absolute risk calculations and the underdetection of classical risk factors. In recent years the differences in pathophysiology and the clinical presentation and treatment of cardiac diseases in women have become fields of interest and research. Several studies have examined gender-related differences in the pathophysiology of hypertension, its prevalence and control. The influence of menopause, obesity and salt-sensitivity on the pathogenesis of hypertension in women has been widely investigated. This article presents current data on differences in prevalence, control and mechanisms of hypertension in women.

  17. Different Pathophysiological Phenotypes among Newly Diagnosed Type 2 Diabetes Patients

    DEFF Research Database (Denmark)

    Stidsen, Jacob

    2013-01-01

    autoimmune diabetes (LADA) (GAD antibody titer >= 20 IE/ml and not T1D), secondary diabetes (recent history of pancreatitis, pancreatectomy or pancreas amylase > 65U/l, and GAD negativity), steroid-induced diabetes (oral glucocorticoid-treated subjects), insulinopenic (f-P-C-peptide ...Type 2 diabetes (T2D) can be considered a syndrome with several different pathophysiological mechanisms leading to hyperglycemia. Nonetheless, T2D is treated according to algorithms as if it was one disease entity. Methods: We investigated the prevalence of different pathophysiological phenotypes...... or secondary diabetes), classic obesity-associated insulin resistant diabetes ( f-P-C-peptide >= 568 pmol/l) and a normoinsulinopenic group (333

  18. Reliability-based optimization of maintenance scheduling of mechanical components under fatigue.

    Science.gov (United States)

    Beaurepaire, P; Valdebenito, M A; Schuëller, G I; Jensen, H A

    2012-05-01

    This study presents the optimization of the maintenance scheduling of mechanical components under fatigue loading. The cracks of damaged structures may be detected during non-destructive inspection and subsequently repaired. Fatigue crack initiation and growth show inherent variability, and as well the outcome of inspection activities. The problem is addressed under the framework of reliability based optimization. The initiation and propagation of fatigue cracks are efficiently modeled using cohesive zone elements. The applicability of the method is demonstrated by a numerical example, which involves a plate with two holes subject to alternating stress.

  19. CISM course on mechanical behaviour of soils under environmentally induced cyclic loads

    CERN Document Server

    Wood, David; Mechanical Behaviour of Soils Under Environmentally Induced Cyclic Loads

    2012-01-01

    The book gives a comprehensive description of the mechanical response of soils (granular and cohesive materials) under cyclic loading. It provides the geotechnical engineer with the theoretical and analytical tools necessary for the evaluation of settlements developng with time under cyclic, einvironmentally idncued loads (such as wave motion, wind actions, water table level variation) and their consequences for the serviceability and durability of structures such as the shallow or deep foundations used in offshore engineering, caisson beakwaters, ballast and airport pavements and also to interpret monitoring data, obtained from both natural and artificial slopes and earth embankments, for the purposes of risk assessment and mitigation.

  20. Scientific conception on mechanisms of calcium homeostasis disorders under low dose effect of ionizing radiation

    International Nuclear Information System (INIS)

    Abylaev, Zh.A.; Dospolova, Zh.G.

    1997-01-01

    Scientific conception of probable consequences of calcium homeostasis disorders in personals, exposed to low dose effect of ionizing radiation has been developed. Principle positions of the conception is that pathologic processes development have different ways of conducting. During predominance of low doses of external gamma-radiation there is leading pathologic mechanism (mechanism 1) of disorder neuroendocrine regulation of both the calcium and the phosphor. In this case sicks have disorders of both the vegetative tonus and the endocrine status. Under internal irradiation (mechanism 2) there is disfunction of organs and systems (bore changes and disorders of hormone status). These changes are considered as consequence of negative action on organism of incorporated long-living radionuclides. Radio-toxic factors action (mechanism 3) provokes the excess of hormones, which acting on bone tissue and could be cause of steroid osteoporosis. Influence of chronic stress factor (mechanism 4) enlarges and burden action on organism of low radiation doses. It is emphasized, that decisive role in development of pathologic processes has mechanism of disturbance of neuroendocrine regulation of calcium exchange

  1. Contact force and mechanical loss of multistage cable under tension and bending

    Science.gov (United States)

    Ru, Yanyun; Yong, Huadong; Zhou, Youhe

    2016-10-01

    A theoretical model for calculating the stress and strain states of cabling structures with different loadings has been developed in this paper. We solve the problem for the first- and second-stage cable with tensile or bending strain. The contact and friction forces between the strands are presented by two-dimensional contact model. Several theoretical models have been proposed to verify the results when the triplet subjected to the tensile strain, including contact force, contact stresses, and mechanical loss. It is found that loadings will affect the friction force and the mechanical loss of the triplet. The results show that the contact force and mechanical loss are dependent on the twist pitch. A shorter twist pitch can lead to higher contact force, while the trend of mechanical loss with twist pitch is complicated. The mechanical loss may be reduced by adjusting the twist pitch reasonably. The present model provides a simple analysis method to investigate the mechanical behaviors in multistage-structures under different loads.

  2. From Sound to Significance: Exploring the Mechanisms Underlying Emotional Reactions to Music.

    Science.gov (United States)

    Juslin, Patrik N; Barradas, Gonçalo; Eerola, Tuomas

    2015-01-01

    A common approach to studying emotional reactions to music is to attempt to obtain direct links between musical surface features such as tempo and a listener's responses. However, such an analysis ultimately fails to explain why emotions are aroused in the listener. In this article we explore an alternative approach, which aims to account for musical emotions in terms of a set of psychological mechanisms that are activated by different types of information in a musical event. This approach was tested in 4 experiments that manipulated 4 mechanisms (brain stem reflex, contagion, episodic memory, musical expectancy) by selecting existing musical pieces that featured information relevant for each mechanism. The excerpts were played to 60 listeners, who were asked to rate their felt emotions on 15 scales. Skin conductance levels and facial expressions were measured, and listeners reported subjective impressions of relevance to specific mechanisms. Results indicated that the target mechanism conditions evoked emotions largely as predicted by a multimechanism framework and that mostly similar effects occurred across the experiments that included different pieces of music. We conclude that a satisfactory account of musical emotions requires consideration of how musical features and responses are mediated by a range of underlying mechanisms.

  3. Exact solution for stresses/displacements in a multilayered hollow cylinder under thermo-mechanical loading

    International Nuclear Information System (INIS)

    Yeo, W.H.; Purbolaksono, J.; Aliabadi, M.H.; Ramesh, S.; Liew, H.L.

    2017-01-01

    In this study, a new analytical solution by the recursive method for evaluating stresses/displacements in multilayered hollow cylinder under thermo-mechanical loading was developed. The results for temperature distribution, displacements and stresses obtained by using the proposed solution were shown to be in good agreement with the FEM results. The proposed analytical solution was also found to produce more accurate results than those by the analytical solution reported in literature. - Highlights: • A new analytical solution for evaluating stresses in multilayered hollow cylinder under thermo-mechanical loading. • A simple computational procedure using a recursive method. • A promising technique for evaluating the operating axial and hoop stresses in pressurized composite vessels.

  4. Music and Memory in Alzheimer's Disease and The Potential Underlying Mechanisms.

    Science.gov (United States)

    Peck, Katlyn J; Girard, Todd A; Russo, Frank A; Fiocco, Alexandra J

    2016-01-01

    With population aging and a projected exponential expansion of persons diagnosed with Alzheimer's disease (AD), the development of treatment and prevention programs has become a fervent area of research and discovery. A growing body of evidence suggests that music exposure can enhance memory and emotional function in persons with AD. However, there is a paucity of research that aims to identify specific underlying neural mechanisms associated with music's beneficial effects in this particular population. As such, this paper reviews existing anecdotal and empirical evidence related to the enhancing effects of music exposure on cognitive function and further provides a discussion on the potential underlying mechanisms that may explain music's beneficial effect. Specifically, this paper will outline the potential role of the dopaminergic system, the autonomic nervous system, and the default network in explaining how music may enhance memory function in persons with AD.

  5. Behavioral Effects of Upper Respiratory Tract Illnesses: A Consideration of Possible Underlying Cognitive Mechanisms

    Directory of Open Access Journals (Sweden)

    Andrew P. Smith

    2012-03-01

    Full Text Available Previous research has shown that both experimentally induced upper respiratory tract illnesses (URTIs and naturally occurring URTIs influence mood and performance. The present study investigated possible cognitive mechanisms underlying the URTI-performance changes. Those who developed a cold (N = 47 had significantly faster, but less accurate, performance than those who remained healthy (N = 54. Illness had no effect on manipulations designed to influence encoding, response organisation (stimulus-response compatilibility or response preparation. Similarly, there was no evidence that different components of working memory were impaired. Overall, the present research confirms that URTIs can have an effect on performance efficiency. Further research is required to identify the physiological and behavioral mechanisms underlying these effects.

  6. Physiological mechanisms contributing to increased water-use efficiency in winter wheat under organic fertilization.

    Science.gov (United States)

    Wang, Linlin; Wang, Shiwen; Chen, Wei; Li, Hongbing; Deng, Xiping

    2017-01-01

    Improving the efficiency of resource utilization has received increasing research attention in recent years. In this study, we explored the potential physiological mechanisms underlying improved grain yield and water-use efficiency of winter wheat (Triticum aestivum L.) following organic fertilizer application. Two wheat cultivars, ChangHan58 (CH58) and XiNong9871 (XN9871), were grown under the same nitrogen (N) fertilizer rate (urea-N, CK; and manure plus urea-N, M) and under two watering regimes (WW, well-watered; and WS, water stress) imposed after anthesis. The M fertilizer treatment had a higher Pn and lower gs and Tr than CK under both water conditions, in particular, it significantly increased WRC and Ψw, and decreased EWLR and MDA under WS. Also, the M treatment increased post-anthesis N uptake by 81.4 and 16.4% under WS and WW, thus increasing post-anthesis photosynthetic capacity and delaying leaf senescence. Consequently, the M treatment increased post-anthesis DM accumulation under WS and WW by 51.5 and 29.6%, WUEB by 44.5 and 50.9%, grain number per plant by 11.5 and 12.2% and 1000-grain weight by 7.3 and 3.6%, respectively, compared with CK. The grain yield under M treatment increased by 23 and 15%, and water use efficiency (WUEg) by 25 and 23%, respectively. The increased WUE under organic fertilizer treatment was due to elevated photosynthesis and decreased Tr and gs. Our results suggest that the organic fertilizer treatment enabled plants to use water more efficiently under drought stress.

  7. Detecting method for crude oil price fluctuation mechanism under different periodic time series

    International Nuclear Information System (INIS)

    Gao, Xiangyun; Fang, Wei; An, Feng; Wang, Yue

    2017-01-01

    Highlights: • We proposed the concept of autoregressive modes to indicate the fluctuation patterns. • We constructed transmission networks for studying the fluctuation mechanism. • There are different fluctuation mechanism under different periodic time series. • Only a few types of autoregressive modes control the fluctuations in crude oil price. • There are cluster effects during the fluctuation mechanism of autoregressive modes. - Abstract: Current existing literatures can characterize the long-term fluctuation of crude oil price time series, however, it is difficult to detect the fluctuation mechanism specifically under short term. Because each fluctuation pattern for one short period contained in a long-term crude oil price time series have dynamic characteristics of diversity; in other words, there exhibit various fluctuation patterns in different short periods and transmit to each other, which reflects the reputedly complicate and chaotic oil market. Thus, we proposed an incorporated method to detect the fluctuation mechanism, which is the evolution of the different fluctuation patterns over time from the complex network perspective. We divided crude oil price time series into segments using sliding time windows, and defined autoregressive modes based on regression models to indicate the fluctuation patterns of each segment. Hence, the transmissions between different types of autoregressive modes over time form a transmission network that contains rich dynamic information. We then capture transmission characteristics of autoregressive modes under different periodic time series through the structure features of the transmission networks. The results indicate that there are various autoregressive modes with significantly different statistical characteristics under different periodic time series. However, only a few types of autoregressive modes and transmission patterns play a major role in the fluctuation mechanism of the crude oil price, and these

  8. Adverse Effects from Clenbuterol and Ractopamine on Nematode Caenorhabditis elegans and the Underlying Mechanism

    OpenAIRE

    Zhuang, Ziheng; Zhao, Yunli; Wu, Qiuli; Li, Min; Liu, Haicui; Sun, Lingmei; Gao, Wei; Wang, Dayong

    2014-01-01

    In the present study, we used Caenorhabditis elegans assay system to investigate in vivo toxicity from clentuberol and ractopamine and the possible underlying mechanism. Both acute and prolonged exposures to clentuberol or ractopamine decreased brood size and locomotion behavior, and induced intestinal autofluorescence and reactive oxygen species (ROS) production. Although acute exposure to the examined concentrations of clentuberol or ractopamine did not induce lethality, prolonged exposure ...

  9. Optimal Contract Design for Cooperative Relay Incentive Mechanism under Moral Hazard

    OpenAIRE

    Zhao, Nan; Wu, Minghu; Xiong, Wei; Liu, Cong

    2015-01-01

    Cooperative relay can effectively improve spectrum efficiency by exploiting the spatial diversity in the wireless networks. However, wireless nodes may acquire different network information with various users’ location and mobility, channels’ conditions, and other factors, which results in asymmetric information between the source and the relay nodes (RNs). In this paper, the relay incentive mechanism between relay nodes and the source is investigated under the asymmetric information. By mode...

  10. Mechanisms underlying reductant-induced reactive oxygen species formation by anticancer copper(II) compounds

    OpenAIRE

    Kowol, Christian R.; Heffeter, Petra; Miklos, Walter; Gille, Lars; Trondl, Robert; Cappellacci, Loredana; Berger, Walter; Keppler, Bernhard K.

    2011-01-01

    Intracellular generation of reactive oxygen species (ROS) via thiol-mediated reduction of copper(II) to copper(I) has been assumed as the major mechanism underlying the anticancer activity of copper(II) complexes. The aim of this study was to compare the anticancer potential of copper(II) complexes of Triapine (3-amino-pyridine-2-carboxaldehyde thiosemicarbazone; currently in phase II clinical trials) and its terminally dimethylated derivative with that of 2-formylpyridine thiosemicarbazone a...

  11. A fracture mechanics study of tungsten failure under high heat flux loads

    International Nuclear Information System (INIS)

    Li, Muyuan

    2015-01-01

    The performance of fusion devices is highly dependent on plasma-facing components. Tungsten is the most promising candidate material for armors in plasma-facing components in ITER and DEMO. However, the brittleness of tungsten below the ductile-to-brittle transition temperature is very critical to the reliability of plasma-facing components. In this work, thermo-mechanical and fracture behaviors of tungsten are predicted numerically under fusion relevant thermal loadings.

  12. The effects and underlying mechanisms of mirror therapy – literature review

    OpenAIRE

    Urška Puh; Sonja Hlebš

    2013-01-01

    Background: Mirror therapy is a relatively new therapeutic modality, where movement of the unaffected limb is used to facilitate performance of the affected limb. Literature review of clinical studies regarding the effectiveness of mirror therapy in different groups of patients was performed. The review focussed on randomised controlled trials and studies, which explore the underlying mechanisms of mirror therapy. Conclusions: The majority of randomised controlled ...

  13. The chemical and mechanical behaviors of polymer / reactive metal systems under high strain rates

    Science.gov (United States)

    Shen, Yubin

    As one category of energetic materials, impact-initiated reactive materials are able to release a high amount of stored chemical energy under high strain rate impact loading, and are used extensively in civil and military applications. In general, polymers are introduced as binder materials to trap the reactive metal powders inside, and also act as an oxidizing agent for the metal ingredient. Since critical attention has been paid on the metal / metal reaction, only a few types of polymer / reactive metal interactions have been studied in the literature. With the higher requirement of materials resistant to different thermal and mechanical environments, the understanding and characterization of polymer / reactive metal interactions are in great demand. In this study, PTFE (Polytetrafluoroethylene) 7A / Ti (Titanium) composites were studied under high strain rates by utilizing the Taylor impact and SHPB tests. Taylor impact tests with different impact velocities, sample dimensions and sample configurations were conducted on the composite, equipped with a high-speed camera for tracking transient images during the sudden process. SHPB and Instron tests were carried out to obtain the stress vs. strain curves of the composite under a wide range of strain rates, the result of which were also utilized for fitting the constitutive relations of the composite based on the modified Johnson-Cook strength model. Thermal analyses by DTA tests under different flow rates accompanied with XRD identification were conducted to study the reaction mechanism between PTFE 7A and Ti when only heat was provided. Numerical simulations on Taylor impact tests and microstructural deformations were also performed to validate the constitutive model built for the composite system, and to investigate the possible reaction mechanism between two components. The results obtained from the high strain rate tests, thermal analyses and numerical simulations were combined to provide a systematic study on

  14. Modulating Conscious Movement Intention by Noninvasive Brain Stimulation and the Underlying Neural Mechanisms

    OpenAIRE

    Douglas, Zachary H.; Maniscalco, Brian; Hallett, Mark; Wassermann, Eric M.; He, Biyu J.

    2015-01-01

    Conscious intention is a fundamental aspect of the human experience. Despite long-standing interest in the basis and implications of intention, its underlying neurobiological mechanisms remain poorly understood. Using high-definition transcranial DC stimulation (tDCS), we observed that enhancing spontaneous neuronal excitability in both the angular gyrus and the primary motor cortex caused the reported time of conscious movement intention to be ∼60–70 ms earlier. Slow brain waves recorded ∼2–...

  15. Diffuse and Focal Brain Injury in a Large Animal Model of PTE: Mechanisms Underlying Epileptogenesis

    Science.gov (United States)

    2017-10-01

    Conclusions: A) Contusion injury validation and neuropathology B) Grid electrode development and testing C) Wireless Large Animal Custom Enclosure...In addition, we will test the NF-L and GFAP immunoassay to begin quantification of this biomarkers, as well as collecting serum from the animals pre...AWARD NUMBER: W81XWH-16-1-0675 TITLE: Diffuse and Focal Brain Injury in a Large Animal Model of PTE: Mechanisms Underlying Epileptogenesis

  16. Different intra- and interspecific facilitation mechanisms between two Mediterranean trees under a climate change scenario.

    Science.gov (United States)

    Gimeno, Teresa E; Escudero, Adrián; Valladares, Fernando

    2015-01-01

    In harsh environments facilitation alleviates biotic and abiotic constraints on tree recruitment. Under ongoing drier climate change, we expect facilitation to increase as a driver of coexistence. However, this might not hold under extreme abiotic stress and when the outcome depends on the interaction with other drivers such as altered herbivore pressure due to land use change. We performed a field water-manipulation experiment to quantify the importance of facilitation in two coexisting Mediterranean trees (dominant Juniperus thurifera and coexisting Quercus ilex subsp. ballota) under a climate change scenario. Shifts in canopy dominance favouring Q. ilex could be based on the extension of heterospecific facilitation to the detriment of conspecific alleviation. We found that saplings of both species transplanted under the canopy of nurse trees had greater survival probability, growth and photochemical efficiency. Intra- and interspecific facilitation mechanisms differed: alleviation of abiotic stress benefited both species during summer and J. thurifera during winter, whereas browsing protection was relevant only for Q. ilex. Facilitation was greater under the dry treatment only for Q. ilex, which partially agreed with the predictions of the stress gradient hypothesis. We conclude that present rainfall availability limits neither J. thurifera nor Q. ilex establishment. Nevertheless, under current global change scenarios, imposing increasing abiotic stress together with altered herbivore browsing, nurse trees could differentially facilitate the establishment of Q. ilex due to species-specific traits, i.e. palatability; drought, heat and cold tolerance, underlying species differences in the facilitation mechanisms and eventually triggering a change from pure juniper woodlands to mixed formations.

  17. FInal Report: First Principles Modeling of Mechanisms Underlying Scintillator Non-Proportionality

    Energy Technology Data Exchange (ETDEWEB)

    Aberg, Daniel [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Sadigh, Babak [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Zhou, Fei [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-01-01

    This final report presents work carried out on the project “First Principles Modeling of Mechanisms Underlying Scintillator Non-Proportionality” at Lawrence Livermore National Laboratory during 2013-2015. The scope of the work was to further the physical understanding of the microscopic mechanisms behind scintillator nonproportionality that effectively limits the achievable detector resolution. Thereby, crucial quantitative data for these processes as input to large-scale simulation codes has been provided. In particular, this project was divided into three tasks: (i) Quantum mechanical rates of non-radiative quenching, (ii) The thermodynamics of point defects and dopants, and (iii) Formation and migration of self-trapped polarons. The progress and results of each of these subtasks are detailed.

  18. Potential neural mechanisms underlying the effectiveness of early intervention for children with autism spectrum disorder

    Science.gov (United States)

    Sullivan, Katherine; Stone, Wendy L.; Dawson, Geraldine

    2014-01-01

    Although evidence supports the efficacy of early intervention for improving outcomes for children with autism spectrum disorder (ASD), the mechanisms underlying their effectiveness remain poorly understood. This paper reviews the research literature on the neural bases of the early core deficits in ASD and proposes three key features of early intervention related to the neural mechanisms that may contribute to its effectiveness in improving deficit areas. These features include (1) the early onset of intensive intervention which capitalizes on the experience-expectant plasticity of the immature brain, (2) the use of treatment strategies that address core deficits in social motivation through an emphasis on positive social engagement and arousal modulation, and (3) promotion of complex neural networks and connectivity through thematic, multi-sensory and multi-domain teaching approaches. Understanding the mechanisms of effective early intervention will enable us to identify common or foundational active ingredients for promoting optimal outcomes in children with ASD. PMID:25108609

  19. Contraction and elongation: Mechanics underlying cell boundary deformations in epithelial tissue.

    Science.gov (United States)

    Hara, Yusuke

    2017-06-01

    The cell-cell boundaries of epithelial cells form cellular frameworks at the apical side of tissues. Deformations in these boundaries, for example, boundary contraction and elongation, and the associated forces form the mechanical basis of epithelial tissue morphogenesis. In this review, using data from recent Drosophila studies on cell boundary contraction and elongation, I provide an overview of the mechanism underlying the bi-directional deformations in the epithelial cell boundary, that are sustained by biased accumulations of junctional and apico-medial non-muscle myosin II. Moreover, how the junctional tensions exist on cell boundaries in different boundary dynamics and morphologies are discussed. Finally, some future perspectives on how recent knowledge about single cell boundary-level mechanics will contribute to our understanding of epithelial tissue morphogenesis are discussed. © 2017 Japanese Society of Developmental Biologists.

  20. Compressive damage mechanism of GFRP composites under off-axis loading: Experimental and numerical investigations

    DEFF Research Database (Denmark)

    Zhou, H.W.; Li, H.Y.; Gui, L.L.

    2013-01-01

    Experimental and computational studies of the microscale mechanisms of damage formation and evolution in unidirectional glass fiber reinforced polymer composites (GFRP) under axial and off-axis compressive loading are carried out. A series of compressive testing of the composites with different...... the angle between the fiber direction and the loading vector goes from 0° to 45° (by 2.3–2.6 times), and then slightly increases (when the angle approaches 80–90°). At the low angles between the fiber and the loading vector, fiber buckling and kinking are the main mechanisms of fiber failure....... With increasing the angle between the fiber and applied loading, failure of glass fibers is mainly controlled by shear cracking. For the computational analysis of the damage mechanisms, 3D multifiber unit cell models of GFRP composites and X-FEM approach to the fracture modeling were used. The computational...

  1. [Progress of researches on mechanism of acupuncture therapy underlying improvement of acute cerebral hemorrhage].

    Science.gov (United States)

    Wang, Fan; Wang, Hai-qiao; Dong, Gui-rong

    2011-04-01

    In the present paper, the authors review the progress of researches on the mechanism of acupuncture therapy underlying improvement of acute cerebral hemorrhage from experimental studies and research methods. The effects of acupuncture intervention mainly involve (1) lessening inflammatory reactions, (2) reducing impairment of free radicals and excitatory amino acids on cerebral neurons, (3) balancing release of vascular bioactive substances to increase regional cerebral blood flow, and (4) promoting repair and regeneration of the neural tissue, etc. In regard to the research methods, many new biological techniques such as biological molecular approaches, neuro-cellular chemical methods, reverse transcription-polymerase chain reaction (RT-PCR) or quantitative real time-PCR, situ hybridization, western blotting, electron microscope, etc., have been extensively applied to researches on the underlying mechanism of acupuncture therapy for cerebral infarction. In addition, the authors also pointed out that in spite of achieving some bigger progresses in experimental studies, most of the results basically reflect static, isolated and regional changes rather than dynamic and whole body changes. For this reason, more vivo research techniques and noninvasive research methods are highly recommended to be used in the future research on the underlying mechanisms of acupuncture therapy for acute cerebral ischemia.

  2. Psychogenic non-epileptic seizures: so-called psychiatric comorbidity and underlying defense mechanisms.

    Science.gov (United States)

    Beghi, Massimiliano; Negrini, Paola Beffa; Perin, Cecilia; Peroni, Federica; Magaudda, Adriana; Cerri, Cesare; Cornaggia, Cesare Maria

    2015-01-01

    In Diagnostic and Statistical Manual of Mental Disorders, fifth edition, psychogenic non-epileptic seizures (PNES) do not have a unique classification as they can be found within different categories: conversion, dissociative, and somatization disorders. The ICD-10, instead, considers PNES within dissociative disorders, merging the dissociative disorders and conversion disorders, although the underlying defense mechanisms are different. The literature data show that PNES are associated with cluster B (mainly borderline) personality disorders and/or to people with depressive or anxiety disorders. Defense mechanisms in patients with PNES with a prevalence of anxious/depressive symptoms are of "neurotic" type; their goal is to lead to a "split", either vertical (dissociation) or horizontal (repression). The majority of patients with this type of PNES have alexithymia traits, meaning that they had difficulties in feeling or perceiving emotions. In subjects where PNES are associated with a borderline personality, in which the symbolic function is lost, the defense mechanisms are of a more archaic nature (denial). PNES with different underlying defense mechanisms have different prognoses (despite similar severity of PNES) and need usually a different treatment (pharmacological or psychological). Thus, it appears superfluous to talk about psychiatric comorbidity, since PNES are a different symptomatic expression of specific psychiatric disorders.

  3. Transcriptional and epigenetic mechanisms underlying enhanced in vitro adipocyte differentiation by the brominated flame retardant BDE-47

    DEFF Research Database (Denmark)

    Kamstra, Jorke H; Hruba, Eva; Blumberg, Bruce

    2014-01-01

    . The mechanisms by which EDCs direct preadipocytes to form adipocytes are poorly understood. Here, we examined transcriptional and epigenetic mechanisms underlying the induction of in vitro adipocyte differentiation by BDE-47. Quantitative high content microscopy revealed concentration-dependent enhanced...

  4. Pathophysiology of overuse tendon injury

    International Nuclear Information System (INIS)

    Kannus, P.; Paavola, M.; Paakkala, T.; Parkkari, J.; Jaervinen, T.; Jaervinen, M.

    2002-01-01

    Overuse tendon injury is one of the most common injuries in sports.The etiology as well as the pathophysilogical mechanisms leading to tendinopathy are of crucial medical importance.At the moment intrinsic and extrinsic factors are assumed as mechanisms of overuse tendon injury. Except for the acute, extrinsic trauma, the chronic overuse tendon injury is a multifactorial process. There are many other factors, such as local hypoxia, less of nutrition, impaired metabolism and local inflammatory that may also contribute to the development of tissue damage.The exact interaction of these factors cannot be explained entirely at the moment.Further studies will be necessary in order to get more information. (orig.) [de

  5. Fracture mechanics study on stress corrosion cracking behavior under corrosive environment

    International Nuclear Information System (INIS)

    Fujii, Tomoyuki; Tohgo, Keiichiro; Shimamura, Yoshinobu; Ishizuka, Naohiro; Takanashi, Masahiro; Itabashi, Yu; Nakayama, Gen; Sakakibara, Yohei; Hirano, Takashi

    2013-01-01

    This paper deals with applicability of non-linear fracture mechanics to crack growth by stress corrosion cracking (SCC) under large-scale yielding and in a plastically deformed area. Crack growth test by compact tension specimen is carried out to evaluate crack growth rate under small-scale and large-scale yielding conditions. To evaluate the crack growth behavior from a crack initiated in a plastically deformed area, crack growth test is also carried out for a very short pre-crack in a plastically deformed four-point bending specimen. Conventional stress intensity factor (K) and equivalent stress intensity factor (K J ) defined by J integral are used as fracture mechanics parameters which characterize the crack growth rate. On da/dt-K diagram, a data band shows wide scatter, especially the crack growth rate in a plastically deformed area is higher than that under small-scale yielding condition. On the other hand, da/dt-K J diagram exhibits narrower scatter on a data band than da/dt-K diagram. The equivalent stress intensity factor is appropriate for characterization of crack growth rate by SCC under small-scale yielding through large scale yielding conditions and in a plastically deformed area. (author)

  6. Mechanical behavior of confined self-compacting reinforced concrete circular columns under concentric axial loading

    Directory of Open Access Journals (Sweden)

    Fouad Khairallah

    2013-12-01

    Full Text Available While there is abundant research information on ordinary confined concrete, there are little data on the behavior of Self-Compacting Concrete (SCC under such condition. Due to higher shrinkage and lower coarse aggregate content of SCC compared to that of Normal Concrete (NC, its composite performance under confined conditions needs more investigation. This paper has been devoted to investigate and compare the mechanical behavior of confined concrete circular columns cast with SCC and NC under concentric axial loading. The parameters affecting are including concrete compressive strength and confinement configuration. Twenty column specimens were casted and confined using four confinement techniques, CFRP wrap, FRP tube, GFRP wrap, and spiral steel hoops. The performance of the tested column specimens is evaluated based on mode of failure, load–displacement curve, stress–strain characteristics, ultimate strength, ductility, and degree of confinement.

  7. First-principles calculations of mechanical and electronic properties of silicene under strain

    Directory of Open Access Journals (Sweden)

    Rui Qin

    2012-06-01

    Full Text Available We perform first-principles calculations of mechanical and electronic properties of silicene under strains. The in-plane stiffness of silicene is much smaller than that of graphene. The yielding strain of silicene under uniform expansion in the ideal conditions is about 20%. The homogeneous strain can introduce a semimetal-metal transition. The semimetal state of silicene, in which the Dirac cone locates at the Fermi level, can only persist up to tensile strain of 7% with nearly invariant Fermi velocity. For larger strains, silicene changes into a conventional metal. The work function is found to change significantly under biaxial strain. Our calculations show that strain tuning is important for applications of silicene in nanoelectronics.

  8. Skin transcriptome reveals the intrinsic molecular mechanisms underlying hair follicle cycling in Cashmere goats under natural and shortened photoperiod conditions.

    Science.gov (United States)

    Yang, Min; Song, Shen; Dong, Kunzhe; Chen, XiaoFei; Liu, Xuexue; Rouzi, Marhaba; Zhao, Qianjun; He, Xiaohong; Pu, Yabin; Guan, Weijun; Ma, Yuehui; Jiang, Lin

    2017-10-18

    The growth of cashmere exhibits a seasonal pattern arising from photoperiod change. However, the underlying molecular mechanism remains unclear. We profiled the skin transcriptome of six goats at seven time points during hair follicle cycling via RNA-seq. The six goats comprised three goats exposed to a natural photoperiod and three exposed to a shortened photoperiod. During hair cycle transition, 1713 genes showed differential expression, and 332 genes showed a pattern of periodic expression. Moreover, a short photoperiod induced the hair follicle to enter anagen early, and 246 genes overlapped with the periodic genes. Among these key genes, cold-shock domain containing C2 (CSDC2) was highly expressed in the epidermis and dermis of Cashmere goat skin, although its function in hair-follicle development remains unknown. CSDC2 silencing in mouse fibroblasts resulted in the decreased mRNA expression of two key hair-follicle factors, leading to reduced cell numbers and a lower cell density. Cashmere growth or molting might be controlled by a set of periodic regulatory genes. The appropriate management of short light exposure can induce hair follicles to enter full anagen early through the activation of these regulators. The CSDC2 gene is a potentially important transcription factor in the hair growth cycle.

  9. Modeling and numerical analysis of granite rock specimen under mechanical loading and fire

    Directory of Open Access Journals (Sweden)

    Luc Leroy Ngueyep. Mambou

    2015-02-01

    Full Text Available The effect of ISO 834 fire on the mechanical properties of granite rock specimen submitted to uniaxial loading is numerically investigated. Based on Newton's second law, the rate-equation model of granite rock specimen under mechanical load and fire is established. The effect of heat treatment on the mechanical performance of granite is analyzed at the center and the ends of specimen. At the free end of granite rock specimen, it is shown that from 20 °C to 500 °C, the internal stress and internal strain are weak; whereas above 500 °C, they start to increase rapidly, announcing the imminent collapse. At the center of specimen, the analysis of the internal stress and internal strain reveals that the fire reduces the mechanical performance of granite significantly. Moreover, it is found that after 3 min of exposure to fire, the mechanical energy necessary to fragment the granite can be reduced up to 80%.

  10. New developments on the neurobiological and pharmaco-genetic mechanisms underlying internet and videogame addiction.

    Science.gov (United States)

    Weinstein, Aviv; Lejoyeux, Michel

    2015-03-01

    There is emerging evidence that the psychobiological mechanisms underlying behavioral addictions such as internet and videogame addiction resemble those of addiction for substances of abuse. Review of brain imaging, treatment and genetic studies on videogame and internet addiction. Literature search of published articles between 2009 and 2013 in Pubmed using "internet addiction" and "videogame addiction" as the search word. Twenty-nine studies have been selected and evaluated under the criteria of brain imaging, treatment, and genetics. Brain imaging studies of the resting state have shown that long-term internet game playing affected brain regions responsible for reward, impulse control and sensory-motor coordination. Brain activation studies have shown that videogame playing involved changes in reward and loss of control and that gaming pictures have activated regions similarly to those activated by cue-exposure to drugs. Structural studies have shown alterations in the volume of the ventral striatum possible as result of changes in reward. Furthermore, videogame playing was associated with dopamine release similar in magnitude to those of drugs of abuse and that there were faulty inhibitory control and reward mechanisms videogame addicted individuals. Finally, treatment studies using fMRI have shown reduction in craving for videogames and reduced associated brain activity. Videogame playing may be supported by similar neural mechanisms underlying drug abuse. Similar to drug and alcohol abuse, internet addiction results in sub-sensitivity of dopamine reward mechanisms. Given the fact that this research is in its early stage it is premature to conclude that internet addiction is equivalent to substance addictions. © American Academy of Addiction Psychiatry.

  11. Fibromyalgia and Bipolar Disorder: Emerging Epidemiological Associations and Shared Pathophysiology.

    Science.gov (United States)

    Bortolato, B; Berk, M; Maes, M; McIntyre, R S; Carvalho, A F

    2016-01-01

    Fibromyalgia (FM) is a prevalent disorder defined by the presence of chronic widespread pain in association with fatigue, sleep disturbances and cognitive dysfunction. Recent studies indicate that bipolar spectrum disorders frequently co-occur in individuals with FM. Furthermore, shared pathophysiological mechanisms anticipate remarkable phenomenological similarities between FM and BD. A comprehensive search of the English literature was carried out in the Pubmed/MEDLINE database through May 10th, 2015 to identify unique references pertaining to the epidemiology and shared pathophysiology between FM and bipolar disorder (BD). Overlapping neural circuits may underpin parallel clinical manifestations of both disorders. Fibromyalgia and BD are both characterized by functional abnormalities in the hypothalamic-pituitary-adrenal axis, higher levels of inflammatory mediators, oxidative and nitrosative stress as well as mitochondrial dysfunction. An over-activation of the kynurenine pathway in both illnesses drives tryptophan away from the production of serotonin and melatonin, leading to affective symptoms, circadian rhythm disturbances and abnormalities in pain processing. In addition, both disorders are associated with impaired neuroplasticity (e.g., altered brain-derived neurotrophic factor signaling). The recognition of the symptomatic and pathophysiological overlapping between FM and bipolar spectrum disorders has relevant etiological, clinical and therapeutic implications that deserve future research consideration.

  12. Microscale experimental investigation of deformation and damage of argillaceous rocks under cyclic hydric and mechanical loads

    International Nuclear Information System (INIS)

    Wang, Linlin; Yang, Diansen; Heripre, Eva; Chanchole, Serge; Bornert, Michel; Pouya, Ahmad; Halphen, Bernard

    2012-01-01

    Document available in abstract form only. Argillaceous rocks are possible host rocks for underground nuclear waste repositories. They exhibit complex coupled thermo-hydro-chemo-mechanical behavior, the description of which would strongly benefit from an improved experimental insight on their deformation and damage mechanisms at microscale. We present some recent observations of the evolution of these rocks at the scale of their composite microstructure, essentially made of a clay matrix with embedded carbonates and quartz particles with sizes ranging from a few to several tens of micrometers, when they are subjected to cyclic variations of relative humidity and mechanical loading. They are based on the combination of high definition and high resolution imaging in an environmental scanning electron microscope (ESEM), in situ hydro-mechanical loading of the samples, and digital image correlation techniques. Samples, several millimeters in diameter, are held at a constant temperature of 2 deg. Celsius while the vapor pressure in the ESEM chamber is varied from a few to several hundreds of Pascals, generating a relative humidity ranging from about 10% up to 90%. Results show a strongly heterogeneous deformation field at microscale, which is the result of complex hydro-mechanical interactions. In particular, it can be shown that local swelling incompatibilities can generate irreversible deformations in the clay matrix, even if the overall hydric deformations seem reversible. In addition, local damage can be generated, in the form of a network of microcracks, located in the bulk of the clay matrix and/or at the interface between clay and other mineral particles. The morphology of this network, described in terms of crack length, orientation and preferred location, has been observed to be dependent on the speed of the variation of the relative humidity, and is different in a saturation or desaturation process. Besides studying the deformation and damage under hydric

  13. The redox biology network in cancer pathophysiology and therapeutics

    Directory of Open Access Journals (Sweden)

    Gina Manda

    2015-08-01

    Full Text Available The review pinpoints operational concepts related to the redox biology network applied to the pathophysiology and therapeutics of solid tumors. A sophisticated network of intrinsic and extrinsic cues, integrated in the tumor niche, drives tumorigenesis and tumor progression. Critical mutations and distorted redox signaling pathways orchestrate pathologic events inside cancer cells, resulting in resistance to stress and death signals, aberrant proliferation and efficient repair mechanisms. Additionally, the complex inter-cellular crosstalk within the tumor niche, mediated by cytokines, redox-sensitive danger signals (HMGB1 and exosomes, under the pressure of multiple stresses (oxidative, inflammatory, metabolic, greatly contributes to the malignant phenotype. The tumor-associated inflammatory stress and its suppressive action on the anti-tumor immune response are highlighted. We further emphasize that ROS may act either as supporter or enemy of cancer cells, depending on the context. Oxidative stress-based therapies, such as radiotherapy and photodynamic therapy, take advantage of the cytotoxic face of ROS for killing tumor cells by a non-physiologically sudden, localized and intense oxidative burst. The type of tumor cell death elicited by these therapies is discussed. Therapy outcome depends on the differential sensitivity to oxidative stress of particular tumor cells, such as cancer stem cells, and therefore co-therapies that transiently down-regulate their intrinsic antioxidant system hold great promise. We draw attention on the consequences of the damage signals delivered by oxidative stress-injured cells to neighboring and distant cells, and emphasize the benefits of therapeutically triggered immunologic cell death in metastatic cancer. An integrative approach should be applied when designing therapeutic strategies in cancer, taking into consideration the mutational, metabolic, inflammatory and oxidative status of tumor cells, cellular

  14. Myelination of parvalbumin interneurons: a parsimonious locus of pathophysiological convergence in schizophrenia

    Science.gov (United States)

    Stedehouder, J; Kushner, S A

    2017-01-01

    Schizophrenia is a debilitating psychiatric disorder characterized by positive, negative and cognitive symptoms. Despite more than a century of research, the neurobiological mechanism underlying schizophrenia remains elusive. White matter abnormalities and interneuron dysfunction are the most widely replicated cellular neuropathological alterations in patients with schizophrenia. However, a unifying model incorporating these findings has not yet been established. Here, we propose that myelination of fast-spiking parvalbumin (PV) interneurons could be an important locus of pathophysiological convergence in schizophrenia. Myelination of interneurons has been demonstrated across a wide diversity of brain regions and appears highly specific for the PV interneuron subclass. Given the critical influence of fast-spiking PV interneurons for mediating oscillations in the gamma frequency range (~30–120 Hz), PV myelination is well positioned to optimize action potential fidelity and metabolic homeostasis. We discuss this hypothesis with consideration of data from human postmortem studies, in vivo brain imaging and electrophysiology, and molecular genetics, as well as fundamental and translational studies in rodent models. Together, the parvalbumin interneuron myelination hypothesis provides a falsifiable model for guiding future studies of schizophrenia pathophysiology. PMID:27646261

  15. Functional anatomy and pathophysiologic principles in mitral regurgitation: Non-invasive assessment.

    Science.gov (United States)

    Maréchaux, Sylvestre; Illman, Jeffery E; Huynh, James; Michelena, Hector I; Nkomo, Vuyisile T; Tribouilloy, Christophe

    Mitral regurgitation (MR) is the most prevalent cause of valvular heart disease (VHD) in western countries. In the Euro Heart Survey on VHD, MR was the second most common heart VHD requiring surgery. It is also the most common form of VHD in community and population-based studies from the United States. The categorization of MR based on causes and mechanisms is a major determinant of clinical outcome, of possible therapies for the MR and of the effectiveness of these therapies. Surgical mitral valve (MV) repair has been shown to improve survival in patients with severe primary MR compared with MV replacement. In addition, new percutaneous repair and replacement procedures have been recently developed. Hence, accurate understanding of the functional anatomy of the MV and the pathophysiologic principles underlying MR is needed to appropriately target valve lesions. Recent advances in cardiac imaging have allowed to deeply strengthen the knowledge of the function of the MV. The present review aims at describing the functional anatomy and pathophysiology of MR through different cardiac imaging modalities. Copyright © 2017 Anesthesia History Association. Published by Elsevier Inc. All rights reserved.

  16. Interactive evolution concept for analyzing a rock salt cavern under cyclic thermo-mechanical loading

    Science.gov (United States)

    König, Diethard; Mahmoudi, Elham; Khaledi, Kavan; von Blumenthal, Achim; Schanz, Tom

    2016-04-01

    The excess electricity produced by renewable energy sources available during off-peak periods of consumption can be used e.g. to produce and compress hydrogen or to compress air. Afterwards the pressurized gas is stored in the rock salt cavities. During this process, thermo-mechanical cyclic loading is applied to the rock salt surrounding the cavern. Compared to the operation of conventional storage caverns in rock salt the frequencies of filling and discharging cycles and therefore the thermo-mechanical loading cycles are much higher, e.g. daily or weekly compared to seasonally or yearly. The stress strain behavior of rock salt as well as the deformation behavior and the stability of caverns in rock salt under such loading conditions are unknown. To overcome this, existing experimental studies have to be supplemented by exploring the behavior of rock salt under combined thermo-mechanical cyclic loading. Existing constitutive relations have to be extended to cover degradation of rock salt under thermo-mechanical cyclic loading. At least the complex system of a cavern in rock salt under these loading conditions has to be analyzed by numerical modeling taking into account the uncertainties due to limited access in large depth to investigate material composition and properties. An interactive evolution concept is presented to link the different components of such a study - experimental modeling, constitutive modeling and numerical modeling. A triaxial experimental setup is designed to characterize the cyclic thermo-mechanical behavior of rock salt. The imposed boundary conditions in the experimental setup are assumed to be similar to the stress state obtained from a full-scale numerical simulation. The computational model relies primarily on the governing constitutive model for predicting the behavior of rock salt cavity. Hence, a sophisticated elasto-viscoplastic creep constitutive model is developed to take into account the dilatancy and damage progress, as well as

  17. Pathophysiology of heatstroke in dogs - revisited.

    Science.gov (United States)

    Bruchim, Yaron; Horowitz, Michal; Aroch, Itamar

    2017-01-01

    Heatstroke results from a failure to dissipate accumulated heat during exposure to hot environments, or during strenuous physical exercise under heat stress. It is characterized by core body temperatures > 41°C, with central nervous system dysfunction. Functional morphology and thermoregulatory effectors differences between dogs and humans may require special heatstroke protective adaptations in dogs, however, the risk factors for developing heatstroke are similar in both. In dogs, these include hot, especially highly humid environments, excessive physical activity, obesity, large (>15 kg) body weight, being of certain breed (e.g., Labrador retrievers and brachycephalic breeds), upper airway obstruction and prolonged seizures. Lack of acclimation to heat and physical fitness decreases the survival of heat stroked dogs. At the systemic level, blood pooling within the large internal organs (e.g., spleen, liver) is a major contributor to the development of shock and consequent intestinal ischemia, hypoxia and endothelial hyperpermeability, commonly occurring in heatstroke patients. Evoked serious complications include rhabdomyolysis, acute kidney injury, acute respiratory distress syndrome and ultimately, sepsis and disseminated intravascular coagulation. The most common clinical signs in dogs include acute collapse, tachypnea, spontaneous bleeding, shock signs and mental abnormalities, including depression, disorientation or delirium, seizures, stupor and coma. In such dogs, presence of peripheral blood nucleated red blood cells uniquely occurs, and is a highly sensitive diagnostic and prognostic biomarker. Despite early, appropriate body cooling, and intensive supportive treatment, with no available specific treatment to ameliorate the severe inflammatory and hemostatic derangements, the mortality rate is around 50%, similar to that of human heatstroke victims. This review discusses the pathophysiology of canine heatstroke from a veterinarian's point of view

  18. Corporate debts ad credit performance under the new mechanism of reorganization of the Russian banks

    Directory of Open Access Journals (Sweden)

    Sergey A. Andryushin

    2017-09-01

    Full Text Available Objective to explore the dynamics and factors of formation of corporate debts the characteristics of low credit activity of the Russian banks and regulation of liquidity deficit of enterprises under the new reorganization mechanism in the Russian banking sector. Methods systematic approach to the cognition of economic phenomena which allows to study them in their dynamic development taking into account the influence of various environmental factors. The systematic approach determined selection of specific research methods empirical logical comparative and statistical. Results the article is devoted to the problems of declining credit activity of commercial banks under the conditions of economic activity revival as well as to assessing the impact of the new reorganization mechanism on this process. It is shown that in the recent years the nonfinancial sector faces the trend of optimizing the corporate debts and the liquidity deficit which reduced the demand for loans and as a consequence decreased the banksrsquo credit activity. To analyze the dynamics of deficitsurplus of liquidity in the corporate sector a new classification of liquidity deficitsurplus levels was introduced. Based on the proposed classification the risk factors were identified that influenced the dynamics of indebtedness in the corporate sector. The article also analyses the modern monetary mechanism of money supply in the economy and its transformation. It was determined that the main limitation of credit issuance by commercial banks is their capital not the reserve multiplier. The new mechanism of credit institutionsrsquo financial recovery and its impact on the banksrsquo credit activity was estimated. The conditions of liquidity deficiency reduction in the Russian companies were analyzed in the medium term. Scientific novelty for the first time on the basis of system analysis methods the growth factors of the corporate debt load were identified the peculiarities of low

  19. Theoretical modeling of mechanical homeostasis of a mammalian cell under gravity-directed vector.

    Science.gov (United States)

    Zhou, Lüwen; Zhang, Chen; Zhang, Fan; Lü, Shouqin; Sun, Shujin; Lü, Dongyuan; Long, Mian

    2018-02-01

    Translocation of dense nucleus along gravity vector initiates mechanical remodeling of a eukaryotic cell. In our previous experiments, we quantified the impact of gravity vector on cell remodeling by placing an MC3T3-E1 cell onto upward (U)-, downward (D)-, or edge-on (E)- orientated substrate. Our experimental data demonstrate that orientation dependence of nucleus longitudinal translocation is positively correlated with cytoskeletal (CSK) remodeling of their expressions and structures and also is associated with rearrangement of focal adhesion complex (FAC). However, the underlying mechanism how CSK network and FACs are reorganized in a mammalian cell remains unclear. In this paper, we developed a theoretical biomechanical model to integrate the mechanosensing of nucleus translocation with CSK remodeling and FAC reorganization induced by a gravity vector. The cell was simplified as a nucleated tensegrity structure in the model. The cell and CSK filaments were considered to be symmetrical. All elements of CSK filaments and cytomembrane that support the nucleus were simplified as springs. FACs were simplified as an adhesion cluster of parallel bonds with shared force. Our model proposed that gravity vector-directed translocation of the cell nucleus is mechanically balanced by CSK remodeling and FAC reorganization induced by a gravitational force. Under gravity, dense nucleus tends to translocate and exert additional compressive or stretching force on the cytoskeleton. Finally, changes of the tension force acting on talin by microfilament alter the size of FACs. Results from our model are in qualitative agreement with those from experiments.

  20. Mechanisms of Mining Seismicity under Large Scale Exploitation with Multikey Strata

    Directory of Open Access Journals (Sweden)

    Hu He

    2015-01-01

    Full Text Available The dynamic disasters are aggravating with the increase of exploitation scale and intensity in Chinese coal mines, to further understand this problem, we studied the mechanisms of mining tremors induced by key strata movement and instability under large scale exploitation. First the mechanisms were categorized into two groups that is main key strata fracture and movement as well as subkey strata instability again under adjacent mining activities. Based on the key strata theory in ground control we revealed three basic mechanisms of key strata destabilization that are rotary and sliding of low subkey strata, shear sliding of the high subkey strata, and the main key strata rupture and cave at limit span, respectively. The microseismic observing systems were applied to monitor the mining tremor events and verify the theoretical analysis in different coal mines. The characteristics of time-space evolution of tremors show that low inferior key strata causing the most, followed by the high inferior key strata and the main key strata least, however the released energy was just opposite.

  1. An investigation of the mechanical behavior of initially curved microplates under electrostatic actuation

    KAUST Repository

    Saghir, Shahid

    2018-03-28

    In this article, we investigate the mechanical behavior of initially curved microplates under electrostatic actuation. Microplates are essential components of many Micro-Electro-Mechanical System devices; however, they commonly undergo an initial curvature imperfection, due to the microfabrication process. Initial curvature imperfection significantly affects the mechanical behavior of microplates. In this work, we derive a dynamic analogue of the von Kármán governing equation for such plates. These equations are then used to develop a reduced order model based on the Galerkin procedure to simulate the static and dynamic behavior of the microplate. Two profiles of initial curvature commonly encountered in microfabricated structures are considered, where one assumes a variation in shape along one dimension of the plate only (cylindrical bending shape) while the other assumes a variation in shape along both dimensions of the plate. Their effects on both the static and dynamic responses of the microplates are examined and compared. We validate the reduced order model by comparing the calculated static behavior and the fundamental natural frequency with those computed by a finite element model over a range of the initial plate rise. The static behavior of the microplate is investigated when varying the DC voltage. Then, the dynamic behavior of the microplate is examined under the application of a harmonic AC voltage superimposed to a DC voltage.

  2. Music and literature: are there shared empathy and predictive mechanisms underlying their affective impact?

    Directory of Open Access Journals (Sweden)

    Diana eOmigie

    2015-08-01

    Full Text Available It has been suggested that music and language had a shared evolutionary precursor before becoming mainly responsible for the communication of emotive and referential meaning respectively. However, emphasis on potential differences between music and language may discourage a consideration of the commonalities that music and literature share. Indeed, one possibility is that common mechanisms underlie their affective impact, and the current paper carefully reviews relevant neuroscientific findings to examine such a prospect. First and foremost, it will be demonstrated that considerable evidence of a common role of empathy and predictive processes now exists for the two domains. However, it will also be noted that an important open question remains: namely, whether the mechanisms underlying the subjective experience of uncertainty differ between the two with respect to recruitment of phylogenetically ancient emotion areas. It will be concluded that a comparative approach may not only help to reveal general mechanisms underlying our responses to music and literature, but may also help us better understand any idiosyncrasies in their capacity for affective impact.

  3. The pathologic mechanisms underlying lumbar distraction spinal cord injury in rabbits.

    Science.gov (United States)

    Wu, Di; Zheng, Chao; Wu, Ji; Xue, Jing; Huang, Rongrong; Wu, Di; Song, Yueming

    2017-11-01

    A reliable experimental rabbit model of distraction spinal cord injury (SCI) was established to successfully simulate gradable and replicable distraction SCI. However, further research is needed to elucidate the pathologic mechanisms underlying distraction SCI. The aim of this study was to investigate the pathologic mechanisms underlying lumbar distraction SCI in rabbits. This is an animal laboratory study. Using a self-designed spine distractor, the experimental animals were divided into a control group and 10%, 20%, and 30% distraction groups. Pathologic changes to the spinal cord microvessels in the early stage of distraction SCI were identified by perfusion of the spinal cord vasculature with ink, production of transparent specimens, observation by light microscopy, and observation of corrosion casts of the spinal cord microvascular architecture by scanning electron microscopy. Malondialdehyde (MDA) and superoxide dismutase (SOD) concentrations in the injured spinal cord tissue were measured after 8 hours. With an increasing degree and duration of distraction, the spinal cord microvessels were only partially filled and had the appearance of spasm until rupture and hemorrhage were observed. The MDA concentration increased and the SOD concentration decreased in the spinal cord tissue. Changes to the internal and external spinal cord vessels led to spinal cord ischemia, which is a primary pathologic mechanism of distraction SCI. Lipid peroxidation mediated by free radicals took part in secondary pathologic damage of distraction SCI. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Linear Analytical Solutions of Mechanical Sensitivity in Large Deflection of Unsymmetrically Layered Piezoelectric Plate under Pretension

    Directory of Open Access Journals (Sweden)

    Chun-Fu Chen

    2014-03-01

    Full Text Available Linear analytical study on the mechanical sensitivity in large deflection of unsymmetrically layered and laterally loaded piezoelectric plate under pretension is conducted. von Karman plate theory for large deflection is utilized but extended to the case of an unsymmetrically layered plate embedded with a piezoelectric layer. The governing equations thus obtained are simplified by omitting the arising nonlinear terms, yielding a Bessel or modified Bessel equation for the lateral slope. Depending on the relative magnitude of the piezoelectric effect, for both cases, analytical solutions of various geometrical responses are developed and formulated via Bessel and modified Bessel functions. The associated ultimate radial stresses are further derived following lamina constitutive law to evaluate the mechanical sensitivity of the considered plate. For a nearly monolithic plate under a very low applied voltage, the results are in good agreement with those for a single-layered case due to pure mechanical load available in literature, and thus the present approach is checked. For a two-layered unsymmetric plate made of typical silicon-based materials, a sound piezoelectric effect is illustrated particularly in a low pretension condition.

  5. Cellular and deafness mechanisms underlying connexin mutation induced hearing loss – A common hereditary deafness

    Directory of Open Access Journals (Sweden)

    Jeffrey C Wingard

    2015-05-01

    Full Text Available Hearing loss due to mutations in the connexin gene family which encodes gap junctional proteins is a common form of hereditary deafness. In particular, connexin 26 (Cx26, GJB2 mutations are responsible for ~50% of nonsyndromic hearing loss, which is the highest incidence of genetic disease. In the clinic, Cx26 mutations cause various auditory phenotypes ranging from profound congenital deafness at birth to mild, progressive hearing loss in late childhood. Recent experiments demonstrate that congenital deafness mainly results from cochlear developmental disorders rather than hair cell degeneration and endocochlear potential (EP reduction, while late-onset hearing loss results from reduction of active cochlear amplification, even though cochlear hair cells have no connexin expression. Moreover, new experiments further demonstrate that the hypothesized K+-recycling disruption is not a principal deafness mechanism for connexin deficiency induced hearing loss. Additionally, there is no clear relationship between specific changes in connexin (channel functions and the phenotypes of mutation-induced hearing loss. Cx30, Cx29, Cx31, and Cx43 mutations can also cause hearing loss with distinct pathological changes in the cochlea. These new studies provide invaluable information about deafness mechanisms underlying connexin mutation induced hearing loss and also provide important information for developing new protective and therapeutic strategies for this common deafness. However, the detailed cellular mechanisms underlying these pathological changes and pathogeneses of specific-mutation induced hearing loss remain unclear. Finally, little information is available for humans. Further studies to address these deficiencies are urgently required.

  6. Mechanism Underlying the Spatial Pattern Formation of Dominant Tree Species in a Natural Secondary Forest.

    Directory of Open Access Journals (Sweden)

    Guodong Jia

    Full Text Available Studying the spatial pattern of plant species may provide significant insights into processes and mechanisms that maintain stand stability. To better understand the dynamics of naturally regenerated secondary forests, univariate and bivariate Ripley's L(r functions were employed to evaluate intra-/interspecific relationships of four dominant tree species (Populus davidiana, Betula platyphylla, Larix gmelinii and Acer mono and to distinguish the underlying mechanism of spatial distribution. The results showed that the distribution of soil, water and nutrients was not fragmented but presented clear gradients. An overall aggregated distribution existed at most distances. No correlation was found between the spatial pattern of soil conditions and that of trees. Both positive and negative intra- and interspecific relationships were found between different DBH classes at various distances. Large trees did not show systematic inhibition of the saplings. By contrast, the inhibition intensified as the height differences increased between the compared pairs. Except for Larix, universal inhibition of saplings by upper layer trees occurred among other species, and this reflected the vertical competition for light. Therefore, we believe that competition for light rather than soil nutrients underlies the mechanism driving the formation of stand spatial pattern in the rocky mountainous areas examined.

  7. Pathophysiology and Treatment of Hyperhidrosis.

    Science.gov (United States)

    Fujimoto, Tomoko

    2016-01-01

    Primary focal hyperhidrosis is a disease of unknown cause with profuse perspiration of local sites (head, face, palms, soles of feet, and axillae) that adversely affects daily life. Guidelines have been proposed in the USA [1], Canada [2], and Japan [3]. The symptoms impair quality of life, with significant negative effects on daily existence and personal relationships. The current goal in medical practice for patients with hyperhidrosis is to provide guidance and encourage coping skills for a normal daily life, as well as give appropriate advice regarding treatment options. On occasion, in order to improve quality of life, it is necessary to recommend surgical therapy when conservative treatment fails; this requires an understanding of the mechanisms of available treatments and their effects. This paper reviews theories of primary focal hyperhidrosis with regard to pathology, epidemiology, and treatment. © 2016 S. Karger AG, Basel.

  8. Pathophysiology of Acute Kidney Injury

    Science.gov (United States)

    Basile, David P.; Anderson, Melissa D.; Sutton, Timothy A.

    2014-01-01

    Acute kidney injury (AKI) is the leading cause of nephrology consultation and is associated with high mortality rates. The primary causes of AKI include ischemia, hypoxia or nephrotoxicity. An underlying feature is a rapid decline in GFR usually associated with decreases in renal blood flow. Inflammation represents an important additional component of AKI leading to the extension phase of injury, which may be associated with insensitivity to vasodilator therapy. It is suggested that targeting the extension phase represents an area potential of treatment with the greatest possible impact. The underlying basis of renal injury appears to be impaired energetics of the highly metabolically active nephron segments (i.e., proximal tubules and thick ascending limb) in the renal outer medulla, which can trigger conversion from transient hypoxia to intrinsic renal failure. Injury to kidney cells can be lethal or sublethal. Sublethal injury represents an important component in AKI, as it may profoundly influence GFR and renal blood flow. The nature of the recovery response is mediated by the degree to which sublethal cells can restore normal function and promote regeneration. The successful recovery from AKI depends on the degree to which these repair processes ensue and these may be compromised in elderly or CKD patients. Recent data suggest that AKI represents a potential link to CKD in surviving patients. Finally, earlier diagnosis of AKI represents an important area in treating patients with AKI that has spawned increased awareness of the potential that biomarkers of AKI may play in the future. PMID:23798302

  9. Sepsis: pathophysiology and clinical management.

    Science.gov (United States)

    Gotts, Jeffrey E; Matthay, Michael A

    2016-05-23

    Sepsis, severe sepsis, and septic shock represent increasingly severe systemic inflammatory responses to infection. Sepsis is common in the aging population, and it disproportionately affects patients with cancer and underlying immunosuppression. In its most severe form, sepsis causes multiple organ dysfunction that can produce a state of chronic critical illness characterized by severe immune dysfunction and catabolism. Much has been learnt about the pathogenesis of sepsis at the molecular, cell, and intact organ level. Despite uncertainties in hemodynamic management and several treatments that have failed in clinical trials, investigational therapies increasingly target sepsis induced organ and immune dysfunction. Outcomes in sepsis have greatly improved overall, probably because of an enhanced focus on early diagnosis and fluid resuscitation, the rapid delivery of effective antibiotics, and other improvements in supportive care for critically ill patients. These improvements include lung protective ventilation, more judicious use of blood products, and strategies to reduce nosocomial infections. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  10. Signaling mechanism underlying the histamine-modulated action of hypoglossal motoneurons.

    Science.gov (United States)

    Liu, Zi-Long; Wu, Xu; Luo, Yan-Jia; Wang, Lu; Qu, Wei-Min; Li, Shan-Qun; Huang, Zhi-Li

    2016-04-01

    Histamine, an important modulator of the arousal states of the central nervous system, has been reported to contribute an excitatory drive at the hypoglossal motor nucleus to the genioglossus (GG) muscle, which is involved in the pathogenesis of obstructive sleep apnea. However, the effect of histamine on hypoglossal motoneurons (HMNs) and the underlying signaling mechanisms have remained elusive. Here, whole-cell patch-clamp recordings were conducted using neonatal rat brain sections, which showed that histamine excited HMNs with an inward current under voltage-clamp and a depolarization membrane potential under current-clamp via histamine H1 receptors (H1Rs). The phospholipase C inhibitor U-73122 blocked H1Rs-mediated excitatory effects, but protein kinase A inhibitor and protein kinase C inhibitor did not, indicating that the signal transduction cascades underlying the excitatory action of histamine on HMNs were H1R/Gq/11 /phospholipase C/inositol-1,4,5-trisphosphate (IP3). The effects of histamine were also dependent on extracellular Na(+) and intracellular Ca(2+), which took place via activation of Na(+)-Ca(2+) exchangers. These results identify the signaling molecules associated with the regulatory effect of histamine on HMNs. The findings of this study may provide new insights into therapeutic approaches in obstructive sleep apnea. We proposed the post-synaptic mechanisms underlying the modulation effect of histamine on hypoglossal motoneuron. Histamine activates the H1Rs via PLC and IP3, increases Ca(2+) releases from intracellular stores, promotes Na(+) influx and Ca(2+) efflux via the NCXs, and then produces an inward current and depolarizes the neurons. Histamine modulates the excitability of HMNs with other neuromodulators, such as noradrenaline, serotonin and orexin. We think that these findings should provide an important new direction for drug development for the treatment of obstructive sleep apnea. © 2016 International Society for Neurochemistry.

  11. Ablation characteristics and reaction mechanism of insulation materials under slag deposition condition

    Science.gov (United States)

    Guan, Yiwen; Li, Jiang; Liu, Yang

    2017-07-01

    Current understanding of the physical and chemical processes involved in the ablation of insulation materials by highly aluminized solid propellants is limited. The study on the heat transfer and ablation principle of ethylene propylene diene monomer (EPDM) materials under slag deposition condition is essential for future design or modification of large solid rocket motors (SRMs) for launch application. In this paper, the alumina liquid flow pattern and the deposition principle in full-scale SRM engines are discussed. The interaction mechanism between the alumina droplets and the wall are analyzed. Then, an experimental method was developed to simulate the insulation material ablation under slag deposition condition. Experimental study was conducted based on a laboratory-scale device. Meanwhile, from the analysis of the cross-sectional morphology and chemical composition of the charring layer after ablation, the reaction mechanism of the charring layer under deposition condition was discussed, and the main reaction equation was derived. The numerical simulation and experimental results show the following. (i) The alumina droplet flow in the deposition section of the laboratory-scale device is similar to that of a full-scale SRM. (ii) The charring layer of the EPDM insulator displays a porous tight/loose structure under high-temperature slag deposition condition. (iii) A seven-step carbothermal reduction in the alumina is derived and established under high-pressure and high-temperature environment in the SRM combustion chamber. (iv) The analysis using thermodynamic software indicates that the reaction of the alumina and charring layer initially forms Al4C3 during the operation. Then, Al element and Al2OC compound are subsequently produced with the reduction in the release of gas CO as well with continuous environmental heating.

  12. Risks of flexible ureterorenoscopy: pathophysiology and prevention.

    Science.gov (United States)

    Osther, Palle J S

    2018-02-01

    Currently, indications for flexible ureterorenoscopy (fURS) are expanding, mainly due to technological advancements. Although data from clinical series definitely presents fURS as a safe procedure, serious complications including sepsis and ureteral lesions do occur. These complications seem to be a result of the unique elements of fURS, ureteral access and irrigation, pushing normal upper urinary tract physiology into pathophysiological processes, including intrarenal/pyelo-veneous backflow and ureteral contractions, potentially resulting in septic, haemorrhagic and ureteral lesional complications. Knowledge on normal upper urinary tract physiology are crucial for understanding how these harmful effects of fURS may be avoided or minimized. The pathophysiology of intrarenal pressure increases and ureteral access will be discussed as a basis for understanding preventive measures. Role of antibiotics, ureteral access sheaths, safty guidewires, pain medication, prestenting and pharmacologic modulation of pyeloureteral dynamics are reviewed from a pathophysiological perspective.

  13. Neuronal mechanisms underlying differences in spatial resolution between darks and lights in human vision.

    Science.gov (United States)

    Pons, Carmen; Mazade, Reece; Jin, Jianzhong; Dul, Mitchell W; Zaidi, Qasim; Alonso, Jose-Manuel

    2017-12-01

    Artists and astronomers noticed centuries ago that humans perceive dark features in an image differently from light ones; however, the neuronal mechanisms underlying these dark/light asymmetries remained unknown. Based on computational modeling of neuronal responses, we have previously proposed that such perceptual dark/light asymmetries originate from a luminance/response saturation within the ON retinal pathway. Consistent with this prediction, here we show that stimulus conditions that increase ON luminance/response saturation (e.g., dark backgrounds) or its effect on light stimuli (e.g., optical blur) impair the perceptual discrimination and salience of light targets more than dark targets in human vision. We also show that, in cat visual cortex, the magnitude of the ON luminance/response saturation remains relatively constant under a wide range of luminance conditions that are common indoors, and only shifts away from the lowest luminance contrasts under low mesopic light. Finally, we show that the ON luminance/response saturation affects visual salience mostly when the high spatial frequencies of the image are reduced by poor illumination or optical blur. Because both low luminance and optical blur are risk factors in myopia, our results suggest a possible neuronal mechanism linking myopia progression with the function of the ON visual pathway.

  14. Mechanisms of weight maintenance under high- and low-protein, low-glycaemic index diets.

    Science.gov (United States)

    Rubio-Aliaga, Isabel; Marvin-Guy, Laure F; Wang, Ping; Wagniere, Sandrine; Mansourian, Robert; Fuerholz, Andreas; Saris, Wim H M; Astrup, Arne; Mariman, Edwin C M; Kussmann, Martin

    2011-11-01

    Weight maintenance after intended weight loss is a challenge in an obesogenic environment. In a large multicentre dietary intervention study (DiOGenes), it has recently been demonstrated that a high-protein/low-glycaemic index (HP/LGI) diet was slightly more efficient in maintaining weight loss than low-protein/LGI or high-GI (LP/LGI or HGI) diets. Here, we use a proteomic approach to assess the molecular mechanisms behind this positive effect. A subset of the most successful (weight loser, n=12) and unsuccessful (weight re-gainer, n=12) individuals consuming the LGI diets with either high- or low-protein content (HP or LP/LGI), following an initial calorie deficit run-in weight loss phase, were analyzed at the plasma protein level. Proteomic analysis revealed 18 proteins regulated after 6 months of the dietary weight maintenance phase. Furthermore, 12 proteins were significantly regulated as a function of success rate under an HP diet, arising as candidate biomarkers of mechanisms of successful weight maintenance under an HP/LGI diet. Pregnancy-zone protein (PZP) and protein S (PROS1) were revealed as novel biomarkers of weight maintenance showing opposite effects. Semantic network analysis of the 12 regulated proteins revealed that under an HP/LGI an anti-atherogenic effect and alterations of fat metabolism were associated with the success of maintaining the initial weight loss. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Megaureter: classification, pathophysiology, and management.

    Science.gov (United States)

    Simoni, F; Vino, L; Pizzini, C; Benini, D; Fanos, V

    2000-01-01

    The term megaureter does not define a specific pathological condition, because it can be due to different underlying abnormalities. The most used classification includes three groups: refluxing megaureter, associated with vesicoureteral reflux (VUR); obstructive megaureter, associated with urine flow impairment at the vesicoureteral junction; non-refluxing non-obstructive megaureter, if neither obstruction nor reflux can be identified. Each group can be divided into two subgroups: primary megaureter; secondary megaureter. With the advent of antenatal ultrasound an increased number of cases are identified prior to the onset of symptoms. The common used investigation are: urinary tract ultrasound, voiding cystourethrography, urography, serial diuretic renography and pressure-perfusion studies (Whitaker test). The advent of prenatal and neonatal echography has modified the natural history of megaureter. Nowadays non operative management is preferred. Operative intervention is indicated only in these cases: significant impairment to urine flow; worsening renal function during the observation time; recurrent UTI in spite of adequate antibiotic prophylaxis.

  16. Mechanical properties and fracture behaviour of defective phosphorene nanotubes under uniaxial tension

    Science.gov (United States)

    Liu, Ping; Pei, Qing-Xiang; Huang, Wei; Zhang, Yong-Wei

    2017-12-01

    The easy formation of vacancy defects and the asymmetry in the two sublayers of phosphorene nanotubes (PNTs) may result in brand new mechanical properties and failure behaviour. Herein, we investigate the mechanical properties and fracture behaviour of defective PNTs under uniaxial tension using molecular dynamics simulations. Our simulation results show that atomic vacancies cause local stress concentration and thus significantly reduce the fracture strength and fracture strain of PNTs. More specifically, a 1% defect concentration is able to reduce the fracture strength and fracture strain by as much as 50% and 66%, respectively. Interestingly, the reduction in the mechanical properties is found to depend on the defect location: a defect located in the outer sublayer has a stronger effect than one located in the inner layer, especially for PNTs with a small diameter. Temperature is also found to strongly influence the mechanical properties of both defect-free and defective PNTs. When the temperature is increased from 0 K to 400 K, the fracture strength and fracture strain of defective PNTs with a defect concentration of 1% are reduced further by 71% and 61%, respectively. These findings are of great importance for the structural design of PNTs as building blocks in nanodevices.

  17. Peripheral afferent mechanisms underlying acupuncture inhibition of cocaine behavioral effects in rats.

    Directory of Open Access Journals (Sweden)

    Seol Ah Kim

    Full Text Available Administration of cocaine increases locomotor activity by enhancing dopamine transmission. To explore the peripheral mechanisms underlying acupuncture treatment for drug addiction, we developed a novel mechanical acupuncture instrument (MAI for objective mechanical stimulation. The aim of this study was to evaluate whether acupuncture inhibition of cocaine-induced locomotor activity is mediated through specific peripheral nerves, the afferents from superficial or deep tissues, or specific groups of nerve fibers. Mechanical stimulation of acupuncture point HT7 with MAI suppressed cocaine-induced locomotor activity in a stimulus time-dependent manner, which was blocked by severing the ulnar nerve or by local anesthesia. Suppression of cocaine-induced locomotor activity was elicited after HT7 stimulation at frequencies of either 50 (for Meissner corpuscles or 200 (for Pacinian corpuscles Hz and was not affected by block of C/Aδ-fibers in the ulnar nerve with resiniferatoxin, nor generated by direct stimulation of C/Aδ-fiber afferents with capsaicin. These findings suggest that HT7 inhibition of cocaine-induced locomotor activity is mediated by A-fiber activation of ulnar nerve that originates in superficial and deep tissue.

  18. Kidney branching morphogenesis under the control of a ligand-receptor-based Turing mechanism

    Science.gov (United States)

    Menshykau, Denis; Iber, Dagmar

    2013-08-01

    The main signalling proteins that control early kidney branching have been defined. Yet the underlying mechanism is still elusive. We have previously shown that a Schnakenberg-type Turing mechanism can recapitulate the branching and protein expression patterns in wild-type and mutant lungs, but it is unclear whether this mechanism would extend to other branched organs that are regulated by other proteins. Here, we show that the glial cell line-derived neurotrophic factor-RET regulatory interaction gives rise to a Schnakenberg-type Turing model that reproduces the observed budding of the ureteric bud from the Wolffian duct, its invasion into the mesenchyme and the observed branching pattern. The model also recapitulates all relevant protein expression patterns in wild-type and mutant mice. The lung and kidney models are both based on a particular receptor-ligand interaction and require (1) cooperative binding of ligand and receptor, (2) a lower diffusion coefficient for the receptor than for the ligand and (3) an increase in the receptor concentration in response to receptor-ligand binding (by enhanced transcription, more recycling or similar). These conditions are met also by other receptor-ligand systems. We propose that ligand-receptor-based Turing patterns represent a general mechanism to control branching morphogenesis and other developmental processes.

  19. An easily reversible structural change underlies mechanisms enabling desert crust cyanobacteria to survive desiccation.

    Science.gov (United States)

    Bar-Eyal, Leeat; Eisenberg, Ido; Faust, Adam; Raanan, Hagai; Nevo, Reinat; Rappaport, Fabrice; Krieger-Liszkay, Anja; Sétif, Pierre; Thurotte, Adrien; Reich, Ziv; Kaplan, Aaron; Ohad, Itzhak; Paltiel, Yossi; Keren, Nir

    2015-10-01

    Biological desert sand crusts are the foundation of desert ecosystems, stabilizing the sands and allowing colonization by higher order organisms. The first colonizers of the desert sands are cyanobacteria. Facing the harsh conditions of the desert, these organisms must withstand frequent desiccation-hydration cycles, combined with high light intensities. Here, we characterize structural and functional modifications to the photosynthetic apparatus that enable a cyanobacterium, Leptolyngbya sp., to thrive under these conditions. Using multiple in vivo spectroscopic and imaging techniques, we identified two complementary mechanisms for dissipating absorbed energy in the desiccated state. The first mechanism involves the reorganization of the phycobilisome antenna system, increasing excitonic coupling between antenna components. This provides better energy dissipation in the antenna rather than directed exciton transfer to the reaction center. The second mechanism is driven by constriction of the thylakoid lumen which limits diffusion of plastocyanin to P700. The accumulation of P700(+) not only prevents light-induced charge separation but also efficiently quenches excitation energy. These protection mechanisms employ existing components of the photosynthetic apparatus, forming two distinct functional modes. Small changes in the structure of the thylakoid membranes are sufficient for quenching of all absorbed energy in the desiccated state, protecting the photosynthetic apparatus from photoinhibitory damage. These changes can be easily reversed upon rehydration, returning the system to its high photosynthetic quantum efficiency. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. The pathophysiology of restless legs syndrome

    International Nuclear Information System (INIS)

    Miyamoto, Masayuki; Miyamoto, Tomoyuki; Iwanami, Masaoki; Suzuki, Keisuke; Hirata, Koichi

    2009-01-01

    Restless legs syndrome (RLS) is a sensorimotor disorder that is frequently associated with periodic leg movements (PLMS). RLS is generally considered to be a central nervous system (CNS)-related disorder although no specific lesion has been found to be associated with the syndrome. Reduced intracortical inhibition has been demonstrated in RLS by transcranial magnetic stimulation. Some MRI studies have revealed the presence of morphologic changes in the somatosensory cortex, motor cortex and thalamic gray matter. The results of single photon emission computed tomography (SPECT) and positron emission tomography (PET) studies showed that the limbic and opioid systems also play important roles in the pathophysiology of RLS. A functional MRI study revealed abnormal bilateral cerebellar and thalamic activation during the manifestation of sensory symptoms, with additional red nucleus and reticular formation activity during PLMS. PLMS is likely to occur in patients with spinal cord lesions, and some patients with sensory polyneuropathy may exhibit RLS symptoms. RLS symptoms seem to depend on abnormal spinal sensorimotor integration at the spinal cord level and abnormal central somatosensory processing. PLMS appears to depend on increased excitability of the spinal cord and a decreased supraspinal inhibitory mechanism from the A11 diencephalic dopaminergic system. RLS symptoms respond very dramatically to dopaminergic therapy. The results of analysis by PET and SPECT studies of striatal D2 receptor binding in humans are inconclusive. However, studies in animal models suggest that the participation of the A11 dopaminergic system and the D3 receptor in RLS symptoms. The symptoms of RLS are aggravated in those with iron deficiency, and iron treatment ameliorates the symptoms in some patients. Neuroimaging studies, analysis of the cerebrospinal fluid, and studies on postmortem tissue and use of animal models have indicated that low brain iron concentrations and dysfunction of

  1. Signaling Mechanisms Underlying Resistance Responses: What Have We Learned, and How Is It Being Applied?

    Science.gov (United States)

    Kachroo, Aardra; Vincelli, Paul; Kachroo, Pradeep

    2017-12-01

    Plants have evolved highly specific mechanisms to resist pathogens including preformed barriers and the induction of elaborate signaling pathways. Induced signaling requires recognition of the pathogen either via conserved pathogen-derived factors or specific pathogen-encoded proteins called effectors. Recognition of these factors by host encoded receptor proteins can result in the elicitation of different tiers of resistance at the site of pathogen infection. In addition, plants induce a type of systemic immunity which is effective at the whole plant level and protects against a broad spectrum of pathogens. Advances in our understanding of pathogen-recognition mechanisms, identification of the underlying molecular components, and their significant conservation across diverse plant species has enabled the development of novel strategies to combat plant diseases. This review discusses key advances in plant defense signaling that have been adapted or have the potential to be adapted for plant protection against microbial diseases.

  2. A hypothesis regarding the molecular mechanism underlying dietary soy-induced effects on seizure propensity.

    Directory of Open Access Journals (Sweden)

    Cara Jean Westmark

    2014-09-01

    Full Text Available Numerous neurological disorders including fragile X syndrome, Down syndrome, autism and Alzheimer’s disease are comorbid with epilepsy. We have observed elevated seizure propensity in mouse models of these disorders dependent on diet. Specifically, soy-based diets exacerbate audiogenic-induced seizures in juvenile mice. We have also found potential associations between the consumption of soy-based infant formula and seizure incidence, epilepsy comorbidity and autism diagnostic scores in autistic children by retrospective analyses of medical record data. In total, these data suggest that consumption of high levels of soy protein during postnatal development may affect neuronal excitability. Herein, we present our theory regarding the molecular mechanism underlying soy-induced effects on seizure propensity. We hypothesize that soy phytoestrogens interfere with metabotropic glutamate receptor signaling through an estrogen receptor-dependent mechanism, which results in elevated production of key synaptic proteins and decreased seizure threshold.

  3. Mechanisms Underlying the Anti-Aging and Anti-Tumor Effects of Lithocholic Bile Acid

    Directory of Open Access Journals (Sweden)

    Anthony Arlia-Ciommo

    2014-09-01

    Full Text Available Bile acids are cholesterol-derived bioactive lipids that play essential roles in the maintenance of a heathy lifespan. These amphipathic molecules with detergent-like properties display numerous beneficial effects on various longevity- and healthspan-promoting processes in evolutionarily distant organisms. Recent studies revealed that lithocholic bile acid not only causes a considerable lifespan extension in yeast, but also exhibits a substantial cytotoxic effect in cultured cancer cells derived from different tissues and organisms. The molecular and cellular mechanisms underlying the robust anti-aging and anti-tumor effects of lithocholic acid have emerged. This review summarizes the current knowledge of these mechanisms, outlines the most important unanswered questions and suggests directions for future research.

  4. Fatigue degradation and failure of rotating composite structures - Materials characterisation and underlying mechanisms

    DEFF Research Database (Denmark)

    Gamstedt, Kristofer; Andersen, Svend Ib Smidt

    2001-01-01

    The present review concerns rotating composite structures, in which fatigue degradation is of key concern for in-service failure. Such applications are for instance rotor blades in wind turbines, helicopter rotor blades, flywheels for energy storage,marine and aeronautical propellers, and rolls...... for paper machines. The purpose is to identify areas where impending efforts should be made to make better use of composite materials in these applications. In order to obtain better design methodologies,which would allow more reliable and slender structures, improved test methods are necessary. Furthermore......, the relation between structural, component and specimen test results should be better understood than what is presently the case. Improvedpredictive methods rely on a better understanding of the underlying damage mechanisms. With mechanism-based models, the component substructure or even the material...

  5. Molecular and Microbial Mechanisms Increasing Soil C Storage Under Future Rates of Anthropogenic N Deposition

    Energy Technology Data Exchange (ETDEWEB)

    Zak, Donald R.

    2017-11-17

    A growing body of evidence reveals that anthropogenic N deposition can reduce the microbial decay of plant detritus and increase soil C storage across a wide range of terrestrial ecosystems. This aspect of global change has the potential to constrain the accumulation of anthropogenic CO2 in the Earth’s atmosphere, and hence slow the pace of climate warming. The molecular and microbial mechanisms underlying this biogeochemical response are not understood, and they are not a component of any coupled climate-biogeochemical model estimating ecosystem C storage, and hence, the future climate of an N-enriched Earth. Here, we report the use of genomic-enabled approaches to identify the molecular underpinnings of the microbial mechanisms leading to greater soil C storage in response to anthropogenic N deposition, thereby enabling us to better anticipate changes in soil C storage.

  6. Mechanisms underlying REBT in mood disordered patients: predicting depression from the hybrid model of learning.

    Science.gov (United States)

    Jackson, Chris J; Izadikah, Zahra; Oei, Tian P S

    2012-06-01

    Jackson's (2005, 2008a) hybrid model of learning identifies a number of learning mechanisms that lead to the emergence and maintenance of the balance between rationality and irrationality. We test a general hypothesis that Jackson's model will predict depressive symptoms, such that poor learning is related to depression. We draw comparisons between Jackson's model and Ellis' (2004) Rational Emotive Behavior Therapy and Theory (REBT) and thereby provide a set of testable learning mechanisms potentially underlying REBT. Results from 80 patients diagnosed with depression completed the learning styles profiler (LSP; Jackson, 2005) and two measures of depression. Results provide support for the proposed model of learning and further evidence that low rationality is a key predictor of depression. We conclude that the hybrid model of learning has the potential to explain some of the learning and cognitive processes related to the development and maintenance of irrational beliefs and depression. Copyright © 2011. Published by Elsevier B.V.

  7. Hypertension and dyslipidaemia in obesity and insulin resistance: pathophysiology, impact on atherosclerotic disease and pharmacotherapy.

    Science.gov (United States)

    Chapman, M John; Sposito, Andrei C

    2008-03-01

    Hypertension, a prevalent risk factor for cardiovascular disease, frequently occurs in conjunction with metabolic disturbances and in particular with dyslipidaemia; such comorbidity presents in more than one-third of hypertensive patients. Moreover, hypertension and dyslipidaemia often manifest concomitantly in the clinical context of obesity and insulin resistance. In this setting, distinct metabolic anomalies may account for the development of both conditions, and may equally act to exacerbate their effects on vascular dysfunction. Significantly, hypertension and dyslipidaemia are linked mechanistically and may act in synergy at the arterial wall to enhance atherosclerosis. In this review, we identify potential mechanisms underlying the pathophysiological interaction between hypertension and dyslipidaemia at the cellular and molecular levels, and which may underlie elevated cardiovascular risk in obesity and insulin resistance. Finally, the clinical evidence supporting the beneficial effects of an integrated pharmacotherapeutic strategy to the reduction of cardiovascular risk in patients with insulin resistance, type 2 diabetes and the metabolic syndrome is critically discussed.

  8. Redox signaling in cardiovascular pathophysiology: A focus on hydrogen peroxide and vascular smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Chang Hyun Byon

    2016-10-01

    Full Text Available Oxidative stress represents excessive intracellular levels of reactive oxygen species (ROS, which plays a major role in the pathogenesis of cardiovascular disease. Besides having a critical impact on the development and progression of vascular pathologies including atherosclerosis and diabetic vasculopathy, oxidative stress also regulates physiological signaling processes. As a cell permeable ROS generated by cellular metabolism involved in intracellular signaling, hydrogen peroxide (H2O2 exerts tremendous impact on cardiovascular pathophysiology. Under pathological conditions, increased oxidase activities and/or impaired antioxidant systems results in uncontrolled production of ROS. In a pro-oxidant environment, vascular smooth muscle cells (VSMC undergo phenotypic changes which can lead to the development of vascular dysfunction such as vascular inflammation and calcification. Investigations are ongoing to elucidate the mechanisms for cardiovascular disorders induced by oxidative stress. This review mainly focuses on the role of H2O2 in regulating physiological and pathological signals in VSMC.

  9. Association of oxidative stress with the pathophysiology of depresion and bipolar disorder

    Directory of Open Access Journals (Sweden)

    Lačković Maja

    2013-01-01

    Full Text Available The production of free radicals in an organism is under the control of various antioxidant mechanisms. If their production overcomes the capacity of antioxidant protection, oxidative stress occurs which is capable of damaging different cellular structures and biomolecules, leading to various diseases. The importance of oxidative stress was proven in many psychiatric diseases among which are depression and bipolar disorder. Different studies show the significant improvement of clinical presentation when antioxidant substances are administered, suggesting that redox imbalance can influence their symptoms appearance and severity. In addition, oxidative stress is intercrossed with the different comorbidities that appear among depressive and bipolar patients. Beside the clinical presentation, oxidative stress influences the chronicity of depression, which was demonstrated in patients with recurrent depressive disorder. Better understanding of oxidant/antioxidant imbalance and its role in the pathophysiology of depression and bipolar disorder could be useful for the development of a novel therapeutic approach to the management of these diseases.

  10. Transcriptomic and hormone analyses reveal mechanisms underlying petal elongation in Chrysanthemum morifolium 'Jinba'.

    Science.gov (United States)

    Wang, Jingjing; Wang, Haibin; Ding, Lian; Song, Aiping; Shen, Feng; Jiang, Jiafu; Chen, Sumei; Chen, Fadi

    2017-04-01

    Auxin regulates chrysanthemum petal elongation by promoting cell elongation. Transcriptomic analysis shows that auxin signal transduction may connect with other transcription factors by TCPs to regulate chrysanthemum petal elongation. As an ornamental species, Chrysanthemum morifolium has high ornamental and economic value. Petal size is the primary factor that influences the ornamental value of chrysanthemum, but the mechanism underlying the development of C. morifolium petals remains unclear. In our study, we tracked the growth of petals and found that the basal region of 'Jinba' petals showed a higher elongation rate, exhibiting rapid cell elongation during petal growth. During petal elongation growth, auxin was demonstrated to promote cell elongation and an increase in cell numbers in the petal basal region. To further study the molecular mechanisms underlying petal growth, the RNA-seq (high-throughput cDNA sequencing) technique was employed. Four cDNA libraries were assembled from petals in the budding, bud breaking, early blooming and full blooming stages of 'Jinba' flower development. Analysis of differentially expressed genes (DEGs) showed that auxin was the most important regulator in controlling petal growth. The TEOSINTEBRANCHED 1, CYCLOIDEA and PCF transcription factor genes (TCPs), basic helix-loop-helix-encoding gene (bHLH), glutaredoxin-C (GRXC) and other zinc finger protein genes exhibited obvious up-regulation and might have significant effects on the growth of 'Jinba' petals. Given the interaction between these genes in Arabidopsis thaliana, we speculated that auxin signal transduction might exhibit a close relationship with transcription factors through TCPs. In summary, we present the first comprehensive transcriptomic and hormone analyses of C. morifolium petals. The results offer direction in identifying the mechanism underlying the development of chrysanthemum petals in the elongated phase and have great significance in improving the

  11. Mechanical properties of the human spinal cord under the compressive loading.

    Science.gov (United States)

    Karimi, Alireza; Shojaei, Ahmad; Tehrani, Pedram

    2017-12-01

    The spinal cord as the most complex and critical part of the human body is responsible for the transmission of both motor and sensory impulses between the body and the brain. Due to its pivotal role any types of physical injury in that disrupts its function following by shortfalls, including the minor motor and sensory malfunctions as well as complicate quadriplegia and lifelong ventilator dependency. In order to shed light on the injuries to the spinal cord, the application of the computational models to simulate the trauma impact loading to that are deemed required. Nonetheless, it has not been fulfilled since there is a paucity of knowledge about the mechanical properties of the spinal cord, especially the cervical one, under the compressive loading on the grounds of the difficulty in obtaining this tissue from the human body. This study was aimed at experimentally measuring the mechanical properties of the human cervical spinal cord of 24 isolated fresh samples under the unconfined compressive loading at a relatively low strain rate. The stress-strain data revealed the elastic modulus and maximum/failure stress of 40.12±6.90 and 62.26±5.02kPa, respectively. Owing to the nonlinear response of the spinal cord, the Yeoh, Ogden, and Mooney-Rivlin hyperelastic material models have also been employed. The results may have implications not only for understanding the linear elastic and nonlinear hyperelastic mechanical properties of the cervical spinal cord under the compressive loading, but also for providing a raw data for investigating the injury as a result of the trauma thru the numerical simulations. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Modeling of the mechanical behavior of austenitic stainless steels under pure fatigue and fatigue relaxation loadings

    International Nuclear Information System (INIS)

    Hajjaji-Rachdi, Fatima

    2015-01-01

    Austenitic stainless steels are potential candidates for structural components of sodium-cooled fast neutron reactors. Many of these components will be subjected to cyclic loadings including long hold times (1 month) under creep or relaxation at high temperature. These hold times are unattainable experimentally. The aim of the present study is to propose mechanical models which take into account the involved mechanisms and their interactions during such complex loadings. First, an experimental study of the pure fatigue and fatigue-relaxation behavior of 316L(N) at 500 C has been carried out with very long hold times (10 h and 50 h) compared with the ones studied in literature. Tensile tests at 600 C with different applied strain rates have been undertaken in order to study the dynamic strain ageing phenomenon. Before focusing on more complex loadings, the mean field homogenization approach has been used to predict the mechanical behavior of different FCC metals and alloys under low cycle fatigue at room temperature. Both Hill-Hutchinson and Kroener models have been used. Next, a physically-based model based on dislocation densities has been developed and its parameters measured. The model allows predictions in a qualitative agreement with experimental data for tensile loadings. Finally, this model has been enriched to take into account visco-plasticity, dislocation climb and interaction between dislocations and solute atoms, which are influent during creep-fatigue or fatigue relaxation at high temperature. The proposed model uses three adjustable parameters only and allows rather accurate prediction of the behavior of 316L(N) steel under tensile loading and relaxation. (author) [fr

  13. Evaluation of Possible Proximate Mechanisms Underlying the Kinship Theory of Intragenomic Conflict in Social Insects.

    Science.gov (United States)

    Galbraith, David A; Yi, Soojin V; Grozinger, Christina M

    2016-12-01

    Kinship theory provides a universal framework in which to understand the evolution of altruism, but there are many molecular and genetic mechanisms that can generate altruistic behaviors. Interestingly, kinship theory specifically predicts intragenomic conflict between maternally-derived alleles (matrigenes) and paternally-derived alleles (patrigenes) over the generation of altruistic behavior in cases where the interests of the matrigenes and patrigenes are not aligned. Under these conditions, individual differences in selfish versus altruistic behavior are predicted to arise from differential expression of the matrigenes and patrigenes (parent-specific gene expression or PSGE) that regulate selfish versus altruistic behaviors. As one of the leading theories to describe PSGE and genomic imprinting, kinship theory has been used to generate predictions to describe the reproductive division of labor in social insect colonies, which represents an excellent model system to test the hypotheses of kinship theory and examine the underlying mechanisms driving it. Recent studies have confirmed the predicted differences in the influence of matrigenes and patrigenes on reproductive division of labor in social insects, and demonstrated that these differences are associated with differences in PSGE of key genes involved in regulating reproductive physiology, providing further support for kinship theory. However, the mechanisms mediating PSGE in social insects, and how PSGE leads to differences in selfish versus altruistic behavior, remain to be determined. Here, we review the available supporting evidence for three possible epigenetic mechanisms (DNA methylation, piRNAs, and histone modification) that may generate PSGE in social insects, and discuss how these may lead to variation in social behavior. © The Author 2016. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email

  14. Experimental study of the anisotropic properties of argillite under moisture and mechanical loads

    International Nuclear Information System (INIS)

    Yang, D.S.; Chanchole, S.; Wang, L.L.; Bornert, M.; Gatmiri, B.

    2012-01-01

    Document available in extended abstract form only. Due to various factors, such as sedimentation, layered morphology of clay mineral, in-situ stress, etc., the behavior of argillite rocks is often anisotropic. In order to study the anisotropy of the Callovo-Oxfordian (COx) argillite considered as a possible host rock for high-level radioactive nuclear waste repository in France, a series of tests including uniaxial compression and dehydration and hydration at different constant applied stress levels, are carried out using a specific setup combining mechanical and moisture loading devices. During these hydro-mechanical tests, this specific setup can also continuously capture images of the sample surfaces to be subsequently analyzed using Digital Image Correlation techniques (DIC) in order to determine full-field strains. In this study, three sampling directions are used with the angle θ between the bedding plane and the cylindrical sample axis equal to 45 deg., 60 deg. and 90 deg.. To investigate the mechanical anisotropy, uniaxial compressive tests with mechanical loading and unloading cycles are performed on several different samples at the same moisture level. The results show that the mechanical parameters (apparent modulus, failure stress) depend on loading orientation relative to the stratification plane. For a given water content, the failure stress reaches maximum values for θ =90 deg. and minimum values for θ =45 deg.. To study the hydric anisotropy, dehydration and hydration tests under stress-free conditions are performed on two cylindrical samples (θ=90 deg. and θ=60 deg.). Three cycles of hydration and dehydration are carried out by varying the relative humidity between 40% and 95%. The sample weight, the deformation measured by strain gages and the relative humidity are continuously recorded during the test by means of another specific setup described in [Pham et al., 2007]. Fig.1a illustrates the evolution of the strains of the sample EST28030-No

  15. The underlying mechanisms for development of hypertension in the metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Yoshida Hiroshi

    2008-04-01

    Full Text Available Abstract High blood pressure is an important constituent of the metabolic syndrome. However, the underlying mechanisms for development of hypertension in the metabolic syndrome are very complicated and remain still obscure. Visceral/central obesity, insulin resistance, sympathetic overactivity, oxidative stress, endothelial dysfunction, activated renin-angiotensin system, increased inflammatory mediators, and obstructive sleep apnea have been suggested to be possible factors to develop hypertension in the metabolic syndrome. Here, we will discuss how these factors influence on development of hypertension in the metabolic syndrome.

  16. Experimental Evaluation of Mechanical Properties of Friction Welded Dissimilar Steels under Varying Axial Pressures

    Directory of Open Access Journals (Sweden)

    Handa Amit

    2016-07-01

    Full Text Available The present study emphasizes on joints two industrially important materials AISI 304 with AISI 1021steels, produced by friction welding have been investigated. Samples were welded under different axial pressures ranging from 75MPa to 135MPa, at constant speed of 920rpm. The tensile strength, torsional strength, impact strength and micro hardness values of the weldments were determined and evaluated. Simultaneously the fractrography of the tensile tested specimens were carried out, so as to understand the failure analysis. It was observed that improved mechanical properties were noticed at higher axial pressures. Ductile failures of weldments were also observed at 120MPa and 135MPa axial pressures during fractography analysis.

  17. Mechanical behavior of irradiated fuel-pin cladding evaluated under transient heating and pressure conditions

    International Nuclear Information System (INIS)

    Hamilton, M.L.; Johnson, G.D.; Hunter, C.W.; Duncan, D.R.

    1982-11-01

    Fast breeder fuel-pin cladding has been tested under experimental conditions simulating the temperature and pressure history characteristic of anticipated transient events. Irradiation induces severe reductions in both strength and ductility. Ductility losses are independent of the rate of temperature increase and saturate by a fluence of approx. 2 x 10 22 n/cm 2 (E > 0.1 MeV). Losses in strength are dependent on the rate of temperature increase but saturate at a fluence of approx.5 x 10 22 n/cm 2 . Evidence is presented to show that fission products are probably responsible for the degradation in mechanical properties

  18. Fracture mechanics characterization of crack growth under creep and fatigue conditions

    International Nuclear Information System (INIS)

    Hollstein, T.; Kienzler, R.

    1987-01-01

    Based on theoretical considerations and experimental evidence, several concepts have been investigated to correlate crack growth under high-temperature conditions with material parameters of fracture mechanics, e.g., stress-intensity factor K, and line integrals J and C * . It could be shown for different materials that these parameters describe the behavior of cracks independent of geometry and loading conditions within certain limits of validity. The laboratory results then can be transferred to real structures for (residual) lifetime predictions or safety analyses (Incoloy 800H, Thermon 4972, 9% chromium steel). With 45 refs., 3 tabs., 56 figs [de

  19. Morphological features and mechanics of destruction of materials with different structures under impact drop cyclic loading

    Directory of Open Access Journals (Sweden)

    Varavka Valery N.

    2017-01-01

    Full Text Available The process of erosion destruction of steels with austenitic, sorbitol and martensitic structure under the influence of high-speed liquid-drop collisions is studied. The characteristics of the morphological features and mechanisms of the process of surface degradation of steels with different structures are given. Their classification criterion is proposed on the basis of the diagrams of limiting states. Based on the theory of Paris-Erdogan, the computational and analytical model of the fatigue fracture of martensitic steel has been developed.

  20. Radiation pneumonitis and fibrosis: mechanisms underlying its pathogenesis and implications for future research.

    Science.gov (United States)

    Tsoutsou, Pelagia G; Koukourakis, Michael I

    2006-12-01

    Radiation pneumonitis and subsequent radiation pulmonary fibrosis are the two main dose-limiting factors when irradiating the thorax that can have severe implications for patients' quality of life. In this article, the current concepts about the pathogenetic mechanisms underlying radiation pneumonitis and fibrosis are presented. The clinical course of fibrosis, a postulated acute inflammatory stage, and a late fibrotic and irreversible stage are discussed. The interplay of cells and the wide variety of molecules orchestrating the immunologic response to radiation, their interactions with specific receptors, and the cascade of events they trigger are elucidated. Finally, the implications of this knowledge with respect to the therapeutic interventions are critically presented.

  1. Acoustic and Vibration Control for an Underwater Structure under Mechanical Excitation

    Directory of Open Access Journals (Sweden)

    Shi-Jian Zhu

    2014-01-01

    Full Text Available Acoustic and vibration control for an underwater structure under mechanical excitation has been investigated by using negative feedback control algorithm. The underwater structure is modeled with cylindrical shells, conical shells, and circular bulkheads, of which the motion equations are built with the variational approach, respectively. Acoustic property is analyzed by the Helmholtz integration formulation with boundary element method. Based on negative feedback control algorithm, a control loop with a coupling use of piezoelectric sensor and actuator is built, and accordingly some numerical examples are carried out on active control of structural vibration and acoustic response. Effects of geometrical and material parameters on acoustic and vibration properties are investigated and discussed.

  2. An Investigation of the Mechanism Underlying Teacher Aggression: Testing I[superscript 3] Theory and the General Aggression Model

    Science.gov (United States)

    Montuoro, Paul; Mainhard, Tim

    2017-01-01

    Background: Considerable research has investigated the deleterious effects of teachers responding aggressively to students who misbehave, but the mechanism underlying this dysfunctional behaviour remains unknown. Aims: This study investigated whether the mechanism underlying teacher aggression follows I[superscript 3] theory or General Aggression…

  3. Optimal Contract Design for Cooperative Relay Incentive Mechanism under Moral Hazard

    Directory of Open Access Journals (Sweden)

    Nan Zhao

    2015-01-01

    Full Text Available Cooperative relay can effectively improve spectrum efficiency by exploiting the spatial diversity in the wireless networks. However, wireless nodes may acquire different network information with various users’ location and mobility, channels’ conditions, and other factors, which results in asymmetric information between the source and the relay nodes (RNs. In this paper, the relay incentive mechanism between relay nodes and the source is investigated under the asymmetric information. By modelling multiuser cooperative relay as a labour market, a contract model with moral hazard for relay incentive is proposed. To effectively incentivize the potential RNs to participate in cooperative relay, the optimization problems are formulated to maximize the source’s utility while meeting the feasible conditions under both symmetric and asymmetric information scenarios. Numerical simulation results demonstrate the effectiveness of the proposed contract design scheme for cooperative relay.

  4. Computational modeling of dynamic mechanical properties of pure polycrystalline magnesium under high loading strain rates

    Directory of Open Access Journals (Sweden)

    Li Qizhen

    2015-01-01

    Full Text Available Computational simulations were performed to investigate the dynamic mechanical behavior of pure polycrystalline magnesium under different high loading strain rates with the values of 800, 1000, 2000, and 3600 s−1. The Johnson-Cook model was utilized in the simulations based on finite element modeling. The results showed that the simulations provided well-matched predictions of the material behavior such as the strain rate-time history, the stress-strain curve, and the temperature increase. Under high loading strain rates, the tested material experienced linear strain hardening at the early stage of plastic deformation, increased strain hardening at the intermediate plastic deformation region, and decreased strain hardening at the region before fracture. The strain hardening rates for the studied high loading strain rate cases do not vary much with the change of strain rates.

  5. Experimental Investigation of Mechanical Properties of PVC Polymer under Different Heating and Cooling Conditions

    Directory of Open Access Journals (Sweden)

    Sarkawt Rostam

    2016-01-01

    Full Text Available Due to a widely increasing usage of polymers in various industrial applications, there should be a continuous need in doing research investigations for better understanding of their properties. These applications require the usage of the polymer in different working environments subjecting the material to various temperature ranges. In this paper, an experimental investigation of mechanical properties of polyvinyl chloride (PVC polymer under heating and cooling conditions is presented. For this purpose standard samples are prepared and tested in laboratory using universal material testing apparatus. The samples are tested under different conditions including the room temperature environment, cooling in a refrigerator, and heating at different heating temperatures. It is observed that the strength of the tested samples decreases with the increasing of heating temperature and accordingly the material becomes softer. Meanwhile the cooling environments give a clear increasing to the strength of the material.

  6. Macrocrack propagation in concrete specimens under sustained loading: Study of the physical mechanisms

    International Nuclear Information System (INIS)

    Rossi, Pierre; Boulay, Claude; Tailhan, Jean-Louis; Martin, Eric; Desnoyers, Dominic

    2014-01-01

    This study presents a series of 4-point bending tests performed to describe the delayed behavior of unreinforced pre-cracked beams under low, moderate and high sustained loading levels. The deflection creep rate, the failure time and the load level were assessed. A linear relation, in a semi-log scale, was found for the deflection creep rate at high load levels. In addition, a linear relation, in a log–log scale, between the secondary deflection creep rate and failure time was observed. Besides, it was shown that the secondary creep deflection rate increases with the sustained loading level and the macrocrack propagation rate when macrocrack propagation occurs during the sustained loading. Physical mechanisms are proposed to explain these results and may be summarized as follows: the delayed behavior of an unreinforced cracked concrete specimen under sustained loading is mainly due to the cracking evolution, thus the creation of microcracks and/or the propagation of a macrocrack

  7. A novel approach to mechanical foot stimulation during human locomotion under body weight support.

    Science.gov (United States)

    Gravano, S; Ivanenko, Y P; Maccioni, G; Macellari, V; Poppele, R E; Lacquaniti, F

    2011-04-01

    Input from the foot plays an essential part in perceiving support surfaces and determining kinematic events in human walking. To simulate adequate tactile pressure inputs under body weight support (BWS) conditions that represent an effective form of locomotion training, we here developed a new method of phasic mechanical foot stimulation using light-weight pneumatic insoles placed inside the shoes (under the heel and metatarsus). To test the system, we asked healthy participants to walk on a treadmill with different levels of BWS. The pressure under the stimulated areas of the feet and subjective sensations were higher at high levels of BWS and when applied to the ball and toes rather than heels. Foot stimulation did not disturb significantly the normal motor pattern, and in all participants we evoked a reliable step-synchronized triggering of stimuli for each leg separately. This approach has been performed in a general framework looking for "afferent templates" of human locomotion that could be used for functional sensory stimulation. The proposed technique can be used to imitate or partially restore surrogate contact forces under body weight support conditions. Copyright © 2010 Elsevier B.V. All rights reserved.

  8. Phosphoproteomics-based modeling defines the regulatory mechanism underlying aberrant EGFR signaling.

    Directory of Open Access Journals (Sweden)

    Shinya Tasaki

    Full Text Available BACKGROUND: Mutation of the epidermal growth factor receptor (EGFR results in a discordant cell signaling, leading to the development of various diseases. However, the mechanism underlying the alteration of downstream signaling due to such mutation has not yet been completely understood at the system level. Here, we report a phosphoproteomics-based methodology for characterizing the regulatory mechanism underlying aberrant EGFR signaling using computational network modeling. METHODOLOGY/PRINCIPAL FINDINGS: Our phosphoproteomic analysis of the mutation at tyrosine 992 (Y992, one of the multifunctional docking sites of EGFR, revealed network-wide effects of the mutation on EGF signaling in a time-resolved manner. Computational modeling based on the temporal activation profiles enabled us to not only rediscover already-known protein interactions with Y992 and internalization property of mutated EGFR but also further gain model-driven insights into the effect of cellular content and the regulation of EGFR degradation. Our kinetic model also suggested critical reactions facilitating the reconstruction of the diverse effects of the mutation on phosphoproteome dynamics. CONCLUSIONS/SIGNIFICANCE: Our integrative approach provided a mechanistic description of the disorders of mutated EGFR signaling networks, which could facilitate the development of a systematic strategy toward controlling disease-related cell signaling.

  9. Investigation of deterioration mechanism of electrical ceramic insulating materials under high temperature

    International Nuclear Information System (INIS)

    Mizutani, Yoshinobu; Ito, Tetsuo; Okamoto, Tatsuki; Kumazawa, Ryoji; Aizawa, Rie; Moriyama, Hideshige

    2000-01-01

    It is thought that ceramic insulator can be applied to electric power equipments that are under high temperature not to be able use organic materials. Our research has suggested components of mica-alumina combined insulation. As the results of and carried out temperature accelerating test, combined insulation life is expected long term over 40 years at over 500-Celsius degrees. However to construct high reliable insulating system, it is clarified deterioration mechanism on combined insulation and evaluates life of that. Therefore we carried out metal behavior test and voltage aging test using mica-sheet and alumina-cloth that are components of combined insulation under high temperature in nitrogen gas atmosphere. It is cleared two metal behavior mechanisms: One is that the opening of insulator are filled up with copper that is oxidized, the other is the metal diffuses in alumina-cloth through surface. And distance of metal behavior is able to be estimated at modulate temperature and in modulate time. It is also cleared that alumina-cloth is deteriorated by metal behavior into alumina-cloth. These results indicate that combined insulation is deteriorated from electrode side by metal behavior and is finally broken down through alumina-cloth. (author)

  10. Mechanical Behavior of Red Sandstone under Incremental Uniaxial Cyclical Compressive and Tensile Loading

    Directory of Open Access Journals (Sweden)

    Baoyun Zhao

    2017-01-01

    Full Text Available Uniaxial experiments were carried out on red sandstone specimens to investigate their short-term and creep mechanical behavior under incremental cyclic compressive and tensile loading. First, based on the results of short-term uniaxial incremental cyclic compressive and tensile loading experiments, deformation characteristics and energy dissipation were analyzed. The results show that the stress-strain curve of red sandstone has an obvious memory effect in the compressive and tensile loading stages. The strains at peak stresses and residual strains increase with the cycle number. Energy dissipation, defined as the area of the hysteresis loop in the stress-strain curves, increases nearly in a power function with the cycle number. Creep test of the red sandstone was also conducted. Results show that the creep curve under each compressive or tensile stress level can be divided into decay and steady stages, which cannot be described by the conventional Burgers model. Therefore, an improved Burgers creep model of rock material is constructed through viscoplastic mechanics, which agrees very well with the experimental results and can describe the creep behavior of red sandstone better than the Burgers creep model.

  11. Leakage current transport mechanism under reverse bias in Au/Ni/GaN Schottky barrier diode

    Science.gov (United States)

    Peta, Koteswara Rao; Kim, Moon Deock

    2018-01-01

    The leakage current transport mechanism under reverse bias of Au/Ni/GaN Schottky diode is studied using temperature dependent current-voltage (I-V-T) and capacitance-voltage (C-V) characteristics. I-V measurement in this study is in the range of 140 K-420 K in steps of 10 K. A reduction in voltage dependent barrier height and a strong internal electric field in depletion region under reverse bias suggested electric field enhanced thermionic emission in carrier transport via defect states in Au/Ni/GaN SBD. A detailed analysis of reverse leakage current revealed two different predominant transport mechanisms namely variable-range hopping (VRH) and Poole-Frenkel (PF) emission conduction at low (260 K) temperatures respectively. The estimated thermal activation energies (0.20-0.39 eV) from Arrhenius plot indicates a trap assisted tunneling of thermally activated electrons from a deep trap state into a continuum of states associated with each conductive threading dislocation.

  12. Mechanisms Underlying the Risk to Develop Drug Addiction, Insights From Studies in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Julia Ryvkin

    2018-04-01

    Full Text Available The ability to adapt to environmental changes is an essential feature of biological systems, achieved in animals by a coordinated crosstalk between neuronal and hormonal programs that allow rapid and integrated organismal responses. Reward systems play a key role in mediating this adaptation by reinforcing behaviors that enhance immediate survival, such as eating or drinking, or those that ensure long-term survival, such as sexual behavior or caring for offspring. Drugs of abuse co-opt neuronal and molecular pathways that mediate natural rewards, which under certain circumstances can lead to addiction. Many factors can contribute to the transition from drug use to drug addiction, highlighting the need to discover mechanisms underlying the progression from initial drug use to drug addiction. Since similar responses to natural and drug rewards are present in very different animals, it is likely that the central systems that process reward stimuli originated early in evolution, and that common ancient biological principles and genes are involved in these processes. Thus, the neurobiology of natural and drug rewards can be studied using simpler model organisms that have their systems stripped of some of the immense complexity that exists in mammalian brains. In this paper we review studies in Drosophila melanogaster that model different aspects of natural and drug rewards, with an emphasis on how motivational states shape the value of the rewarding experience, as an entry point to understanding the mechanisms that contribute to the vulnerability of drug addiction.

  13. Molecular mechanisms underlying cardiac antihypertrophic and antifibrotic effects of natriuretic peptides.

    Science.gov (United States)

    Calvieri, Camilla; Rubattu, Speranza; Volpe, Massimo

    2012-01-01

    Natriuretic peptides (NPs) exert well-characterized protective effects on the cardiovascular system, such as vasorelaxation, natri- and diuresis, increase of endothelial permeability, and inhibition of renin-angiotensin-aldosterone system. It has been reported that they also possess antihypertrophic and antifibrotic properties and contribute actively to cardiac remodeling. As a consequence, they are involved in several aspects of cardiovascular diseases. Antihypertrophic and antifibrotic actions of NPs appear to be mediated by specific signaling pathways within a more complex cellular network. Elucidation of the molecular mechanisms underlying the effects of NPs on cardiac remodeling represents an important research objective in order to gain more insights on the complex network leading to cardiac hypertrophy, ventricular dysfunction, and transition to heart failure, and in the attempt to develop novel therapeutic agents. The aim of the present article is to review well-characterized molecular mechanisms underlying the antihypertrophic and antifibrotic effects of NPs in the heart that appear to be mainly mediated by guanylyl cyclase type A receptor. In particular, we discuss the calcineurin/NFAT, the sodium exchanger NHE-1, and the TGFβ1/Smad signaling pathways. The role of guanylyl cyclase type B receptor, along with the emerging functional significance of natriuretic peptide receptor type C as mediators of CNP antihypertrophic and antifibrotic actions in the heart are also considered.

  14. Mechanisms of action underlying the anti-inflammatory and immunomodulatory effects of propolis: a brief review

    Directory of Open Access Journals (Sweden)

    Marcio A. R. Araujo

    2012-02-01

    Full Text Available Many biological properties have been attributed to various types of propolis, including anti-inflammatory, antimicrobial, antioxidant, antitumor, wound healing, and immunomodulatory activities. This article reviewed studies published that investigated the anti-inflammatory activity of propolis of different origins and/or its isolated components, focusing on the mechanisms of action underlying this activity and also addressing some aspects of immunomodulatory effects. The search was performed of the following databases: PubMed, Science Direct, HighWire Press, Scielo, Google Academics, Research Gate and ISI Web of Knowledgement. The anti-inflammatory activity was associated with propolis or compounds such as polyphenols (flavonoids, phenolic acids and their esters, terpenoids, steroids and amino acids. CAPE is the most studied compounds. The main mechanisms underlying the anti-inflammatory activity of propolis included the inhibition of cyclooxygenase and consequent inhibition of prostaglandin biosynthesis, free radical scavenging, inhibition of nitric oxide synthesis, reduction in the concentration of inflammatory cytokines and immunosuppressive activity. Propolis was found to exert an anti-inflammatory activity in vivo and in vitro models of acute and chronic inflammation and others studies, indicating its promising potential as anti-inflammatory agent of natural origin and as a source of chemical compounds for the development of new drugs.

  15. Mechanical modeling of creep, swelling and damage under irradiation for polycrystalline metals

    International Nuclear Information System (INIS)

    Murakami, S.; Mizuno, M.; Okamoto, T.

    1991-01-01

    A constitutive equation of creep, swelling and damage under irradiation for polycrystalline metals applicable to structural analyses in multiaxial state of stress is developed. After reviewing microscopic mechanisms of irradiation creep and swelling, the relevant theories proposed so far from the view point of metallurgical physics and their applicability are discussed first. Then a constitutive model is developed by assuming that creep under irradiation can be decomposed into irradiation-affected thermal creep and irradiation-induced creep. By taking account of the Stress-Induced Preferential Absorption (SIPA) mechanism, the irradiation-induced creep is represented by an isotropic tensor function of order one and zero with respect to stress, which is, at the same time, the function of neutron flux and neutron fluence. The volumetric part of the irradiation-induced creep is identified with swelling. The irradiation-affected thermal creep is described by modifying Kachanov-Rabotnov theory for stress-controlled creep and creep damage by incorporating the effect of irradiation. Finally irradiation creep and swelling of 20% cold-worked type 316 stainless steel at elevated temperature are predicted by the proposed constitutive equations, and the numerical results are compared with the corresponding experimental results. (orig.)

  16. Mechanical damage in a lithium-ion pouch cell under indentation loads

    Science.gov (United States)

    Luo, Hailing; Xia, Yong; Zhou, Qing

    2017-07-01

    The short circuit of lithium-ion batteries induced by mechanical abuse is a great concern in electric vehicle design. It remains a challenge to fully understand the nature of the mechanical damage process with the aim of improving battery crash safety. The present paper investigates the evolution of the damage process for a lithium-ion pouch cell under indentation by loading the cell to various force levels. A significant inflection point on the force-indentation curve is observed before the force peak. Post-mortem examinations indicate that the characteristic change in the local slope of the curve is related to the change occurring at the local interfaces, including three phenomena - formation of tight adhesion on the anode-separator interfaces, delamination in the separators and decoating of graphite particles from the anodes. Analysis of the fracture sequence at the onset of short circuit clearly shows that the number of short-circuited electrode pairs is equal to the number of anode layers adhered with delaminated separator material before fracture occurs. The experimental study in the present paper implies that the inflection point on the force-indentation curve may be an indicator of damage initiation inside pouch cells under indentation.

  17. Mechanisms of action underlying the anti-inflammatory and immunomodulatory effects of propolis: a brief review

    Directory of Open Access Journals (Sweden)

    Marcio A. R. Araujo

    2011-09-01

    Full Text Available Many biological properties have been attributed to various types of propolis, including anti-inflammatory, antimicrobial, antioxidant, antitumor, wound healing, and immunomodulatory activities. This article reviewed studies published that investigated the anti-inflammatory activity of propolis of different origins and/or its isolated components, focusing on the mechanisms of action underlying this activity and also addressing some aspects of immunomodulatory effects. The search was performed of the following databases: PubMed, Science Direct, HighWire Press, Scielo, Google Academics, Research Gate and ISI Web of Knowledgement. The anti-inflammatory activity was associated with propolis or compounds such as polyphenols (flavonoids, phenolic acids and their esters, terpenoids, steroids and amino acids. CAPE is the most studied compounds. The main mechanisms underlying the anti-inflammatory activity of propolis included the inhibition of cyclooxygenase and consequent inhibition of prostaglandin biosynthesis, free radical scavenging, inhibition of nitric oxide synthesis, reduction in the concentration of inflammatory cytokines and immunosuppressive activity. Propolis was found to exert an anti-inflammatory activity in vivo and in vitro models of acute and chronic inflammation and others studies, indicating its promising potential as anti-inflammatory agent of natural origin and as a source of chemical compounds for the development of new drugs.

  18. Heavy metal poisoning: clinical presentations and pathophysiology.

    Science.gov (United States)

    Ibrahim, Danyal; Froberg, Blake; Wolf, Andrea; Rusyniak, Daniel E

    2006-03-01

    Humans have had a long and tumultuous relationship with heavy metals. Their ubiquitous nature and our reliance on them for manufacturing have resulted at times in exposures sufficient to cause systemic toxicity. Their easy acquisition and potent toxicity have also made them popular choices for criminal poisonings. This article examines the clinical manifestation and pathophysiology of poisoning from lead, mercury, arsenic, and thallium.

  19. Pathophysiology of Increased Fetal Nuchal Translucency Thickness

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2010-06-01

    Full Text Available Increased fetal nuchal translucency thickness is associated with trisomy 13, trisomy 18, trisomy 21, Turner syndrome, other sex chromosome abnormalities, as well as many fetal anomalies and genetic syndromes. This article provides a comprehensive review of the cardinal proposed pathophysiology including altered composition of the extracellular matrix, abnormalities of the heart and great arteries, and disturbed or delayed lymphatic development.

  20. Pathophysiology of diurnal drooling in Parkinson's disease

    NARCIS (Netherlands)

    Kalf, J.G.; Munneke, M.; Engel-Hoek, L. van den; Swart, B.J.M. de; Borm, G.F.; Bloem, B.R.; Zwarts, M.J.

    2011-01-01

    Drooling is an incapacitating feature of Parkinson's disease. Better pathophysiological insights are needed to improve treatment. In this study, we tested the hypothesis that the cause of drooling is multifactorial. We examined 15 patients with Parkinson's disease with distinct diurnal saliva loss

  1. Pathophysiology, Functional Implications and Management of ...

    African Journals Online (AJOL)

    The management of spasticity in stroke requires a multidisciplinary approach but more importantly, an understanding of the pathophysiology of its consequences. This paper reviews different definitions from neurophysiology and medical literature which try to place spasticity in stroke in its proper context and describes the ...

  2. Hemodynamic instability in the critically ill neonate: An approach to cardiovascular support based on disease pathophysiology.

    Science.gov (United States)

    Giesinger, Regan E; McNamara, Patrick J

    2016-04-01

    Hemodynamic disturbance in the sick neonate is common, highly diverse in underlying pathophysiology and dynamic. Dysregulated systemic and cerebral blood flow is hypothesized to have a negative impact on neurodevelopmental outcome and survival. An understanding of the physiology of the normal neonate, disease pathophysiology, and the properties of vasoactive medications may improve the quality of care and lead to an improvement in survival free from disability. In this review we present a modern approach to cardiovascular therapy in the sick neonate based on a more thoughtful approach to clinical assessment and actual pathophysiology. Targeted neonatal echocardiography offers a more detailed insight into disease processes and offers longitudinal assessment, particularly response to therapeutic intervention. The pathophysiology of common neonatal conditions and the properties of cardiovascular agents are described. In addition, we outline separate treatment algorithms for various hemodynamic disturbances that are tailored to clinical features, disease characteristics and echocardiographic findings. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  3. Neural mechanisms underlying transcranial direct current stimulation in aphasia: A feasibility study.

    Directory of Open Access Journals (Sweden)

    Lena eUlm

    2015-10-01

    Full Text Available Little is known about the neural mechanisms by which transcranial direct current stimulation (tDCS impacts on language processing in post-stroke aphasia. This was addressed in a proof-of-principle study that explored the effects of tDCS application in aphasia during simultaneous functional magnetic resonance imaging (fMRI. We employed a single subject, cross-over, sham-tDCS controlled design and the stimulation was administered to an individualized perilesional stimulation site that was identified by a baseline fMRI scan and a picture naming task. Peak activity during the baseline scan was located in the spared left inferior frontal gyrus (IFG and this area was stimulated during a subsequent cross-over phase. tDCS was successfully administered to the target region and anodal- vs. sham-tDCS resulted in selectively increased activity at the stimulation site. Our results thus demonstrate that it is feasible to precisely target an individualized stimulation site in aphasia patients during simultaneous fMRI which allows assessing the neural mechanisms underlying tDCS application. The functional imaging results of this case report highlight one possible mechanism that may have contributed to beneficial behavioural stimulation effects in previous clinical tDCS trials in aphasia. In the future, this approach will allow identifying distinct patterns of stimulation effects on neural processing in larger cohorts of patients. This may ultimately yield information about the variability of tDCS-effects on brain functions in aphasia.

  4. Mechanical behavior and modelisation of Ti-6Al-4V titanium sheet under hot stamping conditions

    Science.gov (United States)

    Sirvin, Q.; Velay, V.; Bonnaire, R.; Penazzi, L.

    2017-10-01

    The Ti-6Al-4V titanium alloy is widely used for the manufacture of aeronautical and automotive parts (solid parts). In aeronautics, this alloy is employed for its excellent mechanical behavior associated with low density, outstanding corrosion resistance and good mechanical properties up to 600°C. It is especially used for the manufacture of fuselage frames, on the pylon for carrying out the primary structure (machining forged blocks) and the secondary structure in sheet form. In this last case, the sheet metal forming can be done through various methods: at room temperature by drawing operation, at very high temperature (≃900°C) by superplastic forming (SPF) and at intermediate temperature (≥750°C) by hot forming (HF). In order to reduce production costs and environmental troubles, the cycle times reduction associated with a decrease of temperature levels are relevant. This study focuses on the behavior modelling of Ti-6Al-4V alloy at temperatures above room temperature to obtained greater formability and below SPF condition to reduce tools workshop and energy costs. The displacement field measurement obtained by Digital Image Correlation (DIC) is based on innovative surface preparation pattern adapted to high temperature exposures. Different material parameters are identified to define a model able to predict the mechanical behavior of Ti-6Al-4V alloy under hot stamping conditions. The hardening plastic model identified is introduced in FEM to simulate an omega shape forming operation.

  5. Mitochondrial Ca2+ overload underlies Abeta oligomers neurotoxicity providing an unexpected mechanism of neuroprotection by NSAIDs.

    Directory of Open Access Journals (Sweden)

    Sara Sanz-Blasco

    Full Text Available Dysregulation of intracellular Ca(2+ homeostasis may underlie amyloid beta peptide (Abeta toxicity in Alzheimer's Disease (AD but the mechanism is unknown. In search for this mechanism we found that Abeta(1-42 oligomers, the assembly state correlating best with cognitive decline in AD, but not Abeta fibrils, induce a massive entry of Ca(2+ in neurons and promote mitochondrial Ca(2+ overload as shown by bioluminescence imaging of targeted aequorin in individual neurons. Abeta oligomers induce also mitochondrial permeability transition, cytochrome c release, apoptosis and cell death. Mitochondrial depolarization prevents mitochondrial Ca(2+ overload, cytochrome c release and cell death. In addition, we found that a series of non-steroidal anti-inflammatory drugs (NSAIDs including salicylate, sulindac sulfide, indomethacin, ibuprofen and R-flurbiprofen depolarize mitochondria and inhibit mitochondrial Ca(2+ overload, cytochrome c release and cell death induced by Abeta oligomers. Our results indicate that i mitochondrial Ca(2+ overload underlies the neurotoxicity induced by Abeta oligomers and ii inhibition of mitochondrial Ca(2+ overload provides a novel mechanism of neuroprotection by NSAIDs against Abeta oligomers and AD.

  6. Change of plans: an evaluation of the effectiveness and underlying mechanisms of successful talent transfer.

    Science.gov (United States)

    Collins, Rosie; Collins, Dave; MacNamara, Aine; Jones, Martin Ian

    2014-01-01

    Talent transfer (TT) is a recently formalised process used to identify and develop talented athletes by selecting individuals who have already succeeded in one sport and transferring them to another. Despite the increasing popularity of TT amongst national organisations and sport governing body professionals, however, there is little empirical evidence as to its efficacy or how it may be most efficiently employed. Accordingly, this investigation was designed to gain a deeper understanding of the effectiveness and underlying mechanisms of TT, achieved through a two-part study. Stage 1 provided a quantitative analysis of the incidence and distribution or, in this respect, epidemiology of TT, finding the most popular transfer to be sprinting to bobsleigh, with an average transfer age of 19 years. Stage 2 scrutinised the TT process and explored the specific cases revealed in stage 1 by examining the perceptions of four sport science support specialists who had worked in TT settings, finding several emergent themes which, they felt, could explain the TT processes. The most prominent theme was the psychosocial mechanism of TT, an aspect currently missing from TT initiatives, suggesting that current TT systems are poorly structured and should redress their approach to develop a more integrated scheme that encompasses all potential mechanisms of transfer.

  7. Herb pair Danggui-Honghua: mechanisms underlying blood stasis syndrome by system pharmacology approach

    Science.gov (United States)

    Yue, Shi-Jun; Xin, Lan-Ting; Fan, Ya-Chu; Li, Shu-Jiao; Tang, Yu-Ping; Duan, Jin-Ao; Guan, Hua-Shi; Wang, Chang-Yun

    2017-01-01

    Herb pair Danggui-Honghua has been frequently used for treatment of blood stasis syndrome (BSS) in China, one of the most common clinical pathological syndromes in traditional Chinese medicine (TCM). However, its therapeutic mechanism has not been clearly elucidated. In the present study, a feasible system pharmacology model based on chemical, pharmacokinetic and pharmacological data was developed via network construction approach to clarify the mechanisms of this herb pair. Thirty-one active ingredients of Danggui-Honghua possessing favorable pharmacokinetic profiles and biological activities were selected, interacting with 42 BSS-related targets to provide potential synergistic therapeutic actions. Systematic analysis of the constructed networks revealed that these targets such as HMOX1, NOS2, NOS3, HIF1A and PTGS2 were mainly involved in TNF signaling pathway, HIF-1 signaling pathway, estrogen signaling pathway and neurotrophin signaling pathway. The contribution index of every active ingredient also indicated six compounds, including hydroxysafflor yellow A, safflor yellow A, safflor yellow B, Z-ligustilide, ferulic acid, and Z-butylidenephthalide, as the principal components of this herb pair. These results successfully explained the polypharmcological mechanisms underlying the efficiency of Danggui-Honghua for BSS treatment, and also probed into the potential novel therapeutic strategies for BSS in TCM.

  8. Nuclear power for greenhouse gas mitigation under the Kyoto protocol: The Clean Development Mechanism (CDM)

    International Nuclear Information System (INIS)

    Rogner, H.-H.

    2000-01-01

    At the 43rd regular session of the IAEA General Conference, Member States requested the IAEA to help countries in assessing nuclear power's role in light of global environmental challenges and energy needs. Such assistance should include support for implementing national case studies, and facilitating access to relevant information about nuclear power's role in achieving sustainable development in developing countries and in mitigating GHG emissions. The dissemination of information on CDM is of particular importance to developing countries, so as to enable Member States interested in the mechanism to take an active and informed role in the debate regarding the Kyoto Protocol and eligible CDM technologies. Therefore, the Secretariat organized a series of information seminars, workshops and training courses for Member States on the Kyoto Protocol, the Clean Development Mechanism, Joint Implementation and Emissions Trading with particular emphasis on the potential role of nuclear power for GHG mitigation. On request, the Secretariat also provided training and assistance to several Member States in the preparation of national case studies that explore the potential role of nuclear power as a CDM technology. These case studies will be presented by the respective national study teams during this side event at the 44th IAEA General Conference. Within the general criteria included in the Kyoto Protocol, the decision on which technologies are eligible for GHG mitigation under the flexibility mechanisms is a sovereign decision of each country

  9. Revealing the Neural Mechanisms Underlying the Beneficial Effects of Tai Chi: A Neuroimaging Perspective.

    Science.gov (United States)

    Yu, Angus P; Tam, Bjorn T; Lai, Christopher W; Yu, Doris S; Woo, Jean; Chung, Ka-Fai; Hui, Stanley S; Liu, Justina Y; Wei, Gao X; Siu, Parco M

    2018-01-01

    Tai Chi Chuan (TCC), a traditional Chinese martial art, is well-documented to result in beneficial consequences in physical and mental health. TCC is regarded as a mind-body exercise that is comprised of physical exercise and meditation. Favorable effects of TCC on body balance, gait, bone mineral density, metabolic parameters, anxiety, depression, cognitive function, and sleep have been previously reported. However, the underlying mechanisms explaining the effects of TCC remain largely unclear. Recently, advances in neuroimaging technology have offered new investigative opportunities to reveal the effects of TCC on anatomical morphologies and neurological activities in different regions of the brain. These neuroimaging findings have provided new clues for revealing the mechanisms behind the observed effects of TCC. In this review paper, we discussed the possible effects of TCC-induced modulation of brain morphology, functional homogeneity and connectivity, regional activity and macro-scale network activity on health. Moreover, we identified possible links between the alterations in brain and beneficial effects of TCC, such as improved motor functions, pain perception, metabolic profile, cognitive functions, mental health and sleep quality. This paper aimed to stimulate further mechanistic neuroimaging studies in TCC and its effects on brain morphology, functional homogeneity and connectivity, regional activity and macro-scale network activity, which ultimately lead to a better understanding of the mechanisms responsible for the beneficial effects of TCC on human health.

  10. Fatigue degradation and failure of rotating composite structures - Materials characterisation and underlying mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Gamstedt, E.K.; Andersen, S.I.

    2001-03-01

    The present review concerns rotating composite structures, in which fatigue degradation is of key concern for in-service failure. Such applications are for instance rotor blades in wind turbines, helicopter rotor blades, flywheels for energy storage, marine and aeronautical propellers, and rolls for paper machines. The purpose is to identify areas where impending efforts should be made to make better use of composite materials in these applications. In order to obtain better design methodologies, which would allow more reliable and slender structures, improved test methods are necessary. Furthermore, the relation between structural, component and specimen test results should be better understood than what is presently the case. Improved predictive methods rely on a better understanding of the underlying damage mechanisms. With mechanism-based models, the component substructure or even the material microstructure could be optimised for best possible fatigue resistance. These issues are addressed in the present report, with special emphasis on test methods, and scaling from damage mechanisms to relevant material properties. (au)

  11. Stability of Newton black films under mechanical stretch--a molecular dynamics study.

    Science.gov (United States)

    Shen, Zhe; Sun, Huai; Liu, Xiaoyan; Liu, Wenting; Tang, Ming

    2013-09-10

    The stability of Newton black films (NBFs) under lateral mechanical stretch was investigated by nonequilibrium molecular dynamics (NEMD) simulations using force field parameters validated by accurate prediction of surface tensions. The applied strains accelerated film ruptures, enabling efficient measurements of the critical thicknesses of the films. Two representative surfactants, sodium dodecyl sulfate (SDS) for ionic surfactant and pentaethylene glycol monododecyl ether (C12EO5H) for nonionic surfactant, were investigated and compared. The predicted critical thickness of C12EO5H-coated film is smaller than that of the SDS-coated film, which is consistent with previously reported experimental observations. Our simulation results show that while the two surfactant-coated films exhibit similar dynamic properties attributed to the Marangoni-Gibbs effect, their surface structural characteristics are quite different. Consequently the two films demonstrate distinct rupture mechanisms in which rupture starts at uncovered water domains in the SDS-coated film, but at lateral surfactant/water interfaces in the C12EO5H-coated film. Our findings provide new insights into the stabilization mechanisms of NBFs and will facilitate the design and development of new films with improved properties.

  12. Insights into Pathophysiology from Medication-induced Tremor

    Directory of Open Access Journals (Sweden)

    John C. Morgan

    2017-10-01

    Full Text Available Background: Medication-induced tremor (MIT is common in clinical practice and there are many medications/drugs that can cause or exacerbate tremors. MIT typically occurs by enhancement of physiological tremor (EPT, but not all drugs cause tremor in this way. In this manuscript, we review how some common examples of MIT have informed us about the pathophysiology of tremor.Methods: We performed a PubMed literature search for published articles dealing with MIT and attempted to identify articles that especially dealt with the medication’s mechanism of inducing tremor.Results: There is a paucity of literature that deals with the mechanisms of MIT, with most manuscripts only describing the frequency and clinical settings where MIT is observed. That being said, MIT emanates from multiple mechanisms depending on the drug and it often takes an individualized approach to manage MIT in a given patient.Discussion: MIT has provided some insight into the mechanisms of tremors we see in clinical practice. The exact mechanism of MIT is unknown for most medications that cause tremor, but it is assumed that in most cases physiological tremor is influenced by these medications. Some medications (epinephrine that cause EPT likely lead to tremor by peripheral mechanisms in the muscle (β-adrenergic agonists, but others may influence the central component (amitriptyline. Other drugs can cause tremor, presumably by blockade of dopamine receptors in the basal ganglia (dopamine-blocking agents, by secondary effects such as causing hyperthyroidism (amiodarone, or by other mechanisms. We will attempt to discuss what is known and unknown about the pathophysiology of the most common MITs.

  13. Underlying mechanism of antimicrobial activity of chitosan microparticles and implications for the treatment of infectious diseases.

    Directory of Open Access Journals (Sweden)

    Soo Jin Jeon

    Full Text Available The emergence of antibiotic resistant microorganisms is a great public health concern and has triggered an urgent need to develop alternative antibiotics. Chitosan microparticles (CM, derived from chitosan, have been shown to reduce E. coli O157:H7 shedding in a cattle model, indicating potential use as an alternative antimicrobial agent. However, the underlying mechanism of CM on reducing the shedding of this pathogen remains unclear. To understand the mode of action, we studied molecular mechanisms of antimicrobial activity of CM using in vitro and in vivo methods. We report that CM are an effective bactericidal agent with capability to disrupt cell membranes. Binding assays and genetic studies with an ompA mutant strain demonstrated that outer membrane protein OmpA of E. coli O157:H7 is critical for CM binding, and this binding activity is coupled with a bactericidal effect of CM. This activity was also demonstrated in an animal model using cows with uterine diseases. CM treatment effectively reduced shedding of intrauterine pathogenic E. coli (IUPEC in the uterus compared to antibiotic treatment. Since Shiga-toxins encoded in the genome of bacteriophage is often overexpressed during antibiotic treatment, antibiotic therapy is generally not recommended because of high risk of hemolytic uremic syndrome. However, CM treatment did not induce bacteriophage or Shiga-toxins in E. coli O157:H7; suggesting that CM can be a potential candidate to treat infections caused by this pathogen. This work establishes an underlying mechanism whereby CM exert antimicrobial activity in vitro and in vivo, providing significant insight for the treatment of diseases caused by a broad spectrum of pathogens including antibiotic resistant microorganisms.

  14. Mechanical characterisation of porcine rectus sheath under uniaxial and biaxial tension.

    LENUS (Irish Health Repository)

    Lyons, Mathew

    2014-06-03

    Incisional hernia development is a significant complication after laparoscopic abdominal surgery. Intra-abdominal pressure (IAP) is known to initiate the extrusion of intestines through the abdominal wall, but there is limited data on the mechanics of IAP generation and the structural properties of rectus sheath. This paper presents an explanation of the mechanics of IAP development, a study of the uniaxial and biaxial tensile properties of porcine rectus sheath, and a simple computational investigation of the tissue. Analysis using Laplace׳s law showed a circumferential stress in the abdominal wall of approx. 1.1MPa due to an IAP of 11kPa, commonly seen during coughing. Uniaxial and biaxial tensile tests were conducted on samples of porcine rectus sheath to characterise the stress-stretch responses of the tissue. Under uniaxial tension, fibre direction samples failed on average at a stress of 4.5MPa at a stretch of 1.07 while cross-fibre samples failed at a stress of 1.6MPa under a stretch of 1.29. Under equi-biaxial tension, failure occurred at 1.6MPa with the fibre direction stretching to only 1.02 while the cross-fibre direction stretched to 1.13. Uniaxial and biaxial stress-stretch plots are presented allowing detailed modelling of the tissue either in silico or in a surrogate material. An FeBio computational model of the tissue is presented using a combination of an Ogden and an exponential power law model to represent the matrix and fibres respectively. The structural properties of porcine rectus sheath have been characterised and add to the small set of human data in the literature with which it may be possible to develop methods to reduce the incidence of incisional hernia development.

  15. Colloid and radionuclide retention mechanisms in fractured rock under near-natural flow conditions

    International Nuclear Information System (INIS)

    Delos, A.; Schaefer, T.; Geckeis, H.; Guimera, J.; Carrera, J.; Fanghaenel, T.

    2005-01-01

    Full text of publication follows: Experiments in fractured host rock (Grimsel Test Site, GTS, Switzerland) revealed that the colloid relevance for actinide migration is high due to the specific geochemical groundwater conditions [1]. However, even under such conditions it is found that retention of colloids and colloid-borne actinides becomes significant under near-natural groundwater flow rates (1-10 m/a) [2]. Underlying mechanisms of colloid and radionuclide retention are not well understood up to now. The present study co-funded by the NoE ACTINET-6 focuses on (i) the kinetics of actinide-colloid interactions and (ii) the relevance of matrix diffusion as a competition process to other retention mechanisms which affect the actinides behavior in fractured rock systems such as the Grimsel granodiorite. Colloid migration is studied with well defined model colloids as e.g. fluorescence dyed carboxylated polystyrene particles, and natural colloids extracted from bentonite (FEBEX) and from fracture filling material (GTS). In order to study the influence of matrix porosity on actinides migration, those experiments are performed in columns of well defined geometry filled with microporous unmodified silica spheres, porous ceramic material and natural fracture filling material from the GTS. The behaviour of actinides (Pu(IV) and Am(III)) sorbed onto bentonite colloids is investigated in column and batch experiments. All experiments are performed under anoxic conditions. Colloid characterization methods used in this study include the combination of photon correlation spectroscopy (PCS), laser-induced breakdown detection (LIBD), fluorimetry and field flow fractionation (FFF). Experimental results and their application to the parametrisation of reactive colloid transport models are discussed. [1] Geckeis H, Schaefer T, Hauser W, Rabung T, Missana T, Degueldre C, Moeri A, Eikenberg J, Fierz T, Alexander WR (2004) Results of the Colloid and Radionuclide Retention experiment

  16. Elbow Matching Accuracy in Young and Elderly Humans under Unusual Mechanical Constraints.

    Science.gov (United States)

    Talis, Vera L; Levik, Yuri S

    2016-01-01

    Experiment was carried out to study the proprioception accuracy of elderly (61-83 years old) and young (22-36 years old) subjects during contralateral elbow matching in sagittal plane. The subjects performed the task under ordinary condition and under experimental condition (matching forearm attached to the rocking cylindrical platform of low (LS), or high (HS) height, so that the elbow flexion was associated with tilting movement of the support and with backward movement of the upper arm). Control matching of young and elderly subjects does not differ significantly in terms of constant and absolute error. First block of LS and HS induced absolute error increase and matching arm velocity decrease in both groups, but in the second block of matching on rocking supports both arms velocity of elderly subject decreased and absolute error of elderly subjects toward the second block of rocking condition appeared lower than those of young subjects. Aftereffect of the restricted matching could be observed in elderly as a significant increase of matching arm velocity and corresponding constant error increase. It could be concluded that under unusual mechanical constraints elderly subjects tended to use "conservative" strategy followed by significant aftereffect toward the final ordinary support condition.

  17. Analysis of pellet cladding mechanical interaction margins in PWR fuel under power ramp condition

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Jong Sung; Lee, Jin Seok; Kim, Hyeong Koo; Chung, Jing On [Korea Nuclear Fuel, Daejeon (Korea, Republic of); Mitchell, David; Aleshin, Yuriy [Westinghouse Electric Company, South Carolina (Colombia)

    2008-10-15

    Small flaws in PWR and BWR fuel such as a missing pellet surface (MPS), pellet fragmentation and cladding defects, play an important role during conditions when there is pellet-cladding mechanical interaction (PCMI) under power ramp conditions. In order to confirm the margin against PWR fuel failure by PCMI with the pellet and cladding imperfections, first the separating hoop stress for cladding failure is determined using the ANSYS FEA model for failed and intact fuel rods under various power ramp conditions. Second, the idealized rod power history is developed to achieve the maximum uniform cladding stress during the normal operational transients. Finally, the stress multiplication factor is calculated with the FEA model to deal with the effect of various shapes and sizes of MPS, pellet fragmentation and cladding defects on the PCMI behavior. Then the stress multiplication factor with pellet imperfections and cladding defects allowed by manufacturing tolerances is applied to the fuel performance analysis code results using the idealized power history to confirm margin to PCMI under power ramp condition.

  18. Experimental study of the behavioural mechanisms underlying self-organization in human crowds.

    Science.gov (United States)

    Moussaïd, Mehdi; Helbing, Dirk; Garnier, Simon; Johansson, Anders; Combe, Maud; Theraulaz, Guy

    2009-08-07

    In animal societies as well as in human crowds, many observed collective behaviours result from self-organized processes based on local interactions among individuals. However, models of crowd dynamics are still lacking a systematic individual-level experimental verification, and the local mechanisms underlying the formation of collective patterns are not yet known in detail. We have conducted a set of well-controlled experiments with pedestrians performing simple avoidance tasks in order to determine the laws ruling their behaviour during interactions. The analysis of the large trajectory dataset was used to compute a behavioural map that describes the average change of the direction and speed of a pedestrian for various interaction distances and angles. The experimental results reveal features of the decision process when pedestrians choose the side on which they evade, and show a side preference that is amplified by mutual interactions. The predictions of a binary interaction model based on the above findings were then compared with bidirectional flows of people recorded in a crowded street. Simulations generate two asymmetric lanes with opposite directions of motion, in quantitative agreement with our empirical observations. The knowledge of pedestrian behavioural laws is an important step ahead in the understanding of the underlying dynamics of crowd behaviour and allows for reliable predictions of collective pedestrian movements under natural conditions.

  19. Elbow matching accuracy in young and elderly humans under unusual mechanical constraints

    Directory of Open Access Journals (Sweden)

    Vera Talis

    2016-11-01

    Full Text Available Experiment was carried out to study the proprioception accuracy of elderly (61-83 years old and young (22-36 years old subjects during contralateral elbow matching in sagittal plane. The subjects performed the task under ordinary condition and under experimental condition (matching forearm attached to the rocking cylindrical platform of low (LS, or high (HS height, so that the elbow flexion was associated with tilting movement of the support and with backward movement of the upper arm. Control matching of young and elderly subjects does not differ significantly in terms of constant and absolute error. First block of LS and HS induced absolute error increase and matching arm velocity decrease in both groups, but in the second block of matching on rocking supports both arms velocity of elderly subject decreased and absolute error of elderly subjects towards the second block of rocking condition appeared lower than those of young subjects. Aftereffect of the restricted matching could be observed in elderly as a significant increase of matching arm velocity and corresponding constant error increase. It could be concluded that under unusual mechanical constraints elderly subjects tended to use conservative strategy followed by significant aftereffect towards the final ordinary support condition.

  20. Mitral valve replacement in patients under 65 years of age: mechanical or biological valves?

    Science.gov (United States)

    Reineke, David C; Heinisch, Paul Philipp; Winkler, Bernhard; Englberger, Lars; Carrel, Thierry P

    2015-03-01

    There is controversy regarding the optimal choice of prosthetic valves in patients less than 65 years of age requiring mitral valve replacement (MVR). Recently, trends for valve replacement are moving towards biological prosthesis also in younger patients, which is justified by the fact that a later valve-in-valve procedure is feasible in the case of degeneration of the tissue valve. This strategy is increasingly recommended in aortic valve surgery but is questionable for MVR. The purpose of this review is to evaluate current guidelines and analyse evidence for biological MVR in patients under 65 years. There are differences between guidelines of the American Heart Association and those of the European Society of Cardiology concerning the choice of prostheses in patients undergoing MVR. Although the European Society of Cardiology recommends a mechanical mitral valve in patients under 65 years of age, the American Heart Association does not provide detailed advice for these patients. Mitral valve replacement with biological valves in patients under 65 years is associated with higher rates of reoperation due to structural valve deterioration. In addition, several studies showed a decreased survival after biological MVR. Evidence for biological MVR in patients less than 65 years without comorbidities or contraindication for oral anticoagulation does not exist. Recommendations for patients less than 65 years of age should not be blurred by current 'en-vogue' methods for promising but not yet proven valve-in-valve strategies.