Science.gov

Sample records for advance current understanding

  1. Therapeutic Mechanisms of Lithium in Bipolar Disorder: Recent Advances and Current Understanding.

    PubMed

    Malhi, Gin S; Outhred, Tim

    2016-10-01

    Lithium is the most effective and well established treatment for bipolar disorder, and it has a broad array of effects within cellular pathways. However, the specific processes through which therapeutic effects occur and are maintained in bipolar disorder remain unclear. This paper provides a timely update to an authoritative review of pertinent findings that was published in CNS Drugs in 2013. A literature search was conducted using the Scopus database, and was limited by year (from 2012). There has been a resurgence of interest in lithium therapy mechanisms, perhaps driven by technical advancements in recent years that permit the examination of cellular mechanisms underpinning the effects of lithium-along with the reuptake of lithium in clinical practice. Recent research has further cemented glycogen synthase kinase 3β (GSK3β) inhibition as a key mechanism, and the inter-associations between GSK3β-mediated neuroprotective, anti-oxidative and neurotransmission mechanisms have been further elucidated. In addition to highly illustrative cellular research, studies examining higher-order biological systems, such as circadian rhythms, as well as employing innovative animal and human models, have increased our understanding of how lithium-induced changes at the cellular level possibly translate to changes at behavioural and clinical levels. Neural circuitry research is yet to identify clear mechanisms of change in bipolar disorder in response to treatment with lithium, but important structural findings have demonstrated links to the modulation of cellular mechanisms, and peripheral marker and pharmacogenetic studies are showing promising findings that will likely inform the exploration for predictors of lithium treatment response. With a deeper understanding of lithium's therapeutic mechanisms-from the cellular to clinical levels of investigation-comes the opportunity to develop predictive models of lithium treatment response and identify novel drug targets, and

  2. Advances in understanding hypopituitarism

    PubMed Central

    Stieg, Mareike R.; Renner, Ulrich; Stalla, Günter K.; Kopczak, Anna

    2017-01-01

    The understanding of hypopituitarism has increased over the last three years. This review provides an overview of the most important recent findings. Most of the recent research in hypopituitarism has focused on genetics. New diagnostic techniques like next-generation sequencing have led to the description of different genetic mutations causative for congenital dysfunction of the pituitary gland while new molecular mechanisms underlying pituitary ontogenesis have also been described. Furthermore, hypopituitarism may occur because of an impairment of the distinctive vascularization of the pituitary gland, especially by disruption of the long vessel connection between the hypothalamus and the pituitary. Controversial findings have been published on post-traumatic hypopituitarism. Moreover, autoimmunity has been discussed in recent years as a possible reason for hypopituitarism. With the use of new drugs such as ipilimumab, hypopituitarism as a side effect of pharmaceuticals has come into focus. Besides new findings on the pathomechanism of hypopituitarism, there are new diagnostic tools in development, such as new growth hormone stimulants that are currently being tested in clinical trials. Moreover, cortisol measurement in scalp hair is a promising tool for monitoring cortisol levels over time. PMID:28299199

  3. Advances in understanding COPD

    PubMed Central

    Anderson, Gary P.

    2016-01-01

    In recent years, thousands of publications on chronic obstructive pulmonary disease (COPD) and its related biology have entered the world literature, reflecting the increasing scientific and medical interest in this devastating condition. This article is a selective review of several important emerging themes that offer the hope of creating new classes of COPD medicines. Whereas basic science is parsing molecular pathways in COPD, its comorbidities, and asthma COPD overlap syndrome (ACOS) with unprecedented sophistication, clinical translation is disappointingly slow. The article therefore also considers solutions to current difficulties that are impeding progress in translating insights from basic science into clinically useful treatments. PMID:27746898

  4. Advances in understanding begomovirus satellites.

    PubMed

    Zhou, Xueping

    2013-01-01

    Begomoviruses are numerous and geographically widespread viruses that cause devastating diseases in many crops. Monopartite begomoviruses are frequently associated with betasatellites or alphasatellites. Both betasatellite and alphasatellite DNA genomes are approximately half the size of begomovirus DNA genomes. Betasatellites are essential for induction of typical disease symptoms. The βC1 genes encoded by the betasatellites have important roles in symptom induction, in suppression of transcriptional and posttranscriptional gene silencing, and they can affect jasmonic acid responsive genes. Host plants of begomoviruses have evolved diverse innate defense mechanisms against the βC1 protein to counter these challenges. Alphasatellites have been identified mainly in monopartite begomoviruses that associate with betasatellites and have no known contributions to pathogenesis of begomovirus-betasatellite disease complexes. Applications of current molecular tools are facilitating viral diagnosis and the discovery of novel species of geminiviruses and satellite DNAs and are also advancing our understanding of the global diversity and evolution of satellite DNAs.

  5. Recent advances in understanding dengue

    PubMed Central

    Yacoub, Sophie; Mongkolsapaya, Juthathip; Screaton, Gavin

    2016-01-01

    Dengue is an emerging threat to billions of people worldwide. In the last 20 years, the incidence has increased four-fold and this trend appears to be continuing. Caused by one of four viral serotypes, dengue can present as a wide range of clinical phenotypes with the severe end of the spectrum being defined by a syndrome of capillary leak, coagulopathy, and organ impairment. The pathogenesis of severe disease is thought to be in part immune mediated, but the exact mechanisms remain to be defined. The current treatment of dengue relies on supportive measures with no licensed therapeutics available to date. There have been recent advances in our understanding of a number of areas of dengue research, of which the following will be discussed in this review: the drivers behind the global dengue pandemic, viral structure and epitope binding, risk factors for severe disease and its pathogenesis, as well as the findings of recent clinical trials including therapeutics and vaccines. We conclude with current and future dengue control measures and key areas for future research. PMID:26918159

  6. Current concepts on burn wound conversion-A review of recent advances in understanding the secondary progressions of burns.

    PubMed

    Salibian, Ara A; Rosario, Angelica Tan Del; Severo, Lucio De Almeida Moura; Nguyen, Long; Banyard, Derek A; Toranto, Jason D; Evans, Gregory R D; Widgerow, Alan D

    2016-08-01

    Burn wound conversion describes the process by which superficial partial thickness burns convert into deeper burns necessitating surgical intervention. Fully understanding and thus controlling this phenomenon continues to defy burn surgeons. However, potentially guiding burn wound progression so as to obviate the need for surgery while still bringing about healing with limited scarring is the major unmet challenge. Comprehending the pathophysiologic background contributing to deeper progression of these burns is an essential prerequisite to planning any intervention. In this study, a review of articles examining burn wound progression over the last five years was conducted to analyze trends in recent burn progression research, determine changes in understanding of the pathogenesis of burn conversion, and subsequently examine the direction for future research in developing therapies. The majority of recent research focuses on applying therapies from other disease processes to common underlying pathogenic mechanisms in burn conversion. While ischemia, inflammation, and free oxygen radicals continue to demonstrate a critical role in secondary necrosis, novel mechanisms such as autophagy have also been shown to contribute affect significantly burn progression significantly. Further research will have to determine whether multiple mechanisms should be targeted when developing clinical therapies.

  7. Recent advances in understanding vitiligo

    PubMed Central

    Manga, Prashiela; Elbuluk, Nada; Orlow, Seth J.

    2016-01-01

    Vitiligo, an acquired depigmentation disorder, manifests as white macules on the skin and can cause significant psychological stress and stigmatization. Recent advances have shed light on key components that drive disease onset and progression as well as therapeutic approaches. Vitiligo can be triggered by stress to the melanin pigment-producing cells of the skin, the melanocytes. The triggers, which range from sunburn to mechanical trauma and chemical exposures, ultimately cause an autoimmune response that targets melanocytes, driving progressive skin depigmentation. The most significant progress in our understanding of disease etiology has been made on three fronts: (1) identifying cellular responses to stress, including antioxidant pathways and the unfolded protein response (UPR), as key players in disease onset, (2) characterizing immune responses that target melanocytes and drive disease progression, and (3) identifying major susceptibility genes. The current model for vitiligo pathogenesis postulates that oxidative stress causes cellular disruptions, including interruption of protein maturation in the endoplasmic reticulum (ER), leading to the activation of the UPR and expression of UPR-regulated chemokines such as interleukin 6 (IL-6) and IL-8. These chemokines recruit immune components to the skin, causing melanocytes to be targeted for destruction. Oxidative stress can further increase melanocyte targeting by promoting antigen presentation. Two key components of the autoimmune response that promote disease progression are the interferon (IFN)-γ/CXCL10 axis and IL-17-mediated responses. Several genome-wide association studies support a role for these pathways, with the antioxidant gene NRF2, UPR gene XBP1, and numerous immune-related genes including class I and class II major histocompatibility genes associated with a risk for developing vitiligo. Novel approaches to promote repigmentation in vitiligo are being investigated and may yield effective, long

  8. Recent advances in understanding neutrophils

    PubMed Central

    Deniset, Justin F.; Kubes, Paul

    2016-01-01

    Neutrophils have long been regarded as key effectors of the innate immune response during acute inflammation. Recent evidence has revealed a greater functional diversity for these cells than previously appreciated, expanding roles for neutrophils in adaptive immunity and chronic pathologies. In this review, we summarize some of the evolving paradigms in the neutrophil field and highlight key advances that have contributed to our understanding of neutrophil behavior and function in vivo. We examine the concept of neutrophil subsets and polarization, we discuss novel immunomodulatory roles for neutrophils in shaping the immune response, and, finally, we identify technical advances that will further enhance our ability to track the function and fate of neutrophils. PMID:28105328

  9. Recent advances in understanding schizophrenia

    PubMed Central

    Haller, Chiara S.; Padmanabhan, Jaya L.; Lizano, Paulo; Torous, John

    2014-01-01

    Schizophrenia is a highly disabling disorder whose causes remain to be better understood, and treatments have to be improved. However, several recent advances have been made in diagnosis, etiopathology, and treatment. Whereas reliability of diagnosis has improved with operational criteria, including Diagnostic and Statistical Manual of Mental Disorders, (DSM) Fifth Edition, validity of the disease boundaries remains unclear because of substantive overlaps with other psychotic disorders. Recent emphasis on dimensional approaches and translational bio-behavioral research domain criteria may eventually help move toward a neuroscience-based definition of schizophrenia. The etiology of schizophrenia is now thought to be multifactorial, with multiple small-effect and fewer large-effect susceptibility genes interacting with several environmental factors. These factors may lead to developmentally mediated alterations in neuroplasticity, manifesting in a cascade of neurotransmitter and circuit dysfunctions and impaired connectivity with an onset around early adolescence. Such etiopathological understanding has motivated a renewed search for novel pharmacological as well as psychotherapeutic targets. Addressing the core features of the illness, such as cognitive deficits and negative symptoms, and developing hypothesis-driven early interventions and preventive strategies are high-priority goals for the field. Schizophrenia is a severe, chronic mental disorder and is among the most disabling disorders in all of medicine. It is estimated by the National Institute of Mental Health (NIMH) that 2.4 million people over the age of 18 in the US suffer from schizophrenia. This illness typically begins in adolescence and derails the formative goals of school, family, and work, leading to considerable suffering and disability and reduced life expectancy by about 20 years. Treatment outcomes are variable, and some people are successfully treated and reintegrated (i.e. go back to work

  10. Recent advances in understanding noroviruses

    PubMed Central

    Bartnicki, Eric; Cunha, Juliana Bragazzi; Kolawole, Abimbola O.; Wobus, Christiane E.

    2017-01-01

    Noroviruses are the leading cause of acute gastroenteritis around the world. An individual living in the United States is estimated to develop norovirus infection five times in his or her lifetime. Despite this, there is currently no antiviral or vaccine to combat the infection, in large part because of the historical lack of cell culture and small animal models. However, the last few years of norovirus research were marked by a number of ground-breaking advances that have overcome technical barriers and uncovered novel aspects of norovirus biology. Foremost among them was the development of two different in vitro culture systems for human noroviruses. Underappreciated was the notion that noroviruses infect cells of the immune system as well as epithelial cells within the gastrointestinal tract and that human norovirus infection of enterocytes requires or is promoted by the presence of bile acids. Furthermore, two proteinaceous receptors are now recognized for murine norovirus, marking the first discovery of a functional receptor for any norovirus. Recent work further points to a role for certain bacteria, including those found in the gut microbiome, as potential modulators of norovirus infection in the host, emphasizing the importance of interactions with organisms from other kingdoms of life for viral pathogenesis. Lastly, we will highlight the adaptation of drop-based microfluidics to norovirus research, as this technology has the potential to reveal novel insights into virus evolution. This review aims to summarize these new findings while also including possible future directions. PMID:28163914

  11. Resistance to AHAS inhibitor herbicides: current understanding.

    PubMed

    Yu, Qin; Powles, Stephen B

    2014-09-01

    Acetohydroxyacid synthase (AHAS) inhibitor herbicides currently comprise the largest site-of-action group (with 54 active ingredients across five chemical groups) and have been widely used in world agriculture since they were first introduced in 1982. Resistance evolution in weeds to AHAS inhibitors has been rapid and identified in populations of many weed species. Often, evolved resistance is associated with point mutations in the target AHAS gene; however non-target-site enhanced herbicide metabolism occurs as well. Many AHAS gene resistance mutations can occur and be rapidly enriched owing to a high initial resistance gene frequency, simple and dominant genetic inheritance and lack of major fitness cost of the resistance alleles. Major advances in the elucidation of the crystal structure of the AHAS (Arabidopsis thaliana) catalytic subunit in complex with various AHAS inhibitor herbicides have greatly improved current understanding of the detailed molecular interactions between AHAS, cofactors and herbicides. Compared with target-site resistance, non-target-site resistance to AHAS inhibitor herbicides is less studied and hence less understood. In a few well-studied cases, non-target-site resistance is due to enhanced rates of herbicide metabolism (metabolic resistance), mimicking that occurring in tolerant crop species and often involving cytochrome P450 monooxygenases. However, the specific herbicide-metabolising, resistance-endowing genes are yet to be identified in resistant weed species. The current state of mechanistic understanding of AHAS inhibitor herbicide resistance is reviewed, and outstanding research issues are outlined.

  12. Recent advances in understanding & managing male infertility

    PubMed Central

    Bieniek, Jared M.; Lo, Kirk C.

    2016-01-01

    Male infertility remains a struggle to definitively diagnose and treat with many men labelled as “idiopathic infertility” and eventually requiring assisted reproductive techniques.  Along those lines, research groups are continuing to explore current social and environmental factors, including the obesity epidemic, and their effects on male fertility potential.  Novel biomarkers of natural fertility status and azoospermia etiology have additionally seen recent attention with ACRV1 and TEX101/ECM1 assays either currently or soon to be commercially available.  Despite these advancements, however, medical treatment options have seen little progress.  Though surgical therapies have similarly seen little transformation, groups are exploring the use of testicular sperm for couples with elevated sperm DNA fragmentation and either planned or previously failed IVF/ICSI.  Concerted collaborative efforts will be needed as we move forward to better understand the challenges men face when struggling to conceive. PMID:27990271

  13. Current understanding of Pneumocystis immunology

    PubMed Central

    Kelly, Michelle N; Shellito, Judd E

    2013-01-01

    Pneumocystis jirovecii is the opportunistic fungal organism that causes Pneumocystis pneumonia (PCP) in humans. Similar to other opportunistic pathogens, Pneumocystis causes disease in individuals who are immunocompromised, particularly those infected with HIV. PCP remains the most common opportunistic infection in patients with AIDS. Incidence has decreased greatly with the advent of HAART. However, an increase in the non-HIV immunocompromised population, noncompliance with current treatments, emergence of drug-resistant strains and rise in HIV+ cases in developing countries makes Pneumocystis a pathogen of continued interest and a public health threat. A great deal of research interest has addressed therapeutic interventions to boost waning immunity in the host to prevent or treat PCP. This article focuses on research conducted during the previous 5 years regarding the host immune response to Pneumocystis, including innate, cell-mediated and humoral immunity, and associated immunotherapies tested against PCP. PMID:20020829

  14. Eimeriosis in cattle: current understanding.

    PubMed

    Daugschies, A; Najdrowski, M

    2005-12-01

    environment (cool and dry, disinfection procedures) will help to reduce infection pressure on the herd. Of the various pharmacological compounds used to treat coccidiosis, those which act against the late developmental stages, administered during prepatency (metaphylactically rather than therapeutically), are currently considered most effective.

  15. Recent advances in understanding apicomplexan parasites

    PubMed Central

    Seeber, Frank; Steinfelder, Svenja

    2016-01-01

    Intracellular single-celled parasites belonging to the large phylum Apicomplexa are amongst the most prevalent and morbidity-causing pathogens worldwide. In this review, we highlight a few of the many recent advances in the field that helped to clarify some important aspects of their fascinating biology and interaction with their hosts. Plasmodium falciparum causes malaria, and thus the recent emergence of resistance against the currently used drug combinations based on artemisinin has been of major interest for the scientific community. It resulted in great advances in understanding the resistance mechanisms that can hopefully be translated into altered future drug regimens. Apicomplexa are also experts in host cell manipulation and immune evasion. Toxoplasma gondii and Theileria sp., besides Plasmodium sp., are species that secrete effector molecules into the host cell to reach this aim. The underlying molecular mechanisms for how these proteins are trafficked to the host cytosol ( T. gondii and Plasmodium) and how a secreted protein can immortalize the host cell ( Theileria sp.) have been illuminated recently. Moreover, how such secreted proteins affect the host innate immune responses against T. gondii and the liver stages of Plasmodium has also been unraveled at the genetic and molecular level, leading to unexpected insights. Methodological advances in metabolomics and molecular biology have been instrumental to solving some fundamental puzzles of mitochondrial carbon metabolism in Apicomplexa. Also, for the first time, the generation of stably transfected Cryptosporidium parasites was achieved, which opens up a wide variety of experimental possibilities for this understudied, important apicomplexan pathogen. PMID:27347391

  16. Current Understanding in Pathogenesis of Atopic Dermatitis

    PubMed Central

    McPherson, Tess

    2016-01-01

    There have been advances in our understanding of the complex pathogenesis of atopic eczema over the past few decades. This article examines the multiple factors which are implicated in this process. PMID:27904184

  17. Recent advances in understanding Streptomyces.

    PubMed

    Chater, Keith F

    2016-01-01

    About 2,500 papers dated 2014-2016 were recovered by searching the PubMed database for Streptomyces, which are the richest known source of antibiotics. This review integrates around 100 of these papers in sections dealing with evolution, ecology, pathogenicity, growth and development, stress responses and secondary metabolism, gene expression, and technical advances. Genomic approaches have greatly accelerated progress. For example, it has been definitively shown that interspecies recombination of conserved genes has occurred during evolution, in addition to exchanges of some of the tens of thousands of non-conserved accessory genes. The closeness of the association of Streptomyces with plants, fungi, and insects has become clear and is reflected in the importance of regulators of cellulose and chitin utilisation in overall Streptomyces biology. Interestingly, endogenous cellulose-like glycans are also proving important in hyphal growth and in the clumping that affects industrial fermentations. Nucleotide secondary messengers, including cyclic di-GMP, have been shown to provide key input into developmental processes such as germination and reproductive growth, while late morphological changes during sporulation involve control by phosphorylation. The discovery that nitric oxide is produced endogenously puts a new face on speculative models in which regulatory Wbl proteins (peculiar to actinobacteria) respond to nitric oxide produced in stressful physiological transitions. Some dramatic insights have come from a new model system for Streptomyces developmental biology, Streptomyces venezuelae, including molecular evidence of very close interplay in each of two pairs of regulatory proteins. An extra dimension has been added to the many complexities of the regulation of secondary metabolism by findings of regulatory crosstalk within and between pathways, and even between species, mediated by end products. Among many outcomes from the application of chromosome

  18. Recent advances in understanding Streptomyces

    PubMed Central

    Chater, Keith F.

    2016-01-01

    About 2,500 papers dated 2014–2016 were recovered by searching the PubMed database for Streptomyces, which are the richest known source of antibiotics. This review integrates around 100 of these papers in sections dealing with evolution, ecology, pathogenicity, growth and development, stress responses and secondary metabolism, gene expression, and technical advances. Genomic approaches have greatly accelerated progress. For example, it has been definitively shown that interspecies recombination of conserved genes has occurred during evolution, in addition to exchanges of some of the tens of thousands of non-conserved accessory genes. The closeness of the association of Streptomyces with plants, fungi, and insects has become clear and is reflected in the importance of regulators of cellulose and chitin utilisation in overall Streptomyces biology. Interestingly, endogenous cellulose-like glycans are also proving important in hyphal growth and in the clumping that affects industrial fermentations. Nucleotide secondary messengers, including cyclic di-GMP, have been shown to provide key input into developmental processes such as germination and reproductive growth, while late morphological changes during sporulation involve control by phosphorylation. The discovery that nitric oxide is produced endogenously puts a new face on speculative models in which regulatory Wbl proteins (peculiar to actinobacteria) respond to nitric oxide produced in stressful physiological transitions. Some dramatic insights have come from a new model system for Streptomyces developmental biology, Streptomyces venezuelae, including molecular evidence of very close interplay in each of two pairs of regulatory proteins. An extra dimension has been added to the many complexities of the regulation of secondary metabolism by findings of regulatory crosstalk within and between pathways, and even between species, mediated by end products. Among many outcomes from the application of chromosome

  19. Advances in Understanding the Biosynthesis of Fumonisins

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fumonisins are a group of economically important mycotoxins that are derived polyketides. Since the cloning of the fumonisin polyketide synthase (PKS) gene from Fusarium verticillioides in 1999, significant advances have been made in understanding the molecular mechanisms for fumonisin biosynthesis...

  20. Advancing the understanding of autism disease mechanisms through genetics

    PubMed Central

    de la Torre-Ubieta, Luis; Won, Hyejung; Stein, Jason L; Geschwind, Daniel H

    2016-01-01

    Progress in understanding the genetic etiology of autism spectrum disorders (ASD) has fueled remarkable advances in our understanding of its potential neurobiological mechanisms. Yet, at the same time, these findings highlight extraordinary causal diversity and complexity at many levels ranging from molecules to circuits and emphasize the gaps in our current knowledge. Here we review current understanding of the genetic architecture of ASD and integrate genetic evidence, neuropathology and studies in model systems with how they inform mechanistic models of ASD pathophysiology. Despite the challenges, these advances provide a solid foundation for the development of rational, targeted molecular therapies. PMID:27050589

  1. Peritoneal mesothelioma: current understanding and management

    PubMed Central

    Chua, Terence C.; Yan, Tristan D.; Morris, David L.

    2009-01-01

    Mesothelioma is an asbestos-related tumour. Mesothelioma in the thorax occurs on the pleura and is known as pleural mesothelioma. It is the more common form of mesothelioma, accounting for 70% of cases. The other form occurs in the abdomen. It accounts for much of the remaining 30% and is known as peritoneal mesothelioma. Early diagnosis of peritoneal mesothelioma is often difficult because the early symptoms are often overlooked as being a benign ailment of the gastrointestinal tract. Therefore, diagnosis often occurs at an advanced stage when disease is widespread throughout the peritoneal cavity. Treatment approaches have evolved in the last decade from systemic chemotherapy and palliative surgery to aggressive cytoreductive surgery and perioperative intraperitoneal chemotherapy. This has led to a marked increase in survival among patients who were once classified as “preterminal.” We update on the current understanding of peritoneal mesothelioma from a clinical perspective in hope that greater clinician awareness will promote best practice management of this condition. PMID:19234654

  2. Advancing Drought Understanding, Monitoring and Prediction

    NASA Technical Reports Server (NTRS)

    Mariotti, Annarita; Schubert, Siegfried D.; Mo, Kingtse; Peters-Lidard, Christa; Wood, Andy; Pulwarty, Roger; Huang, Jin; Barrie, Dan

    2013-01-01

    Having the capacity to monitor droughts in near-real time and providing accurate drought prediction from weeks to seasons in advance can greatly reduce the severity of social and economic damage caused by drought, a leading natural hazard for North America. The congressional mandate to establish the National Integrated Drought Information System (NIDIS; Public Law 109-430) in 2006 was a major impulse to develop, integrate, and provide drought information to meet the challenges posed by this hazard. Significant progress has been made on many fronts. On the research front, efforts by the broad scientific community have resulted in improved understanding of North American droughts and improved monitoring and forecasting tools. We now have a better understanding of the droughts of the twentieth century including the 1930s "Dust Bowl"; we have developed a broader array of tools and datasets that enhance the official North American Drought Monitor based on different methodologies such as state-of-the-art land surface modeling (e.g., the North American Land Data Assimilation System) and remote sensing (e.g., the evaporative stress index) to better characterize the occurrence and severity of drought in its multiple manifestations. In addition, we have new tools for drought prediction [including the new National Centers for Environmental Prediction (NCEP) Climate Forecast System, version 2, for operational prediction and an experimental National Multimodel Ensemble] and have explored diverse methodologies including ensemble hydrologic prediction approaches. Broad NIDIS-inspired progress is influencing the development of a Global Drought Information System (GDIS) under the auspices of the World Climate Research Program. Despite these advances, current drought monitoring and forecasting capabilities still fall short of users' needs, especially the need for skillful and reliable drought forecasts at regional and local scales. To tackle this outstanding challenging problem

  3. Advances in understanding drug-induced neuropathies.

    PubMed

    Peltier, Amanda C; Russell, James W

    2006-01-01

    Many commonly used medications have neurotoxic adverse effects; the most common of these is peripheral neuropathy. Neuropathy can be a dose-limiting adverse effect for many medications used in life-threatening conditions, such as malignancy and HIV-related disease. Epidemiological evidence supports previous case reports of HMG-CoA reductase inhibitors (or 'statins') causing an axonal sensorimotor neuropathy or a purely small-fibre neuropathy in some patients. The neuropathy improves when the medication is withdrawn. Despite the association between HMG-CoA reductase inhibitors and neuropathy, the risk is low compared with the significant vascular protective benefits. Oxaliplatin, a new platinum chemotherapy agent designed to have fewer adverse effects than other such agents, has been shown to cause a transient initial dysaesthesia in addition to an axonal polyneuropathy. Thalidomide, an old therapy currently being utilised for new therapeutic indications (e.g. treatment of haematological malignancies), is associated with a painful, axonal sensorimotor neuropathy that does not improve on withdrawal of the drug. Nucleoside reverse transcriptase inhibitors are important components of highly active antiretroviral therapy, but are associated with a sensory neuropathy that is likely to be due to a direct effect of these drugs on mitochondrial DNA replication. New research demonstrates that lactate levels may help discriminate between neuropathy caused by nucleoside analogues and HIV-induced neuropathy. Understanding the mechanism of drug-induced neuropathy has led to advances in preventing this disabling condition.

  4. Recent advances in understanding idiopathic pulmonary fibrosis

    PubMed Central

    Daccord, Cécile; Maher, Toby M.

    2016-01-01

    Despite major research efforts leading to the recent approval of pirfenidone and nintedanib, the dismal prognosis of idiopathic pulmonary fibrosis (IPF) remains unchanged. The elaboration of international diagnostic criteria and disease stratification models based on clinical, physiological, radiological, and histopathological features has improved the accuracy of IPF diagnosis and prediction of mortality risk. Nevertheless, given the marked heterogeneity in clinical phenotype and the considerable overlap of IPF with other fibrotic interstitial lung diseases (ILDs), about 10% of cases of pulmonary fibrosis remain unclassifiable. Moreover, currently available tools fail to detect early IPF, predict the highly variable course of the disease, and assess response to antifibrotic drugs. Recent advances in understanding the multiple interrelated pathogenic pathways underlying IPF have identified various molecular phenotypes resulting from complex interactions among genetic, epigenetic, transcriptional, post-transcriptional, metabolic, and environmental factors. These different disease endotypes appear to confer variable susceptibility to the condition, differing risks of rapid progression, and, possibly, altered responses to therapy. The development and validation of diagnostic and prognostic biomarkers are necessary to enable a more precise and earlier diagnosis of IPF and to improve prediction of future disease behaviour. The availability of approved antifibrotic therapies together with potential new drugs currently under evaluation also highlights the need for biomarkers able to predict and assess treatment responsiveness, thereby allowing individualised treatment based on risk of progression and drug response. This approach of disease stratification and personalised medicine is already used in the routine management of many cancers and provides a potential road map for guiding clinical care in IPF. PMID:27303645

  5. Advances in Understanding Air Pollution and CVD.

    PubMed

    Kaufman, Joel D; Spalt, Elizabeth W; Curl, Cynthia L; Hajat, Anjum; Jones, Miranda R; Kim, Sun-Young; Vedal, Sverre; Szpiro, Adam A; Gassett, Amanda; Sheppard, Lianne; Daviglus, Martha L; Adar, Sara D

    2016-09-01

    The MESA Air (Multi-Ethnic Study of Atherosclerosis and Air Pollution) leveraged the platform of the MESA cohort into a prospective longitudinal study of relationships between air pollution and cardiovascular health. MESA Air researchers developed fine-scale, state-of-the-art air pollution exposure models for the MESA Air communities, creating individual exposure estimates for each participant. These models combine cohort-specific exposure monitoring, existing monitoring systems, and an extensive database of geographic and meteorological information. Together with extensive phenotyping in MESA-and adding participants and health measurements to the cohort-MESA Air investigated environmental exposures on a wide range of outcomes. Advances by the MESA Air team included not only a new approach to exposure modeling, but also biostatistical advances in addressing exposure measurement error and temporal confounding. The MESA Air study advanced our understanding of the impact of air pollutants on cardiovascular disease and provided a research platform for advances in environmental epidemiology.

  6. Recent advances in understanding and managing asthma

    PubMed Central

    Loo, Su-Ling; Wark, Peter A.B.

    2016-01-01

    This review highlights the important articles published in the area of asthma research from January 2015 to July 2016. In basic science, significant advances have been made in understanding the link between the innate immune response and type II acquired immune responses in asthma and the role of the airway epithelium. Novel information continues to emerge with regard to the pathogenesis and heterogeneity of severe asthma. There have been important translational clinical trials in the areas of childhood asthma, treatment of allergy to improve asthma outcomes, and improving drug delivery to optimize the management of asthma. In addition, there are increasing data concerning the application of biological agents to the management of severe asthma. This body of work discusses the most notable advances in the understanding and management of asthma. PMID:27610226

  7. Recent advances in managing and understanding uveitis

    PubMed Central

    Chen, Shih-Chou; Sheu, Shwu-Jiuan

    2017-01-01

    Uveitis is a sight-threatening disease entity with intraocular inflammation that arises from various causes. It mainly affects working-age individuals and may lead to irreversible visual loss if not treated properly in a timely manner. This article reviews recent advances in the management and understanding of uveitis since 2014, including treatment with new immunosuppressive therapies that use biological agents, local therapy with steroid implants, and imaging studies for the evaluation of uveitis. PMID:28357059

  8. Recent advances in understanding and managing gout.

    PubMed

    Igel, Talia F; Krasnokutsky, Svetlana; Pillinger, Michael H

    2017-01-01

    Gout is the most common crystal arthropathy and the leading cause of inflammatory arthritis. It is associated with functional impairment and, for many, a diminished health-related quality of life. Numerous studies have demonstrated the impact of gout and its associated conditions on patient morbidity and mortality. Unfortunately, gout remains under-diagnosed and under-treated in the general community. Despite major advances in treatment strategies, as many as 90% of patients with gout are poorly controlled or improperly managed and their hyperuricemia and recurrent flares continue. The introduction of novel urate-lowering therapies, new imaging modalities, and a deeper understanding of the pathogenesis of gout raise the possibility of better gout care and improved patient outcomes. Here, we spotlight recent advances in the diagnosis and management of gout and discuss novel therapeutics in gout treatment.

  9. Recent advances in understanding and managing gout

    PubMed Central

    Igel, Talia F.; Krasnokutsky, Svetlana; Pillinger, Michael H.

    2017-01-01

    Gout is the most common crystal arthropathy and the leading cause of inflammatory arthritis. It is associated with functional impairment and, for many, a diminished health-related quality of life. Numerous studies have demonstrated the impact of gout and its associated conditions on patient morbidity and mortality. Unfortunately, gout remains under-diagnosed and under-treated in the general community. Despite major advances in treatment strategies, as many as 90% of patients with gout are poorly controlled or improperly managed and their hyperuricemia and recurrent flares continue. The introduction of novel urate-lowering therapies, new imaging modalities, and a deeper understanding of the pathogenesis of gout raise the possibility of better gout care and improved patient outcomes. Here, we spotlight recent advances in the diagnosis and management of gout and discuss novel therapeutics in gout treatment. PMID:28357052

  10. Current understanding of the aeronomy of Mars

    NASA Astrophysics Data System (ADS)

    Nagy, Andrew F.; Grebowsky, Joseph M.

    2015-12-01

    This paper provides a short overview of our current understanding of the upper atmosphere/ionosphere of Mars including the escaping neutral atmosphere to space that plays a key role in the current state of the Mars upper atmosphere. The proper definition of the word "aeronomy" relates to the upper atmosphere where ionization is important. Currently there is a paucity of measurements of the internal physical structure of the Martian upper atmosphere/ionosphere. Much that we know has been deduced from theoretical models that predict many more things than thus far measured. The newest Mars orbital missions, the US MAVEN and Indian MOM missions, just beginning their science analyses, will provide the measurements needed to fully characterize the aeronomy of Mars.

  11. Current advances in perinatal medicine.

    PubMed

    Stern, L

    1979-01-01

    The enhancement of pulmonary maturation with the resultant ability to prevent hyaline membrane disease has given rise to the use of a number of drugs experimentally including corticosteroids, thyroxine, aminophylline, heroin, and several suggested others for this purpose. In clinical use to date only the corticosteroids have been widely utilized in man but it is clear that these agents are capable of effecting an advancement in the maturation of the surfactant system of the lung and a subsequent reduction in the incidence of severity of hyaline membrane disease. However, all agents which act by the enhancement of maturation also carry with them a resultant arrest to replication of tissues and there have been demonstrable effects on both the lung and possibly the brain of the organisms to whom these agents have been administreted. In this connection it is, therefore, important to realize that the advantages gained from these agents may be counterbalanced by disadvantages from their usage and that a reasoned and careful approach in each individual case is mandatory when use of such agents is considered. Experimental and clinical studies suggest the possibility that Vitamin E acting as a free radical scavenger may be important in the prevention of oxygen toxicity both to the eye (retrolental fibroplasia) as well as ameliorating the oxygen component of the destructive effects of respirator lung disease (bronchopulmonary dysplasia). The action of Vitamin E under these circumstances is not dependent upon its actual quantitative level in the plasma of premature infants but in utilization to its excess. Although phototherapy has been universally and widely used since 1958, precise studies of its mechanism of action have not been revealing. Recent work has suggested that following exposure to photoirradiation, bilirubin in its unconjugated form can be seen to appear in the excretory bile ducts suggesting the transport of unconjugated bilirubin through the liver. More recent

  12. Current advances in orthodontic pain

    PubMed Central

    Long, Hu; Wang, Yan; Jian, Fan; Liao, Li-Na; Yang, Xin; Lai, Wen-Li

    2016-01-01

    Orthodontic pain is an inflammatory pain that is initiated by orthodontic force-induced vascular occlusion followed by a cascade of inflammatory responses, including vascular changes, the recruitment of inflammatory and immune cells, and the release of neurogenic and pro-inflammatory mediators. Ultimately, endogenous analgesic mechanisms check the inflammatory response and the sensation of pain subsides. The orthodontic pain signal, once received by periodontal sensory endings, reaches the sensory cortex for pain perception through three-order neurons: the trigeminal neuron at the trigeminal ganglia, the trigeminal nucleus caudalis at the medulla oblongata and the ventroposterior nucleus at the thalamus. Many brain areas participate in the emotion, cognition and memory of orthodontic pain, including the insular cortex, amygdala, hippocampus, locus coeruleus and hypothalamus. A built-in analgesic neural pathway—periaqueductal grey and dorsal raphe—has an important role in alleviating orthodontic pain. Currently, several treatment modalities have been applied for the relief of orthodontic pain, including pharmacological, mechanical and behavioural approaches and low-level laser therapy. The effectiveness of nonsteroidal anti-inflammatory drugs for pain relief has been validated, but its effects on tooth movement are controversial. However, more studies are needed to verify the effectiveness of other modalities. Furthermore, gene therapy is a novel, viable and promising modality for alleviating orthodontic pain in the future. PMID:27341389

  13. Recent advances in understanding and treating vasculitis

    PubMed Central

    Koster, Matthew J.; Warrington, Kenneth J.

    2016-01-01

    Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are near universally fatal conditions if untreated. Although effective therapeutic options are available for these diseases, treatment regimens are associated with both short- and long-term adverse effects. The recent identification of effective B-cell-targeted therapy with an anti-CD20 monoclonal antibody has transformed the treatment landscape of AAV. Questions, nevertheless, remain regarding the appropriate timing, dose, frequency, duration, and long-term effects of treatment. The aim of this article is to provide an overview of the current information, recent advances, ongoing clinical trials, and future treatment possibilities in AAV. PMID:27347395

  14. Current understanding of rheumatoid arthritis therapy.

    PubMed

    Colmegna, Inés; Ohata, Brent R; Menard, Henri A

    2012-04-01

    Progress in understanding the cellular and molecular mechanisms of rheumatoid arthritis (RA), together with the availability of new therapies, has changed the way we think about RA. The paradigm shift in RA therapy has been from controlling symptoms to controlling the disease process with the abrogation of inflammation. Challenges that are still unresolved include the issues in disease prevention, treatment specificity to restore tolerance, approaches to facilitate tissue repair, and treatment optimization to fit the individual patient's disease phenotype and comorbidity context. This review summarizes the pathogenesis-related rationales for the current therapeutic strategies in RA and for emerging therapies and potential approaches to restoring immune tolerance in RA.

  15. Current understanding of multi-species biofilms

    PubMed Central

    Yang, Liang; Liu, Yang; Wu, Hong; Høiby, Niels; Molin, Søren; Song, Zhi-jun

    2011-01-01

    Direct observation of a wide range of natural microorganisms has revealed the fact that the majority of microbes persist as surface-attached communities surrounded by matrix materials, called biofilms. Biofilms can be formed by a single bacterial strain. However, most natural biofilms are actually formed by multiple bacterial species. Conventional methods for bacterial cleaning, such as applications of antibiotics and/or disinfectants are often ineffective for biofilm populations due to their special physiology and physical matrix barrier. It has been estimated that billions of dollars are spent every year worldwide to deal with damage to equipment, contaminations of products, energy losses, and infections in human beings resulted from microbial biofilms. Microorganisms compete, cooperate, and communicate with each other in multi-species biofilms. Understanding the mechanisms of multi-species biofilm formation will facilitate the development of methods for combating bacterial biofilms in clinical, environmental, industrial, and agricultural areas. The most recent advances in the understanding of multi-species biofilms are summarized and discussed in the review. PMID:21485311

  16. Current understanding of multi-species biofilms.

    PubMed

    Yang, Liang; Liu, Yang; Wu, Hong; Hóiby, Niels; Molin, Søren; Song, Zhi-jun

    2011-04-01

    Direct observation of a wide range of natural microorganisms has revealed the fact that the majority of microbes persist as surface-attached communities surrounded by matrix materials, called biofilms. Biofilms can be formed by a single bacterial strain. However, most natural biofilms are actually formed by multiple bacterial species. Conventional methods for bacterial cleaning, such as applications of antibiotics and/or disinfectants are often ineffective for biofilm populations due to their special physiology and physical matrix barrier. It has been estimated that billions of dollars are spent every year worldwide to deal with damage to equipment, contaminations of products, energy losses, and infections in human beings resulted from microbial biofilms. Microorganisms compete, cooperate, and communicate with each other in multi-species biofilms. Understanding the mechanisms of multi-species biofilm formation will facilitate the development of methods for combating bacterial biofilms in clinical, environmental, industrial, and agricultural areas. The most recent advances in the understanding of multi-species biofilms are summarized and discussed in the review.

  17. [Understanding current therapies in metastatic melanoma].

    PubMed

    Rodríguez, Rocío; Parra, Angela; González, Sergio; Molgó, Montserrat; Droppelmann, Nicolás; Acevedo, Francisco; Peña, José; Uribe, Pablo

    2016-11-01

    Cutaneous melanoma is a highly aggressive tumor developing from melanocytes, its incidence is increasing, and prognosis in advanced stages is daunting. New therapies have been approved during the recent years with unprecedented results, including inhibitors of MAPK/ERK pathway and immune checkpoint blockade (anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) as ipilimumab, anti-programmed cell death protein 1 (PD-L1) as pembrolizumab and anti-programmed cell death protein 1 ligand (PD-L1), among many others). The aim of this paper is to review currently available metastatic melanoma therapies focusing mainly on new therapies that have demonstrated effectiveness, after several decades of little progress in the treatment of this disease.

  18. Palate Morphogenesis: Current Understanding and Future Directions

    PubMed Central

    Greene, Robert M.; Pisano, M. Michele

    2011-01-01

    In the past, most scientists conducted their inquiries of nature via inductivism, the patient accumulation of “pieces of information” in the pious hope that the sum of the parts would clarify the whole. Increasingly, modern biology employs the tools of bioinformatics and systems biology in attempts to reveal the “big picture.” Most successful laboratories engaged in the pursuit of the secrets of embryonic development, particularly those whose research focus is craniofacial development, pursue a middle road where research efforts embrace, rather than abandon, what some have called the “pedestrian” qualities of inductivism, while increasingly employing modern data mining technologies. The secondary palate has provided an excellent paradigm that has enabled examination of a wide variety of developmental processes. Examination of cellular signal transduction, as it directs embryogenesis, has proven exceptionally revealing with regard to clarification of the “facts” of palatal ontogeny—at least the facts as we currently understand them. Herein, we review the most basic fundamentals of orofacial embryology and discuss how functioning of TGFβ, BMP, Shh, and Wnt signal transduction pathways contributes to palatal morphogenesis. Our current understanding of palate medial edge epithelial differentiation is also examined. We conclude with a discussion of how the rapidly expanding field of epigenetics, particularly regulation of gene expression by miRNAs and DNA methylation, is critical to control of cell and tissue differentiation, and how examination of these epigenetic processes has already begun to provide a better understanding of, and greater appreciation for, the complexities of palatal morphogenesis. PMID:20544696

  19. Recent advances in understanding antitumor immunity

    PubMed Central

    Munhoz, Rodrigo Ramella; Postow, Michael Andrew

    2016-01-01

    The term “antitumor immunity” refers to innate and adaptive immune responses which lead to tumor control. Turning the immune system into a destructive force against tumors has been achieved in a broad range of human cancers with the use of non-specific immunotherapies, vaccines, adoptive-cell therapy, and, more recently with significant success, through blockade of immune checkpoints. Nevertheless, the efficacy of these approaches is not universal, and tools to identify long-term responders and primarily refractory patients are warranted. In this article, we review recent advances in understanding the complex mechanisms of antitumor immunity and how these developments can be used to address open questions in a setting of growing clinical indications for the use of immunotherapy. PMID:27803807

  20. Current understanding of SEP acceleration and propagation

    NASA Astrophysics Data System (ADS)

    Klecker, B.

    2013-02-01

    The solar energetic particle (SEP) populations of electrons and ions are highly variable in space and time, in intensity, energy, and composition. Over the last ~20 years advanced instrumentation onboard many spacecraft (e.g. ACE, Coronas, GOES, Hinode, RHESSI, SAMPEX, SDO, SOHO, STEREO, TRACE, Ulysses, Yokoh, to name a few) extended our ability to explore the characteristics of solar energetic particles by in-situ measurements in interplanetary space and by observing their source characteristics near the Sun by remote-sensing observation of electromagnetic emission over a wide frequency range. These measurements provide crucial information for understanding the sources of the particle populations and the acceleration and propagation processes involved. We are now able to measure intensity-time profiles and anisotropies, energy spectra, elemental and isotopic abundances, and the ionic charge of particles over an extended energy range of 0.01 to several 100 MeV/nuc and for a large dynamic range of particle intensities. Furthermore, multi-spacecraft in-situ observations at different solar longitudes and latitudes provide new insight into the acceleration and propagation processes of SEPs near the Sun and in interplanetary space. In this paper we present an overview of SEP observations, their implications for SEP acceleration and propagation processes, and discuss open questions.

  1. Recent advances in understanding multiple myeloma.

    PubMed

    Dhakal, Binod; Girnius, Saulius; Hari, Parameswaran

    2016-01-01

    There have been major recent advancements in the understanding and management of multiple myeloma. Diagnostic criteria have been revised and former ultra-high-risk smoldering multiple myeloma is now considered multiple myeloma in need of treatment. Understanding clonal progression, evolution, and tides not only has helped elucidate the disease behavior but might help expand therapeutic choices in order to select appropriate treatment for patients. Unprecedented response rates with modern triplet induction therapies containing proteasome inhibitor and immunomodulators have made this approach standard for initial treatment. The US Food and Drug Administration approved four new drugs (two targeted antibodies and two oral agents) in 2015 in relapsed/refractory multiple myeloma and these drugs along with the other already-available drugs have now increased the choices of regimens. Even drugs without single-agent activity, such as panobinostat and elotuzumab, have an important role, especially in the proteasome inhibitor refractory setting. Recent studies done in the context of novel agent induction suggest that high-dose therapy followed by autologous transplant continues to improve response rates and progression-free survival, thus underscoring their role in transplant-eligible patients. Evolving paradigms in the treatment of multiple myeloma include newer promising immune approaches, such as adoptive cellular therapies, vaccines, or antibody-based immune manipulations. Though multiple myeloma is still considered incurable, it is clear that with the improved understanding of disease biology and clonal architecture of relapse combined with the availability of multi-targeted approaches, we are ever closer to a lasting cure or transformation into indolent and long-lasting disease courses or both.

  2. Recent advances in understanding multiple myeloma

    PubMed Central

    Dhakal, Binod; Girnius, Saulius; Hari, Parameswaran

    2016-01-01

    There have been major recent advancements in the understanding and management of multiple myeloma. Diagnostic criteria have been revised and former ultra-high-risk smoldering multiple myeloma is now considered multiple myeloma in need of treatment. Understanding clonal progression, evolution, and tides not only has helped elucidate the disease behavior but might help expand therapeutic choices in order to select appropriate treatment for patients. Unprecedented response rates with modern triplet induction therapies containing proteasome inhibitor and immunomodulators have made this approach standard for initial treatment. The US Food and Drug Administration approved four new drugs (two targeted antibodies and two oral agents) in 2015 in relapsed/refractory multiple myeloma and these drugs along with the other already-available drugs have now increased the choices of regimens. Even drugs without single-agent activity, such as panobinostat and elotuzumab, have an important role, especially in the proteasome inhibitor refractory setting. Recent studies done in the context of novel agent induction suggest that high-dose therapy followed by autologous transplant continues to improve response rates and progression-free survival, thus underscoring their role in transplant-eligible patients. Evolving paradigms in the treatment of multiple myeloma include newer promising immune approaches, such as adoptive cellular therapies, vaccines, or antibody-based immune manipulations. Though multiple myeloma is still considered incurable, it is clear that with the improved understanding of disease biology and clonal architecture of relapse combined with the availability of multi-targeted approaches, we are ever closer to a lasting cure or transformation into indolent and long-lasting disease courses or both. PMID:27610224

  3. Current Understandings of Plant Nonhost Resistance.

    PubMed

    Lee, Hyun-Ah; Lee, Hye-Young; Seo, Eunyoung; Lee, Joohyun; Kim, Saet-Byul; Oh, Soohyun; Choi, Eunbi; Choi, Eunhye; Lee, So Eui; Choi, Doil

    2017-01-01

    Nonhost resistance, a resistance of plant species against all nonadapted pathogens, is considered the most durable and efficient immune system of plants but yet remains elusive. The underlying mechanism of nonhost resistance has been investigated at multiple levels of plant defense for several decades. In this review, we have comprehensively surveyed the latest literature on nonhost resistance in terms of preinvasion, metabolic defense, pattern-triggered immunity, effector-triggered immunity, defense signaling, and possible application in crop protection. Overall, we summarize the current understanding of nonhost resistance mechanisms. Pre- and postinvasion is not much deviated from the knowledge on host resistance, except for a few specific cases. Further insights on the roles of the pattern recognition receptor gene family, multiple interactions between effectors from nonadapted pathogen and plant factors, and plant secondary metabolites in host range determination could expand our knowledge on nonhost resistance and provide efficient tools for future crop protection using combinational biotechnology approaches. [Formula: see text] Copyright © 2017 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

  4. Current Understandings of Spontaneous Isolated Superior Mesenteric Artery Dissection

    PubMed Central

    Kim, Young-Wook

    2016-01-01

    Spontaneous isolated superior mesenteric artery dissection (SISMAD) has been known as a rare vascular disease. However it is increasingly reported in these days with the development of advanced imaging technology. Underlying etiology, natural course or an optimal management strategy of SISMAD is not exactly known at the moment. During the past 10 years, we have had an interest in this rare vascular disease and collected clinical and image data in 100 or more patients with SISMAD. In this review article, I would like to describe my current understanding of SISMAD on the base of our recent publications in the major vascular surgery journals. PMID:27386450

  5. Advances in Understanding Decadal Climate Variability

    NASA Technical Reports Server (NTRS)

    Busalacchi, Antonio J.

    1999-01-01

    Recently, a joint Brazil-France-U.S. program, known as PIRATA (Pilot Research moored Array in the Tropical Atlantic), was proposed to begin the deployment of moored measurement platforms in the tropical Atlantic in order to enhance the existing observational data base and subsequent understanding of the processes by which the ocean and atmosphere couple in key regions of the tropical Atlantic Ocean. Empirical studies have suggested that there are strong relationships between tropical Atlantic upper ocean variability, SST, ocean-atmosphere coupling and regional climate variability. During the early 1980's a coordinated set of surface wind, subsurface thermal structure, and subsurface current observations were obtained as part of the U.S.-France SEQUAL-FOCAL process experiment designed to observe the seasonal response of the tropical Atlantic Ocean to surface forcing. Since that time, however, the observational data base for the tropical Atlantic Ocean has disintegrated to a few ship-tracks measuring ocean temperatures and a small collection of tide gauge stations measuring sea level. A more comprehensive set of observations, modeling and empirical studies is now in order to make progress on understanding the regional climate variability. The proposed PIRATA program will use mooring platforms similar to the tropical Pacific Ocean TAO array to measure surface fluxes of momentum and heat and the corresponding changes in the upper ocean thermal structure. It is anticipated that the oceanic data from this monitoring array will also be used in a predictive mode for initialization studies of regional coupled climate models. Of particular interest are zonal and meridional modes of ocean-atmosphere variability within the tropical Atlantic basin that have significant impacts on the regional climate of the bordering continents.

  6. Advances in Understanding Decadal Climate Variability

    NASA Technical Reports Server (NTRS)

    Busalaacchi, Antonio J.

    1998-01-01

    Recently, a joint Brazil-France-U.S. program, known as PIRATA (Pilot Research moored Array in the Tropical Atlantic), was proposed to begin the deployment of moored measurement platforms in the tropical Atlantic in order to enhance the existing observational data base and subsequent understanding of the processes by which the ocean and atmosphere couple in key regions of the tropical Atlantic Ocean. Empirical studies have suggested that there are strong relationships between tropical Atlantic upper ocean variability, SST, ocean-atmosphere coupling and regional climate variability. During the early 1980's a coordinated set of surface wind, subsurface thermal structure, and subsurface current observations were obtained as part of the U.S.-France SEQUAL- FOCAL process experiment designed to observe the seasonal response of the tropical Atlantic Ocean to surface forcing. Since that time, however, the observational data base for the tropical Atlantic Ocean has disintegrated to a few shiptracks measuring ocean temperatures and a small collection of tide gauge stations measuring sea level. A more comprehensive set of observations, modeling and empirical studies is now in order to make progress on understanding the regional climate variability. The proposed PIRATA program will use mooring platforms similar to the tropical Pacific Ocean TAO array to measure surface fluxes of momentum and heat and the corresponding changes in the upper ocean thermal structure. It is anticipated that the oceanic data from this monitoring array will also be used in a predictive mode for initialization studies of regional coupled climate models. Of particular interest are zonal and meridional modes of ocean-atmosphere variability within the tropical Atlantic basin that have significant impacts on the regional climate of the bordering continents.

  7. Progress in understanding halo current at JET

    NASA Astrophysics Data System (ADS)

    Riccardo, V.; Arnoux, G.; Beaumont, P.; Hacquin, S.; Hobirk, J.; Howell, D.; Huber, A.; Joffrin, E.; Koslowski, R.; Lam, N.; Leggate, H.; Rachlew, E.; Sergienko, G.; Stephen, A.; Todd, T.; Zerbini, M.; Delogu, R.; Grando, L.; Marcuzzi, D.; Peruzzo, S.; Pomaro, N.; Sonato, P.; JET EFDA Contributors

    2009-05-01

    The poloidal distribution of the halo current density on the top dump plate in JET can now be measured thanks to a new set of Rogowskii coils. These are the first measurements in JET able to offer an insight in the width of the halo current interaction with the wall. Therefore they offer both validation of the assumption made for JET disruption design criteria and one additional point in the extrapolation of the expected halo current width, and hence halo current density (and related local electro-mechanical loads on in-vessel components) for ITER. During upward events, the measured current density is consistent with the measured total poloidal halo current. The halo footprint extends over most of the upper dump plate, converting to a halo current flux tube width of ~100 mm. A set of four toridal field pick-up coils installed 90° apart now allows a more accurate measurement of the poloidal halo current, in particular its toroidal peaking factor, and direct comparison between halo and plasma asymmetries.

  8. Advances in understanding basic mechanisms of epilepsy and seizures.

    PubMed

    Jefferys, John G R

    2010-12-01

    Sixty years ago the clinical neurophysiology of epilepsy had progressed to the stage that it posed questions that could be addressed by major advances in cellular electrophysiology made around the that time. However, it took about 25-30 years to build up serious momentum in understanding the mechanisms of epileptic discharges. Over the past 2-3 decades developments in pharmacology and molecular biology have substantially increased the depth and complexity of our insights into the nervous system in general and the epileptic brain in particular. One of the biggest advances in our understanding of the brain is in its plasticity in the adult - that is its ability to modify its structure and function. The current state of play is that for most chronic epileptic foci it is possible to identify multiple differences from normal brain tissue in both the structure and function of neurons, neuronal networks and glia. This review will chart some of this progress to give an idea of the pace of advances over the decades.

  9. Eosinophilic esophagitis: current understanding and evolving concepts

    PubMed Central

    Kweh, Barry; Thien, Francis

    2017-01-01

    Eosinophilic esophagitis (EoE) is now considered to represent a form of food allergy and this is demonstrated by a response to elimination diet in many patients. A critical additional factor may be an inherent impairment in epithelial barrier integrity, possibly worsened by reflux of gastric contents and improved with proton pump inhibitor (PPI) use. Key clinic challenges are posed by the absence of reliable allergy tests to guide elimination diet, and the subsequent need for invasive endoscopic assessment following empirical food challenge, meaning that corticosteroids will remain the mainstay of therapy for many. From a research standpoint, determining if impairments in barrier integrity are innate, and how PPIs address this deficit (which may be pH independent) are important questions that when answered may allow future therapeutic advancement. PMID:28154800

  10. Current understanding of mdig/MINA in human cancers

    PubMed Central

    Thakur, Chitra; Chen, Fei

    2015-01-01

    Mineral dust-induced gene, mdig has recently been identified and is known to be overexpressed in a majority of human cancers and holds predictive power in the poor prognosis of the disease. Mdig is an environmentally expressed gene that is involved in cell proliferation, neoplastic transformation and immune regulation. With the advancement in deciphering the prognostic role of mdig in human cancers, our understanding on how mdig renders a normal cell to undergo malignant transformation is still very limited. This article reviews the current knowledge of the mdig gene in context to human neoplasias and its relation to the clinico-pathologic factors predicting the outcome of the disease in patients. It also emphasizes on the promising role of mdig that can serve as a potential candidate for biomarker discovery and as a therapeutic target in inflammation and cancers. Considering the recent advances in understanding the underlying mechanisms of tumor formation, more preclinical and clinical research is required to validate the potential of using mdig as a novel biological target of therapeutic and diagnostic value. Summary Expression level of mdig influences the prognosis of several human cancers especially cancers of the breast and lung. Evaluation of mdig in cancers can offer novel biomarker with potential therapeutic interventions for the early assessment of cancer development in patients. PMID:26413213

  11. Current Understanding of Mercury's Magnetosphere before MESSENGER

    NASA Astrophysics Data System (ADS)

    Krimigis, S. M.

    The MESSENGER spacecraft is scheduled to be launched mid-May, 2004 on a trajectory that includes two flybys (October 07, July 08) and eventual orbit insertion in July 2009 around the planet Mercury. Embedded in its payload are instruments to examine the basic properties of the planet's magnetosphere, including magnetometer, plasma, and energetic particle measurements (Gold et al, 2001). Our present knowledge of Mercury's magnetosphere is derived from two nightside Mariner 10 flybys in 1974, 1975 that established the presence of an intrinsic magnetic field and some energetic particles. Unfortunately not even the magnetic dipole term was well-resolved, and the fluxes and identity of energetic particles have been a subject of extensive discussion and varying interpretations (e.g. Armstrong et al, 1975, Christon, 1989). There has been evidence of field-aligned currents (e.g. Slavin et al, 1997), but alternative interpretations of magnetic signatures suggest that the magnetosphere may be driven by changing external boundary conditions (Luhman et al, 1998). These uncertainties, coupled with the observed presence of volatiles (H, He, O, Na, K, Ca) raise obvious questions on current closure, hot plasma injection and acceleration, the frequency with which the planetary surface is exposed to the solar wind, and potential sputtering of material due to particle impingement on the regolith. The talk will review our current knowledge and describe the measurements expected from MESSENGER that will address some of the key science questions. Armstrong et al, JGR, 80, 4015, 1975 Gold et al, Planet and Space Sci, 49, 1467, 2001 Christon, S.P., JGR, 94, 6481, 1989 Slavin et al, Planet and Space Sci, 45, 133, 1997 Luhman et al, JGR, 103, 9113, 1998

  12. Recent advances in understanding and managing chordomas

    PubMed Central

    Youssef, Carl; Aoun, Salah; Moreno, Jessica R.; Bagley, Carlos A.

    2016-01-01

    Chordomas are rare primary bone tumors arising from embryonic remnants of the notochord. They are slow-growing, locally aggressive, and destructive and typically involve the axial skeleton. Genetic studies have identified several mutations implicated in the pathogenesis of these tumors. Treatment poses a challenge given their insidious progression, degree of local invasion at presentation, and high recurrence rate. They tend to respond poorly to conventional chemotherapy and radiation. This makes radical resection the mainstay of their treatment. Recent advances in targeted chemotherapy and focused particle beam radiation, however, have improved the management and prognosis of these tumors. PMID:28105324

  13. Advances in understanding and managing bullous pemphigoid

    PubMed Central

    Zhao, Cathy Y.; Murrell, Dedee F.

    2015-01-01

    Bullous pemphigoid (BP) is the commonest subtype of autoimmune blistering disease in most countries of the world. It occurs most frequently in elderly patients and is characterised clinically by large, tense blisters in the skin preceded by urticarial plaques and pruritus. Immunopathologically, it is characterised by autoantibodies directed against the 180 kD antigen (BP180) and the 230 kD antigen (BP230). New knowledge regarding BP is being continually uncovered. This article reviews the recent advances in BP, including newer diagnostic tests, standardised outcome measures and emerging therapeutic options, as well as the evidence supporting their use. PMID:26918143

  14. Advancing Future Network Science through Content Understanding

    DTIC Science & Technology

    2014-05-01

    used a metaphor of gaining situational awareness in the context of cars parked at a sports event stadium. Likening this to content understanding...nature of defense for insurgency versus counter insurgency is move-counter move. Tivnen looks at this problem as a Red Queen Dance , as per Alice in

  15. Advanced techniques in current signature analysis

    NASA Astrophysics Data System (ADS)

    Smith, S. F.; Castleberry, K. N.

    1992-02-01

    In general, both ac and dc motors can be characterized as weakly nonlinear systems, in which both linear and nonlinear effects occur simultaneously. Fortunately, the nonlinearities are generally well behaved and understood and can be handled via several standard mathematical techniques already well developed in the systems modeling area; examples are piecewise linear approximations and Volterra series representations. Field measurements of numerous motors and motor-driven systems confirm the rather complex nature of motor current spectra and illustrate both linear and nonlinear effects (including line harmonics and modulation components). Although previous current signature analysis (CSA) work at Oak Ridge and other sites has principally focused on the modulation mechanisms and detection methods (AM, PM, and FM), more recent studies have been conducted on linear spectral components (those appearing in the electric current at their actual frequencies and not as modulation sidebands). For example, large axial-flow compressors (approximately 3300 hp) in the US gaseous diffusion uranium enrichment plants exhibit running-speed (approximately 20 Hz) and high-frequency vibrational information (greater than 1 kHz) in their motor current spectra. Several signal-processing techniques developed to facilitate analysis of these components, including specialized filtering schemes, are presented. Finally, concepts for the designs of advanced digitally based CSA units are offered, which should serve to foster the development of much more computationally capable 'smart' CSA instrumentation in the next several years.

  16. Advances in understanding paternally transmitted Chromosomal Abnormalities

    SciTech Connect

    Marchetti, F; Sloter, E; Wyrobek, A J

    2001-03-01

    Multicolor FISH has been adapted for detecting the major types of chromosomal abnormalities in human sperm including aneuploidies for clinically-relevant chromosomes, chromosomal aberrations including breaks and rearrangements, and other numerical abnormalities. The various sperm FISH assays have been used to evaluate healthy men, men of advanced age, and men who have received mutagenic cancer therapy. The mouse has also been used as a model to investigate the mechanism of paternally transmitted genetic damage. Sperm FISH for the mouse has been used to detect chromosomally abnormal mouse sperm, while the PAINT/DAPI analysis of mouse zygotes has been used to evaluate the types of chromosomal defects that can be paternally transmitted to the embryo and their effects on embryonic development.

  17. Hemiconvulsion-hemiplegia-epilepsy syndrome: current understandings.

    PubMed

    Auvin, Stéphane; Bellavoine, Vanina; Merdariu, Dana; Delanoë, Catherine; Elmaleh-Bergés, Monique; Gressens, Pierre; Boespflug-Tanguy, Odile

    2012-09-01

    Hemiconvulsion-Hemiplegia (HH) syndrome is an uncommon consequence of prolonged focal febrile convulsive seizures in infancy and early childhood. It is characterized by the occurrence of prolonged clonic seizures with unilateral predominance occurring in a child and followed by the development of hemiplegia. Neuroradiological studies showed unilateral edematous swelling of the epileptic hemisphere at the time of initial status epilepticus (SE). This acute phase is followed by characteristic cerebral hemiatrophy with subsequent appearance of epilepsy, so called Hemiconvulsion-Hemiplegia-Epilepsy (HHE) syndrome. The etiologies and the underlying mechanisms remain to be understood. Using a review of the literature, we summarized the data of the last 20 years. It appears that idiopathic HH/HHE syndrome is the most common reported form. The basic science data suggest that immature brain is relatively resistant to SE-induced cell injury. Several factors might contribute to the pathogenesis of HH/HHE syndrome: 1. prolonged febrile seizure in which inflammation may worsen the level of cell injury; 2. inflammation and prolonged ictal activity that act on blood-brain-barrier permeability; 3. predisposing factors facilitating prolonged seizure such as genetic factors or focal epileptogenic lesion. However, these factors cannot explain the elective involvement of an entire hemisphere. We draw new hypothesis that may explain the involvement of one hemisphere such as maturation of brain structure such as corpus callosum or genetic factors (CACNA1A gene) that are specifically discussed. An early diagnosis and a better understanding of the underlying mechanisms of HHE are needed to improve the outcome of this condition.

  18. Cirrhosis and autoimmune liver disease: Current understanding

    PubMed Central

    Liberal, Rodrigo; Grant, Charlotte R

    2016-01-01

    Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) constitute the classic autoimmune liver diseases (AILDs). While AIH target the hepatocytes, in PBC and PSC the targets of the autoimmune attack are the biliary epithelial cells. Persistent liver injury, associated with chronic AILD, leads to un-resolving inflammation, cell proliferation and the deposition of extracellular matrix proteins by hepatic stellate cells and portal myofibroblasts. Liver cirrhosis, and the resultant loss of normal liver function, inevitably ensues. Patients with cirrhosis have higher risks or morbidity and mortality, and that in the decompensated phase, complications of portal hypertension and/or liver dysfunction lead to rapid deterioration. Accurate diagnosis and monitoring of cirrhosis is, therefore of upmost importance. Liver biopsy is currently the gold standard technique, but highly promising non-invasive methodology is under development. Liver transplantation (LT) is an effective therapeutic option for the management of end-stage liver disease secondary to AIH, PBC and PSC. LT is indicated for AILD patients who have progressed to end-stage chronic liver disease or developed intractable symptoms or hepatic malignancy; in addition, LT may also be indicated for patients presenting with acute liver disease due to AIH who do not respond to steroids. PMID:27729952

  19. Recent advances in understanding ichthyosis pathogenesis

    PubMed Central

    Marukian, Nareh V.; Choate, Keith A.

    2016-01-01

    The ichthyoses, also known as disorders of keratinization (DOK), encompass a heterogeneous group of skin diseases linked by the common finding of abnormal barrier function, which initiates a default compensatory pathway of hyperproliferation, resulting in the characteristic clinical manifestation of localized and/or generalized scaling. Additional cutaneous findings frequently seen in ichthyoses include generalized xerosis, erythroderma, palmoplantar keratoderma, hypohydrosis, and recurrent infections. In 2009, the Ichthyosis Consensus Conference established a classification consensus for DOK based on pathophysiology, clinical manifestations, and mode of inheritance. This nomenclature system divides DOK into two main groups: nonsyndromic forms, with clinical findings limited to the skin, and syndromic forms, with involvement of additional organ systems. Advances in next-generation sequencing technology have allowed for more rapid and cost-effective genetic analysis, leading to the identification of novel, rare mutations that cause DOK, many of which represent phenotypic expansion. This review focuses on new findings in syndromic and nonsyndromic ichthyoses, with emphasis on novel genetic discoveries that provide insight into disease pathogenesis. PMID:27408699

  20. Advances in understanding and treating ADHD

    PubMed Central

    2011-01-01

    Attention deficit hyperactivity disorder (ADHD) is a neurocognitive behavioral developmental disorder most commonly seen in childhood and adolescence, which often extends to the adult years. Relative to a decade ago, there has been extensive research into understanding the factors underlying ADHD, leading to far more treatment options available for both adolescents and adults with this disorder. Novel stimulant formulations have made it possible to tailor treatment to the duration of efficacy required by patients, and to help mitigate the potential for abuse, misuse and diversion. Several new non-stimulant options have also emerged in the past few years. Among these, cognitive behavioral interventions have proven popular in the treatment of adult ADHD, especially within the adult population who cannot or will not use medications, along with the many medication-treated patients who continue to show residual disability. PMID:21658285

  1. Advances in understanding the leukaemia microenvironment.

    PubMed

    Tabe, Yoko; Konopleva, Marina

    2014-03-01

    Dynamic interactions between leukaemic cells and cells of the bone marrow are a feature of haematological malignancies. Two distinct microenvironmental niches in the bone marrow, the 'osteoblastic (endosteal)' and 'vascular' niches, provide a sanctuary for subpopulations of leukaemic cells to evade chemotherapy-induced death and allow acquisition of drug resistance. Key components of the bone marrow microenvironment as a home for normal haematopoietic stem cells and the leukaemia stem cell niches, and the molecular pathways critical for microenvironment/leukaemia interactions via cytokines, chemokines and adhesion molecules as well as hypoxic conditions, are described in this review. Finally, the genetic abnormalities of leukaemia-associated stroma are discussed. Further understanding of the contribution of the bone marrow niche to the process of leukaemogenesis may provide new targets that allow destruction of leukaemia stem cells without adversely affecting normal stem cell self-renewal.

  2. Advances in understanding hydration of Portland cement

    SciTech Connect

    Scrivener, Karen L.; Juilland, Patrick; Monteiro, Paulo J.M.

    2015-12-15

    Progress in understanding hydration is summarized. Evidence supports the geochemistry dissolution theory as an explanation for the induction period, in preference to the inhibiting layer theory. The growth of C–S–H is the principal factor controlling the main heat evolution peak. Electron microscopy indicates that C–S–H “needles” grow from the surface of grains. At the peak, the surface is covered, but deceleration cannot be attributed to diffusion control. The shoulder peak comes from renewed reaction of C{sub 3}A after depletion of sulfate in solution, but release of sulfate absorbed on C–S–H means that ettringite continues to form. After several days space becomes the major factor controlling hydration. The use of new analytical technique is improving our knowledge of the action of superplasticizers and leading to the design of molecules for different applications. Atomistic modeling is becoming a topic of increasing interest. Recent publications in this area are reviewed.

  3. Recent advances in understanding provoked vestibulodynia

    PubMed Central

    Lev-Sagie, Ahinoam; Witkin, Steven S.

    2016-01-01

    Vulvodynia refers to pain in the vulva of at least 3 months’ duration in the absence of a recognized underlying cause. Provoked, localized vestibulodynia is the term used to describe superficial pain confined to the vulvar vestibule, provoked by touch. This review will focus on provoked vestibulodynia with regard to its suggested causative factors and will discuss the role of inflammation, vulvovaginal infections, mucosal nerve fiber proliferation, hormonal associations, central pain mechanisms, pelvic floor muscle dysfunction, and genetic factors. Clinical observations, epidemiological studies, and data from basic research emphasize the heterogeneity of vulvar pain syndromes. There is a critical need to perform prospective, longitudinal studies that will allow better diagnostic criteria and subgrouping of patients that would lead to improvements in our understanding of provoked vestibulodynia and its treatment. PMID:27853523

  4. Recent advances in understanding hepatic drug transport

    PubMed Central

    Stieger, Bruno; Hagenbuch, Bruno

    2016-01-01

    Cells need to strictly control their internal milieu, a function which is performed by the plasma membrane. Selective passage of molecules across the plasma membrane is controlled by transport proteins. As the liver is the central organ for drug metabolism, hepatocytes are equipped with numerous drug transporters expressed at the plasma membrane. Drug disposition includes absorption, distribution, metabolism, and elimination of a drug and hence multiple passages of drugs and their metabolites across membranes. Consequently, understanding the exact mechanisms of drug transporters is essential both in drug development and in drug therapy. While many drug transporters are expressed in hepatocytes, and some of them are well characterized, several transporters have only recently been identified as new drug transporters. Novel powerful tools to deorphanize (drug) transporters are being applied and show promising results. Although a large set of tools are available for studying transport in vitro and in isolated cells, tools for studying transport in living organisms, including humans, are evolving now and rely predominantly on imaging techniques, e.g. positron emission tomography. Imaging is an area which, certainly in the near future, will provide important insights into "transporters at work" in vivo. PMID:27781095

  5. Recent advances in understanding and managing urolithiasis

    PubMed Central

    Strohmaier, Walter L.

    2016-01-01

    During the last few years, there has been relevant progress in both understanding and managing urolithiasis. Our knowledge of stone formation has changed; although the importance of urine biochemistry was questioned by several investigators years ago, the decisive role of cellular processes (induced by oxidative stress) and the renal papilla has only recently been generally accepted as the most important step in stone formation. For calcium oxalate urolithiasis, the formation of papillary calcifications plays a key role and is of prognostic relevance. Further research has to concentrate on these aspects of preventing urolithiasis. Stone prevention (metaphylaxis) is a major issue when considering the burden it places on healthcare systems. An effective metaphylaxis could lower the cost of stone therapy significantly. For uric acid urolithiasis, so far there is only preliminary information available showing that papillary plaques are not as important as they are in calcium oxalate urolithiasis. Concerning stone management, endourology has improved stone therapy significantly during the last few years. Morbidity decreased and success (stone-free) rates increased. Therefore, the indications for extracorporeal shockwave lithotripsy (ESWL) narrowed. ESWL, however, still has its place in stone therapy. There is not one single treatment modality that is equally effective for all situations. It is important to observe the differential indications for different stones depending on size, localization, and composition. PMID:27853528

  6. Recent advances in understanding antiphospholipid syndrome

    PubMed Central

    Bertolaccini, Maria Laura; Sanna, Giovanni

    2016-01-01

    Antiphospholipid syndrome (APS), also known as Hughes Syndrome, is a systemic autoimmune disease characterized by thrombosis and/or pregnancy morbidity in the presence of persistently positive antiphospholipid antibodies. A patient with APS must meet at least one of two clinical criteria (vascular thrombosis or complications of pregnancy) and at least one of two laboratory criteria including the persistent presence of lupus anticoagulant (LA), anticardiolipin antibodies (aCL), and/or anti-b2 glycoprotein I (anti-b2GPI) antibodies of IgG or IgM isotype at medium to high titres in patient’s plasma. However, several other autoantibodies targeting other coagulation cascade proteins (i.e. prothrombin) or their complex with phospholipids (i.e. phosphatidylserine/prothrombin complex), or to some domains of β2GPI, have been proposed to be also relevant to APS. In fact, the value of testing for new aPL specificities in the identification of APS in thrombosis and/or pregnancy morbidity patients is currently being investigated. PMID:28105326

  7. Recent advances in understanding antiphospholipid syndrome.

    PubMed

    Bertolaccini, Maria Laura; Sanna, Giovanni

    2016-01-01

    Antiphospholipid syndrome (APS), also known as Hughes Syndrome, is a systemic autoimmune disease characterized by thrombosis and/or pregnancy morbidity in the presence of persistently positive antiphospholipid antibodies. A patient with APS must meet at least one of two clinical criteria (vascular thrombosis or complications of pregnancy) and at least one of two laboratory criteria including the persistent presence of lupus anticoagulant (LA), anticardiolipin antibodies (aCL), and/or anti-b2 glycoprotein I (anti-b2GPI) antibodies of IgG or IgM isotype at medium to high titres in patient's plasma. However, several other autoantibodies targeting other coagulation cascade proteins (i.e. prothrombin) or their complex with phospholipids (i.e. phosphatidylserine/prothrombin complex), or to some domains of β2GPI, have been proposed to be also relevant to APS. In fact, the value of testing for new aPL specificities in the identification of APS in thrombosis and/or pregnancy morbidity patients is currently being investigated.

  8. Advances in understanding angiogenesis through molecular studies

    SciTech Connect

    Kwon, Mijung; Libutti, Steven K. . E-mail: steven_libutti@nih.gov

    2006-01-01

    Tumors, in most cases, need angiogenesis for their sustained growth. A great deal of evidence has suggested that the process of angiogenesis is regulated by the balance between proangiogenic and antiangiogenic factors. Thus, the inhibition of tumor angiogenesis has been considered to be one of the key targets in anticancer therapy, and more than 60 antiangiogenic compounds are currently under clinical evaluation in cancer patients. However, the molecular mechanisms responsible for the activity of many of these antiangiogenic compounds are still not well understood. The recent development of microarray technology has allowed us to investigate the mechanism of action of these inhibitors more rapidly and extensively. With the use of microarray technology, novel molecules and pathways are shown to play a role in angiogenesis. This article also reviews new experimental approaches combined with microarray analysis to identify the molecular pathways involved in tumor-host interactions. Elucidation of the pathways that mediate both angiogenic and antiangiogenic responses will help us to develop better anticancer therapies.

  9. Advances In Understanding Solar And Stellar Flares

    NASA Astrophysics Data System (ADS)

    Kowalski, Adam F.

    2016-07-01

    Flares result from the sudden reconnection and relaxation of magnetic fields in the coronae of stellar atmospheres. The highly dynamic atmospheric response produces radiation across the electromagnetic spectrum, from the radio to X-rays, on a range of timescales, from seconds to days. New high resolution data of solar flares have revealed the intrinsic spatial properties of the flaring chromosphere, which is thought to be where the majority of the flare energy is released as radiation in the optical and near-UV continua and emission lines. New data of stellar flares have revealed the detailed properties of the broadband (white-light) continuum emission, which provides straightforward constraints for models of the transformation of stored magnetic energy in the corona into thermal energy of the lower atmosphere. In this talk, we discuss the physical processes that produce several important spectral phenomena in the near-ultraviolet and optical as revealed from new radiative-hydrodynamic models of flares on the Sun and low mass stars. We present recent progress with high-flux nonthermal electron beams in reproducing the observed optical continuum color temperature of T 10,000 K and the Balmer jump properties in the near-ultraviolet. These beams produce dense, heated chromospheric condensations, which can explain the shape and strength of the continuum emission in M dwarf flares and the red-wing asymmetries in the chromospheric emission lines in recent observations of solar flares from the Interface Region Imaging Spectrograph. Current theoretical challenges and future modeling directions will be discussed, as well as observational synergies between solar and stellar flares.

  10. What I Wish: Three Advancement Professionals Discuss What Their Colleagues Need to Understand about Their Jobs

    ERIC Educational Resources Information Center

    Gurd, Andy; Peirce, Susan; Morris, Sarah

    2012-01-01

    Three advancement professionals discuss what their colleagues need to understand about their jobs. The Ohio State University Alumni Association is currently integrating into the university's advancement office at the behest of the board of trustees, so Andy Gurd is now working more closely with his development and communications colleagues than…

  11. Advanced Science Students' Understandings on Nature of Science in Finland

    ERIC Educational Resources Information Center

    Sormunen, Kari; Köksal, Mustafa Serdar

    2014-01-01

    Majority of NOS studies comprise of determination or assessment studies conducted with ordinary students. In order to gain further understanding on variation in NOS understandings among the students, there should be different research attempts focusing on unconventional students such as academically advanced students. The purpose of this study is…

  12. Current Comparison of Advanced Fuel Cycle Options

    SciTech Connect

    Steven J. Piet; B. W. Dixon; A. Goldmann; R. N. Hill; J. J. Jacobson; G. E. Matthern; J. D. Smith; A. M. Yacout

    2006-03-01

    The nuclear fuel cycle includes mining, enrichment, nuclear power plants, recycling (if done), and residual waste disposition. The U.S. Advanced Fuel Cycle Initiative (AFCI) has four program objectives to guide research on how best to glue these pieces together, as follows: waste management, proliferation resistance, energy recovery, and systematic management/economics/safety. We have developed a comprehensive set of metrics to evaluate fuel cycle options against the four program objectives. The current list of metrics is long-term heat, long-term dose, radiotoxicity and weapons usable material. This paper describes the current metrics and initial results from comparisons made using these metrics. The data presented were developed using a combination of “static” calculations and a system dynamic model, DYMOND. In many cases, we examine the same issue both dynamically and statically to determine the robustness of the observations. All analyses are for the U.S. reactor fleet. This work aims to clarify many of the issues being discussed within the AFCI program, including Inert Matrix Fuel (IMF) versus Mixed Oxide (MOX) fuel, single-pass versus multi-pass recycling, thermal versus fast reactors, and the value of separating cesium and strontium. The results from a series of dynamic simulations evaluating these options are included in this report. The model interface includes a few “control knobs” for flying or piloting the fuel cycle system into the future. The results from the simulations show that the future is dark (uncertain) and that the system is sluggish with slow time response times to changes (i.e., what types of reactors are built, what types of fuels are used, and the capacity of separation and fabrication plants). Piloting responsibilities are distributed among utilities, government, and regulators, compounding the challenge of making the entire system work and respond to changing circumstances. We identify four approaches that would increase our

  13. Recent advances in understanding and treating nephrotic syndrome

    PubMed Central

    Bierzynska, Agnieszka; Saleem, Moin

    2017-01-01

    Idiopathic nephrotic syndrome (INS) is one of the most common glomerular diseases in children and adults, and the central event is podocyte injury. INS is a heterogeneous disease, and treatment is largely empirical and in many cases unsuccessful, and steroids are the initial mainstay of therapy. Close to 70% of children with INS have some response to steroids and are labelled as steroid-‘sensitive’, and the rest as steroid-‘resistant’ (also termed focal segmental glomerulosclerosis), and single-gene mutations underlie a large proportion of the latter group. The burden of morbidity is enormous, both to patients with lifelong chronic disease and to health services, particularly in managing dialysis and transplantation. The target cell of nephrotic syndrome is the glomerular podocyte, and podocyte biology research has exploded over the last 15 years. Major advances in genetic and biological understanding now put clinicians and researchers at the threshold of a major reclassification of the disease and testing of targeted therapies both identified and novel. That potential is based on complete genetic analysis, deep clinical phenotyping, and the introduction of mechanism-derived biomarkers into clinical practice. INS can now be split off into those with a single-gene defect, of which currently at least 53 genes are known to be causative, and the others. Of the others, the majority are likely to be immune-mediated and caused by the presence of a still-unknown circulating factor or factors, and whether there is a third (or more) mechanistic group or groups remains to be discovered. Treatment is therefore now being refined towards separating out the monogenic cases to minimise immunosuppression and further understanding how best to stratify and appropriately direct immunosuppressive treatments within the immune group. Therapies directed specifically towards the target cell, the podocyte, are in their infancy but hold considerable promise for the near future. PMID

  14. Recent Advances in Studies of Current Noise

    NASA Astrophysics Data System (ADS)

    Blanter, Yaroslav M.

    This is a brief review of recent activities in the field of current noise intended for newcomers. We first briefly discuss main properties of shot noise in nanostructures, and then turn to recent developments, concentrating on issues related to experimental progress: non-symmetrized cumulants and quantum noise; counting statistics; super-Poissonian noise; current noise and interferometry

  15. Recent Advances in Understanding, Diagnosing, and Treating Ovarian Cancer

    PubMed Central

    Mills, Kathryn; Fuh, Katherine

    2017-01-01

    Ovarian cancer, a term that encompasses ovarian, fallopian, and peritoneal cancers, is the leading cause of gynecologic cancer mortality. To improve patient outcomes, the field is currently focused on defining the mechanisms of cancer formation and spread, early diagnosis and prevention, and developing novel therapeutic options. This review summarizes recent advances in these areas. PMID:28184293

  16. Understanding Current Safety Issues for Trajectory Based Operations

    NASA Technical Reports Server (NTRS)

    Feary, Michael; Stewart, Michael

    2016-01-01

    Increases in procedural complexity were investigated as a possible contributor to flight path deviations in airline operations. Understanding current operational issues and their causes must be embraced to maintain current safety standards while increasing future functionality. ASRS data and expert narratives were used to discover factors relating to pilot deviations. Our investigation pointed to ATC intervention, automation confusion, procedure design, and mixed equipment as primary issues. Future work will need to include objective data and mitigation strategies.

  17. Fish Vaccines: Current State and Future Advances

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In aquaculture, the development and use of vaccines is now making rapid progress to achieve its full potential as an effective disease prevention tool. Currently, USDA, APHIS, CVB licenses 17 fish vaccines of which 2 are modified live and 14 are killed vaccines. The objective of vaccination is to pr...

  18. Primary processes in sensory cells: current advances.

    PubMed

    Frings, Stephan

    2009-01-01

    In the course of evolution, the strong and unremitting selective pressure on sensory performance has driven the acuity of sensory organs to its physical limits. As a consequence, the study of primary sensory processes illustrates impressively how far a physiological function can be improved if the survival of a species depends on it. Sensory cells that detect single-photons, single molecules, mechanical motions on a nanometer scale, or incredibly small fluctuations of electromagnetic fields have fascinated physiologists for a long time. It is a great challenge to understand the primary sensory processes on a molecular level. This review points out some important recent developments in the search for primary processes in sensory cells that mediate touch perception, hearing, vision, taste, olfaction, as well as the analysis of light polarization and the orientation in the Earth's magnetic field. The data are screened for common transduction strategies and common transduction molecules, an aspect that may be helpful for researchers in the field.

  19. Nursing staff's understanding expressions of people with advanced dementia disease.

    PubMed

    Eggers, Thomas; Ekman, Sirkka-Liisa; Norberg, Astrid

    2013-01-01

    People with advanced dementia disease (ADD) are known to have communication difficulties and thus it presents a challenge in understanding the expressions of these people. Because successful communication presupposes cooperation at least between 2 individuals, both individual's actions must be acknowledged. The aim of this study is to describe nursing staff's ways of understanding the expressions of people with ADD when communicating with them. Interviews from 8 nursing staff were analyzed using qualitative content analysis. Two themes were constructed: "Being in communication" and "Doing communication." Being in communication means that nursing staff perceive people with ADD as being capable of communication. Doing communication means that nursing staff attempt different individualized strategies to understand what people with ADD communicate. Good care of people with ADD presupposes nursing staff that are willing and able to relate to other people and to maintain good care for people with ADD continuous education and supervision are needed.

  20. A Hydrological Perspective to Advance Understanding of the Water Cycle

    NASA Astrophysics Data System (ADS)

    Berghuijs, W.

    2014-12-01

    In principle hydrologists are scientists that study relationships within the water cycle. Yet, current technology makes it tempting for hydrology students to lose their "hydrological perspective" and become instead full-time computer programmers or statisticians. I assert that students should ensure their hydrological perspective thrives, notwithstanding the importance and possibilities of current technology. This perspective is necessary to advance the science of hydrology. As other hydrologists have pondered similar views before, I make no claims of originality here. I just hope that in presenting my perspective on this issue I may spark the interest of other early career hydrologists.

  1. Behavioral cardiology: current advances and future directions.

    PubMed

    Rozanski, Alan

    2014-07-08

    Growing epidemiological evidence identifies key domains relevant to behavioral cardiology, including health behaviors, emotions, mental mindsets, stress management, social connectedness, and a sense of purpose. Each of these domains exists along a continuum, ranging from positive factors that promote health, to negative factors, which are pathophysiological. To date, there has been relatively little translation of this growing knowledge base into cardiology practice. Four initiatives are proposed to meet this challenge: 1) promulgating greater awareness of the potency of psychosocial risks factors; 2) overcoming a current "artificial divide" between conventional and psychosocial risk factors; 3) developing novel cost-effective interventions using Internet and mobile health applications, group-based counseling, and development of tiered-care behavioral management; and 4) in recognition that "one size does not fit all" with respect to behavioral interventions, developing specialists who can counsel patients in multidisciplinary fashion and use evidence-based approaches for promoting patient motivation and execution of health goals.

  2. Current advances in esophageal cancer proteomics.

    PubMed

    Uemura, Norihisa; Kondo, Tadashi

    2015-06-01

    We review the current status of proteomics for esophageal cancer (EC) from a clinician's viewpoint. The ultimate goal of cancer proteomics is the improvement of clinical outcome. The proteome as a functional translation of the genome is a straightforward representation of genomic mechanisms that trigger carcinogenesis. Cancer proteomics has identified the mechanisms of carcinogenesis and tumor progression, detected biomarker candidates for early diagnosis, and provided novel therapeutic targets for personalized treatments. Our review focuses on three major topics in EC proteomics: diagnostics, treatment, and molecular mechanisms. We discuss the major histological differences between EC types, i.e., esophageal squamous cell carcinoma and adenocarcinoma, and evaluate the clinical significance of published proteomics studies, including promising diagnostic biomarkers and novel therapeutic targets, which should be further validated prior to launching clinical trials. Multi-disciplinary collaborations between basic scientists, clinicians, and pathologists should be established for inter-institutional validation. In conclusion, EC proteomics has provided significant results, which after thorough validation, should lead to the development of novel clinical tools and improvement of the clinical outcome for esophageal cancer patients. This article is part of a Special Issue entitled: Medical Proteomics.

  3. Current advances in systems and integrative biology

    PubMed Central

    Robinson, Scott W.; Fernandes, Marco; Husi, Holger

    2014-01-01

    Systems biology has gained a tremendous amount of interest in the last few years. This is partly due to the realization that traditional approaches focusing only on a few molecules at a time cannot describe the impact of aberrant or modulated molecular environments across a whole system. Furthermore, a hypothesis-driven study aims to prove or disprove its postulations, whereas a hypothesis-free systems approach can yield an unbiased and novel testable hypothesis as an end-result. This latter approach foregoes assumptions which predict how a biological system should react to an altered microenvironment within a cellular context, across a tissue or impacting on distant organs. Additionally, re-use of existing data by systematic data mining and re-stratification, one of the cornerstones of integrative systems biology, is also gaining attention. While tremendous efforts using a systems methodology have already yielded excellent results, it is apparent that a lack of suitable analytic tools and purpose-built databases poses a major bottleneck in applying a systematic workflow. This review addresses the current approaches used in systems analysis and obstacles often encountered in large-scale data analysis and integration which tend to go unnoticed, but have a direct impact on the final outcome of a systems approach. Its wide applicability, ranging from basic research, disease descriptors, pharmacological studies, to personalized medicine, makes this emerging approach well suited to address biological and medical questions where conventional methods are not ideal. PMID:25379142

  4. Recent advances in understanding Epstein-Barr virus

    PubMed Central

    Stanfield, Brent A.; Luftig, Micah A.

    2017-01-01

    Epstein-Barr virus (EBV) is a common human herpes virus known to infect the majority of the world population. Infection with EBV is often asymptomatic but can manifest in a range of pathologies from infectious mononucleosis to severe cancers of epithelial and lymphocytic origin. Indeed, in the past decade, EBV has been linked to nearly 10% of all gastric cancers. Furthermore, recent advances in high-throughput next-generation sequencing and the development of humanized mice, which effectively model EBV pathogenesis, have led to a wealth of knowledge pertaining to strain variation and host-pathogen interaction. This review highlights some recent advances in our understanding of EBV biology, focusing on new findings on the early events of infection, the role EBV plays in gastric cancer, new strain variation, and humanized mouse models of EBV infection.

  5. Recent advances in understanding the cellular roles of GSK-3

    PubMed Central

    Cormier, Kevin W.; Woodgett, James R.

    2017-01-01

    Glycogen synthase kinase-3 (GSK-3) is a ubiquitously expressed protein kinase that sits at the nexus of multiple signaling pathways. Its deep integration into cellular control circuits is consummate to its implication in diseases ranging from mood disorders to diabetes to neurodegenerative diseases and cancers. The selectivity and insulation of such a promiscuous kinase from unwanted crosstalk between pathways, while orchestrating a multifaceted response to cellular stimuli, offer key insights into more general mechanisms of cell regulation. Here, we review recent advances that have contributed to the understanding of GSK-3 and its role in driving appreciation of intracellular signal coordination. PMID:28299185

  6. Recent advances in understanding nuclear size and shape.

    PubMed

    Mukherjee, Richik N; Chen, Pan; Levy, Daniel L

    2016-04-25

    Size and shape are important aspects of nuclear structure. While normal cells maintain nuclear size within a defined range, altered nuclear size and shape are associated with a variety of diseases. It is unknown if altered nuclear morphology contributes to pathology, and answering this question requires a better understanding of the mechanisms that control nuclear size and shape. In this review, we discuss recent advances in our understanding of the mechanisms that regulate nuclear morphology, focusing on nucleocytoplasmic transport, nuclear lamins, the endoplasmic reticulum, the cell cycle, and potential links between nuclear size and size regulation of other organelles. We then discuss the functional significance of nuclear morphology in the context of early embryonic development. Looking toward the future, we review new experimental approaches that promise to provide new insights into mechanisms of nuclear size control, in particular microfluidic-based technologies, and discuss how altered nuclear morphology might impact chromatin organization and physiology of diseased cells.

  7. Microscopic understanding of spin current probed by shot noise

    NASA Astrophysics Data System (ADS)

    Arakawa, Tomonori

    The spin currents is one of key issue in the spintronics field and the generation and detection of those have been intensively studied by using various materials. The analysis of experiments, however, relies on phenomenological parameters such as spin relaxation length and spin flip time. The microscopic nature of the spin current such as energy distribution and energy relaxation mechanism, has not yet well understood. To establish a better microscopic understanding of spin currents, I focused on the shot noise measurement which is well established technique in the field of mesoscopic physics [Y. M. Blanter and M. B üttiker, Phys. Rep. 336, 1 (2000).]. Although there are many theoretically works about shot noise in the presence of spin currents, for example detection of spin accumulation [J. Meair, P. Stano, and P. Jacquod, Phys. Rev. B 84 (2011).], estimation of spin flip currents, and so on, these predictions have never been experimentally confirmed. In this context, we reported the first experimental detention of shot noise in the presence of the spin accumulation in a (Ga,Mn)As/tunnel barrier/n-GaAs based lateral spin valve device [T. Arakawa et al., Phys. Rev. Lett. 114, 016601 (2015).]. Together with this result, we found however that the effective temperature of the spin current drastically increases due to the spin injection process. This heating of electron system could be a big problem to realize future spin current devices by using quantum coherence, because the effective temperature rise directly related to the destruction of the coherence of the spin current. Therefore, then we focused on the mechanism of this heating and the energy relaxation in a diffusive channel. By measuring current noise and the DC offset voltage in the usual non-local spin valve signal as a function of the spin diffusion channel length, we clarified that the electron-electron interaction length, which is the characteristic length for the relaxation of the electron system, is

  8. Understanding the Current Dynamical States of Globular Clusters

    NASA Astrophysics Data System (ADS)

    Pooley, David

    2008-09-01

    We appear to be on the verge of a major paradigm shift in our understanding of the current dynamical states of Galactic globular clusters. Fregeau (2008) brought together two recent theoretical breakthroughs as well as an observational breakthrough made possible by Chandra -- that a globular cluster's X-ray source population scales with its dynamical encounter frequency -- to persuasively argue that we have misunderstood the dynamical states of Galactic globular clusters. The observational evidence hinges on Chandra results from clusters which are classified as "core collapsed," of which there are only a handful of observations. I propose a nearly complete census with Chandra of the rest of the "core collapsed" globular clusters.

  9. Understanding the advances in biology of orthodontic tooth movement for improved ortho-perio interdisciplinary approach

    PubMed Central

    Patil, Anand K.; Shetty, Adarsh S.; Setty, Swati; Thakur, Srinath

    2013-01-01

    This article provides an insight on detailed current advances in molecular understandings of periodontal ligament cells and the influence of orthodontic force on them in the light of recent advances in molecular and genetic sciences. It sequentially unfolds the cellular events beginning from the mechanical force initiated events of cellular responses to bone remodeling. It also highlights the risks and limitations of orthodontic treatment in certain periodontal conditions, the important areas of team work, orthodontic expectations from periodontal treatment and the possibility of much more future combined research to improve the best possible periodontal health and esthetic outcome of the patient. PMID:24049330

  10. Current preclinical models for the advancement of translational bladder cancer research.

    PubMed

    DeGraff, David J; Robinson, Victoria L; Shah, Jay B; Brandt, William D; Sonpavde, Guru; Kang, Yibin; Liebert, Monica; Wu, Xue-Ru; Taylor, John A

    2013-02-01

    Bladder cancer is a common disease representing the fifth most diagnosed solid tumor in the United States. Despite this, advances in our understanding of the molecular etiology and treatment of bladder cancer have been relatively lacking. This is especially apparent when recent advances in other cancers, such as breast and prostate, are taken into consideration. The field of bladder cancer research is ready and poised for a series of paradigm-shifting discoveries that will greatly impact the way this disease is clinically managed. Future preclinical discoveries with translational potential will require investigators to take full advantage of recent advances in molecular and animal modeling methodologies. We present an overview of current preclinical models and their potential roles in advancing our understanding of this deadly disease and for advancing care.

  11. Current advances in synchrotron radiation instrumentation for MX experiments

    SciTech Connect

    Owen, Robin L.; Juanhuix, Jordi; Fuchs, Martin

    2016-04-01

    Following pioneering work 40 years ago, synchrotron beamlines dedicated to macromolecular crystallography (MX) have improved in almost every aspect as instrumentation has evolved. Beam sizes and crystal dimensions are now on the single micron scale while data can be collected from proteins with molecular weights over 10 MDa and from crystals with unit cell dimensions over 1000 Å. Moreover, it is possible to collect a complete data set in seconds, and obtain the resulting structure in minutes. The impact of MX synchrotron beamlines and their evolution is reflected in their scientific output, and MX is now the method of choice for a variety of aims from ligand binding to structure determination of membrane proteins, viruses and ribosomes, resulting in a much deeper understanding of the machinery of life. One main driving force of beamline evolution have been advances in almost every aspect of the instrumentation comprising a synchrotron beamline. In this review we aim to provide an overview of the current status of instrumentation at modern MX experiments. Furthermore, we discuss the most critical optical components, aspects of endstation design, sample delivery, visualisation and positioning, the sample environment, beam shaping, detectors and data acquisition and processing.

  12. Current advances in synchrotron radiation instrumentation for MX experiments

    DOE PAGES

    Owen, Robin L.; Juanhuix, Jordi; Fuchs, Martin

    2016-04-01

    Following pioneering work 40 years ago, synchrotron beamlines dedicated to macromolecular crystallography (MX) have improved in almost every aspect as instrumentation has evolved. Beam sizes and crystal dimensions are now on the single micron scale while data can be collected from proteins with molecular weights over 10 MDa and from crystals with unit cell dimensions over 1000 Å. Moreover, it is possible to collect a complete data set in seconds, and obtain the resulting structure in minutes. The impact of MX synchrotron beamlines and their evolution is reflected in their scientific output, and MX is now the method of choicemore » for a variety of aims from ligand binding to structure determination of membrane proteins, viruses and ribosomes, resulting in a much deeper understanding of the machinery of life. One main driving force of beamline evolution have been advances in almost every aspect of the instrumentation comprising a synchrotron beamline. In this review we aim to provide an overview of the current status of instrumentation at modern MX experiments. Furthermore, we discuss the most critical optical components, aspects of endstation design, sample delivery, visualisation and positioning, the sample environment, beam shaping, detectors and data acquisition and processing.« less

  13. Advanced Ceramics for NASA's Current and Future Needs

    NASA Technical Reports Server (NTRS)

    Jaskowiak, Martha H.

    2006-01-01

    Ceramic composites and monolithics are widely recognized by NASA as enabling materials for a variety of aerospace applications. Compared to traditional materials, ceramic materials offer higher specific strength which can enable lighter weight vehicle and engine concepts, increased payloads, and increased operational margins. Additionally, the higher temperature capabilities of these materials allows for increased operating temperatures within the engine and on the vehicle surfaces which can lead to improved engine efficiency and vehicle performance. To meet the requirements of the next generation of both rocket and air-breathing engines, NASA is actively pursuing the development and maturation of a variety of ceramic materials. Anticipated applications for carbide, nitride and oxide-based ceramics will be presented. The current status of these materials and needs for future goals will be outlined. NASA also understands the importance of teaming with other government agencies and industry to optimize these materials and advance them to the level of maturation needed for eventual vehicle and engine demonstrations. A number of successful partnering efforts with NASA and industry will be highlighted.

  14. Understanding current causes of women's underrepresentation in science.

    PubMed

    Ceci, Stephen J; Williams, Wendy M

    2011-02-22

    Explanations for women's underrepresentation in math-intensive fields of science often focus on sex discrimination in grant and manuscript reviewing, interviewing, and hiring. Claims that women scientists suffer discrimination in these arenas rest on a set of studies undergirding policies and programs aimed at remediation. More recent and robust empiricism, however, fails to support assertions of discrimination in these domains. To better understand women's underrepresentation in math-intensive fields and its causes, we reprise claims of discrimination and their evidentiary bases. Based on a review of the past 20 y of data, we suggest that some of these claims are no longer valid and, if uncritically accepted as current causes of women's lack of progress, can delay or prevent understanding of contemporary determinants of women's underrepresentation. We conclude that differential gendered outcomes in the real world result from differences in resources attributable to choices, whether free or constrained, and that such choices could be influenced and better informed through education if resources were so directed. Thus, the ongoing focus on sex discrimination in reviewing, interviewing, and hiring represents costly, misplaced effort: Society is engaged in the present in solving problems of the past, rather than in addressing meaningful limitations deterring women's participation in science, technology, engineering, and mathematics careers today. Addressing today's causes of underrepresentation requires focusing on education and policy changes that will make institutions responsive to differing biological realities of the sexes. Finally, we suggest potential avenues of intervention to increase gender fairness that accord with current, as opposed to historical, findings.

  15. Advancing Understanding of Earthquakes by Drilling an Eroding Convergent Margin

    NASA Astrophysics Data System (ADS)

    von Huene, R.; Vannucchi, P.; Ranero, C. R.

    2010-12-01

    A program of IODP with great societal relevance is sampling and instrumenting the seismogenic zone. The zone generates great earthquakes that trigger tsunamis, and submarine slides thereby endangering coastal communities containing over sixty percent of the earth’s population. To asses and mitigate this endangerment it is urgent to advance understanding of fault dynamics that allows more timely anticipation of hazardous seismicity. Seismogenesis on accreting and eroding convergent plate boundaries apparently differ because of dissimilar materials along the interplate fault. As the history of instrumentally recorded earthquakes expands the difference becomes clearer. The more homogeneous clay, silt and sand subducted at accreting margins is associated with great earthquakes (M 9) whereas the fragmented upper plate rock that can dominate subducted material along an eroding margin plate interface is associated with many tsunamigenic earthquakes (Bilek, 2010). Few areas have been identified where the seismogenic zone can be reached with scientific drilling. In IODP accreting margins are studied on the NanTroSeize drill transect off Japan where the ultimate drilling of the seismogenic interface may occur by the end of IODP. The eroding Costa Rica margin will be studied in CRISP where a drill program will begin in 2011. The Costa Rican geophysical site survey will be complete with acquisition and processing of 3D seismic data in 2011 but the entire drilling will not be accomplished in IODP. It is appropriate that the accreting margin study be accomplished soon considering the indications of a pending great earthquake that will affect a country that has devoted enormous resources to IODP. However, understanding the erosional end-member is scientifically as important to an understanding of fault mechanics. Transoceanic tsunamis affect the entire Pacific rim where most subduction zones are eroding margins. The Costa Rican subduction zone is less complex operationally and

  16. Current understanding of organically bound tritium (OBT) in the environment.

    PubMed

    Kim, S B; Baglan, N; Davis, P A

    2013-12-01

    It has become increasingly recognized that organically bound tritium (OBT) is the more significant tritium fraction with respect to understanding tritium behaviour in the environment. There are many different terms associated with OBT; such as total OBT, exchangeable OBT, non-exchangeable OBT, soluble OBT, insoluble OBT, tritiated organics, and buried tritium, etc. A simple classification is required to clarify understanding within the tritium research community. Unlike for tritiated water (HTO), the environmental quantification and behaviour of OBT are not well known. Tritiated water cannot bio-accumulate in the environment. However, it is not clear whether or not this is the case for OBT. Even though OBT can be detected in terrestrial biological materials, aquatic biological materials and soil samples, its behaviour is still in question. In order to evaluate the radiation dose from OBT accurately, further study will be required to understand OBT measurements and determine OBT fate in the environment. The relationship between OBT speciation and the OBT/HTO ratio in environmental samples will be useful in this regard, providing information on the previous tritium exposure conditions in the environment and the current tritium dynamics.

  17. Recent advances in understanding Antarctic subglacial lakes and hydrology.

    PubMed

    Siegert, Martin J; Ross, Neil; Le Brocq, Anne M

    2016-01-28

    It is now well documented that over 400 subglacial lakes exist across the bed of the Antarctic Ice Sheet. They comprise a variety of sizes and volumes (from the approx. 250 km long Lake Vostok to bodies of water less than 1 km in length), relate to a number of discrete topographic settings (from those contained within valleys to lakes that reside in broad flat terrain) and exhibit a range of dynamic behaviours (from 'active' lakes that periodically outburst some or all of their water to those isolated hydrologically for millions of years). Here we critique recent advances in our understanding of subglacial lakes, in particular since the last inventory in 2012. We show that within 3 years our knowledge of the hydrological processes at the ice-sheet base has advanced considerably. We describe evidence for further 'active' subglacial lakes, based on satellite observation of ice-surface changes, and discuss why detection of many 'active' lakes is not resolved in traditional radio-echo sounding methods. We go on to review evidence for large-scale subglacial water flow in Antarctica, including the discovery of ancient channels developed by former hydrological processes. We end by predicting areas where future discoveries may be possible, including the detection, measurement and significance of groundwater (i.e. water held beneath the ice-bed interface).

  18. Advancing our understanding of the human microbiome using QIIME

    PubMed Central

    Navas-Molina, José A.; Peralta-Sánchez, Juan M.; González, Antonio; McMurdie, Paul J.; Vázquez-Baeza, Yoshiki; Xu, Zhenjiang; Ursell, Luke K.; Lauber, Christian; Zhou, Hongwei; Song, Se Jin; Huntley, James; Ackermann, Gail L.; Berg-Lyons, Donna; Holmes, Susan; Caporaso, J. Gregory; Knight, Rob

    2014-01-01

    High-throughput DNA sequencing technologies, coupled with advanced bioinformatics tools, have enabled rapid advances in microbial ecology and our understanding of the human microbiome. QIIME (Quantitative Insights Into Microbial Ecology) is an open-source bioinformatics software package designed for microbial community analysis based on DNA sequence data, which provides a single analysis framework for analysis of raw sequence data through publication quality statistical analyses and interactive visualizations. In this paper, we demonstrate the use of the QIIME pipeline to analyze microbial communities obtained from several sites on the bodies of transgenic and wild-type mice, as assessed using 16S rRNA gene sequences generated on the Illumina MiSeq platform. We present our recommended pipeline for performing microbial community analysis, and provide guidelines for making critical choices in the process. We present examples of some of the types of analyses that are enabled by QIIME, and discuss how other tools, such as phyloseq and R, can be applied to expand upon these analyses. PMID:24060131

  19. Recent advances in understanding Antarctic subglacial lakes and hydrology

    PubMed Central

    Siegert, Martin J.; Ross, Neil; Le Brocq, Anne M.

    2016-01-01

    It is now well documented that over 400 subglacial lakes exist across the bed of the Antarctic Ice Sheet. They comprise a variety of sizes and volumes (from the approx. 250 km long Lake Vostok to bodies of water less than 1 km in length), relate to a number of discrete topographic settings (from those contained within valleys to lakes that reside in broad flat terrain) and exhibit a range of dynamic behaviours (from ‘active’ lakes that periodically outburst some or all of their water to those isolated hydrologically for millions of years). Here we critique recent advances in our understanding of subglacial lakes, in particular since the last inventory in 2012. We show that within 3 years our knowledge of the hydrological processes at the ice-sheet base has advanced considerably. We describe evidence for further ‘active’ subglacial lakes, based on satellite observation of ice-surface changes, and discuss why detection of many ‘active’ lakes is not resolved in traditional radio-echo sounding methods. We go on to review evidence for large-scale subglacial water flow in Antarctica, including the discovery of ancient channels developed by former hydrological processes. We end by predicting areas where future discoveries may be possible, including the detection, measurement and significance of groundwater (i.e. water held beneath the ice-bed interface). PMID:26667914

  20. Understanding the operational environment: implications for advanced visualizations

    NASA Astrophysics Data System (ADS)

    Aleva, Denise; Fitzhugh, Elisabeth; Dixon, Sharon

    2009-05-01

    With the changing character of warfare, information superiority is a high priority. Given the complexity of current and future operating environments, analysts, strategists and planners need a multidimensional understanding of the battlespace. Asymmetric warfare necessitates that our strategists look beyond targets-based operations, where we simply identify and destroy enemy entities. Effects-based operations models the enemy as a system which reacts to our actions. This requires the capability to predict the adversary response to a selected action. Actions may be diplomatic, information, military or economic (DIME). Effects may be political, military, economic, social, information or infrastructure (PMESII). Timing must be explicitly considered and effects dynamically assessed. Visualizations of intelligence information are needed which will promote full understanding of all aspects of adversary strengths and weaknesses by providing the extensive data about adversary forces, organic essentials, infrastructure, leadership, population, and science and technology in an easily accessible and understandable format. This will enhance Effectsbased operations, and therefore, the capability to predict and counter adversary courses of action. This paper outlines a systems engineering approach to designing visualizations which convey the multidimensional information to decision makers. Visualization issues inherent in understanding the multidimensional operational environment will be discussed.

  1. Advances in understanding the interrelations between leptin resistance and obesity.

    PubMed

    Pan, Haitao; Guo, Jiao; Su, Zhengquan

    2014-05-10

    Obesity, which has developed into a global epidemic, is a risk factor in most chronic diseases and some forms of malignancy. The discovery of leptin in 1994 has opened a new field in obesity research. Currently, we know that leptin is the primary signal from energy stores and exerts negative feedback effects on energy intake. However, most individuals with diet-induced obesity (DIO) develop leptin resistance, which is characterized by elevated circulating leptin levels and decreased leptin sensitivity. To date, though various mechanisms have been proposed to explain leptin resistance, the exact mechanisms of leptin resistance in obesity are poorly understood. Consequently, it's an important issue worth discussing regarding what the exact interrelations between leptin resistance and obesity are. Here, we review the latest advancements in the molecular mechanisms of leptin resistance and the exact interrelations between leptin resistance, obesity, and obesity-related diseases, in order to supply new ideas for the study of obesity.

  2. Current understanding of androgenetic alopecia. Part I: etiopathogenesis.

    PubMed

    Hoffmann, R; Happle, R

    2000-06-01

    Androgenetic alopecia (AGA) is the most common type of hair loss in men and women. This continuous process results in a type of alopecia that follows a definite pattern in those individuals who are genetically predisposed. At present the predisposing genes are unknown but the relatively strong concordance of the degree of baldness in fathers and sons is not consistent with a simple Mendelian trait and a polygenic basis is therefore most likely. AGA can be defined as a DHT-dependent process with continuous miniaturization of sensitive HF. Today we do not understand the molecular steps involved in androgen-dependent beard growth versus androgen-dependent hair loss in AGA. However, recent experimental and clinical advances enable us to explain some pathogenetic steps leading to androgenetic hair loss. Among other steroidogenic isoenzymes such as 17b- and 3b- hydroxysteroid dehydrogenases, the type 2 5a-reductase within the dermal papilla plays a central role by the intrafollicular conversion of T to DHT.

  3. Asthma in the Elderly: Current Understanding and Future Research Needs

    PubMed Central

    Hanania, Nicola A.; King, Monroe J.; Braman, Sidney S.; Saltoun, Carol; Wise, Robert A.; Enright, Paul; Falsey, Ann A; Mathur, Sameer K.; Ramsdell, Joe W.; Rogers, Linda; Stempel, David A.; Lima, John J.; Fish, James E.; Wilson, Sandra R.; Boyd, Cynthia; Patel, Kushang V.; Irvin, Charles G.; Yawn, Barbara P.; Halm, Ethan A; Wasserman, Stephen I.; Sands, Mark F.; Ershler, William B.; Ledford, Dennis K.

    2011-01-01

    Asthma in the elderly (AIE) is under diagnosed and under treated and there is a paucity of knowledge. The National Institute on Aging convened this workshop to identify what is known, what gaps in knowledge remain and suggest research directions needed to improve the understanding and care of AIE. Asthma presenting at an advanced age often has similar clinical and physiologic consequences as seen with younger individuals but co-morbid illnesses and the psychosocial effects of aging may affect the diagnosis, clinical presentation and care of asthma in this population. At least two phenotypes exist among elderly asthma; those with long-standing asthma have more severe airflow limitation and less complete reversibility than those with late-onset asthma. Many challenges exist in the recognition and treatment of asthma in the elderly. Furthermore, the pathophysiological mechanisms of AIE are likely to be different from those seen in young asthmatics and these differences may influence the clinical course and outcomes of asthma in this population. PMID:21872730

  4. Newcastle disease virus: current status and our understanding.

    PubMed

    Ganar, Ketan; Das, Moushumee; Sinha, Sugandha; Kumar, Sachin

    2014-05-12

    Newcastle disease (ND) is one of the highly pathogenic viral diseases of avian species. ND is economically significant because of the huge mortality and morbidity associated with it. The disease is endemic in many third world countries where agriculture serves as the primary source of national income. Newcastle disease virus (NDV) belongs to the family Paramyxoviridae and is well characterized member among the avian paramyxovirus serotypes. In recent years, NDV has lured the virologists not only because of its pathogenic potential, but also for its oncolytic activity and its use as a vaccine vector for both humans and animals. The NDV based recombinant vaccine offers a pertinent choice for the construction of live attenuated vaccine due to its modular nature of transcription, minimum recombination frequency, and lack of DNA phase during replication. Our current understanding about the NDV biology is expanding rapidly because of the availability of modern molecular biology tools and high-throughput complete genome sequencing.

  5. Current understanding of magnetic storms: Storm-substorm relationships

    SciTech Connect

    Kamide, Y.; Gonzalez, W.D.; Baumjohann, W.; Daglis, I.A.; Grande, M.; Joselyn, J.A.; Singer, H.J.; McPherron, R.L.; Phillips, J.L.; Reeves, E.G.; Rostoker, G.; Sharma, A.S.; Tsurutani, B.T.

    1998-08-01

    This paper attempts to summarize the current understanding of the storm/substorm relationship by clearing up a considerable amount of controversy and by addressing the question of how solar wind energy is deposited into and is dissipated in the constituent elements that are critical to magnetospheric and ionospheric processes during magnetic storms. (1) Four mechanisms are identified and discussed as the primary causes of enhanced electric fields in the interplanetary medium responsible for geomagnetic storms. It is pointed out that in reality, these four mechanisms, which are not mutually exclusive, but interdependent, interact differently from event to event. Interplanetary coronal mass ejections (ICMEs) and corotating interaction regions (CIRs) are found to be the primary phenomena responsible for the main phase of geomagnetic storms. The other two mechanisms, i.e., HILDCAA (high-intensity, long-duration, continuous auroral electrojet activity) and the so-called Russell-McPherron effect, work to make the ICME and CIR phenomena more geoeffective. The solar cycle dependence of the various sources in creating magnetic storms has yet to be quantitatively understood. (2) A serious controversy exists as to whether the successive occurrence of intense substorms plays a direct role in the energization of ring current particles or whether the enhanced electric field associated with southward IMF enhances the effect of substorm expansions. While most of the {ital Dst} variance during magnetic storms can be solely reproduced by changes in the large-scale electric field in the solar wind and the residuals are uncorrelated with substorms, recent satellite observations of the ring current constituents during the main phase of magnetic storms show the importance of ionospheric ions. This implies that ionospheric ions, which are associated with the frequent occurrence of intense substorms, are accelerated upward along magnetic field lines, contributing to the energy density of

  6. Recent advances in the understanding and management of delayed puberty.

    PubMed

    Wei, Christina; Crowne, Elizabeth Clare

    2016-05-01

    Delayed puberty, especially in boys, is a common presentation in paediatrics. Recent advances have improved our understanding of the neuroendocrine, genetic and environmental factors controlling pubertal development, and hence inform the pathophysiology of delayed puberty. The discovery of kisspeptin signalling through its receptor identified neuroendocrine mechanisms controlling the gonadotrophin-releasing hormone (GnRH) pulse generator at the onset of puberty. Genetic mechanisms from single gene mutations to single nucleotide polymorphism associated with delayed puberty are being identified. Environmental factors, including nutritional factors and endocrine disruptors, have also been implicated in changes in secular trends and abnormal timing of puberty. Despite these advances, the key clinical question is to distinguish delayed puberty associated with an underlying pathology or hypogonadism from constitutional delay in growth and puberty, which remains challenging as biochemical tests are not always discriminatory. The diagnostic accuracies of newer investigations, including 36-hour luteinising hormone releasing hormone (LHRH) tests, GnRH-agonist tests, antimullerian hormone and inhibin-B, require further evaluation. Sex hormone replacement remains the main available treatment for delayed puberty, the choice of which is largely dictated by clinical practice and availability of the various sex steroid preparations. Spontaneous reversal of hypogonadism has been reported in boys with idiopathic hypogonadotrophic hypogonadism after a period of sex steroid treatment, highlighting the importance of reassessment at the end of pubertal induction. Novel therapies with a more physiological basis such as gonadotrophins or kisspeptin-agonist are being investigated for the management of hypogonadotrophic hypogonadism. Careful clinical assessment and appreciation of the normal physiology remain the key approach to patients with delayed puberty.

  7. Pressure ulcers: Current understanding and newer modalities of treatment.

    PubMed

    Bhattacharya, Surajit; Mishra, R K

    2015-01-01

    This article reviews the mechanism, symptoms, causes, severity, diagnosis, prevention and present recommendations for surgical as well as non-surgical management of pressure ulcers. Particular focus has been placed on the current understandings and the newer modalities for the treatment of pressure ulcers. The paper also covers the role of nutrition and pressure-release devices such as cushions and mattresses as a part of the treatment algorithm for preventing and quick healing process of these wounds. Pressure ulcers develop primarily from pressure and shear; are progressive in nature and most frequently found in bedridden, chair bound or immobile people. They often develop in people who have been hospitalised for a long time generally for a different problem and increase the overall time as well as cost of hospitalisation that have detrimental effects on patient's quality of life. Loss of sensation compounds the problem manifold, and failure of reactive hyperaemia cycle of the pressure prone area remains the most important aetiopathology. Pressure ulcers are largely preventable in nature, and their management depends on their severity. The available literature about severity of pressure ulcers, their classification and medical care protocols have been described in this paper. The present treatment options include various approaches of cleaning the wound, debridement, optimised dressings, role of antibiotics and reconstructive surgery. The newer treatment options such as negative pressure wound therapy, hyperbaric oxygen therapy, cell therapy have been discussed, and the advantages and disadvantages of current and newer methods have also been described.

  8. Pressure ulcers: Current understanding and newer modalities of treatment

    PubMed Central

    Bhattacharya, Surajit; Mishra, R. K.

    2015-01-01

    This article reviews the mechanism, symptoms, causes, severity, diagnosis, prevention and present recommendations for surgical as well as non-surgical management of pressure ulcers. Particular focus has been placed on the current understandings and the newer modalities for the treatment of pressure ulcers. The paper also covers the role of nutrition and pressure-release devices such as cushions and mattresses as a part of the treatment algorithm for preventing and quick healing process of these wounds. Pressure ulcers develop primarily from pressure and shear; are progressive in nature and most frequently found in bedridden, chair bound or immobile people. They often develop in people who have been hospitalised for a long time generally for a different problem and increase the overall time as well as cost of hospitalisation that have detrimental effects on patient's quality of life. Loss of sensation compounds the problem manifold, and failure of reactive hyperaemia cycle of the pressure prone area remains the most important aetiopathology. Pressure ulcers are largely preventable in nature, and their management depends on their severity. The available literature about severity of pressure ulcers, their classification and medical care protocols have been described in this paper. The present treatment options include various approaches of cleaning the wound, debridement, optimised dressings, role of antibiotics and reconstructive surgery. The newer treatment options such as negative pressure wound therapy, hyperbaric oxygen therapy, cell therapy have been discussed, and the advantages and disadvantages of current and newer methods have also been described. PMID:25991879

  9. Halo current diagnostic system of experimental advanced superconducting tokamak

    NASA Astrophysics Data System (ADS)

    Chen, D. L.; Shen, B.; Granetz, R. S.; Sun, Y.; Qian, J. P.; Wang, Y.; Xiao, B. J.

    2015-10-01

    The design, calibration, and installation of disruption halo current sensors for the Experimental Advanced Superconducting Tokamak are described in this article. All the sensors are Rogowski coils that surround conducting structures, and all the signals are analog integrated. Coils with two different cross-section sizes have been fabricated, and their mutual inductances are calibrated. Sensors have been installed to measure halo currents in several different parts of both the upper divertor (tungsten) and lower divertor (graphite) at several toroidal locations. Initial measurements from disruptions show that the halo current diagnostics are working well.

  10. Halo current diagnostic system of experimental advanced superconducting tokamak

    SciTech Connect

    Chen, D. L.; Shen, B.; Sun, Y.; Qian, J. P. Wang, Y.; Xiao, B. J.; Granetz, R. S.

    2015-10-15

    The design, calibration, and installation of disruption halo current sensors for the Experimental Advanced Superconducting Tokamak are described in this article. All the sensors are Rogowski coils that surround conducting structures, and all the signals are analog integrated. Coils with two different cross-section sizes have been fabricated, and their mutual inductances are calibrated. Sensors have been installed to measure halo currents in several different parts of both the upper divertor (tungsten) and lower divertor (graphite) at several toroidal locations. Initial measurements from disruptions show that the halo current diagnostics are working well.

  11. Halo current diagnostic system of experimental advanced superconducting tokamak.

    PubMed

    Chen, D L; Shen, B; Granetz, R S; Sun, Y; Qian, J P; Wang, Y; Xiao, B J

    2015-10-01

    The design, calibration, and installation of disruption halo current sensors for the Experimental Advanced Superconducting Tokamak are described in this article. All the sensors are Rogowski coils that surround conducting structures, and all the signals are analog integrated. Coils with two different cross-section sizes have been fabricated, and their mutual inductances are calibrated. Sensors have been installed to measure halo currents in several different parts of both the upper divertor (tungsten) and lower divertor (graphite) at several toroidal locations. Initial measurements from disruptions show that the halo current diagnostics are working well.

  12. Recent Advances in Understanding Enteric Pathogenic Escherichia coli

    PubMed Central

    Croxen, Matthew A.; Law, Robyn J.; Scholz, Roland; Keeney, Kristie M.; Wlodarska, Marta

    2013-01-01

    SUMMARY Although Escherichia coli can be an innocuous resident of the gastrointestinal tract, it also has the pathogenic capacity to cause significant diarrheal and extraintestinal diseases. Pathogenic variants of E. coli (pathovars or pathotypes) cause much morbidity and mortality worldwide. Consequently, pathogenic E. coli is widely studied in humans, animals, food, and the environment. While there are many common features that these pathotypes employ to colonize the intestinal mucosa and cause disease, the course, onset, and complications vary significantly. Outbreaks are common in developed and developing countries, and they sometimes have fatal consequences. Many of these pathotypes are a major public health concern as they have low infectious doses and are transmitted through ubiquitous mediums, including food and water. The seriousness of pathogenic E. coli is exemplified by dedicated national and international surveillance programs that monitor and track outbreaks; unfortunately, this surveillance is often lacking in developing countries. While not all pathotypes carry the same public health profile, they all carry an enormous potential to cause disease and continue to present challenges to human health. This comprehensive review highlights recent advances in our understanding of the intestinal pathotypes of E. coli. PMID:24092857

  13. Recent Advances in Understanding Audiovestibular Loss of a Vascular Cause

    PubMed Central

    Kim, Hyun-Ah; Lee, Hyung

    2017-01-01

    Acute audiovestibular loss is characterized by abrupt onset of prolonged (lasting days) vertigo and hearing loss. Acute ischemic stroke in the distribution of the anterior inferior cerebellar artery (AICA) is known to be the leading cause of acute audiovestibular loss. So far, eight subgroups of AICA territory infarction have been identified according to the patterns of audiovestibular dysfunctions, among which the most common pattern is the combined loss of auditory and vestibular functions. Unlike inner ear dysfunction of a viral cause, which can commonly present as an isolated vestibular (i.e., vestibular neuritis) or cochlear loss (i.e., sudden deafness), labyrinthine dysfunction of a vascular cause rarely results in isolated loss of vestibular or auditory function. As audiovestibular loss may precede the central symptoms or signs of an ischemic stroke in the posterior circulation, early diagnosis and proper management of audiovestiubular loss may provide a window to prevent the progression of infarction to larger areas of the posterior circulation. A clinician should consider the possibility that acute audiovestibular loss may herald impending AICA territory infarction, especially when patients have basilar artery occlusive disease close to the origin of the AICA on brain MRA. This review aims to highlight the recent advances in understanding audiovestibular loss of a vascular cause and to address its clinical significance. PMID:28030893

  14. Recent advances in understanding and managing psoriatic arthritis

    PubMed Central

    Gladman, Dafna D.

    2016-01-01

    This article reviews recent advances in psoriatic arthritis (PsA) over the past several years with emphasis on early diagnosis, better understanding of pathogenesis, and new therapeutic approaches. Early diagnosis is important, since people who present late do not fare as well. There are a number of clinical, laboratory, and ultrasound features that can help identify patients destined to develop PsA, and several screening tools have been developed. It is recognized that genetic and epigenetic factors, as well as T cells and cytokines, play a role in the pathogenesis of PsA, and several targets have been identified for therapeutic interventions. New therapies have been developed and tested in PsA and have been found to be highly effective for both skin and joint manifestations of the disease. The expectation is that, in the future, PsA patients will be treated early and more aggressively and that there will not be significant progression of joint damage. Moreover, with effective treatment of the skin and joint disease and management of risk factors for the comorbidities, we can expect to reduce their occurrence and further reduce the excess mortality and reduced quality of life and function in these patients. PMID:27928500

  15. Women in science: Current advances and challenges in Belarus

    NASA Astrophysics Data System (ADS)

    Tashlykova-Bushkevich, Iya I.

    2015-12-01

    Women constitute 49% of all natural scientists in Belarus. However, fewer than 18% of Belarusian natural scientists who hold a doctor of science degree are women. The proportion of women decreases with increasing rank at universities and institutes in Belarus. Gender imbalance at the level of full professor is striking at just 17.5% women, and illuminates the vertical segregation of women in the natural sciences. This report reviews the positions of women in science in Belarus to draw out current advances and challenges encountered by female scientists in the former socialist country. New statistical data are broken down by gender and aimed at advancing the general agenda for women in science.

  16. Recent Advances in Understanding and Managing Autism Spectrum Disorders

    PubMed Central

    Germain, Blair; Eppinger, Melissa A.; Mostofsky, Stewart H.; DiCicco-Bloom, Emanuel; Maria, Bernard L.

    2017-01-01

    Autism spectrum disorder in children is a group of neurodevelopmental disorders characterized by difficulties with social communication and behavior. Growing scientific evidence in addition to clinical practice has led the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) to categorize several disorders into the broader category of autism spectrum disorder. As more is learned about how autism spectrum disorder manifests, progress has been made toward better clinical management including earlier diagnosis, care, and when specific interventions are required. The 2014 Neurobiology of Disease in Children symposium, held in conjunction with the 43rd annual meeting of the Child Neurology Society, aimed to (1) describe the clinical concerns involving diagnosis and treatment, (2) review the current status of understanding in the pathogenesis of autism spectrum disorder, (3) discuss clinical management and therapies for autism spectrum disorder, and (4) define future directions of research. The article summarizes the presentations and includes an edited transcript of question-and-answer sessions. PMID:26336201

  17. History of the current understanding and management of tethered spinal cord.

    PubMed

    Safavi-Abbasi, Sam; Mapstone, Timothy B; Archer, Jacob B; Wilson, Christopher; Theodore, Nicholas; Spetzler, Robert F; Preul, Mark C

    2016-07-01

    An understanding of the underlying pathophysiology of tethered cord syndrome (TCS) and modern management strategies have only developed within the past few decades. Current understanding of this entity first began with the understanding and management of spina bifida; this later led to the gradual recognition of spina bifida occulta and the symptoms associated with tethering of the filum terminale. In the 17th century, Dutch anatomists provided the first descriptions and initiated surgical management efforts for spina bifida. In the 19th century, the term "spina bifida occulta" was coined and various presentations of spinal dysraphism were appreciated. The association of urinary, cutaneous, and skeletal abnormalities with spinal dysraphism was recognized in the 20th century. Early in the 20th century, some physicians began to suspect that traction on the conus medullaris caused myelodysplasia-related symptoms and that prophylactic surgical management could prevent the occurrence of clinical manifestations. It was not, however, until later in the 20th century that the term "tethered spinal cord" and the modern management of TCS were introduced. This gradual advancement in understanding at a time before the development of modern imaging modalities illustrates how, over the centuries, anatomists, pathologists, neurologists, and surgeons used clinical examination, a high level of suspicion, and interest in the subtle and overt clinical appearances of spinal dysraphism and TCS to advance understanding of pathophysiology, clinical appearance, and treatment of this entity. With the availability of modern imaging, spinal dysraphism can now be diagnosed and treated as early as the intrauterine stage.

  18. Proteomics Advances in the Understanding of Pollen–Pistil Interactions

    PubMed Central

    Fu, Ziyang; Yang, Pingfang

    2014-01-01

    The first key point to the successful pollination and fertilization in plants is the pollen-pistil interaction, referring to the cellular and molecular levels, which mainly involve the haploid pollen and the diploid pistil. The process is defined as “siphonogamy”, which starts from the capture of pollen by the epidermis of stigma and ends up with the fusion of sperm with egg. So far, the studies of the pollen-pistil interaction have been explicated around the self-compatibility and self-incompatibility (SI) process in different species from the molecular genetics and biochemistry to cellular and signal levels, especially the mechanism of SI system. Among them, numerous proteomics studies based on the advanced technologies from gel-system to gel-free system were conducted, focusing on the interaction, in order to uncover the mechanism of the process. The current review mainly focuses on the recent developments in proteomics of pollen-pistil interaction from two aspects: self-incompatible and compatible pollination. It might provide a comprehensive insight on the proteins that were involved in the regulation of pollen-pistil interaction. PMID:28250391

  19. Meteorological Conditions Causing Jet-Engine Poweloss Events: Current Understanding

    NASA Astrophysics Data System (ADS)

    Strapp, J. W.; Ratvasky, T. P.

    2009-09-01

    The aviation industry is currently investigating a regular occurrence of jet engine-powerloss events which have now been attributed to the ingestion of atmospheric ice particles, usually in the vicinity of deep convection. There is a limited amount of information on the cloud microphysical properties near the cores of deep convection due to the potential hazards of flying in these areas, and due to the fact that it is a very challenging environment for current instrumentation. Most of the information that has been used to deduce the details of the conditions that cause engine powerloss has been extracted from the event-aircraft flight data recorders, pilot interviews, ground radar and satellite, a series of flight test programs in the 1950s and again in the 1990s, and the most recently available limited data from the cloud physics community. These have led to the conclusion that engine events occur due to flight through high mass concentrations of ice particles, probably with ice water contents (IWCs) in excess of 2 grams per cubic meter, and perhaps as high as 8. The limited microphysical data available has been used to suggest a median mass diameter of the ice particles of ~200 microns, with some evidence that it may be as low as 40 microns. These small particle sizes in the presence of high mass concentration is consistent with the lack of radar echoes > 20 dBZ observed on the pilot's radar, a consistent observation during engine events. The Engine Harmonization Working Group, an industry/regulator/government committee investigating engine powerloss, has concluded that the level of understanding of the properties of these clouds is inadequate to provide guidance to industry for engine design and testing. In order to address this issue, NASA and Environment Canada are planning to instrument an aircraft to make measurements in high IWC regions of tropical monsoon and continental convection. There is also a significant effort to upgrade and develop new

  20. Spinal pain: current understanding, trends, and the future of care

    PubMed Central

    Parkin-Smith, Gregory F; Amorin-Woods, Lyndon G; Davies, Stephanie J; Losco, Barrett E; Adams, Jon

    2015-01-01

    This commissioned review paper offers a summary of our current understanding of nonmalignant spinal pain, particularly persistent pain. Spinal pain can be a complex problem, requiring management that addresses both the physical and psychosocial components of the pain experience. We propose a model of care that includes the necessary components of care services that would address the multidimensional nature of spinal pain. Emerging care services that tailor care to the individual person with pain seems to achieve better outcomes and greater consumer satisfaction with care, while most likely containing costs. However, we recommend that any model of care and care framework should be developed on the basis of a multidisciplinary approach to care, with the scaffold being the principles of evidence-based practice. Importantly, we propose that any care services recommended in new models or frameworks be matched with available resources and services – this matching we promote as the fourth principle of evidence-based practice. Ongoing research will be necessary to offer insight into clinical outcomes of complex interventions, while practice-based research would uncover consumer needs and workforce capacity. This kind of research data is essential to inform health care policy and practice. PMID:26604815

  1. Gulf War Syndrome: a review of current knowledge and understanding.

    PubMed

    Minshall, D

    2014-01-01

    The 1991 Persian Gulf War was a resounding military success for coalition forces, who liberated Kuwait following the Iraqi invasion. The medical legacy we have from the conflict is the poorly understood, yet remarkable, phenomenon of Gulf War Syndrome, which surfaced soon after. Epidemiological research has proven beyond doubt that Gulf War veterans report a wide variety of symptoms, in excess of appropriately matched control subjects, and experience worse general health. Numerous toxic environmental hazards have been suggested as causes of Gulf War Syndrome, yet exhaustive scientific study has failed to provide conclusive proof of any link. No novel or recognised disease has been found to account for the symptomatic burden of veterans, and the optimal treatment remains uncertain. This understanding can be added to from an anthropological perspective, where the narratives of those afflicted provide further insight. The nature of military life was changing at the time of the Gulf War, challenging the identity and beliefs of some veterans and causing socio-cultural distress. The symptomatic presentation of Gulf War Syndrome can be considered an articulation of this disharmony. Gulf War Syndrome can also be considered within the group of post-combat disorders such as shellshock, the like of which have occurred after major wars in the last century. With the current withdrawal from Afghanistan, the Defence Medical Services (DMS) should heed the lessons of history.

  2. Advanced gastric cancer: Current treatment landscape and future perspectives

    PubMed Central

    Digklia, Antonia; Wagner, Anna Dorothea

    2016-01-01

    Gastric cancer currently ranks fourth in cancer-related mortality worldwide. In the western world, it is most often diagnosed at an advanced stage, after becoming metastatic at distant sites. Patients with advanced disease (locally advanced or metastatic) have a somber prognosis, with a median overall survival of 10-12 mo, and palliative chemotherapy is the mainstay of treatment. In recent years, novel approaches using inhibition of human epidermal growth factor receptor 2 (HER2) have demonstrated significant improvements in progression-free and overall survival, compared with chemotherapy alone, in first-line treatment of patients with overexpression of HER2. In addition, both second-line chemotherapy and treatment with the vascular endothelial growth factor receptor-inhibitor ramucirumab demonstrated significant benefits in terms of overall survival, compared with best supportive care, in randomized studies. Moreover, ramucirumab in combination with chemotherapy demonstrated further significant benefits in terms of progression-free and overall survival, compared with chemotherapy alone, in second-line treatment for patients with metastatic gastric cancer. A recently published molecular classification of gastric cancer is expected to improve patient stratification and selection for clinical trials and provide a roadmap for future drug development. Nevertheless, despite these developments the prognosis of patients with advanced gastric cancer remains poor. In this review we discuss current standards of care and outline major topics of drug development in gastric cancer. PMID:26937129

  3. Current treatments and advances in pain and anxiety management.

    PubMed

    Huang, David; Wun, Edmund; Stern, Avichai

    2011-07-01

    In light of preoperative and postoperative mortality and morbidity, continued advancement in pain and anxiety management would benefit millions. Although significant strides have been made in the past few decades, it is imperative that research and development continue. This article discusses types of pain and anxiety, the relationship between pain and anxiety, the physiology of pain and anxiety, and current trends in pain and anxiety management.

  4. Leakage Currents and Gas Generation in Advanced Wet Tantalum Capacitors

    NASA Technical Reports Server (NTRS)

    Teverovsky, Alexander

    2015-01-01

    Currently, military grade, established reliability wet tantalum capacitors are among the most reliable parts used for space applications. This has been achieved over the years by extensive testing and improvements in design and materials. However, a rapid insertion of new types of advanced, high volumetric efficiency capacitors in space systems without proper testing and analysis of degradation mechanisms might increase risks of failures. The specifics of leakage currents in wet electrolytic capacitors is that the conduction process is associated with electrolysis of electrolyte and gas generation resulting in building up of internal gas pressure in the parts. The risk associated with excessive leakage currents and increased pressure is greater for high value advanced wet tantalum capacitors, but it has not been properly evaluated yet. In this work, in Part I, leakages currents in various types of tantalum capacitors have been analyzed in a wide range of voltages, temperatures, and time under bias. Gas generation and the level of internal pressure have been calculated in Part II for different case sizes and different hermeticity leak rates to assess maximal allowable leakage currents. Effects related to electrolyte penetration to the glass seal area have been studied and the possibility of failures analyzed in Part III. Recommendations for screening and qualification to reduce risks of failures have been suggested.

  5. Historical water control maps - key to understand current challenges?

    NASA Astrophysics Data System (ADS)

    Mészáros, János

    2014-05-01

    The 19th century and post-World War II decades were the main eras of water controlling in former Hungarian Kingdom and Hungary. Due to those large projects, the number and frequency of big floods were minimized but changes caused several other problems what we have to face off in the present. The main help to understand or highlight the fundamentals of those problems can be the flood control maps which, in some cases, show the original, natural riverbed and neighbouring areas of the river. There is other advantage of these maps compared to other surveys: while the main focus of the water control surveys was the river, there was sufficient time to measure the fine differences of land-use and relief in detail. Our sample area is the middle part of Tisza river and three different maps were chosen to show the changes before and after the regulations: Map of the Middle-Tisza, mapping until 1790 by János Lietzner This map is the earliest, known, topographic scale map about the river. Due to its age, the sheets are in bad state, especially their parts close to the edges and corners. A photographed, greyscale copy exists about the sheets, that was used in our research. Despite such bad conditions, it contains lots of information about the river and settlements, as well as detailed land-use before any flood regulation. New survey of Tisza river, mapping until 1932 by the Directorate of Water and Construction Because of the changes, due to time and regulation, several new surveys were ordered at the end of 19th century and between the world wars. During those new surveys, the river was re-triangulated and mapped, although cross and longitudinal section measurements also were carried out. This map clearly shows the results and changes of regulations, especially on populated areas, newly built dykes etc. but before the changes happened between 1950 and 1980. Topographic maps of the Hungarian Defence Forces - Geoinformation Services As a current, base-dataset, topographic maps

  6. Modelling Monsoons: Understanding and Predicting Current and Future Behaviour

    SciTech Connect

    Turner, A; Sperber, K R; Slingo, J M; Meehl, G A; Mechoso, C R; Kimoto, M; Giannini, A

    2008-09-16

    including, but not limited to, the Mei-Yu/Baiu sudden onset and withdrawal, low-level jet orientation and variability, and orographic forced rainfall. Under anthropogenic climate change many competing factors complicate making robust projections of monsoon changes. Without aerosol effects, increased land-sea temperature contrast suggests strengthened monsoon circulation due to climate change. However, increased aerosol emissions will reflect more solar radiation back to space, which may temper or even reduce the strength of monsoon circulations compared to the present day. A more comprehensive assessment is needed of the impact of black carbon aerosols, which may modulate that of other anthropogenic greenhouse gases. Precipitation may behave independently from the circulation under warming conditions in which an increased atmospheric moisture loading, based purely on thermodynamic considerations, could result in increased monsoon rainfall under climate change. The challenge to improve model parameterizations and include more complex processes and feedbacks pushes computing resources to their limit, thus requiring continuous upgrades of computational infrastructure to ensure progress in understanding and predicting the current and future behavior of monsoons.

  7. Advances in the molecular understanding of gonadotropins-receptors interactions.

    PubMed

    el Tayar, N

    1996-12-20

    The extracellular domain (ECD) of gonadotropin receptors belong to the leucine-rich repeat (LRR) protein superfamily and their transmembrane domain (TMD) is characteristic of the seven alpha-helices G-protein-coupled receptors (GPCR). The availability of the X-ray structures of porcine ribonuclease inhibitor (RI), a LRR protein, and bacteriorhodopsin (bR) allows the construction of 3D models of the ECD and the TMD of gonadotropin receptors, respectively. The predicted models are to a large extent consistent with currently available biochemical and mutational data. The models provide a reliable basis for understanding how the hormone binds and activates its receptor. The ECD, in particular the LRR region, serves as a baseball glove which efficiently catches the large hormone and optimally orient the appropriate parts of it for interaction with the seven-transmembrane-helix domain of the receptor. This in turn is expected to lead to a conformational change to be sensed by the appropriate G-protein complex leading to the stimulation of cAMP synthesis and steroids production.

  8. Current understanding and issues on electron beam injection in space

    NASA Technical Reports Server (NTRS)

    Papadopoulos, K.; Szuszczewicz, E. P.

    1988-01-01

    The status of the physics understanding involved in electron beam injection in space is reviewed. The paper examines our understanding of beam plasma interactions and their associated wave and energized particle spectra of the processes involved in the beam plasma discharge, and of the vehicle charge neutralization. 'Strawman' models are presented for comparison with experimental observations.

  9. Beyond Homophily: A Decade of Advances in Understanding Peer Influence Processes

    PubMed Central

    Brechwald, Whitney A.; Prinstein, Mitchell J.

    2013-01-01

    This article reviews empirical and theoretical contributions to a multidisciplinary understanding of peer influence processes in adolescence over the past decade. Five themes of peer influence research from this decade were identified, including a broadening of the range of behaviors for which peer influence occurs, distinguishing the sources of influence, probing the conditions under which influence is amplified/attenuated (moderators), testing theoretically based models of peer influence processes (mechanisms), and preliminary exploration of behavioral neuroscience perspectives on peer influence. This review highlights advances in each of these areas, underscores gaps in current knowledge of peer influence processes, and outlines important challenges for future research. PMID:23730122

  10. Current understanding and approach to well differentiated lung neuroendocrine tumors: an update on classification and management

    PubMed Central

    Hilal, Talal

    2016-01-01

    Neuroendocrine tumors (NETs) are rare neoplasms that can arise from any tissue. They are classified based on embryonic gut derivative (i.e. foregut, midgut and hindgut) with midgut tumors being the most common (e.g. gastrointestinal NET). The second most common category of NETs is that which arises from the lung. In fact, 25% of primary lung cancers are NETs, including small cell lung cancer (SCLC), which comprises 20% of all lung cancers. The remaining 5% are large cell neuroendocrine cancer (LCNEC, 3%), typical carcinoids (TCs, 1.8%), and atypical carcinoids (ACs, 0.2%). The less common TCs/ACs are well differentiated lung NETs. Their incidence has been increasing in more recent years and although these tumors are slow growing, advanced disease is associated with poor survival. There have been advances in classification of lung NETs that have allowed for more appropriate management upfront. They are cured by surgical resection when disease is limited. However, advanced and metastatic disease requires medical therapy that is ever changing and expanding. In this review, the aim is to summarize the current understanding and classification of well differentiated lung NETs (i.e. TCs and ACs), and focus on recent updates in medical management of advanced disease, along with a brief discussion on potential future discoveries. PMID:28344664

  11. Reef sharks: recent advances in ecological understanding to inform conservation.

    PubMed

    Osgood, G J; Baum, J K

    2015-12-01

    Sharks are increasingly being recognized as important members of coral-reef communities, but their overall conservation status remains uncertain. Nine of the 29 reef-shark species are designated as data deficient in the IUCN Red List, and three-fourths of reef sharks had unknown population trends at the time of their assessment. Fortunately, reef-shark research is on the rise. This new body of research demonstrates reef sharks' high site restriction, fidelity and residency on coral reefs, their broad trophic roles connecting reef communities and their high population genetic structure, all information that should be useful for their management and conservation. Importantly, recent studies on the abundance and population trends of the three classic carcharhinid reef sharks (grey reef shark Carcharhinus amblyrhynchos, blacktip reef shark Carcharhinus melanopterus and whitetip reef shark Triaenodon obesus) may contribute to reassessments identifying them as more vulnerable than currently realized. Because over half of the research effort has focused on only these three reef sharks and the nurse shark Ginglymostoma cirratum in only a few locales, there remain large taxonomic and geographic gaps in reef-shark knowledge. As such, a large portion of reef-shark biodiversity remains uncharacterized despite needs for targeted research identified in their red list assessments. A research agenda for the future should integrate abundance, life history, trophic ecology, genetics, habitat use and movement studies, and expand the breadth of such research to understudied species and localities, in order to better understand the conservation requirements of these species and to motivate effective conservation solutions.

  12. Advancing understanding of executive function impairments and psychopathology: bridging the gap between clinical and cognitive approaches

    PubMed Central

    Snyder, Hannah R.; Miyake, Akira; Hankin, Benjamin L.

    2015-01-01

    Executive function (EF) is essential for successfully navigating nearly all of our daily activities. Of critical importance for clinical psychological science, EF impairments are associated with most forms of psychopathology. However, despite the proliferation of research on EF in clinical populations, with notable exceptions clinical and cognitive approaches to EF have remained largely independent, leading to failures to apply theoretical and methodological advances in one field to the other field and hindering progress. First, we review the current state of knowledge of EF impairments associated with psychopathology and limitations to the previous research in light of recent advances in understanding and measuring EF. Next, we offer concrete suggestions for improving EF assessment. Last, we suggest future directions, including integrating modern models of EF with state of the art, hierarchical models of dimensional psychopathology as well as translational implications of EF-informed research on clinical science. PMID:25859234

  13. Current Approaches to the Understanding of Early Infantile Autism.

    ERIC Educational Resources Information Center

    Rickman, David L.

    This review of the literature provides summaries of the genetic, neurophysiological, and biochemical approaches to understanding autism, with special reference to neuroanatomic, cognitive, and neuropsychological studies of this disorder. Available instruments for the assessment of autism and various treatment alternatives including drug therapy,…

  14. The current state of public understanding of nanotechnology

    NASA Astrophysics Data System (ADS)

    Waldron, Anna M.; Spencer, Douglas; Batt, Carl A.

    2006-10-01

    The growing importance of nanotechnology in industry and society has not been accompanied by a widespread understanding of the subject among the general public. Simple questions to initially probe the smallest thing that people can see and can think of reveals a divide in the understanding of the general public. A survey of 1500 individuals ranging in age from 6 to 74 has revealed a lack of knowledge of nanotechnology and especially a lack of understanding of the context of nanotechnology in the world that is too small to see. Survey findings are corroborated by in-depth interviews with 400 adults in studies of nanoscience literacy commisioned by University of California, Berkeley and Cornell in 2002 and 2004, respectively. In general, with the exception of 14-28 year olds, over 60% of respondents say they have never heard of nano or nanotechnology. The results suggest that the general public, especially middle-school children, has no firm foundation to understand nanotechnology and likely will continue to be equally impressed by credible scientific information as well as pure fictional accounts of nanotechnology.

  15. Manganese: Recent advances in understanding its transport and neurotoxicity

    SciTech Connect

    Aschner, Michael . E-mail: Michael.Aschner@vanderbilt.edu; Guilarte, Tomas R.; Schneider, Jay S.; Zheng Wei

    2007-06-01

    The present review is based on presentations from the meeting of the Society of Toxicology in San Diego, CA (March 2006). It addresses recent developments in the understanding of the transport of manganese (Mn) into the central nervous system (CNS), as well as brain imaging and neurocognitive studies in non-human primates aimed at improving our understanding of the mechanisms of Mn neurotoxicity. Finally, we discuss potential therapeutic modalities for treating Mn intoxication in humans.

  16. Continuing education course #2: current understanding of hemostasis.

    PubMed

    Gale, Andrew J

    2011-01-01

    The goal of this review is to briefly summarize the two primary pathways of hemostasis, primary hemostasis and secondary hemostasis, as well as to summarize anticoagulant mechanisms and fibrinolysis. In addition, this review will discuss pathologies of hemostasis and the mechanisms of the various drugs that are available to impact these pathways to prevent either thrombosis or bleeding. While many of the main drugs that are used to treat disorders of hemostasis have been used for decades, greater understanding of hemostasis has led to development of various new drugs that have come onto the market recently or are close to coming onto the market. Thus, improved understanding of hemostasis continues to lead to benefits for patients.

  17. Recent advances in pathophysiology and current management of itch.

    PubMed

    Greaves, Malcolm W

    2007-09-01

    The neurophysiology of itch, the dominant symptom of skin disease, has previously received scant attention. Recent advances in the neurophysiology and molecular basis of itch include the use of microneurography to demonstrate the existence of a subset of itch-dedicated afferent C neurons distinct from neurons which transmit pain; use of functional positron emission tomography (PET) and magnetic resonance imaging (MRI) of the brain to reveal an itch-specific activation matrix, and new evidence of a functional "dialogue" between C neuron terminals and dermal mast cells in which recently described proteinase-activated receptor type 2 (PAR2) and transient receptor potential vanilloid 1 (TRPV1) receptors, proteases and endovanilloids play a major role. As a necessary prerequisite to diagnosis and management, a pathophysiologically based classification of itch is proposed. Recent advances in understanding of the pathomechanisms of itch of cholestasis include the role of opioids and opioid antagonists. Focusing on neurogenic itch (itch without visible rash), common causes are reviewed and guidelines for laboratory and radiological investigation are proposed. A stepwise approach to management of generalised itch is recommended, including broadband or narrow band ultraviolet (UV), tricyclics such as doxepin, opioid antagonists including naltrexone and selective serotonin reuptake inhibitors (SSRIs) such as paroxetine. For troublesome localised itches such as insect bite reactions, physical urticaria, lichen simplex chronicus or, less commonly, notalgia paraesthetica, brachioradial pruritus, local cooling devices which rely on the cooling action of dimethyl ethers on thermosensitive TRP voltage-sensitive ion channels are now commercially available for shortterm relief.

  18. Current Understanding of Acute Bovine Liver Disease in Australia

    PubMed Central

    Read, Elizabeth; Edwards, Jacqueline; Deseo, Myrna; Rawlin, Grant; Rochfort, Simone

    2016-01-01

    Acute bovine liver disease (ABLD) is a hepatotoxicity principally of cattle which occurs in southern regions of Australia. Severely affected animals undergo rapid clinical progression with mortalities often occurring prior to the recognition of clinical signs. Less severely affected animals develop photosensitization and a proportion can develop liver failure. The characteristic histopathological lesion in acute fatal cases is severe, with acute necrosis of periportal hepatocytes with hemorrhage into the necrotic areas. Currently there are a small number of toxins that are known to cause periportal necrosis in cattle, although none of these have so far been linked to ABLD. Furthermore, ABLD has frequently been associated with the presence of rough dog’s tail grass (Cynosurus echinatus) and Drechslera spp. fungi in the pasture system, but it is currently unknown if these are etiological factors. Much of the knowledge about ABLD is contained within case reports, with very little experimental research investigating the specific cause(s). This review provides an overview of the current and most recently published knowledge of ABLD. It also draws on wider research and unpublished reports to suggest possible fungi and mycotoxins that may give rise to ABLD. PMID:28035972

  19. Advances in understanding glycosyltransferases from a structural perspective

    PubMed Central

    Gloster, Tracey M

    2014-01-01

    Glycosyltransferases (GTs), the enzymes that catalyse glycosidic bond formation, create a diverse range of saccharides and glycoconjugates in nature. Understanding GTs at the molecular level, through structural and kinetic studies, is important for gaining insights into their function. In addition, this understanding can help identify those enzymes which are involved in diseases, or that could be engineered to synthesize biologically or medically relevant molecules. This review describes how structural data, obtained in the last 3–4 years, have contributed to our understanding of the mechanisms of action and specificity of GTs. Particular highlights include the structure of a bacterial oligosaccharyltransferase, which provides insights into N-linked glycosylation, the structure of the human O-GlcNAc transferase, and the structure of a bacterial integral membrane protein complex that catalyses the synthesis of cellulose, the most abundant organic molecule in the biosphere. PMID:25240227

  20. Inflammation in AKI: Current Understanding, Key Questions, and Knowledge Gaps.

    PubMed

    Rabb, Hamid; Griffin, Matthew D; McKay, Dianne B; Swaminathan, Sundararaman; Pickkers, Peter; Rosner, Mitchell H; Kellum, John A; Ronco, Claudio

    2016-02-01

    Inflammation is a complex biologic response that is essential for eliminating microbial pathogens and repairing tissue after injury. AKI associates with intrarenal and systemic inflammation; thus, improved understanding of the cellular and molecular mechanisms underlying the inflammatory response has high potential for identifying effective therapies to prevent or ameliorate AKI. In the past decade, much knowledge has been generated about the fundamental mechanisms of inflammation. Experimental work in small animal models has revealed many details of the inflammatory response that occurs within the kidney after typical causes of AKI, including insights into the molecular signals released by dying cells, the role of pattern recognition receptors, the diverse subtypes of resident and recruited immune cells, and the phased transition from destructive to reparative inflammation. Although this expansion of the basic knowledge base has increased the number of mechanistically relevant targets of intervention, progress in developing therapies that improve AKI outcomes by modulation of inflammation remains slow. In this article, we summarize the most important recent developments in understanding the inflammatory mechanisms of AKI, highlight key limitations of the commonly used animal models and clinical trial designs that may prevent successful clinical application, and suggest priority approaches for research toward clinical translation in this area.

  1. Wound exudate: a survey of current understanding and clinical competency.

    PubMed

    Tickle, Joy

    A survey was undertaken with the aim of identifying health professionals' understanding of wound exudate and their ability to assess and manage it. The survey was carried out at Wound Expo, which is a large annual event that provides generalist nurses with interactive education on the core aspects of wound care, including wound exudate. The sample comprised 223 delegates. Almost all delegates (89%) included exudate in every wound assessment, but only 20% based assessment of excess exudate on colour, viscosity and malodour, with the majority (67%) basing it on leakage and increased frequency of dressing changes. While almost all (94%) delegates said they always assess exudate colour and most (80%) that they always assess its viscosity, 18% did not understand the clinical significance of exudate colour and 29% were unable to correctly identify the characteristics of low-viscosity exudate. Furthermore, one quarter of the sample did not always take absorbency into account when selecting a wound dressing. The results indicate that exudate assessment is often subjective, and there is scope for greater use of wound exudate assessment tools and exudate descriptors.

  2. Advancing our understanding of charcoal rot in soybeans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Charcoal rot (Macrophomina phaseolina (Tassi) Goid ) of soybean [Glycine max (L.) Merr.], is an important but commonly misidentified disease, and very few summary articles exist on this pathosystem. Research conducted over the last 10 years has improved our understanding of the environment conducive...

  3. Current understanding of the neuropathophysiology of pain in chronic pancreatitis

    PubMed Central

    Atsawarungruangkit, Amporn; Pongprasobchai, Supot

    2015-01-01

    Chronic pancreatitis (CP) is a chronic inflammatory disease of the pancreas. The main symptom of patients with CP is chronic and severe abdominal pain. However, the pathophysiology of pain in CP remains obscure. Traditionally, researchers believed that the pain was caused by anatomical changes in pancreatic structure. However, treatment outcomes based on such beliefs are considered unsatisfactory. The emerging explanations of pain in CP are trending toward neurobiological theories. This article aims to review current evidence regarding the neuropathophysiology of pain in CP and its potential implications for the development of new treatments for pain in CP. PMID:26600977

  4. Current concepts in the understanding and management of hemifacial microsomia.

    PubMed

    Cousley, R R; Calvert, M L

    1997-10-01

    Hemifacial microsomia (HFM) is a complex congenital condition. This review discusses recent research findings which affect all aspects of HFM, and addresses some prevailing misconceptions. Firstly, the broad phenotype is outlined, with an emphasis on the facial anomalies which are important for diagnosis, classification and treatment. The range of HFM anomalies and their possible embryology also account for the varied terms used in the literature. In addition, consideration of causation helps to shape our understanding of HFM as a clinical entity. Aetiology is described with particular emphasis on the involvement of genetic factors, although at present this is largely hypothetical. Finally, the principles of HFM management are reviewed. Attention is given to the integrated planning and team approach necessary to treat such patients. In addition, the possible attributes of new treatments, such as distraction osteogenesis, are highlighted.

  5. Current understanding of the neurobiology of major depressive disorder.

    PubMed

    Chiriţă, Anca Livia; Gheorman, Victor; Bondari, Dan; Rogoveanu, Ion

    2015-01-01

    Depression is highly prevalent worldwide and associated with significant morbidity and mortality. Approximately 340 million people worldwide suffer from depression at any given time. Based on estimates from the World Health Organization (WHO), depression is responsible for the greatest proportion of burden associated with non-fatal health outcomes and accounts for approximately 12% total years lived with disability. Probably no single risk factor can be completely isolated in major depressive disorder (MDD), as interactions between many sources of vulnerability are the most likely explanation. Buttressing the identification of grief, demoralization, hopelessness and styles of psychological coping of the depressed patient are vital, ongoing scientific developments that flow from an increased understanding of this interplay amongst the immune system, endocrine system and brain. The rapidly accumulating body of neurobiological knowledge has catalyzed fundamental changes in how we conceptualize depressive symptoms and has important implications regarding the treatment and even prevention of depressive symptoms in patients.

  6. Current Status of the Advanced High Temperature Reactor

    SciTech Connect

    Holcomb, David Eugene; Ilas, Dan; Qualls, A L; Peretz, Fred J; Varma, Venugopal Koikal; Bradley, Eric Craig; Cisneros, Anselmo T.

    2012-01-01

    The Advanced High Temperature Reactor (AHTR) is a design concept for a central station type [1500 MW(e)] Fluoride salt-cooled High-temperature Reactor (FHR) that is currently under development by Oak Ridge National Laboratory for the U. S. Department of Energy, Office of Nuclear Energy's Advanced Reactor Concepts program. FHRs, by definition, feature low-pressure liquid fluoride salt cooling, coated-particle fuel, a high-temperature power cycle, and fully passive decay heat rejection. The overall goal of the AHTR development program is to demonstrate the technical feasibility of FHRs as low-cost, large-size power producers while maintaining full passive safety. The AHTR design option exploration is a multidisciplinary design effort that combines core neutronic and fuel configuration evaluation with structural, thermal, and hydraulic analysis to produce a reactor and vessel concept and place it within a power generation station. The AHTR design remains at the notional level of maturity, as key technologies require further development and a logically complete integrated design has not been finalized. The present design space exploration, however, indicates that reasonable options exist for the AHTR core, primary heat transport path, and fuel cycle provided that materials and systems technologies develop as anticipated.

  7. Current status of the advanced high temperature reactor

    SciTech Connect

    Holcomb, D. E.; Iias, D.; Quails, A. L.; Peretz, F. J.; Varma, V. K.; Bradley, E. C.; Cisneros, A. T.

    2012-07-01

    The Advanced High Temperature Reactor (AHTR) is a design concept for a central station type [1500 MW(e)] Fluoride salt-cooled High-temperature Reactor (FHR) that is currently under development by Oak Ridge National Laboratory for the U. S. Dept. of Energy, Office of Nuclear Energy's Advanced Reactor Concepts program. FHRs, by definition, feature low-pressure liquid fluoride salt cooling, coated-particle fuel, a high-temperature power cycle, and fully passive decay heat rejection. The overall goal of the AHTR development program is to demonstrate the technical feasibility of FHRs as low-cost, large-size power producers while maintaining full passive safety. The AHTR design option exploration is a multidisciplinary design effort that combines core neutronic and fuel configuration evaluation with structural, thermal, and hydraulic analysis to produce a reactor and vessel concept and place it within a power generation station. The AHTR design remains at the notional level of maturity, as key technologies require further development and a logically complete integrated design has not been finalized. The present design space exploration, however, indicates that reasonable options exist for the AHTR core, primary heat transport path, and fuel cycle provided that materials and systems technologies develop as anticipated. (authors)

  8. Locally advanced prostate cancer: current controversies and optimisation opportunities.

    PubMed

    Sridharan, S; Dal Pra, A; Catton, C; Bristow, R G; Warde, P

    2013-08-01

    Prostate cancer is the most common malignancy in men worldwide. The rate of patients presenting with locally advanced prostate cancer has declined in recent decades, mainly due to prostate-specific antigen screening, but the management of these patients still remains controversial. Current literature suggests that the standard of care for these patients is a combination approach with radiation therapy and androgen deprivation therapy. However, there remain many unresolved issues, including the role of dose-escalated radiation therapy, the additional benefit of surgery and the role of systemic therapy, both standard chemotherapeutic agents and novel agents. Furthermore, in the era of personalised medicine, additional research is needed to evaluate the role of biomarkers to better predict the risk of local and systemic relapse in this population.

  9. Recent advances in understanding and managing liver transplantation

    PubMed Central

    Russo, Francesco Paolo; Ferrarese, Alberto; Zanetto, Alberto

    2016-01-01

    Liver transplantation (LT) has been established as the most effective treatment modality for end-stage liver disease over the last few decades. Currently, patient and graft survival after LT are excellent, with 1- and 5-year survival of 90% and 80%, respectively. However, the timing of referral to LT is crucial for improving survival benefit and outcome. The current shortage of donors and the increasing demand for LT currently lengthen the waiting time. Thus, waiting list mortality is about 10–15%, according to the geographical area. For this reason, over the last several years, alternatives to deceased donor LT and new options for prioritizing patients on the waiting list have been proposed. PMID:28105300

  10. Current advances in the cognitive neuroscience of music.

    PubMed

    Levitin, Daniel J; Tirovolas, Anna K

    2009-03-01

    The study of music perception and cognition is one of the oldest topics in experimental psychology. The last 20 years have seen an increased interest in understanding the functional neuroanatomy of music processing in humans, using a variety of technologies including fMRI, PET, ERP, MEG, and lesion studies. We review current findings in the context of a rich intellectual history of research, organized by the cognitive systems underlying different aspects of human musical behavior. We pay special attention to the perception of components of musical processing, musical structure, laterality effects, cultural issues, links between music and movement, emotional processing, expertise, and the amusias. Current trends are noted, such as the increased interest in evolutionary origins of music and comparisons of music and language. The review serves to demonstrate the important role that music can play in informing broad theories of higher order cognitive processes such as music in humans.

  11. Current advances in DNA repair: regulation of enzymes and pathways involved in maintaining genomic stability.

    PubMed

    Neher, Tracy M; Turchi, John J

    2011-06-15

    Novel discoveries in the DNA repair field have lead to continuous and rapid advancement of our understanding of not only DNA repair but also DNA replication and recombination. Research in the field transcends numerous areas of biology, biochemistry, physiology, and medicine, making significant connections across these broad areas of study. From early studies conducted in bacterial systems to current analyses in eukaryotic systems and human disease, the innovative research into the mechanisms of repair machines and the consequences of ineffective DNA repair has impacted a wide scientific community. This Forum contains a select mix of primary research articles in addition to a number of timely reviews covering a subset of DNA repair pathways where recent advances and novel discoveries are improving our understanding of DNA repair, its regulation, and implications to human disease.

  12. Advanced Curation of Current and Future Extraterrestrial Samples

    NASA Technical Reports Server (NTRS)

    Allen, Carlton C.

    2013-01-01

    Curation of extraterrestrial samples is the critical interface between sample return missions and the international research community. Curation includes documentation, preservation, preparation, and distribution of samples. The current collections of extraterrestrial samples include: Lunar rocks / soils collected by the Apollo astronauts Meteorites, including samples of asteroids, the Moon, and Mars "Cosmic dust" (asteroid and comet particles) collected by high-altitude aircraft Solar wind atoms collected by the Genesis spacecraft Comet particles collected by the Stardust spacecraft Interstellar dust collected by the Stardust spacecraft Asteroid particles collected by the Hayabusa spacecraft These samples were formed in environments strikingly different from that on Earth. Terrestrial contamination can destroy much of the scientific significance of many extraterrestrial materials. In order to preserve the research value of these precious samples, contamination must be minimized, understood, and documented. In addition the samples must be preserved - as far as possible - from physical and chemical alteration. In 2011 NASA selected the OSIRIS-REx mission, designed to return samples from the primitive asteroid 1999 RQ36 (Bennu). JAXA will sample C-class asteroid 1999 JU3 with the Hayabusa-2 mission. ESA is considering the near-Earth asteroid sample return mission Marco Polo-R. The Decadal Survey listed the first lander in a Mars sample return campaign as its highest priority flagship-class mission, with sample return from the South Pole-Aitken basin and the surface of a comet among additional top priorities. The latest NASA budget proposal includes a mission to capture a 5-10 m asteroid and return it to the vicinity of the Moon as a target for future sampling. Samples, tools, containers, and contamination witness materials from any of these missions carry unique requirements for acquisition and curation. Some of these requirements represent significant advances over

  13. Overcoming treatment resistance in cancer: Current understanding and tactics.

    PubMed

    Wu, Guang; Wilson, George; George, Jacob; Liddle, Christopher; Hebbard, Lionel; Qiao, Liang

    2017-02-28

    Chemotherapy is the standard treatment for many, if not all, metastatic cancers. While chemotherapy is often capable of inducing cell death in tumors leading to shrinkage of the tumor bulk, many patients suffer from recurrence and ultimately death due to resistance. During the last decade, treatment resistance has attracted great attention followed by some seminal discoveries, including sequential mutations, cancer stem cells, and bidirectional inter-conversion of stem and non-stem cancer cell populations. Nevertheless, the successful treatment of cancer will require a considerable refinement of our knowledge concerning treatment resistance. In doing so, we expect that a more informed and refined approach to treat cancer will be developed and this may improve prognosis of cancer patients. In this review, we will discuss the current knowledge concerning the failure of cancer treatments and the potential approaches to overcome therapeutic resistance.

  14. Uncertainty of current understanding regarding OBT formation in plants.

    PubMed

    Melintescu, A; Galeriu, D

    2017-02-01

    Radiological impact models are important tools that support nuclear safety. For tritium, a special radionuclide that readily enters the life cycle, the processes involved in its transport into the environment are complex and inadequately understood. For example, tritiated water (HTO) enters plants by leaf and root uptake and is converted to organically bound tritium (OBT) in exchangeable and non-exchangeable forms; however, the observed OBT/HTO ratios in crops exhibit large variability and contradict the current models for routine releases. Non-routine or spike releases of tritium further complicate the prediction of OBT formation. The experimental data for a short and intense atmospheric contamination of wheat are presented together with various models' predictions. The experimental data on wheat demonstrate that the OBT formation is a long process, it is dependent on receptor location and stack dynamics, there are differences between night and day releases, and the HTO dynamics in leaf and ear is a very important contributor to OBT formation.

  15. Advanced UXO Discrimination using Magnetometry: Understanding Remanent Magnetization

    DTIC Science & Technology

    2009-09-01

    of metals and metal- lography, 104(5):469(9), 2007. [12] Richard P. Feynman , Robert B. Leighton, and Matthew Sands. The Feynman Lectures on Physics ...being left in the ground, a comprehensive understanding of the physical phenomena was deemed necessary. This was the impetus for this project. As...are placed on the holder and are slowly spun through two complete rotations. The measurement is repeated after the sample is physically rotated by

  16. Advances in understanding Giardia: determinants and mechanisms of chronic sequelae

    PubMed Central

    Sartor, R. Balfour

    2015-01-01

    Giardia lamblia is a flagellated protozoan that is the most common cause of intestinal parasitic infection in children living in resource-limited settings. The pathogenicity of Giardia has been debated since the parasite was first identified, and clinical outcomes vary across studies. Among recent perplexing findings are diametrically opposed associations between Giardia and acute versus persistent diarrhea and a poorly understood potential for long-term sequelae, including impaired child growth and cognitive development. The mechanisms driving these protean clinical outcomes remain elusive, but recent advances suggest that variability in Giardia strains, host nutritional status, the composition of microbiota, co-infecting enteropathogens, host genetically determined mucosal immune responses, and immune modulation by Giardia are all relevant factors influencing disease manifestations after Giardia infection. PMID:26097735

  17. A view on advances in spheromak understanding and parameters

    SciTech Connect

    Fernandez, J.C.; Chrien, R.E.; Wysocki, F.J.; Mayo, R.M.; Henins, I.

    1990-01-01

    A spheromak is a toroidally-shaped magnetized plasma configuration in which no material (such as coils or vacuum vessels) links the torus, so that the topology of the spheromak boundary is spherical. In the period since the properties of a nearly force-free ({Delta} {times} {rvec B} {approx} {lambda}{rvec B}) spheromak configuration were described using single-fluid MHD theory, and since the first spheromak was formed at the Univ. of Maryland, remarkable theoretical and experimental advances have been made. This paper highlights some of that work. Some of the latest results from the CTX group at Los Alamos are also presented. These include the observation of suprathermal electrons in CTX, evidence by X-ray bursts with photon energies above 1 MeV.

  18. Current Understanding on Pain Mechanism in Migraine and Cluster Headache

    PubMed Central

    Buture, Alina; Gooriah, Rubesh; Nimeri, Randa; Ahmed, Fayyaz

    2016-01-01

    Context Migraine and cluster headache are undoubtedly painful conditions. The respective pathogenesis of these two conditions is incompletely understood. In both cases, the treatments used have largely been empirical and have relied to a much lesser extent on our understanding of the mechanisms causing pain. We hereby review the pain mechanisms in migraine and cluster headache, two of the commonest primary headache disorders. Evidence Acquisition A review of the English literature was conducted by searching PubMed for studies on pain mechanism in migraine and cluster headache. We entered [migraine] and [pain mechanism] in Pubmed and 488 articles were obtained. Articles were then included according to their relevance to the topic. Similarly, [cluster headache] and [pain mechanism] revealed 79 search results. Results There is evidence that the trigeminovascular system and neurogenic inflammation play important roles, together with certain areas of the brain, leading to these conditions being termed ‘neurovascular headaches’. Functional imaging findings suggest a possible role of the dorsolateral pons in generating migraine attacks while the role of the hypothalamus in cluster headache is more firmly established. Conclusions Migraine and cluster headache have complex pathophysiologies. The exact mechanism causing pain in both conditions is incompletely understood and more research needs to be undertaken in this area. PMID:27642579

  19. Current understanding on the neurophysiology of behavioral thermoregulation

    PubMed Central

    Almeida, Maria Camila; Vizin, Robson Cristiano Lillo; Carrettiero, Daniel Carneiro

    2015-01-01

    Temperature influence on the physiology and biochemistry of living organisms has long been recognized, which propels research in the field of thermoregulation. With the cloning and characterization of the transient receptor potential (TRP) ion channels as the principal temperature sensors of the mammalian somatosensory neurons, the understanding, at a molecular level, of thermosensory and thermoregulatory mechanisms became promising. Because thermal environment can be extremely hostile (temperature range on earth's surface is from ∼ −69°C to 58°C), living organisms developed an array of thermoregulatory strategies to guarantee survival, which include both autonomic mechanisms, which aim at increasing or decreasing heat exchange between body, and ambient and behavioral strategies. The knowledge regarding neural mechanisms involved in autonomic thermoregulatory strategies has progressed immensely compared to the knowledge on behavioral thermoregulation. This review aims at collecting the up-to-date knowledge on the neural basis for behavioral thermoregulation in mammals in order to point out perspectives and deployment of this research field. PMID:27227068

  20. Solubility and dissolution enhancement strategies: current understanding and recent trends.

    PubMed

    Jain, Shashank; Patel, Niketkumar; Lin, Senshang

    2015-06-01

    Identification of lead compounds with higher molecular weight and lower aqueous solubility has become increasingly prevalent with the advent of high throughput screening. Poor aqueous solubility of these lipophilic compounds can drastically affect the dissolution rate and subsequently the drug absorbed in the systemic circulation, imposing a significant burden of time and money during drug development process. Various pre-formulation and formulation strategies have been applied in the past that can improve the aqueous solubility of lipophilic compounds by manipulating either the crystal lattice properties or the activity coefficient of a solute in solution or both, if possible. However, despite various strategies available in the armor of formulation scientist, solubility issue still remains an overriding problem in the drug development process. It is perhaps due to the insufficient conceptual understanding of solubility and dissolution phenomenon that hinders the judgment in selecting suitable strategy for improving aqueous solubility and/or dissolution rate. This article, therefore, focuses on (i) revisiting the theoretical and mathematical concepts associated with solubility and dissolution, (ii) their application in making rationale decision for selecting suitable pre-formulation and formulation strategies and (iii) the relevant research performed in this field in past decade.

  1. Cell and molecular biology of intervertebral disc degeneration: current understanding and implications for potential therapeutic strategies.

    PubMed

    Wang, S Z; Rui, Y F; Lu, J; Wang, C

    2014-10-01

    Intervertebral disc degeneration (IDD) is a chronic, complex process associated with low back pain; mechanisms of its occurrence have not yet been fully elucidated. Its process is not only accompanied by morphological changes, but also by systematic changes in its histological and biochemical properties. Many cellular and molecular mechanisms have been reported to be related with IDD and to reverse degenerative trends, abnormal conditions of the living cells and altered cell phenotypes would need to be restored. Promising biological therapeutic strategies still rely on injection of active substances, gene therapy and cell transplantation. With advanced study of tissue engineering protocols based on cell therapy, combined use of seeding cells, bio-active substances and bio-compatible materials, are promising for IDD regeneration. Recently reported progenitor cells within discs themselves also hold prospects for future IDD studies. This article describes the background of IDD, current understanding and implications of potential therapeutic strategies.

  2. Catatonia: Our current understanding of its diagnosis, treatment and pathophysiology

    PubMed Central

    Rasmussen, Sean A; Mazurek, Michael F; Rosebush, Patricia I

    2016-01-01

    Catatonia is a psychomotor syndrome that has been reported to occur in more than 10% of patients with acute psychiatric illnesses. Two subtypes of the syndrome have been identified. Catatonia of the retarded type is characterized by immobility, mutism, staring, rigidity, and a host of other clinical signs. Excited catatonia is a less common presentation in which patients develop prolonged periods of psychomotor agitation. Once thought to be a subtype of schizophrenia, catatonia is now recognized to occur with a broad spectrum of medical and psychiatric illnesses, particularly affective disorders. In many cases, the catatonia must be treated before any underlying conditions can be accurately diagnosed. Most patients with the syndrome respond rapidly to low-dose benzodiazepines, but electroconvulsive therapy is occasionally required. Patients with longstanding catatonia or a diagnosis of schizophrenia may be less likely to respond. The pathobiology of catatonia is poorly understood, although abnormalities in gamma-aminobutyric acid and glutamate signaling have been suggested as causative factors. Because catatonia is common, highly treatable, and associated with significant morbidity and mortality if left untreated, physicians should maintain a high level of suspicion for this complex clinical syndrome. Since 1989, we have systematically assessed patients presenting to our psychiatry service with signs of retarded catatonia. In this paper, we present a review of the current literature on catatonia along with findings from the 220 cases we have assessed and treated. PMID:28078203

  3. Catatonia: Our current understanding of its diagnosis, treatment and pathophysiology.

    PubMed

    Rasmussen, Sean A; Mazurek, Michael F; Rosebush, Patricia I

    2016-12-22

    Catatonia is a psychomotor syndrome that has been reported to occur in more than 10% of patients with acute psychiatric illnesses. Two subtypes of the syndrome have been identified. Catatonia of the retarded type is characterized by immobility, mutism, staring, rigidity, and a host of other clinical signs. Excited catatonia is a less common presentation in which patients develop prolonged periods of psychomotor agitation. Once thought to be a subtype of schizophrenia, catatonia is now recognized to occur with a broad spectrum of medical and psychiatric illnesses, particularly affective disorders. In many cases, the catatonia must be treated before any underlying conditions can be accurately diagnosed. Most patients with the syndrome respond rapidly to low-dose benzodiazepines, but electroconvulsive therapy is occasionally required. Patients with longstanding catatonia or a diagnosis of schizophrenia may be less likely to respond. The pathobiology of catatonia is poorly understood, although abnormalities in gamma-aminobutyric acid and glutamate signaling have been suggested as causative factors. Because catatonia is common, highly treatable, and associated with significant morbidity and mortality if left untreated, physicians should maintain a high level of suspicion for this complex clinical syndrome. Since 1989, we have systematically assessed patients presenting to our psychiatry service with signs of retarded catatonia. In this paper, we present a review of the current literature on catatonia along with findings from the 220 cases we have assessed and treated.

  4. Children and war: current understandings and future directions.

    PubMed

    Berman, H

    2001-01-01

    During the last decade, the number of children whose lives have been disrupted by war, oppression, terror, and other forms of conflict has grown tremendously. When the United Nations High Commission for Refugees was first established during the 1950s to provide international protection to refugees following World War II, it was estimated that there were 1.5 million refugees and displaced persons. Today there are approximately 14 million, about three-fourths of whom are women and children. Although the experiences of refugee children and adolescents vary considerably, many have witnessed or experienced the death or murder of loved ones. Upon resettlement, they face numerous challenges. Research with this population is a relatively new area of investigation, but there is evidence that many of these young people experience long-term physical and emotional health problems. In this article, current research findings are reviewed, the widespread emphasis in the literature on post-traumatic stress disorder (PTSD) is critically examined, future research directions are suggested, and implications for public health nurses are addressed.

  5. Recent advances in understanding cardiac contractility in health and disease

    PubMed Central

    MacLeod, Ken T.

    2016-01-01

    The aim of this review is to provide the reader with a synopsis of some of the emerging ideas and experimental findings in cardiac physiology and pathophysiology that were published in 2015. To provide context for the non-specialist, a brief summary of cardiac contraction and calcium (Ca) regulation in the heart in health and disease is provided. Thereafter, some recently published articles are introduced that indicate the current thinking on (1) the Ca regulatory pathways modulated by Ca/calmodulin-dependent protein kinase II, (2) the potential influences of nitrosylation by nitric oxide or S-nitrosated proteins, (3) newly observed effects of reactive oxygen species (ROS) on contraction and Ca regulation following myocardial infarction and a possible link with changes in mitochondrial Ca, and (4) the effects of some of these signaling pathways on late Na current and pro-arrhythmic afterdepolarizations as well as the effects of transverse tubule disturbances. PMID:27508064

  6. Recent advances in understanding haemochromatosis: a transition state

    PubMed Central

    Robson, K; Merryweather-Clar..., A; Cadet, E; Viprakasit, V; Zaahl, M; Pointon, J; Weatherall, D; Rochette, J

    2004-01-01

    Mutations in the hepcidin gene HAMP and the hemojuvelin gene HJV have recently been shown to result in juvenile haemochromatosis (JH). Hepcidin is an antimicrobial peptide that plays a key role in regulating intestinal iron absorption. Hepcidin levels are reduced in patients with haemochromatosis due to mutations in the HFE and HJV genes. Digenic inheritance of mutations in HFE and HAMP can result in either JH or hereditary haemochromatosis (HH) depending upon the severity of the mutation in HAMP. Here we review these findings and discuss how understanding the different types of haemochromatosis and our increasing knowledge of iron metabolism may help to elucidate the host's response to infection. PMID:15466004

  7. Advanced Imaging in Femoroacetabular Impingement: Current State and Future Prospects.

    PubMed

    Bittersohl, Bernd; Hosalkar, Harish S; Hesper, Tobias; Tiderius, Carl Johan; Zilkens, Christoph; Krauspe, Rüdiger

    2015-01-01

    Symptomatic femoroacetabular impingement (FAI) is now a known precursor of early osteoarthritis (OA) of the hip. In terms of clinical intervention, the decision between joint preservation and joint replacement hinges on the severity of articular cartilage degeneration. The exact threshold during the course of disease progression when the cartilage damage is irreparable remains elusive. The intention behind radiographic imaging is to accurately identify the morphology of osseous structural abnormalities and to accurately characterize the chondrolabral damage as much as possible. However, both plain radiographs and computed tomography (CT) are insensitive for articular cartilage anatomy and pathology. Advanced magnetic resonance imaging (MRI) techniques include magnetic resonance arthrography and biochemically sensitive techniques of delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), T1rho (T1ρ), T2/T2* mapping, and several others. The diagnostic performance of these techniques to evaluate cartilage degeneration could improve the ability to predict an individual patient-specific outcome with non-surgical and surgical care. This review discusses the facts and current applications of biochemical MRI for hip joint cartilage assessment covering the roles of dGEMRIC, T2/T2*, and T1ρ mapping. The basics of each technique and their specific role in FAI assessment are outlined. Current limitations and potential pitfalls as well as future directions of biochemical imaging are also outlined.

  8. Advanced Imaging in Femoroacetabular Impingement: Current State and Future Prospects

    PubMed Central

    Bittersohl, Bernd; Hosalkar, Harish S.; Hesper, Tobias; Tiderius, Carl Johan; Zilkens, Christoph; Krauspe, Rüdiger

    2015-01-01

    Symptomatic femoroacetabular impingement (FAI) is now a known precursor of early osteoarthritis (OA) of the hip. In terms of clinical intervention, the decision between joint preservation and joint replacement hinges on the severity of articular cartilage degeneration. The exact threshold during the course of disease progression when the cartilage damage is irreparable remains elusive. The intention behind radiographic imaging is to accurately identify the morphology of osseous structural abnormalities and to accurately characterize the chondrolabral damage as much as possible. However, both plain radiographs and computed tomography (CT) are insensitive for articular cartilage anatomy and pathology. Advanced magnetic resonance imaging (MRI) techniques include magnetic resonance arthrography and biochemically sensitive techniques of delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), T1rho (T1ρ), T2/T2* mapping, and several others. The diagnostic performance of these techniques to evaluate cartilage degeneration could improve the ability to predict an individual patient-specific outcome with non-surgical and surgical care. This review discusses the facts and current applications of biochemical MRI for hip joint cartilage assessment covering the roles of dGEMRIC, T2/T2*, and T1ρ mapping. The basics of each technique and their specific role in FAI assessment are outlined. Current limitations and potential pitfalls as well as future directions of biochemical imaging are also outlined. PMID:26258129

  9. HIV Vaccine: Recent Advances, Current Roadblocks, and Future Directions

    PubMed Central

    Rubens, Muni; Ramamoorthy, Venkataraghavan; Saxena, Anshul; Shehadeh, Nancy; Appunni, Sandeep

    2015-01-01

    HIV/AIDS is a leading cause of mortality and morbidity worldwide. In spite of successful interventions and treatment protocols, an HIV vaccine would be the ultimate prevention and control strategy. Ever since identification of HIV/AIDS, there have been meticulous efforts for vaccine development. The specific aim of this paper is to review recent vaccine efficacy trials and associated advancements and discuss the current challenges and future directions. Recombinant DNA technologies greatly facilitated development of many viral products which were later incorporated into vectors for effective vaccines. Over the years, a number of scientific approaches have gained popularity and include the induction of neutralizing antibodies in late 1980s, induction of CD8 T cell in early 1990s, and combination approaches currently. Scientists have hypothesized that stimulation of right sequences of somatic hypermutations could induce broadly reactive neutralizing antibodies (bnAbs) capable of effective neutralization and viral elimination. Studies have shown that a number of host and viral factors affect these processes. Similarly, eliciting specific CD8 T cells immune responses through DNA vaccines hold future promises. In summary, future studies should focus on the continuous fight between host immune responses and ever-evasive viral factors for effective vaccines. PMID:26579546

  10. Drugs in development for toxoplasmosis: advances, challenges, and current status

    PubMed Central

    Alday, P Holland; Doggett, Joseph Stone

    2017-01-01

    Toxoplasma gondii causes fatal and debilitating brain and eye diseases. Medicines that are currently used to treat toxoplasmosis commonly have toxic side effects and require prolonged courses that range from weeks to more than a year. The need for long treatment durations and the risk of relapsing disease are in part due to the lack of efficacy against T. gondii tissue cysts. The challenges for developing a more effective treatment for toxoplasmosis include decreasing toxicity, achieving therapeutic concentrations in the brain and eye, shortening duration, eliminating tissue cysts from the host, safety in pregnancy, and creating a formulation that is inexpensive and practical for use in resource-poor areas of the world. Over the last decade, significant progress has been made in identifying and developing new compounds for the treatment of toxoplasmosis. Unlike clinically used medicines that were repurposed for toxoplasmosis, these compounds have been optimized for efficacy against toxoplasmosis during preclinical development. Medicines with enhanced efficacy as well as features that address the unique aspects of toxoplasmosis have the potential to greatly improve toxoplasmosis therapy. This review discusses the facets of toxoplasmosis that are pertinent to drug design and the advances, challenges, and current status of preclinical drug research for toxoplasmosis. PMID:28182168

  11. Operational advances in ring current modeling using RAM-SCB

    SciTech Connect

    Welling, Daniel T; Jordanova, Vania K; Zaharia, Sorin G; Morley, Steven K

    2010-12-03

    The Ring current Atmosphere interaction Model with Self-Consistently calculated 3D Magnetic field (RAM-SCB) combines a kinetic model of the ring current with a force-balanced model of the magnetospheric magnetic field to create an inner magnetospheric model that is magnetically self consistent. RAM-SCB produces a wealth of outputs that are valuable to space weather applications. For example, the anisotropic particle distribution of the KeV-energy population calculated by the code is key for predicting surface charging on spacecraft. Furthermore, radiation belt codes stand to benefit substantially from RAM-SCB calculated magnetic field values and plasma wave growth rates - both important for determining the evolution of relativistic electron populations. RAM-SCB is undergoing development to bring these benefits to the space weather community. Data-model validation efforts are underway to assess the performance of the system. 'Virtual Satellite' capability has been added to yield satellite-specific particle distribution and magnetic field output. The code's outer boundary is being expanded to 10 Earth Radii to encompass previously neglected geosynchronous orbits and allow the code to be driven completely by either empirical or first-principles based inputs. These advances are culminating towards a new, real-time version of the code, rtRAM-SCB, that can monitor the inner magnetosphere conditions on both a global and spacecraft-specific level. This paper summarizes these new features as well as the benefits they provide the space weather community.

  12. Advances in understanding the gravity wave spectrum during MAP

    NASA Technical Reports Server (NTRS)

    Vanzandt, T. E.

    1989-01-01

    Prior to MAP, virtually nothing was known about gravity wave spectra in the atmosphere. The development of observational techniques has played a major role in these studies. Radar and lidar have been particularly important since they can measure atmospheric parameters continuously over large height ranges. Some advances made are: (1) The observed fluctuations and power spectra in the free atmosphere are mostly if not entirely due to a superposition of gravity waves, which can be modeled by the Garrett Munk (GM) model; (2) There is no evidence that 2-D turbulence makes a significant contribution to the observed fluctuations. In any case, the agreement between observations and the GM model shows that the 2DT contribution must be relatively small; (3) Spectra versus vertical wave number are saturated at large wave number, with theory and observations indicating that t approximately equals 3; and (4) Vertical velocity fluctuations and spectra measured near rough terrain are strongly contaminated by mountain waves. But over very flat terrain the spectra are dominated by gravity waves at periods shorter than about 6 hours and apparently by synoptic scale velocities at periods longer than 6 hours. Thus it may be possible to study synoptic scale vertical velocities using radars located in very flat terrain.

  13. Recent advances in our understanding of Streptococcus pneumoniae infection

    PubMed Central

    Anderson, Ronald

    2014-01-01

    A number of significant challenges remain with regard to the diagnosis, treatment, and prevention of infections with Streptococcus pneumoniae (pneumococcus), which remains the most common bacterial cause of community-acquired pneumonia. Although this infection is documented to be extremely common in younger children and in older adults, the burden of pneumonia it causes is considerably underestimated, since the incidence statistics are derived largely from bacteremic infections, because they are easy to document, and yet the greater burden of pneumococcal pneumonias is non-invasive. It has been estimated that for every bacteremic pneumonia that is documented, three non-bacteremic infections occur. Management of these infections is potentially complicated by the increasing resistance of the isolates to the commonly used antibiotics. Furthermore, it is well recognized that despite advances in medical care, the mortality of bacteremic pneumococcal pneumonia has remained largely unchanged over the past 50 years and averages approximately 12%. Much recent research interest in the field of pneumococcal infections has focused on important virulence factors of the organism, on improved diagnostic and prognostication tools, on defining risk factors for death, on optimal treatment strategies involving both antibiotics and adjunctive therapies, and on disease prevention. It is hoped that through these endeavors the outlook of pneumococcal infections will be improved. PMID:25343039

  14. Advances in the understanding, management, and prevention of dengue.

    PubMed

    Hermann, Laura L; Gupta, Swati B; Manoff, Susan B; Kalayanarooj, Siripen; Gibbons, Robert V; Coller, Beth-Ann G

    2015-03-01

    Dengue causes more human morbidity globally than any other vector-borne viral disease. Recent research has led to improved epidemiological methods that predict disease burden and factors involved in transmission, a better understanding of immune responses in infection, and enhanced animal models. In addition, a number of control measures, including preventative vaccines, are in clinical trials. However, significant gaps remain, including the need for better surveillance in large parts of the world, methods to predict which individuals will develop severe disease, and immunologic correlates of protection against dengue illness. During the next decade, dengue will likely expand its geographic reach and become an increasing burden on health resources in affected areas. Licensed vaccines and antiviral agents are needed in order to effectively control dengue and limit disease.

  15. Recent Advances in Understanding and Managing Tourette Syndrome

    PubMed Central

    Thenganatt, Mary Ann; Jankovic, Joseph

    2016-01-01

    Tourette syndrome (TS) is a neurologic and behavioral disorder consisting of motor and phonic tics with onset in childhood or adolescence. The severity of tics can range from barely perceptible to severely impairing due to social embarrassment, discomfort, self-injury, and interference with daily functioning and school or work performance. In addition to tics, most patients with TS have a variety of behavioral comorbidities, including attention deficit hyperactivity disorder and obsessive-compulsive disorder. Studies evaluating the pathophysiology of tics have pointed towards dysfunction of the cortico-striato-thalamo-cortical circuit, but the mechanism of this hyperkinetic movement disorder is not well understood. Treatment of TS is multidisciplinary, typically involving behavioral therapy, oral medications, and botulinum toxin injections. Deep brain stimulation may be considered for “malignant” TS that is refractory to conventional therapy. In this review, we will highlight recent developments in the understanding and management strategies of TS. PMID:26918185

  16. Recent advances in the pathological understanding of eosinophilic esophagitis.

    PubMed

    Cianferoni, Antonella; Spergel, Jonathan M; Muir, Amanda

    2015-01-01

    Eosinophilic esophagitis (EoE) is a chronic allergen-mediated inflammatory disease of the esophagus. This inflammation leads to feeding difficulties, failure to thrive and vomiting in young children, and causes food impaction and esophageal stricture in adolescents and adults. In the 20 years since EoE was first described, we have gained a great deal of knowledge regarding the genetic predisposition of disease, the inflammatory milieu associated with EoE and the long-term complications of chronic inflammation. Herein, we summarize the important breakthroughs in the field including both in vitro and in vivo analysis. We discuss insights that we have gained from large-scale unbiased genetic analysis, a multitude of genetically and chemically altered mouse models of EoE and most importantly, the results of clinical trials of various pharmacologic agents. Understanding these successes and failures may be the key to developing more effective therapeutic strategies.

  17. Recent Advances in Understanding Radiation Damage in Reactor Cavity Concrete

    SciTech Connect

    Rosseel, Thomas M; Field, Kevin G; Le Pape, Yann; Remec, Igor; Giorla, Alain B; Wall, Dr. James Joseph

    2015-01-01

    License renewal up to 60 years and the possibility of subsequent license renewal to 80 years has resulted in a renewed focus on long-term aging of materials at nuclear power plants (NPPs) including concrete. Large irreplaceable sections of most nuclear generating stations include concrete. The Expanded Materials Degradation Analysis, jointly performed by the Department of Energy, the Nuclear Regulatory Commission and Nuclear Industry, identified the urgent need to develop a consistent knowledge base on irradiation effects in concrete (Graves et al., (2014)). Much of the historical mechanical performance data of irradiated concrete (Hilsdorf et al., (1978)) does not accurately reflect typical radiation conditions in NPPs or conditions out to 60 or 80 years of radiation exposure (Kontani et al., (2011)). To address these potential gaps in the knowledge base, the Electric Power Research Institute and Oak Ridge National Laboratory, are working to better understand radiation damage as a degradation mechanism. This paper outlines recent progress toward: 1) assessing the radiation environment in concrete biological shields and defining the upper bound of the neutron and gamma dose levels expected in the biological shield for extended operation, and estimating adsorbed dose, 2) evaluating opportunities to harvest and test irradiated concrete from international NPPs, 3) evaluating opportunities to irradiate prototypical concrete and its components under accelerated neutron and gamma dose levels to establish conservative bounds and inform damage models, 4) developing improved models to enhance the understanding of the effects of radiation on concrete and 5) establishing an international collaborative research and information exchange effort to leverage capabilities and knowledge including developing cooperative test programs to improve confidence in data obtained from various concretes and from accelerated irradiation experiments.

  18. Advanced Curation: Solving Current and Future Sample Return Problems

    NASA Technical Reports Server (NTRS)

    Fries, M.; Calaway, M.; Evans, C.; McCubbin, F.

    2015-01-01

    Advanced Curation is a wide-ranging and comprehensive research and development effort at NASA Johnson Space Center that identifies and remediates sample related issues. For current collections, Advanced Curation investigates new cleaning, verification, and analytical techniques to assess their suitability for improving curation processes. Specific needs are also assessed for future sample return missions. For each need, a written plan is drawn up to achieve the requirement. The plan draws while upon current Curation practices, input from Curators, the analytical expertise of the Astromaterials Research and Exploration Science (ARES) team, and suitable standards maintained by ISO, IEST, NIST and other institutions. Additionally, new technologies are adopted on the bases of need and availability. Implementation plans are tested using customized trial programs with statistically robust courses of measurement, and are iterated if necessary until an implementable protocol is established. Upcoming and potential NASA missions such as OSIRIS-REx, the Asteroid Retrieval Mission (ARM), sample return missions in the New Frontiers program, and Mars sample return (MSR) all feature new difficulties and specialized sample handling requirements. The Mars 2020 mission in particular poses a suite of challenges since the mission will cache martian samples for possible return to Earth. In anticipation of future MSR, the following problems are among those under investigation: What is the most efficient means to achieve the less than 1.0 ng/sq cm total organic carbon (TOC) cleanliness required for all sample handling hardware? How do we maintain and verify cleanliness at this level? The Mars 2020 Organic Contamination Panel (OCP) predicts that organic carbon, if present, will be present at the "one to tens" of ppb level in martian near-surface samples. The same samples will likely contain wt% perchlorate salts, or approximately 1,000,000x as much perchlorate oxidizer as organic carbon

  19. Understanding of Mechanisms for Design of Advanced Superconductors

    NASA Astrophysics Data System (ADS)

    Pickett, Warren

    2007-03-01

    A recent DOE panel considered the future of research in superconducting materials and made a number of recommendations for priority research directions (http://www.er.doe.gov/bes/reports/files/SCrpt.pdf), two of which will be discussed. These items, under the rubric of Enabling Superconductivity, emphasize that Finding the Mechanisms is essential for furthering the field, and that once understood, the prospect of Superconductors by Design becomes a viable line of research. Establishing the mechanism in the high temperature superconducting cuprates continues to attract substantial efforts, with no consensus near. In several superconductors, including some discovered in the past decade or so, having Tc around or above 20 K [(Ba,K)BiO3; LixHfNCl; PuCoGa5] the mechanism is in question. On the more positive side, there are several cases established in the past six years, beginning with MgB2 and extending to elemental metals under pressure (Li, Y, Ca), where the familiar electron-phonon mechanism has provided unexpectedly high Tc and thereby stimulated enthusiasm and optimism into this area of superconductivity research. The clear understanding of this mechanism (at least in many respects) provides a path for improvements in superconducting materials.

  20. [Acute pancreatitis: recent advances in understanding its pathophysiology].

    PubMed

    Telek, G; Fehér, J; Jakab, F; Claude, R

    2000-02-06

    This article reviews the recent changes in the understanding of acute pancreatitis pathophysiology emphasizing results deriving from the more detailed comprehension of the local and systemic aspects of the inflammatory process. The authors briefly discuss those theories that have been influencing the basic philosophies of treatment efforts. The role of premature digestive enzyme activation as the principal determinant of the pathoetiology and mortality of this disease has been questioned lately, and the inflammatory explosion has been placed into the center of attention. Simultaneously with the enzyme activation, the pancreatitogenic noxious event rapidly induces the formation of oxygen derived free radicals, activation of the transcription factor NF kappa-B, with consequent citokine production, cellular adhesion molecule upregulation and leukocyte hyperstimulation. Numerous other mediator cascades are activated in parallel, the uncontrolled surge of proinflammatory stimuli, and activity of the effector cells lead to multiple organ failure in severe cases. A genetically determined catastrophe management program is set forth in the acinar cell with pancreatitis associated protein expression and activation of the apoptosis machinery. Therapeutic approaches based on these recent findings are briefly touched upon.

  1. Recent advances in understanding physical properties of metallurgical slags

    NASA Astrophysics Data System (ADS)

    Min, Dong Joon; Tsukihashi, Fumitaka

    2017-01-01

    Present-day knowledge of the structure and physical properties of metallurgical slags is summarized to address structure-property and inter-property relationships. Physical properties of slags including viscosity, electrical conductivity, and surface tension is reviewed focusing on the effect of slag structure, which is comprehensively evaluated using FT-IT, Raman, and MAS-NMR spectroscopy. The effect of the slag composition on slag structure and property is reviewed in detail: Compositional effect encompasses traditional concepts of basicity, network-forming behaviors of anions, and secondary impact of network-modifying cations. Secondary objective of this review is elucidating the mutual relationship between physical properties of slags. For instance, the relationship between slag viscosity and electrical conductivity is suggested by Walden's rule and discussed based on the experimental results. Slag foaming index is also introduced as a comprehensive understanding method of physical properties of slags. The dimensional analysis was made to address the effect of viscosity, density, and surface tension on the foaming index of slags.

  2. Advances in understanding and utilising ELM control in JET

    NASA Astrophysics Data System (ADS)

    Chapman, I. T.; de la Luna, E.; Lang, P. T.; Liang, Y.; Alper, B.; Denner, P.; Frigione, D.; Garzotti, L.; Ham, C. J.; Huijsmans, G. T. A.; Jachmich, S.; Kocsis, G.; Lennholm, M.; Lupelli, I.; Rimini, F. G.; Sips, A. C. C.; Contributors, JET

    2016-01-01

    Edge localised mode (ELM) control may be essential to develop ITER scenarios with a reasonable lifetime of divertor components, whilst ELM pacing may be essential to develop stationary ITER scenarios with a tungsten divertor. Resonant magnetic perturbations (RMPs) have mitigated ELMs in high collisionality plasmas in JET. The efficacy of RMPs in mitigating the ELMs is found to depend on plasma shaping, with the change in magnetic boundary achieved when non-axisymmetric fields are applied facilitating access to small ELM regimes. The understanding of ELM pacing by vertical kicks or pellets has also been improved in a range of pedestal conditions in JET ({{T}\\text{ped}}=0.7 -1.3 keV) encompassing the ITER-expected domain ({β\\text{N}}=1.4 -2.4, H 98(y, 2)  =  0.8-1.2, {{f}\\text{GW}}˜ 0.7 ). ELM triggering is reliable provided the perturbation is above a threshold which depends on pedestal parameters. ELM triggering is achieved even in the first 10% of the natural ELM cycle suggesting no inherent maximum frequency. At high normalised pressure, the peeling-ballooning modes are stabilised as predicted by ELITE, necessitating a larger perturbation from either kicks or pellets in order to trigger ELMs. Both kicks and pellets have been used to pace ELMs for tungsten flushing. This has allowed stationary plasma conditions with low gas injection in plasmas where the natural ELM frequency is such that it would normally preclude stationary conditions.

  3. Some recent advances in understanding the mineralogy of Earth's deep mantle.

    PubMed

    Duffy, Thomas S

    2008-11-28

    Understanding planetary structure and evolution requires a detailed knowledge of the properties of geological materials under the conditions of deep planetary interiors. Experiments under the extreme pressure-temperature conditions of the deep mantle are challenging, and many fundamental properties remain poorly constrained or are inferred only through uncertain extrapolations from lower pressure-temperature states. Nevertheless, the last several years have witnessed a number of new developments in this area, and a broad overview of the current understanding of the Earth's lower mantle is presented here. Some recent experimental and theoretical advances related to the lowermost mantle are highlighted. Measurements of the equation of state and deformation behaviour of (Mg,Fe)SiO3 in the CaIrO3-type (post-perovskite) structure yield insights into the nature of the core-mantle boundary region. Theoretical studies of the behaviour of MgSiO3 liquids under high pressure-temperature conditions provide constraints on melt volumes, diffusivities and viscosities that are relevant to understanding both the early Earth (e.g. deep magma oceans) and seismic structure observed in the present Earth (e.g. ultra-low-velocity zones).

  4. Some recent advances in understanding the mineralogy of Earth's deep mantle

    SciTech Connect

    Duffy, T S

    2008-12-09

    Understanding planetary structure and evolution requires a detailed knowledge of the properties of geological materials under the conditions of deep planetary interiors. Experiments under the extreme pressure-temperature conditions of the deep mantle are challenging, and many fundamental properties remain poorly constrained or are inferred only through uncertain extrapolations from lower pressure-temperature states. Nevertheless, the last several years have witnessed a number of new developments in this area, and a broad overview of the current understanding of the Earth's lower mantle is presented here. Some recent experimental and theoretical advances related to the lowermost mantle are highlighted. Measurements of the equation of state and deformation behaviour of (Mg,Fe)SiO{sub 3} in the CaIrO{sub 3}-type (post-perovskite) structure yield insights into the nature of the core-mantle boundary region. Theoretical studies of the behaviour of MgSiO3 liquids under high pressure-temperature conditions provide constraints on melt volumes, diffusivities and viscosities that are relevant to understanding both the early Earth (e.g. deep magma oceans) and seismic structure observed in the present Earth (e.g. ultra-low-velocity zones).

  5. von Willebrand disease: advances in pathogenetic understanding, diagnosis, and therapy.

    PubMed

    Lillicrap, David

    2013-01-01

    von Willebrand disease (VWD) is the most common autosomally inherited bleeding disorder. The disease represents a range of quantitative and qualitative pathologies of the adhesive glycoprotein von Willebrand factor (VWF). The pathogenic mechanisms responsible for the type 2 qualitative variants of VWF are now well characterized, with most mutations representing missense substitutions influencing VWF multimer structure and interactions with platelet GPIbα and collagen and with factor VIII. The molecular pathology of type 3 VWD has been similarly well characterized, with an array of different mutation types producing either a null phenotype or the production of VWF that is not secreted. In contrast, the pathogenetic mechanisms responsible for type 1 VWD remain only partially resolved. In the hemostasis laboratory, the measurement of VWF:Ag and VWF:RCo are key components in the diagnostic algorithm for VWD, although the introduction of direct GPIbα-binding assays may become the functional assay of choice. Molecular genetic testing can provide additional benefit, but its utility is currently limited to type 2 and 3 VWD. The treatment of bleeding in VWD involves the use of desmopressin and plasma-derived VWF concentrates and a variety of adjunctive agents. Finally, a new recombinant VWF concentrate has just completed clinical trial evaluation and has demonstrated excellent hemostatic efficacy and safety.

  6. ADVANCING THE FUNDAMENTAL UNDERSTANDING AND SCALE-UP OF TRISO FUEL COATERS VIA ADVANCED MEASUREMENT AND COMPUTATIONAL TECHNIQUES

    SciTech Connect

    Biswas, Pratim; Al-Dahhan, Muthanna

    2012-11-01

    Tri-isotropic (TRISO) fuel particle coating is critical for the future use of nuclear energy produced byadvanced gas reactors (AGRs). The fuel kernels are coated using chemical vapor deposition in a spouted fluidized bed. The challenges encountered in operating TRISO fuel coaters are due to the fact that in modern AGRs, such as High Temperature Gas Reactors (HTGRs), the acceptable level of defective/failed coated particles is essentially zero. This specification requires processes that produce coated spherical particles with even coatings having extremely low defect fractions. Unfortunately, the scale-up and design of the current processes and coaters have been based on empirical approaches and are operated as black boxes. Hence, a voluminous amount of experimental development and trial and error work has been conducted. It has been clearly demonstrated that the quality of the coating applied to the fuel kernels is impacted by the hydrodynamics, solids flow field, and flow regime characteristics of the spouted bed coaters, which themselves are influenced by design parameters and operating variables. Further complicating the outlook for future fuel-coating technology and nuclear energy production is the fact that a variety of new concepts will involve fuel kernels of different sizes and with compositions of different densities. Therefore, without a fundamental understanding the underlying phenomena of the spouted bed TRISO coater, a significant amount of effort is required for production of each type of particle with a significant risk of not meeting the specifications. This difficulty will significantly and negatively impact the applications of AGRs for power generation and cause further challenges to them as an alternative source of commercial energy production. Accordingly, the proposed work seeks to overcome such hurdles and advance the scale-up, design, and performance of TRISO fuel particle spouted bed coaters. The overall objectives of the proposed work are

  7. Medicinal mushroom science: Current perspectives, advances, evidences, and challenges.

    PubMed

    Wasser, Solomon P

    2014-01-01

    The main target of the present review is to draw attention to the current perspectives, advances, evidences, challenges, and future development of medicinal mushroom science in the 21 st century. Medicinal mushrooms and fungi are thought to possess approximately 130 medicinal functions, including antitumor, immunomodulating, antioxidant, radical scavenging, cardiovascular, anti-hypercholesterolemic, antiviral, antibacterial, anti-parasitic, antifungal, detoxification, hepatoprotective, and antidiabetic effects. Many, if not all, higher Basidiomycetes mushrooms contain biologically active compounds in fruit bodies, cultured mycelium, and cultured broth. Special attention is paid to mushroom polysaccharides. The data on mushroom polysaccharides and different secondary metabolites are summarized for approximately 700 species of higher hetero- and homobasidiomycetes. Numerous bioactive polysaccharides or polysaccharide-protein complexes from the medicinal mushrooms described appear to enhance innate and cell-mediated immune responses, and exhibit antitumor activities in animals and humans. Whilst the mechanism of their antitumor actions is still not completely understood, stimulation and modulation of key host immune responses by these mushroom compounds appear central. Polysaccharides and low-molecular-weight secondary metabolites are particularly important due to their antitumor and immunostimulating properties. Several of the mushroom compounds have been subjected to Phase I, II, and III clinical trials, and are used extensively and successfully in Asia to treat various cancers and other diseases. Special attention is given to many important unsolved problems in the study of medicinal mushrooms.

  8. Current advances in precious metal core–shell catalyst design

    PubMed Central

    Wang, Xiaohong; He, Beibei; Hu, Zhiyu; Zeng, Zhigang; Han, Sheng

    2014-01-01

    Precious metal nanoparticles are commonly used as the main active components of various catalysts. Given their high cost, limited quantity, and easy loss of catalytic activity under severe conditions, precious metals should be used in catalysts at low volumes and be protected from damaging environments. Accordingly, reducing the amount of precious metals without compromising their catalytic performance is difficult, particularly under challenging conditions. As multifunctional materials, core–shell nanoparticles are highly important owing to their wide range of applications in chemistry, physics, biology, and environmental areas. Compared with their single-component counterparts and other composites, core–shell nanoparticles offer a new active interface and a potential synergistic effect between the core and shell, making these materials highly attractive in catalytic application. On one hand, when a precious metal is used as the shell material, the catalytic activity can be greatly improved because of the increased surface area and the closed interfacial interaction between the core and the shell. On the other hand, when a precious metal is applied as the core material, the catalytic stability can be remarkably improved because of the protection conferred by the shell material. Therefore, a reasonable design of the core–shell catalyst for target applications must be developed. We summarize the latest advances in the fabrications, properties, and applications of core–shell nanoparticles in this paper. The current research trends of these core–shell catalysts are also highlighted. PMID:27877695

  9. Current advances in precious metal core-shell catalyst design.

    PubMed

    Wang, Xiaohong; He, Beibei; Hu, Zhiyu; Zeng, Zhigang; Han, Sheng

    2014-08-01

    Precious metal nanoparticles are commonly used as the main active components of various catalysts. Given their high cost, limited quantity, and easy loss of catalytic activity under severe conditions, precious metals should be used in catalysts at low volumes and be protected from damaging environments. Accordingly, reducing the amount of precious metals without compromising their catalytic performance is difficult, particularly under challenging conditions. As multifunctional materials, core-shell nanoparticles are highly important owing to their wide range of applications in chemistry, physics, biology, and environmental areas. Compared with their single-component counterparts and other composites, core-shell nanoparticles offer a new active interface and a potential synergistic effect between the core and shell, making these materials highly attractive in catalytic application. On one hand, when a precious metal is used as the shell material, the catalytic activity can be greatly improved because of the increased surface area and the closed interfacial interaction between the core and the shell. On the other hand, when a precious metal is applied as the core material, the catalytic stability can be remarkably improved because of the protection conferred by the shell material. Therefore, a reasonable design of the core-shell catalyst for target applications must be developed. We summarize the latest advances in the fabrications, properties, and applications of core-shell nanoparticles in this paper. The current research trends of these core-shell catalysts are also highlighted.

  10. Advances in Current Rating Techniques for Flexible Printed Circuits

    NASA Technical Reports Server (NTRS)

    Hayes, Ron

    2014-01-01

    Twist Capsule Assemblies are power transfer devices commonly used in spacecraft mechanisms that require electrical signals to be passed across a rotating interface. Flexible printed circuits (flex tapes, see Figure 2) are used to carry the electrical signals in these devices. Determining the current rating for a given trace (conductor) size can be challenging. Because of the thermal conditions present in this environment the most appropriate approach is to assume that the only means by which heat is removed from the trace is thru the conductor itself, so that when the flex tape is long the temperature rise in the trace can be extreme. While this technique represents a worst-case thermal situation that yields conservative current ratings, this conservatism may lead to overly cautious designs when not all traces are used at their full rated capacity. A better understanding of how individual traces behave when they are not all in use is the goal of this research. In the testing done in support of this paper, a representative flex tape used for a flight Solar Array Drive Assembly (SADA) application was tested by energizing individual traces (conductors in the tape) in a vacuum chamber and the temperatures of the tape measured using both fine-gauge thermocouples and infrared thermographic imaging. We find that traditional derating schemes used for bundles of wires do not apply for the configuration tested. We also determine that single active traces located in the center of a flex tape operate at lower temperatures than those on the outside edges.

  11. Cancer Treatment-Related Cardiotoxicity: Understanding the Current State of Knowledge and Developing Future Research Priorities

    Cancer.gov

    Cancer Treatment-Related Cardiotoxicity: Understanding the Current State of Knowledge and Developing Future Research Priorities, a 2013 workshop sponsored by the Epidemiology and Genomics Research Program.

  12. Understanding Material Property Impacts on Co-Current Flame Spread: Improving Understanding Crucial for Fire Safety

    NASA Technical Reports Server (NTRS)

    Ruff, Gary (Technical Monitor); Rangwala, Ali S.; Buckley, Steven G.; Torero, Jose L.

    2004-01-01

    The prospect of long-term manned space flight brings fresh urgency to the development of an integrated and fundamental approach to the study of material flammability. Currently, NASA uses two tests, the upward flame propagation test and heat and visible smoke release rate test, to assess the flammability properties of materials to be used in space under microgravity conditions. The upward flame propagation test can be considered in the context of the 2-D analysis of Emmons. This solution incorporates material properties by a "mass transfer number", B in the boundary conditions.

  13. Primary healthcare NZ nurses' experiences of advance directives: understanding their potential role.

    PubMed

    Davidson, Raewyn; Banister, Elizabeth; de Vries, Kay

    2013-07-01

    Advance directives are one aspect of advance care planning designed to improve end of life care. The New Zealand Nurses Organisation released their first mission statement in 2010 concerning advance directives suggesting an increase in the use of these. A burgeoning older population, expected to rise over the next few years, places the primary healthcare nurse in a pivotal role to address the challenges in constructing advance directives. While literature supports the role for primary healthcare nurses in promoting advance directives, no research was found on this role in the New Zealand context. This paper presents results of a qualitative study conducted in New Zealand with 13 senior primary healthcare nurses with respect to their knowledge, attitudes, and experiences of advance directives. Results of the analysis revealed a dynamic process involving participants coming to understand their potential role in this area. This process included reflection on personal experience with advance directives; values and ethics related to end of life issues; and professional actions.

  14. BOOK REVIEW: New Understanding Physics for Advanced Level

    NASA Astrophysics Data System (ADS)

    Breithaupt, Jim

    2000-09-01

    Breithaupt's new book is big: at 727 pages, it will be a hefty addition to any student's bag. According to the preface, the book is designed to help students achieve the transition from GCSE to A-level and to succeed well at this level. It also aims to cover the requirements of the compulsory parts of all new syllabuses and to cover most of the optional material, too. The book is organized into seven themes along traditional lines: mechanics, materials, fields, waves, electricity, inside the atom, and physics in medicine. Each theme begins with a colourful title page that outlines what the theme is about, lists the applications that students will meet in their reading, identifies prior learning from GCSE and gives a checklist of what students should be able to do once they have finished their reading of the theme. This is all very useful. The text of the book is illustrated with many colourful photographs, pictures and cartoons, but despite this it looks very dense. There are a lot of words on every page in a small font that makes them seem very unfriendly, and although the book claims to be readable I rather doubt that the layout will encourage voluntary reading of the text. Each chapter ends with a useful summary and a selection of short questions that allow students to test their understanding. Each theme has a set of multiple choice and long questions. Some of the questions have an icon referring the student to the accompanying CD (more of this later). There is much up-to-date material in the book. For example, the section on cosmology gives a brief description of the inflationary scenario within the Big Bang model of the origin of the universe, although no mechanism for the inflation is given, which might prove unsatisfying to some students. I do have some reservations about the presentation of some topics within the book: the discussion of relativistic mass, for example, states that `Einstein showed that the mass ... is given by the formula ...' and quotes

  15. Current advancements and challenges in soil-root interactions modelling

    NASA Astrophysics Data System (ADS)

    Schnepf, Andrea; Huber, Katrin; Abesha, Betiglu; Meunier, Felicien; Leitner, Daniel; Roose, Tiina; Javaux, Mathieu; Vanderborght, Jan; Vereecken, Harry

    2015-04-01

    Roots change their surrounding soil chemically, physically and biologically. This includes changes in soil moisture and solute concentration, the exudation of organic substances into the rhizosphere, increased growth of soil microorganisms, or changes in soil structure. The fate of water and solutes in the root zone is highly determined by these root-soil interactions. Mathematical models of soil-root systems in combination with non-invasive techniques able to characterize root systems are a promising tool to understand and predict the behaviour of water and solutes in the root zone. With respect to different fields of applications, predictive mathematical models can contribute to the solution of optimal control problems in plant recourse efficiency. This may result in significant gains in productivity, efficiency and environmental sustainability in various land use activities. Major challenges include the coupling of model parameters of the relevant processes with the surrounding environment such as temperature, nutrient concentration or soil water content. A further challenge is the mathematical description of the different spatial and temporal scales involved. This includes in particular the branched structures formed by root systems or the external mycelium of mycorrhizal fungi. Here, reducing complexity as well as bridging between spatial scales is required. Furthermore, the combination of experimental and mathematical techniques may advance the field enormously. Here, the use of root system, soil and rhizosphere models is presented through a number of modelling case studies, including image based modelling of phosphate uptake by a root with hairs, model-based optimization of root architecture for phosphate uptake from soil, upscaling of rhizosphere models, modelling root growth in structured soil, and the effect of root hydraulic architecture on plant water uptake efficiency and drought resistance.

  16. Current Advancements and Challenges in Soil-Root Interactions Modelling

    NASA Astrophysics Data System (ADS)

    Schnepf, A.; Huber, K.; Abesha, B.; Meunier, F.; Leitner, D.; Roose, T.; Javaux, M.; Vanderborght, J.; Vereecken, H.

    2014-12-01

    Roots change their surrounding soil chemically, physically and biologically. This includes changes in soil moisture and solute concentration, the exudation of organic substances into the rhizosphere, increased growth of soil microorganisms, or changes in soil structure. The fate of water and solutes in the root zone is highly determined by these root-soil interactions. Mathematical models of soil-root systems in combination with non-invasive techniques able to characterize root systems are a promising tool to understand and predict the behaviour of water and solutes in the root zone. With respect to different fields of applications, predictive mathematical models can contribute to the solution of optimal control problems in plant recourse efficiency. This may result in significant gains in productivity, efficiency and environmental sustainability in various land use activities. Major challenges include the coupling of model parameters of the relevant processes with the surrounding environment such as temperature, nutrient concentration or soil water content. A further challenge is the mathematical description of the different spatial and temporal scales involved. This includes in particular the branched structures formed by root systems or the external mycelium of mycorrhizal fungi. Here, reducing complexity as well as bridging between spatial scales is required. Furthermore, the combination of experimental and mathematical techniques may advance the field enormously. Here, the use of root system, soil and rhizosphere models is presented through a number of modelling case studies, including image based modelling of phosphate uptake by a root with hairs, model-based optimization of root architecture for phosphate uptake from soil, upscaling of rhizosphere models, modelling root growth in structured soil, and the effect of root hydraulic architecture on plant water uptake efficiency and drought resistance.

  17. Recent advances in understanding the role of the hypothalamic circuit during aggression

    PubMed Central

    Falkner, Annegret L.; Lin, Dayu

    2014-01-01

    The hypothalamus was first implicated in the classic “fight or flight” response nearly a century ago, and since then, many important strides have been made in understanding both the circuitry and the neural dynamics underlying the generation of these behaviors. In this review, we will focus on the role of the hypothalamus in aggression, paying particular attention to recent advances in the field that have allowed for functional identification of relevant hypothalamic subnuclei. Recent progress in this field has been aided by the development of new techniques for functional manipulation including optogenetics and pharmacogenetics, as well as advances in technology used for chronic in vivo recordings during complex social behaviors. We will examine the role of the hypothalamus through the complimentary lenses of (1) loss of function studies, including pharmacology and pharmacogenetics; (2) gain of function studies, including specific comparisons between results from classic electrical stimulation studies and more recent work using optogenetics; and (3) neural activity, including both immediate early gene and awake-behaving recordings. Lastly, we will outline current approaches to identifying the precise role of the hypothalamus in promoting aggressive motivation and aggressive action. PMID:25309351

  18. Current Advances in Detection and Treatment of Babesiosis

    PubMed Central

    Mosqueda, J; Olvera-Ramírez, A; Aguilar-Tipacamú, G; Cantó, GJ

    2012-01-01

    Babesiosis is a disease with a world-wide distribution affecting many species of mammals principally cattle and man. The major impact occurs in the cattle industry where bovine babesiosis has had a huge economic effect due to loss of meat and beef production of infected animals and death. Nowadays to those costs there must be added the high cost of tick control, disease detection, prevention and treatment. In almost a century and a quarter since the first report of the disease, the truth is: there is no a safe and efficient vaccine available, there are limited chemotherapeutic choices and few low-cost, reliable and fast detection methods. Detection and treatment of babesiosis are important tools to control babesiosis. Microscopy detection methods are still the cheapest and fastest methods used to identify Babesia parasites although their sensitivity and specificity are limited. Newer immunological methods are being developed and they offer faster, more sensitive and more specific options to conventional methods, although the direct immunological diagnoses of parasite antigens in host tissues are still missing. Detection methods based on nucleic acid identification and their amplification are the most sensitive and reliable techniques available today; importantly, most of those methodologies were developed before the genomics and bioinformatics era, which leaves ample room for optimization. For years, babesiosis treatment has been based on the use of very few drugs like imidocarb or diminazene aceturate. Recently, several pharmacological compounds were developed and evaluated, offering new options to control the disease. With the complete sequence of the Babesia bovis genome and the B. bigemina genome project in progress, the post-genomic era brings a new light on the development of diagnosis methods and new chemotherapy targets. In this review, we will present the current advances in detection and treatment of babesiosis in cattle and other animals, with additional

  19. Current Advances in the Metabolomics Study on Lotus Seeds

    PubMed Central

    Zhu, Mingzhi; Liu, Ting; Guo, Mingquan

    2016-01-01

    Lotus (Nelumbo nucifera), which is distributed widely throughout Asia, Australia and North America, is an aquatic perennial that has been cultivated for over 2,000 years. It is very stimulating that almost all parts of lotus have been consumed as vegetable as well as food, especially the seeds. Except for the nutritive values of lotus, there has been increasing interest in its potential as functional food due to its rich secondary metabolites, such as flavonoids and alkaloids. Not only have these metabolites greatly contributed to the biological process of lotus seeds, but also have been reported to possess multiple health-promoting effects, including antioxidant, anti-amnesic, anti-inflammatory, and anti-tumor activities. Thus, comprehensive metabolomic profiling of these metabolites is of key importance to help understand their biological activities, and other chemical biology features. In this context, this review will provide an update on the current technological platforms, and workflow associated with metabolomic studies on lotus seeds, as well as insights into the application of metabolomics for the improvement of food safety and quality, assisting breeding, and promotion of the study of metabolism and pharmacokinetics of lotus seeds; meanwhile it will also help explore new perspectives and outline future challenges in this fast-growing research subject. PMID:27379154

  20. Heat Shock Proteins in Dermatophytes: Current Advances and Perspectives

    PubMed Central

    Martinez-Rossi, Nilce M.; Jacob, Tiago R.; Sanches, Pablo R.; Peres, Nalu T.A.; Lang, Elza A.S.; Martins, Maíra P.; Rossi, Antonio

    2016-01-01

    Heat shock proteins (HSPs) are proteins whose transcription responds rapidly to temperature shifts. They constitute a family of molecular chaperones, involved in the proper folding and stabilisation of proteins under physiological and adverse conditions. HSPs also assist in the protection and recovery of cells exposed to a variety of stressful conditions, including heat. The role of HSPs extends beyond chaperoning proteins, as they also participate in diverse cellular functions, such as the assembly of macromolecular complexes, protein transport and sorting, dissociation of denatured protein aggregates, cell cycle control, and programmed cell death. They are also important antigens from a variety of pathogens, are able to stimulate innate immune cells, and are implicated in acquired immunity. In fungi, HSPs have been implicated in virulence, dimorphic transition, and drug resistance. Some HSPs are potential targets for therapeutic strategies. In this review, we discuss the current understanding of HSPs in dermatophytes, which are a group of keratinophilic fungi responsible for superficial mycoses in humans and animals. Computational analyses were performed to characterise the group of proteins in these dermatophytes, as well as to assess their conservation and to identify DNA-binding domains (5′-nGAAn-3′) in the promoter regions of the hsp genes. In addition, the quantification of the transcript levels of few genes in a pacC background helped in the development of an extended model for the regulation of the expression of the hsp genes, which supports the participation of the pH-responsive transcriptional regulator PacC in this process. PMID:27226766

  1. Advancing the understanding of plasma transport in mid-size stellarators

    NASA Astrophysics Data System (ADS)

    Hidalgo, Carlos; Talmadge, Joseph; Ramisch, Mirko; TJ-II, the; HXS; TJ-K Teams

    2017-01-01

    The tokamak and the stellarator are the two main candidate concepts for magnetically confining fusion plasmas. The flexibility of the mid-size stellarator devices together with their unique diagnostic capabilities make them ideally suited to study the relation between magnetic topology, electric fields and transport. This paper addresses advances in the understanding of plasma transport in mid-size stellarators with an emphasis on the physics of flows, transport control, impurity and particle transport and fast particles. The results described here emphasize an improved physics understanding of phenomena in stellarators that complements the empirical approach. Experiments in mid-size stellarators support the development of advanced plasma scenarios in Wendelstein 7-X (W7-X) and, in concert with better physics understanding in tokamaks, may ultimately lead to an advance in the prediction of burning plasma behaviour.

  2. Current scenario of chalcopyrite bioleaching: a review on the recent advances to its heap-leach technology.

    PubMed

    Panda, Sandeep; Akcil, Ata; Pradhan, Nilotpala; Deveci, Haci

    2015-11-01

    Chalcopyrite is the primary copper mineral used for production of copper metal. Today, as a result of rapid industrialization, there has been enormous demand to profitably process the low grade chalcopyrite and "dirty" concentrates through bioleaching. In the current scenario, heap bioleaching is the most advanced and preferred eco-friendly technology for processing of low grade, uneconomic/difficult-to-enrich ores for copper extraction. This paper reviews the current status of chalcopyrite bioleaching. Advanced information with the attempts made for understanding the diversity of bioleaching microorganisms; role of OMICs based research for future applications to industrial sectors and chemical/microbial aspects of chalcopyrite bioleaching is discussed. Additionally, the current progress made to overcome the problems of passivation as seen in chalcopyrite bioleaching systems have been conversed. Furthermore, advances in the designing of heap bioleaching plant along with microbial and environmental factors of importance have been reviewed with conclusions into the future prospects of chalcopyrite bioleaching.

  3. The trophodynamics of marine top predators: Current knowledge, recent advances and challenges

    NASA Astrophysics Data System (ADS)

    Young, Jock W.; Hunt, Brian P. V.; Cook, Timothée R.; Llopiz, Joel K.; Hazen, Elliott L.; Pethybridge, Heidi R.; Ceccarelli, Daniela; Lorrain, Anne; Olson, Robert J.; Allain, Valerie; Menkes, Christophe; Patterson, Toby; Nicol, Simon; Lehodey, Patrick; Kloser, Rudy J.; Arrizabalaga, Haritz; Anela Choy, C.

    2015-03-01

    We review present understanding of the spatial and temporal diet variability (trophodynamics) of a range of pelagic marine top predators, at both early and adult life history stages. We begin with a review of methodologies used to advance our understanding of the trophodynamics of marine top predators, particularly in relation to climate change. We then explore how these developments are informing our understanding of the major trophic groups in food webs leading to, and including, marine top predators. We examine through specific examples how the impacts of ocean warming may affect pelagic food web relationships from both top-down and bottom-up perspectives. We examine the potential, in the absence of long-term data sets, of using large-scale spatial studies to examine how potential changes in biological oceanography could impact the biomass and composition of prey species, particularly the role of phytoplankton size spectra. We focus on examples from regions where biotic change with respect to climate change is likely. In particular, we detail the effects of climate change on oceanographic and bathymetric "hotspots" and provide the example involving seabirds in the Benguela Current system. We end by urging the development of international collaborations and databases to facilitate comprehensive ocean-scale understanding of climate impacts on marine top predators.

  4. Advancing our understanding of religion and spirituality in the context of behavioral medicine.

    PubMed

    Park, Crystal L; Masters, Kevin S; Salsman, John M; Wachholtz, Amy; Clements, Andrea D; Salmoirago-Blotcher, Elena; Trevino, Kelly; Wischenka, Danielle M

    2017-02-01

    Recognizing and understanding the potentially powerful roles that religiousness and spirituality (RS) may serve in the prevention and amelioration of disease, as well as symptom management and health related quality of life, significantly enhances research and clinical efforts across many areas of behavioral medicine. This article examines the knowledge established to date and suggests advances that remain to be made. We begin with a brief summary of the current knowledge regarding RS as related to three exemplary health conditions: (a) cardiovascular disease; (b) cancer; and, (c) substance abuse. We then focus on particular concerns for future investigations, emphasizing conceptual issues, possible mediators and moderators of relationships or effects, and methodology. Our discussion is framed by a conceptual model that may serve to guide and organize future investigations. This model highlights a number of important issues regarding the study of links between RS and health: (a) RS comprise many diverse constructs, (b) the mechanisms through which RS may influence health outcomes are quite diverse, and (c) a range of different types of health and health relevant outcomes may be influenced by RS. The multidimensional nature of RS and the complexity of related associations with different types of health relevant outcomes present formidable challenges to empirical study in behavioral medicine. These issues are referred to throughout our review and we suggest several solutions to the presented challenges in our summary. We end with a presentation of barriers to be overcome, along with strategies for doing so, and concluding thoughts.

  5. Novel Advances in Understanding of Molecular Pathogenesis of Hepatoblastoma: A Wnt/β-Catenin Perspective

    PubMed Central

    Bell, Danielle; Ranganathan, Sarangarajan; Tao, Junyan; Monga, Satdarshan P. S.

    2017-01-01

    Hepatoblastoma is the most common pediatric liver malignancy, typically striking children within the first 3 years of their young lives. While advances in chemotherapy and newer surgical techniques have improved survival in patients with localized disease, unfortunately, for the 25% of patients with metastasis, the overall survival remains poor. These tumors, which are thought to arise from hepatic progenitors or hepatoblasts, hence the name hepatoblastoma, can be categorized by histological subtyping based on their level of cell differentiation. Genomic and histological analysis of human tumor samples has shown exon-3 deletions or missense mutations in gene coding for β-catenin, a downstream effector of the Wnt signaling pathway, in up to 90% of hepatoblastoma cases. The current article will review key aberrations in molecular pathways that are implicated in various subtypes of hepatoblastoma with an emphasis on Wnt signaling. It will also discuss cooperation among components of pathways such as β-catenin and Yes-associated protein in cancer development. Understanding the complex network of molecular signaling in oncogenesis will undoubtedly aid in the discovery of new therapeutics to help combat hepatoblastoma. PMID:27938502

  6. Understandings of Current Environmental Issues: Turkish Case Study in Six Teacher Education Colleges

    ERIC Educational Resources Information Center

    Cakir, Mustafa; Irez, Serhat; Dogan, Ozgur Kivilcan

    2010-01-01

    The purpose of this study is to profile future science teachers' understandings of current environmental issues in the context of an education reform in Turkey. Knowledge base and understandings of elementary and secondary prospective science teachers about biodiversity, carbon cycle, global warming and ozone layer depletion were targeted in the…

  7. Advancements in the mechanistic understanding of the copper-catalyzed azide-alkyne cycloaddition.

    PubMed

    Berg, Regina; Straub, Bernd F

    2013-12-02

    The copper-catalyzed azide-alkyne cycloaddition (CuAAC) is one of the most broadly applicable and easy-to-handle reactions in the arsenal of organic chemistry. However, the mechanistic understanding of this reaction has lagged behind the plethora of its applications for a long time. As reagent mixtures of copper salts and additives are commonly used in CuAAC reactions, the structure of the catalytically active species itself has remained subject to speculation, which can be attributed to the multifaceted aggregation chemistry of copper(I) alkyne and acetylide complexes. Following an introductory section on common catalyst systems in CuAAC reactions, this review will highlight experimental and computational studies from early proposals to very recent and more sophisticated investigations, which deliver more detailed insights into the CuAAC's catalytic cycle and the species involved. As diverging mechanistic views are presented in articles, books and online resources, we intend to present the research efforts in this field during the past decade and finally give an up-to-date picture of the currently accepted dinuclear mechanism of CuAAC. Additionally, we hope to inspire research efforts on the development of molecularly defined copper(I) catalysts with defined structural characteristics, whose main advantage in contrast to the regularly used precatalyst reagent mixtures is twofold: on the one hand, the characteristics of molecularly defined, well soluble catalysts can be tuned according to the particular requirements of the experiment; on the other hand, the understanding of the CuAAC reaction mechanism can be further advanced by kinetic studies and the isolation and characterization of key intermediates.

  8. Advancements in the mechanistic understanding of the copper-catalyzed azide–alkyne cycloaddition

    PubMed Central

    2013-01-01

    Summary The copper-catalyzed azide–alkyne cycloaddition (CuAAC) is one of the most broadly applicable and easy-to-handle reactions in the arsenal of organic chemistry. However, the mechanistic understanding of this reaction has lagged behind the plethora of its applications for a long time. As reagent mixtures of copper salts and additives are commonly used in CuAAC reactions, the structure of the catalytically active species itself has remained subject to speculation, which can be attributed to the multifaceted aggregation chemistry of copper(I) alkyne and acetylide complexes. Following an introductory section on common catalyst systems in CuAAC reactions, this review will highlight experimental and computational studies from early proposals to very recent and more sophisticated investigations, which deliver more detailed insights into the CuAAC’s catalytic cycle and the species involved. As diverging mechanistic views are presented in articles, books and online resources, we intend to present the research efforts in this field during the past decade and finally give an up-to-date picture of the currently accepted dinuclear mechanism of CuAAC. Additionally, we hope to inspire research efforts on the development of molecularly defined copper(I) catalysts with defined structural characteristics, whose main advantage in contrast to the regularly used precatalyst reagent mixtures is twofold: on the one hand, the characteristics of molecularly defined, well soluble catalysts can be tuned according to the particular requirements of the experiment; on the other hand, the understanding of the CuAAC reaction mechanism can be further advanced by kinetic studies and the isolation and characterization of key intermediates. PMID:24367437

  9. Advanced Aerospace Tribological Systems - Current Status and Future Technology Needs

    NASA Technical Reports Server (NTRS)

    Fusaro, Robert L.

    1993-01-01

    The state of the art of space and aeronautics tribology, the current and future technology problems, and perceived needs for future missions are discussed. Mechanisms of liquid and solid lubrication, and liquid- and solid-lubrication factors are examined. Such current and future tribological problem areas as aerospace plane, space simulation, and accelerated testing are addressed. Consideration is also given to the following novel lubrication technologies: inerted lubrication systems, mist lubrication, vapor deposition, catalytically gas-generated carbon, dense thin films of solid lubricants, powder lubrication, and gas and magnetic bearings. Recommendations for ensuring the success of current and future space and aeronautics missions are presented.

  10. 48 CFR 1552.215-74 - Advanced understanding-uncompensated time.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Advanced understanding-uncompensated time. 1552.215-74 Section 1552.215-74 Federal Acquisition Regulations System ENVIRONMENTAL PROTECTION AGENCY CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Texts of Provisions...

  11. Advances in the understanding of dairy and cheese flavors: Symposium Introduction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A symposium titled “Advances in the Understanding of Dairy and Cheese Flavors” was held in September 2013 at the American Chemical Society’s 246th National Meeting in Indianapolis, IN. The symposium, which was sponsored by the Division of Agricultural and Food Chemistry, was to discuss the state of...

  12. Recent Advances in Our Understanding of the Environmental, Epidemiological, Immunological, and Clinical Dimensions of Coccidioidomycosis

    PubMed Central

    Nguyen, Chinh; Barker, Bridget Marie; Hoover, Susan; Nix, David E.; Ampel, Neil M.; Frelinger, Jeffrey A.; Orbach, Marc J.

    2013-01-01

    SUMMARY Coccidioidomycosis is the endemic mycosis caused by the fungal pathogens Coccidioides immitis and C. posadasii. This review is a summary of the recent advances that have been made in the understanding of this pathogen, including its mycology, genetics, and niche in the environment. Updates on the epidemiology of the organism emphasize that it is a continuing, significant problem in areas of endemicity. For a variety of reasons, the number of reported coccidioidal infections has increased dramatically over the past decade. While continual improvements in the fields of organ transplantation and management of autoimmune disorders and patients with HIV have led to dilemmas with concurrent infection with coccidioidomycosis, they have also led to advances in the understanding of the human immune response to infection. There have been some advances in therapeutics with the increased use of newer azoles. Lastly, there is an overview of the ongoing search for a preventative vaccine. PMID:23824371

  13. Current advances in T-cell-based cancer immunotherapy.

    PubMed

    Wang, Mingjun; Yin, Bingnan; Wang, Helen Y; Wang, Rong-Fu

    2014-01-01

    Cancer is a leading cause of death worldwide; due to the lack of ideal cancer biomarkers for early detection or diagnosis, most patients present with late-stage disease at the time of diagnosis, thus limiting the potential for successful treatment. Traditional cancer treatments, including surgery, chemotherapy and radiation therapy, have demonstrated very limited efficacy for patients with late-stage disease. Therefore, innovative and effective cancer treatments are urgently needed for cancer patients with late-stage and refractory disease. Cancer immunotherapy, particularly adoptive cell transfer, has shown great promise in the treatment of patients with late-stage disease, including those who are refractory to standard therapies. In this review, we will highlight recent advances and discuss future directions in adoptive cell transfer based cancer immunotherapy.

  14. Current Management of Advanced Resectable Oral Cavity Squamous Cell Carcinoma

    PubMed Central

    Ow, Thomas J.

    2011-01-01

    The oral cavity is the most common site of head and neck squamous cell carcinoma, a disease which results in significant morbidity and mortality worldwide. Though the primary modality of treatment for patients with oral cavity cancer remains surgical resection, many patients present with advanced disease and are thus treated using a multi-disciplinary approach. Patients with extracapsular spread of lymphatic metastasis and surgical margins that remain positive have been found to be at high risk for local-regional recurrence and death from disease, and are most often recommended to receive both post-operative radiation as well as systemic chemotherapy. The basis for this approach, as well as scientific developments that underly future trials of novels treatments for patients with high-risk oral cavity cancer are reviewed. PMID:21461056

  15. Human toxocariasis: current advances in diagnostics, treatment, and interventions.

    PubMed

    Moreira, Gustavo Marçal Schmidt Garcia; Telmo, Paula de Lima; Mendonça, Marcelo; Moreira, Angela Nunes; McBride, Alan John Alexander; Scaini, Carlos James; Conceição, Fabricio Rochedo

    2014-09-01

    Toxocariasis is a neglected zoonosis caused by the nematodes Toxocara canis and Toxocara cati. This disease is widespread in many countries, reaching high prevalence independently of the economic conditions. However, the true number of cases of toxocariasis is likely to be underestimated owing to the lack of adequate surveillance programs. Although some diagnostic tests are available, their sensitivity and specificity need to be improved. In addition, treatment options for toxocariasis are limited and are non-specific. Toxocariasis is listed as one of the five most important neglected diseases by the CDC. This review presents recent advances related to the control of toxocariasis, including new immunodiagnostics, therapies, and drug formulations, as well as novel interventions using DNA vaccines, immunomodulators, and probiotics.

  16. Current themes and recent advances in modelling species occurrences

    PubMed Central

    2009-01-01

    Recent years have seen a huge expansion in the range of methods and approaches that are being used to predict species occurrences. This expansion has been accompanied by many improvements in statistical methods, including more accurate ways of comparing models, better null models, methods to cope with autocorrelation, and greater awareness of the importance of scale and prevalence. However, the field still suffers from problems with incorporating temporal variation, overfitted models and poor out-of-sample prediction, confusion between explanation and prediction, simplistic assumptions, and a focus on pattern over process. The greatest advances in recent years have come from integrative studies that have linked species occurrence models with other themes and topics in ecology, such as island biogeography, climate change, disease geography, and invasive species. PMID:20948597

  17. ENHANCING THE ATOMIC-LEVEL UNDERSTANDING OF CO2 MINERAL SEQUESTRATION MECHANISMS VIA ADVANCED COMPUTATIONAL MODELING

    SciTech Connect

    A.V.G. Chizmeshya; M.J. McKelvy; G.H. Wolf; R.W. Carpenter; D.A. Gormley; J.R. Diefenbacher; R. Marzke

    2006-03-01

    significantly improved our understanding of mineral carbonation. Group members at the Albany Research Center have recently shown that carbonation of olivine and serpentine, which naturally occurs over geological time (i.e., 100,000s of years), can be accelerated to near completion in hours. Further process refinement will require a synergetic science/engineering approach that emphasizes simultaneous investigation of both thermodynamic processes and the detailed microscopic, atomic-level mechanisms that govern carbonation kinetics. Our previously funded Phase I Innovative Concepts project demonstrated the value of advanced quantum-mechanical modeling as a complementary tool in bridging important gaps in our understanding of the atomic/molecular structure and reaction mechanisms that govern CO2 mineral sequestration reaction processes for the model Mg-rich lamellar hydroxide feedstock material Mg(OH)2. In the present simulation project, improved techniques and more efficient computational schemes have allowed us to expand and augment these capabilities and explore more complex Mg-rich, lamellar hydroxide-based feedstock materials, including the serpentine-based minerals. These feedstock materials are being actively investigated due to their wide availability, and low-cost CO2 mineral sequestration potential. Cutting-edge first principles quantum chemical, computational solid-state and materials simulation methodology studies proposed herein, have been strategically integrated with our new DOE supported (ASU-Argonne National Laboratory) project to investigate the mechanisms that govern mineral feedstock heat-treatment and aqueous/fluid-phase serpentine mineral carbonation in situ. This unified, synergetic theoretical and experimental approach has provided a deeper understanding of the key reaction mechanisms than either individual approach can alone. We used ab initio techniques to significantly advance our understanding of atomic-level processes at the solid/solution interface by

  18. ENHANCING THE ATOMIC-LEVEL UNDERSTANDING OF CO2 MINERAL SEQUESTRATION MECHANISMS VIA ADVANCED COMPUTATIONAL MODELING

    SciTech Connect

    A.V.G. Chizmeshya

    2003-12-19

    /NETL managed National Mineral Sequestration Working Group we have already significantly improved our understanding of mineral carbonation. Group members at the Albany Research Center have recently shown that carbonation of olivine and serpentine, which naturally occurs over geological time (i.e., 100,000s of years), can be accelerated to near completion in hours. Further process refinement will require a synergetic science/engineering approach that emphasizes simultaneous investigation of both thermodynamic processes and the detailed microscopic, atomic-level mechanisms that govern carbonation kinetics. Our previously funded Phase I Innovative Concepts project demonstrated the value of advanced quantum-mechanical modeling as a complementary tool in bridging important gaps in our understanding of the atomic/molecular structure and reaction mechanisms that govern CO{sub 2} mineral sequestration reaction processes for the model Mg-rich lamellar hydroxide feedstock material Mg(OH){sub 2}. In the present simulation project, improved techniques and more efficient computational schemes have allowed us to expand and augment these capabilities and explore more complex Mg-rich, lamellar hydroxide-based feedstock materials, including the serpentine-based minerals. These feedstock materials are being actively investigated due to their wide availability, and low-cost CO{sub 2} mineral sequestration potential. Cutting-edge first principles quantum chemical, computational solid-state and materials simulation methodology studies proposed herein, have been strategically integrated with our new DOE supported (ASU-Argonne National Laboratory) project to investigate the mechanisms that govern mineral feedstock heat-treatment and aqueous/fluid-phase serpentine mineral carbonation in situ. This unified, synergetic theoretical and experimental approach will provide a deeper understanding of the key reaction mechanisms than either individual approach can alone. Ab initio techniques will also

  19. ENHANCING THE ATOMIC-LEVEL UNDERSTANDING OF CO2 MINERAL SEQUESTRATION MECHANISMS VIA ADVANCED COMPUTATIONAL MODELING

    SciTech Connect

    A.V.G. Chizmeshya

    2002-12-19

    /NETL managed National Mineral Sequestration Working Group we have already significantly improved our understanding of mineral carbonation. Group members at the Albany Research Center have recently shown that carbonation of olivine and serpentine, which naturally occurs over geological time (i.e., 100,000s of years), can be accelerated to near completion in hours. Further process refinement will require a synergetic science/engineering approach that emphasizes simultaneous investigation of both thermodynamic processes and the detailed microscopic, atomic-level mechanisms that govern carbonation kinetics. Our previously funded Phase I Innovative Concepts project demonstrated the value of advanced quantum-mechanical modeling as a complementary tool in bridging important gaps in our understanding of the atomic/molecular structure and reaction mechanisms that govern CO{sub 2} mineral sequestration reaction processes for the model Mg-rich lamellar hydroxide feedstock material Mg(OH){sub 2}. In the present simulation project, improved techniques and more efficient computational schemes have allowed us to expand and augment these capabilities and explore more complex Mg-rich, lamellar hydroxide-based feedstock materials, including the serpentine-based minerals. These feedstock materials are being actively investigated due to their wide availability, and low-cost CO{sub 2} mineral sequestration potential. Cutting-edge first principles quantum chemical, computational solid-state and materials simulation methodology studies proposed herein, have been strategically integrated with our new DOE supported (ASU-Argonne National Laboratory) project to investigate the mechanisms that govern mineral feedstock heat-treatment and aqueous/fluid-phase serpentine mineral carbonation in situ. This unified, synergetic theoretical and experimental approach will provide a deeper understanding of the key reaction mechanisms than either individual approach can alone. Ab initio techniques will also

  20. Development of Lignocellulosic Biorefinery Technologies: Recent Advances and Current Challenges

    SciTech Connect

    Amore, Antonella; Ciesielski, Peter N.; Lin, Chien-Yuan; Salvachua, Davinia; Sanchez i Nogue, Violeta

    2016-06-06

    Recent developments of the biorefinery concept are described within this review, which focuses on the efforts required to make the lignocellulosic biorefinery a sustainable and economically viable reality. Despite the major research and development endeavours directed towards this goal over the past several decades, the integrated production of biofuel and other bio-based products still needs to be optimized from both technical and economical perspectives. This review will highlight recent progress towards the optimization of the major biorefinery processes, including biomass pretreatment and fractionation, saccharification of sugars, and conversion of sugars and lignin into fuels and chemical precursors. In addition, advances in genetic modification of biomass structure and composition for the purpose of enhancing the efficacy of conversion processes, which is emerging as a powerful tool for tailoring biomass fated for the biorefinery, will be overviewed. The continual improvement of these processes and their integration in the format of a modern biorefinery is paving the way for a sustainable bio-economy which will displace large portions of petroleum-derived fuels and chemicals with renewable substitutes.

  1. Advances in pesticide biosensors: current status, challenges, and future perspectives.

    PubMed

    Liu, Shaoqin; Zheng, Zhaozhu; Li, Xinyu

    2013-01-01

    Public concern over pesticide residues has been increasing dramatically owing to the high toxicity and bioaccumulation effects of pesticides and the serious risks that they pose to the environment and human health. It is therefore crucial to monitor pesticide residues by using various analytical methods and techniques, especially highly sensitive, highly selective, simple, rapid, cost-effective, and portable ones. Biosensor strategies have become research hotspots and ideal candidates for pesticide detection, having such features as high sensitivity, fast response, robustness, low cost and miniaturization, as well as in situ and real-time monitoring. This review covers advances in the design and fabrication of biosensors for pesticide detection since 2005. Special emphasis is placed on the state-of-art selection of receptors, the use of different transduction techniques and fast screening strategies, and the application of various biosensors developed in food and environmental safety. Both advantages and drawbacks of these techniques are then summarized. Finally, challenges, strategies, and perspectives in further developing pesticide biosensors are also discussed.

  2. Visualizing epigenetics: current advances and advantages in HDAC PET imaging techniques.

    PubMed

    Wang, C; Schroeder, F A; Hooker, J M

    2014-04-04

    Abnormal gene regulation as a consequence of flawed epigenetic mechanisms may be central to the initiation and persistence of many human diseases. However, the association of epigenetic dysfunction with disease and the development of therapeutic agents for treatment are slow. Developing new methodologies used to visualize chromatin-modifying enzymes and their function in the human brain would be valuable for the diagnosis of brain disorders and drug discovery. We provide an overview of current invasive and noninvasive techniques for measuring expression and functions of chromatin-modifying enzymes in the brain, emphasizing tools applicable to histone deacetylase (HDAC) enzymes as a leading example. The majority of current techniques are invasive and difficult to translate to what is happening within a human brain in vivo. However, recent progress in molecular imaging provides new, noninvasive ways to visualize epigenetics in the human brain. Neuroimaging tool development presents a unique set of challenges in order to identify and validate CNS radiotracers for HDACs and other histone-modifying enzymes. We summarize advances in the effort to image HDACs and HDAC inhibitory effects in the brain using positron emission tomography (PET) and highlight generalizable techniques that can be adapted to investigate other specific components of epigenetic machinery. Translational tools like neuroimaging by PET and magnetic resonance imaging provide the best way to link our current understanding of epigenetic changes with in vivo function in normal and diseased brains. These tools will be a critical addition to ex vivo methods to evaluate - and intervene - in CNS dysfunction.

  3. Visualizing epigenetics: current advances and advantages in HDAC PET imaging techniques

    PubMed Central

    Wang, Changning; Schroeder, Frederick A.; Hooker, Jacob M.

    2013-01-01

    Abnormal gene regulation as a consequence of flawed epigenetic mechanisms may be central to the initiation and persistence of many human diseases. However, the association of epigenetic dysfunction with disease and the development of therapeutic agents for treatment are slow. Developing new methodologies used to visualize chromatin modifying enzymes and their function in the human brain would be valuable for diagnosis of brain disorders and drug discovery. We provide an overview of current invasive and noninvasive techniques for measuring expression and functions of chromatin modifying enzymes in the brain, emphasizing tools applicable to histone deacetylase (HDAC) enzymes as a leading example. The majority of current techniques are invasive and difficult to translate to what is happening within a human brain in vivo. However, recent progress in molecular imaging provides new, noninvasive ways to visualize epigenetics in human brain. Neuroimaging tool development presents a unique set of challenges in order to identify and validate CNS radiotracers for HDACs and other histone modifying enzymes. We summarize advances in the effort to image HDACs and HDAC inhibitory effects in the brain using PET and highlight generalizable techniques that can be adapted to investigate other specific components of epigenetic machinery. Translational tools like neuroimaging by PET and MRI provide the best way to link our current understanding of epigenetic changes with in vivo function in normal and diseased brain. These tools will be a critical addition to ex vivo methods to evaluate - and intervene - in CNS dysfunction. PMID:24051365

  4. Advances in time-dependent current-density functional theory

    NASA Astrophysics Data System (ADS)

    Berger, Arjan

    In this work we solve the problem of the gauge dependence of molecular magnetic properties (magnetizabilities, circular dichroism) using time-dependent current-density functional theory [1]. We also present a new functional that accurately describes the optical absorption spectra of insulators, semiconductors and metals [2] N. Raimbault, P.L. de Boeij, P. Romaniello, and J.A. Berger Phys. Rev. Lett. 114, 066404 (2015) J.A. Berger, Phys. Rev. Lett. 115, 137402 (2015) This study has been partially supported through the Grant NEXT No. ANR-10-LABX-0037 in the framework of the Programme des Investissements d'Avenir.

  5. Low Temperature Heat Source Utilization Current and Advanced Technology

    SciTech Connect

    Anderson, James H. Jr.; Dambly, Benjamin W.

    1992-06-01

    Once a geothermal heat source has been identified as having the potential for development, and its thermal, physical, and chemical characteristics have been determined, a method of utilization must be decided upon. This compendium will touch upon some of these concerns, and hopefully will provide the reader with a better understanding of technologies being developed that will be applicable to geothermal development in East Africa, as well as other parts of the world. The appendices contain detailed reports on Down-the-Well Turbo Pump, The Vapor-Turbine Cycle for Geothermal Power Generation, Heat Exchanger Design for Geothermal Power Plants, and a Feasibility Study of Combined Power and Water Desalting Plant Using Hot Geothermal Water. [DJE-2005

  6. Current Understanding of the Binding Sites, Capacity, Affinity, and Biological Significance of Metals in Melanin

    PubMed Central

    Hong, Lian; Simon, John D.

    2008-01-01

    Metal chelation is often invoked as one of the main biological functions of melanin. In order to understand the interaction between metals and melanin, extensive studies have been carried out to determine the nature of the metal binding sites, binding capacity and affinity. These data are central to efforts aimed at elucidating the role metal binding plays in determining the physical, structural, biological, and photochemical properties of melanin. This article examines the current state of understanding of this field. PMID:17580858

  7. Antifungal Therapy: New Advances in the Understanding and Treatment of Mycosis

    PubMed Central

    Scorzoni, Liliana; de Paula e Silva, Ana C. A.; Marcos, Caroline M.; Assato, Patrícia A.; de Melo, Wanessa C. M. A.; de Oliveira, Haroldo C.; Costa-Orlandi, Caroline B.; Mendes-Giannini, Maria J. S.; Fusco-Almeida, Ana M.

    2017-01-01

    The high rates of morbidity and mortality caused by fungal infections are associated with the current limited antifungal arsenal and the high toxicity of the compounds. Additionally, identifying novel drug targets is challenging because there are many similarities between fungal and human cells. The most common antifungal targets include fungal RNA synthesis and cell wall and membrane components, though new antifungal targets are being investigated. Nonetheless, fungi have developed resistance mechanisms, such as overexpression of efflux pump proteins and biofilm formation, emphasizing the importance of understanding these mechanisms. To address these problems, different approaches to preventing and treating fungal diseases are described in this review, with a focus on the resistance mechanisms of fungi, with the goal of developing efficient strategies to overcoming and preventing resistance as well as new advances in antifungal therapy. Due to the limited antifungal arsenal, researchers have sought to improve treatment via different approaches, and the synergistic effect obtained by the combination of antifungals contributes to reducing toxicity and could be an alternative for treatment. Another important issue is the development of new formulations for antifungal agents, and interest in nanoparticles as new types of carriers of antifungal drugs has increased. In addition, modifications to the chemical structures of traditional antifungals have improved their activity and pharmacokinetic parameters. Moreover, a different approach to preventing and treating fungal diseases is immunotherapy, which involves different mechanisms, such as vaccines, activation of the immune response and inducing the production of host antimicrobial molecules. Finally, the use of a mini-host has been encouraging for in vivo testing because these animal models demonstrate a good correlation with the mammalian model; they also increase the speediness of as well as facilitate the

  8. Antifungal Therapy: New Advances in the Understanding and Treatment of Mycosis.

    PubMed

    Scorzoni, Liliana; de Paula E Silva, Ana C A; Marcos, Caroline M; Assato, Patrícia A; de Melo, Wanessa C M A; de Oliveira, Haroldo C; Costa-Orlandi, Caroline B; Mendes-Giannini, Maria J S; Fusco-Almeida, Ana M

    2017-01-01

    The high rates of morbidity and mortality caused by fungal infections are associated with the current limited antifungal arsenal and the high toxicity of the compounds. Additionally, identifying novel drug targets is challenging because there are many similarities between fungal and human cells. The most common antifungal targets include fungal RNA synthesis and cell wall and membrane components, though new antifungal targets are being investigated. Nonetheless, fungi have developed resistance mechanisms, such as overexpression of efflux pump proteins and biofilm formation, emphasizing the importance of understanding these mechanisms. To address these problems, different approaches to preventing and treating fungal diseases are described in this review, with a focus on the resistance mechanisms of fungi, with the goal of developing efficient strategies to overcoming and preventing resistance as well as new advances in antifungal therapy. Due to the limited antifungal arsenal, researchers have sought to improve treatment via different approaches, and the synergistic effect obtained by the combination of antifungals contributes to reducing toxicity and could be an alternative for treatment. Another important issue is the development of new formulations for antifungal agents, and interest in nanoparticles as new types of carriers of antifungal drugs has increased. In addition, modifications to the chemical structures of traditional antifungals have improved their activity and pharmacokinetic parameters. Moreover, a different approach to preventing and treating fungal diseases is immunotherapy, which involves different mechanisms, such as vaccines, activation of the immune response and inducing the production of host antimicrobial molecules. Finally, the use of a mini-host has been encouraging for in vivo testing because these animal models demonstrate a good correlation with the mammalian model; they also increase the speediness of as well as facilitate the

  9. Advances in modeling of lower hybrid current drive

    NASA Astrophysics Data System (ADS)

    Peysson, Y.; Decker, J.; Nilsson, E.; Artaud, J.-F.; Ekedahl, A.; Goniche, M.; Hillairet, J.; Ding, B.; Li, M.; Bonoli, P. T.; Shiraiwa, S.; Madi, M.

    2016-04-01

    First principle modeling of the lower hybrid (LH) current drive in tokamak plasmas is a longstanding activity, which is gradually gaining in accuracy thanks to quantitative comparisons with experimental observations. The ability to reproduce simulatenously the plasma current and the non-thermal bremsstrahlung radial profiles in the hard x-ray (HXR) photon energy range represents in this context a significant achievement. Though subject to limitations, ray tracing calculations are commonly used for describing wave propagation in conjunction with Fokker-Planck codes, as it can capture prominent features of the LH wave dynamics in a tokamak plasma-like toroidal refraction. This tool has been validated on several machines when the full absorption of the LH wave requires the transfer of a small fraction of power from the main lobes of the launched power spectrum to a tail at a higher parallel refractive index. Conversely, standard modeling based on toroidal refraction only becomes more challenging when the spectral gap is large, except if other physical mechanisms may dominate to bridge it, like parametric instabilities, as suggested for JET LH discharges (Cesario et al 2004 Phys. Rev. Lett. 92 175002), or fast fluctuations of the launched power spectrum or ‘tail’ LH model, as shown for Tore Supra (Decker et al 2014 Phys. Plasma 21 092504). The applicability of the heuristic ‘tail’ LH model is investigated for a broader range of plasma parameters as compared to the Tore Supra study and with different LH wave characteristics. Discrepancies and agreements between simulations and experiments depending upon the different models used are discussed. The existence of a ‘tail’ in the launched power spectrum significantly improves the agreement between modeling and experiments in plasma conditions for which the spectral gap is large in EAST and Alcator C-Mod tokamaks. For the Alcator C-Mod tokamak, the experimental evolution of the HXR profiles with density suggests

  10. Advanced pancreatic adenocarcinoma: a review of current treatment strategies and developing therapies

    PubMed Central

    Teague, Andrea; Lim, Kian-Huat

    2015-01-01

    Pancreatic adenocarcinoma is one of the deadliest solid malignancies. A large proportion of patients are diagnosed with locally advanced or metastatic disease at the time of presentation and, unfortunately, this severely limits the number of patients who can undergo surgical resection, which offers the only chance for cure. Recent therapeutic advances for patients with advanced pancreatic cancer have extended overall survival, but prognosis still remains grim. Given that traditional chemotherapy is ineffective in curing advanced pancreatic adenocarcinoma, current research is taking a multidirectional approach in the hopes of developing more effective treatments. This article reviews the major clinical trial data that is the basis for the current chemotherapy regimens used as first- and second-line treatments for advanced pancreatic adenocarcinoma. We also review the current ongoing clinical trials, which include the use of agents targeting the oncogenic network signaling of K-Ras, agents targeting the extracellular matrix, and immune therapies. PMID:25755680

  11. Advances in materials and current collecting networks for AMTEC electrodes

    NASA Technical Reports Server (NTRS)

    Ryan, M. A.; Jeffries-Nakamura, B.; Williams, R. M.; Underwood, M. L.; O'Connor, D.; Kikkert, S.

    1992-01-01

    Electrode materials for the Alkali Metal Thermal to Electric Converter (AMTEC) play a significant role in the efficiency of the device. RhW and PtW alloys have been studied to determine the best performing material. While RhW electrodes typically have power densities somewhat lower than PtW electrodes, PtW performance is strongly influenced by the Pt/W ratio. The best performing Pt/W ratio is about 3.4. RhW electrodes sinter more slowly than PtW and are predicted to have operating lifetimes up to 40 years; PtW electrodes are predicted to have lifetimes up to 7 years. Interaction with the current collection network can significantly decrease lifetime by inducing metal migration and segregation and by accelerating the sintering rate.

  12. Evaluation of advanced and current leak detection system

    SciTech Connect

    Kupperman, D.S.

    1987-01-01

    US Nuclear Regulatory Commission Guide 1.45 recommends the use of at least three different detection methods in reactors to detect leakage. Monitoring of both sump-flow and airborne particulate radioactivity is mandatory. A third method can involve either monitoring of condensate flow rate from air coolers or monitoring of airborne gaseous radioactivity. Although the methods currently used for leak detection reflect the state of the art, other techniques may be developed and used. Since the recommendations of Regulatory Guide 1.45 are not mandatory, Licensee Event Report Compilations have been reviewed to help establish actual capabilities for leak detection. The review of reports which had previously covered the period June 1985 to August 1986, has been extended. The total number of events of significance is now 83. These reports have provided documented, sometimes detailed summaries of reactor leaks.

  13. Advances toward More Efficient Targeted Delivery of Nanoparticles in Vivo: Understanding Interactions between Nanoparticles and Cells.

    PubMed

    Polo, Ester; Collado, Manuel; Pelaz, Beatriz; Del Pino, Pablo

    2017-03-07

    In this Perspective, we describe current challenges and recent advances in efficient delivery and targeting of nanoparticles in vivo. We discuss cancer therapy, nanoparticle-biomolecule interactions, nanoparticle trafficking in cells, and triggers and responses to nanoparticle-cell interactions. No matter which functionalization strategy to target cancer is chosen, passive or active targeting, more than 99% of the nanoparticles administered in vivo end up in the mononuclear phagocytic system, mainly sequestered by macrophages. Comprehensive studies, such as the one reported by MacParland et al. in this issue of ACS Nano, will help to close the gap between nanotechnology-based drug-delivery solutions and advanced medicinal products.

  14. Drug-induced liver injury: Advances in mechanistic understanding that will inform risk management.

    PubMed

    Mosedale, M; Watkins, P B

    2016-11-09

    Drug-induced liver injury (DILI) is a major public health problem. Intrinsic (dose-dependent) DILI associated with acetaminophen overdose is the number one cause of acute liver failure in the US. However, the most problematic type of DILI impacting drug development is idiosyncratic, occurring only very rarely among treated patients and often only after several weeks or months of treatment with the offending drug. Recent advances in our understanding of the pathogenesis of DILI suggest that three mechanisms may underlie most hepatocyte effects in response to both intrinsic and idiosyncratic DILI drugs: mitochondrial dysfunction, oxidative stress, and alterations in bile acid homeostasis. However, in some cases hepatocyte stress promotes an immune response that results in clinically important idiosyncratic DILI. This review discusses recent advances in our understanding of the pathogenesis of both intrinsic and idiosyncratic DILI as well as emerging tools and techniques that will likely improve DILI risk identification and management.

  15. Advances in the understanding of dairy and cheese flavors: symposium introduction.

    PubMed

    Tunick, Michael H; Gummalla, Sanjay

    2014-06-25

    A symposium titled "Advances in the Understanding of Dairy and Cheese Flavors" was held in September 2013 at the American Chemical Society's 246th National Meeting in Indianapolis, IN, USA. The symposium, which was sponsored by the Division of Agricultural and Food Chemistry, was to discuss the state of the art in the detection and quantitation of flavor in dairy products. The authors of two of the presentations have been selected to expand on their talks by submitting full papers about their research.

  16. Cutaneous wound healing: Current concepts and advances in wound care

    PubMed Central

    Klein, Kenneth C; Guha, Somes Chandra

    2014-01-01

    A non-healing wound is defined as showing no measurable signs of healing for at least 30 consecutive treatments with standard wound care.[1] It is a snapshot of a patient's total health as well as the ongoing battle between noxious factors and the restoration of optimal macro and micro circulation, oxygenation and nutrition. In practice, standard therapies for non-healing cutaneous wounds include application of appropriate dressings, periodic debridement and eliminating causative factors.[2] The vast majority of wounds would heal by such approach with variable degrees of residual morbidity, disability and even mortality. Globally, beyond the above therapies, newer tools of healing are selectively accessible to caregivers, for various logistical or financial reasons. Our review will focus on the use of hyperbaric oxygen therapy (HBOT), as used at our institution (CAMC), and some other modalities that are relatively accessible to patients. HBOT is a relatively safe and technologically simpler way to deliver care worldwide. However, the expense for including HBOT as standard of care for recognized indications per UHMS(Undersea and Hyperbaric Medical Society) may vary widely from country to country and payment system.[3] In the USA, CMS (Centers for Medicare and Medicaid Services) approved indications for HBOT vary from that of the UHMS for logistical reasons.[1] We shall also briefly look into other newer therapies per current clinical usage and general acceptance by the medical community. Admittedly, there would be other novel tools with variable success in wound healing worldwide, but it would be difficult to include all in this treatise. PMID:25593414

  17. Extent to Which Teacher Beliefs and Practices Reflect Current Research on Historical Thinking and Understanding

    ERIC Educational Resources Information Center

    Carroll, Erich C.

    2013-01-01

    This study examined the extent to which teacher beliefs and practices at the high school level reflect current research on historical thinking and understanding. The topic is significant as teachers are a crucial variable in a child's education and evidence over the years has revealed that students have long struggled in developing conceptual…

  18. Vertebrate neurogenic placode development: historical highlights that have shaped our current understanding.

    PubMed

    Stark, Michael R

    2014-10-01

    With the flood of published research encountered today, it is important to occasionally reflect upon how we arrived at our current understanding in a particular scientific discipline, thereby positioning new discoveries into proper context with long-established models. This historical review highlights some of the important scientific contributions in the field of neurogenic placode development. By viewing cumulatively the rich historical data, we can more fully appreciate and apply what has been accomplished. Early descriptive work in fish and experimental approaches in amphibians and chick yielded important conceptual models of placode induction and cellular differentiation. Current efforts to discover genes and their molecular functions continue to expand our understanding of the placodes. Carefully considering the body of work may improve current models and help focus modern experimental design.

  19. Treatment of advanced renal cell carcinoma: recent advances and current role of immunotherapy, surgery, and cryotherapy.

    PubMed

    Mennitto, Alessia; Verzoni, Elena; Calareso, Giuseppina; Spreafico, Carlo; Procopio, Giuseppe

    2017-01-21

    Renal cell carcinoma (RCC) is the 10th most common cancer in Western countries. The prognosis of metastatic disease is unfavorable but may be different according to several risk factors, such as histology and clinical features (Karnofsky performance status, time from nephrectomy, hemoglobin level, neutrophils and thrombocytes count, lactate dehydrogenase and calcium serum value, sites and extension of the disease). In this review, we focused on some recent developments in the use of immunotherapy, surgery and cryotherapy in the treatment of advanced disease. While RCC is unresponsive to chemotherapy, recent advances have emerged with the development of targeted agents and innovative immunotherapy-based treatments. Surgical resection remains the standard of care for patients with small renal lesions but in patients with significant comorbidities ablative therapies such as cryoablation and radiofrequency ablation may lead to local cancer control and avoid surgical complications and morbidity. In the setting of metastatic RCC, radical nephrectomy, or cytoreductive nephrectomy, is considered a palliative surgery, usually part of a multimodality treatment approach that requires systemic treatments.

  20. Current understanding on Villosiclava virens, a unique flower-infecting fungus causing rice false smut disease.

    PubMed

    Fan, Jing; Yang, Juan; Wang, Yu-Qiu; Li, Guo-Bang; Li, Yan; Huang, Fu; Wang, Wen-Ming

    2016-12-01

    Villosiclava virens (Vv) is an ascomycete fungal pathogen that causes false smut disease in rice. Recent reports have revealed some interesting aspects of the enigmatic pathogen to address the question of why it specifically infects rice flowers and converts a grain into a false smut ball. Comparative and functional genomics have suggested specific adaptation of Vv in the colonization of rice flowers. Anatomical studies have disclosed that Vv specifically infects rice stamen filaments before heading and intercepts seed formation. In addition, Vv can occupy the whole inner space of a spikelet embracing all floral organs and activate the rice grain-filling network, presumably for nutrient acquisition to support the development of the false smut ball. This profile provides a general overview of the rice false smut pathogen, and summarizes advances in the Vv life cycle, genomics and genetics, and the molecular Vv-rice interaction. Current understandings of the Vv-rice pathosystem indicate that it is a unique and interesting system which can enrich the study of plant-pathogen interactions. Taxonomy: Ustilaginoidea virens is the anamorph form of the pathogen (Kingdom Fungi; Phylum Ascomycota; Class Ascomycetes; Subclass Incertae sedis; Order Incertae sedis; Family Incertae sedis; Genus Ustilaginoidea). The teleomorph form is Villosiclava virens (Kingdom Fungi; Phylum Ascomycota; Class Ascomycetes; Subclass Sordariomycetes; Order Hypocreales; Family Clavicipitaceae; Genus Villosiclava). Disease symptoms: The only visible symptom is the replacement of rice grains by ball-shaped fungal mycelia, namely false smut balls. When maturing, the false smut ball is covered with powdery chlamydospores, and the colour changes to yellowish, yellowish orange, green, olive green and, finally, to greenish black. Sclerotia are often formed on the false smut balls in autumn. Identification and detection: Vv conidia are round to elliptical, measuring 3-5 μm in diameter. Chlamydospores are

  1. Uncovering the Visual “Alphabet”: Advances in our understanding of object perception

    PubMed Central

    Ungerleider, Leslie G.; Bell, Andrew H.

    2011-01-01

    The ability to rapidly and accurately recognize visual stimuli represents a significant computational challenge. Yet, despite such complexity, the primate brain manages this task effortlessly. How it does so remains largely a mystery. The study of visual perception and object recognition was once limited to investigations of brain-damaged individuals or lesion experiments in animals. However, in the last 25 years, new methodologies, such as functional neuroimaging and advances in electrophysiological approaches, have provided scientists with the opportunity to examine this problem from new perspectives. This review highlights how some of these recent technological advances have contributed to the study of visual processing and where we now stand with respect to our understanding of neural mechanisms underlying object recognition. PMID:20971130

  2. Controlling & understanding the variables: Key to commercializing micowave processing of advanced materials

    SciTech Connect

    Garard, R.S.

    1995-12-31

    Commercial use of microwave energy for processing advanced materials has been a {open_quotes}promising new development{close_quotes} for over a decade. However, the realization of actual commercial use in most advanced material cases has not yet been achieved. As with any new processing technique, the control and application of process conditions must be reliable, repeatable, and thoroughly understood. This paper will discuss the variables associated with both economic analysis and material properties when determining the potential of microwave processing for a given application. The importance of having a microwave system capable of controlling those variables and distributing the microwave energy uniformly over large volumes within a microwave oven is reviewed. The need for a production equipment supplier to combine materials science expertise with strong microwave engineering background is also discussed with emphasis on ensuring that a good understanding of the material/microwave interaction exists for each specific application.

  3. Volatility of Common Protective Oxides in High-Temperature Water Vapor: Current Understanding and Unanswered Questions

    NASA Technical Reports Server (NTRS)

    Opila, Elizabeth J.

    2004-01-01

    Many structural materials rely on the formation of chromia, silica or alumina as a protective layer when exposed in high temperature oxidizing environments. The presence of these oxide layers provides a protective diffusion barrier which slows down further oxidation. In atmospheres containing water vapor, however, reactions to form volatile hydroxide species occur which remove the surface oxide, thus, lowering the protective capability of the oxide scale. This paper summarizes the current understanding of volatility of chromia, silica and alumina in water vapor containing combustion environments. In addition unanswered questions in each system are discussed. Th current paper represents an update on the considerable information learned in the past five years for these systems.

  4. Current therapeutic strategies for advanced pancreatic cancer: A review for clinicians

    PubMed Central

    Spadi, Rosella; Brusa, Federica; Ponzetti, Agostino; Chiappino, Isabella; Birocco, Nadia; Ciuffreda, Libero; Satolli, Maria Antonietta

    2016-01-01

    Pancreatic cancer (PC) would become the second leading cause of cancer death in the near future, despite representing only 3% of new cancer diagnosis. Survival improvement will come from a better knowledge of risk factors, earlier diagnosis, better integration of locoregional and systemic therapies, as well as the development of more efficacious drugs rising from a deeper understanding of disease biology. For patients with unresectable, non-metastatic disease, combined strategies encompassing primary chemotherapy and radiation seems to be promising. In fit patients, new polychemotherapy regimens can lead to better outcomes in terms of slight but significant survival improvement associated with a positive impact on quality of life. The upfront use of these regimes can also increase the rate of radical resections in borderline resectable and locally advanced PC. Second line treatments showed to positively affect both overall survival and quality of life in fit patients affected by metastatic disease. At present, oxaliplatin-based regimens are the most extensively studied. Nonetheless, other promising drugs are currently under evaluation. Presently, in addition to surgery and conventional radiation therapy, new locoregional treatment techniques are emerging as alternative options in the multimodal approach to patients or diseases not suitable for radical surgery. As of today, in contrast with other types of cancer, targeted therapies failed to show relevant activity either alone or in combination with chemotherapy and, thus, current clinical practice does not include them. Up to now, despite the fact of extremely promising results in different tumors, also immunotherapy is not in the actual therapeutic armamentarium for PC. In the present paper, we provide a comprehensive review of the current state of the art of clinical practice and research in PC aiming to offer a guide for clinicians on the most relevant topics in the management of this disease. PMID:26862489

  5. Understanding and preventing acl injuries: current biomechanical and epidemiologic considerations - update 2010.

    PubMed

    Hewett, Timothy E; Ford, Kevin R; Hoogenboom, Barbara J; Myer, Gregory D

    2010-12-01

    This invited clinical commentary summarizes the current state of knowledge in the area of prevention of anterior cruciate ligament (ACL) injuries. ACL injuries occur with a four to six fold greater incidence in female compared to male athletes playing the same high risk sports. The combination of increased risk of ACL injury and a 10-fold increase in sports participation since the enactment of Title IX in 1972 has led to an almost epidemic rise in ACL injuries in female athletes. Examination of the mechanisms responsible for this sex disparity in ACL rupture accelerated in the last two decades. A summary of these findings and a synthesis and framework for understanding the results of the intense investigation of this research are detailed herein. This clinical commentary focuses on the current understanding, identification and interventional targeting of the primary neuromuscular and biomechanical risk factors associated with the ACL injury mechanism in high-risk individuals.

  6. Advances in understanding itching and scratching: a new era of targeted treatments

    PubMed Central

    Sanders, Kristen M.; Nattkemper, Leigh A.; Yosipovitch, Gil

    2016-01-01

    Chronic itch is a significant health burden with few effective treatments. As such, itch researchers seek to understand the mechanisms behind itch and to find potential targets for treatment. The field of itch research is dynamic, and many advances have been made so far this decade. In particular, major steps forward include the identification of new peripheral and central itch mediators and modulators, the discovery of greater roles for immune cells and glia in itch transmission, and a focus on the brain processing of itching and scratching. Finally, several new therapeutic interventions for itch have shown success in clinical trials. PMID:27610225

  7. USE OF COUPLED MULTI-ELECTRODE ARRAYS TO ADVANCE THE UNDERSTANDING OF SELECTED CORROSION PHENOMENA

    SciTech Connect

    N.D. Budiansky; F. Bocher; H. Cong; M.F. Hurley; J.R. Scully

    2006-02-23

    The use of multi-coupled electrode arrays in various corrosion applications is discussed with the main goal of advancing the understanding of various corrosion phenomena. Both close packed and far spaced electrode configurations are discussed. Far spaced electrode arrays are optimized for high throughput experiments capable of elucidating the effects of various variables on corrosion properties. For instance the effects of a statistical distribution of flaws on corrosion properties can be examined. Close packed arrays enable unprecedented spatial and temporal information on the behavior of local anodes and cathodes. Interactions between corrosion sites can trigger or inhibit corrosion phenomena and affect corrosion damage evolution.

  8. a Roadmap to Advance Understanding of the Science of Space Weather

    NASA Astrophysics Data System (ADS)

    Schrijver, K.; Kauristie, K.; Aylward, A.; De Nardin, C. M.; Gibson, S. E.; Glover, A.; Gopalswamy, N.; Grande, M.; Hapgood, M. A.; Heynderickx, D.; Jakowski, N.; Kalegaev, V. V.; Lapenta, G.; Linker, J.; Liu, S.; Mandrini, C. H.; Mann, I. R.; Nagatsuma, T.; Nandy, D.; Obara, T.; O'Brien, T. P., III; Onsager, T. G.; Opgenoorth, H. J.; Terkildsen, M. B.; Valladares, C. E.; Vilmer, N.

    2015-12-01

    There is a growing appreciation that the environmental conditions that we call space weather impact the technological infrastructure that powers the coupled economies around the world. With that comes the need to better shield society against space weather by improving forecasts, environmental specifications, and infrastructure design. A COSPAR/ILWS team recently completed a roadmap that identifies the scientific focus areas and research infrastructure that are needed to significantly advance our understanding of space weather of all intensities and of its implications and costs for society. This presentation provides a summary of the highest-priority recommendations from that roadmap.

  9. Intracranial Pressure and Its Relationship to Glaucoma: Current Understanding and Future Directions

    PubMed Central

    ROY CHOWDHURY, Uttio; FAUTSCH, Michael P.

    2015-01-01

    Retrospective and prospective studies looking at the role of cerebrospinal fluid pressure (CSFP)/intracranial pressure (ICP) have stimulated new theories and hypotheses regarding the underlying causal events for glaucoma. Most recently, studies supporting a low CSFP/ICP as a risk factor for glaucoma have been published. This review summarizes the current understanding of CSFP/ICP and its potential role in the pathogenicity of the disease. PMID:27350948

  10. Manifesto for the current understanding and management of traumatic brain injury-induced hypopituitarism.

    PubMed

    Tanriverdi, F; Agha, A; Aimaretti, G; Casanueva, F F; Kelestimur, F; Klose, M; Masel, B E; Pereira, A M; Popovic, V; Schneider, H J

    2011-01-01

    Traumatic brain injury (TBI)-induced hypopituitarism remains a relevant medical problem, because it may affect a significant proportion of the population. In the last decade important studies have been published investigating pituitary dysfunction after TBI. Recently, a group of experts gathered and revisited the topic of TBI-induced hypopituitarism. During the 2-day meeting, the main issues of this topic were presented and discussed, and current understanding and management of TBI-induced hypopituitarism are summarized here.

  11. Current understanding of the formation and adaptation of metabolic systems based on network theory.

    PubMed

    Takemoto, Kazuhiro

    2012-07-12

    Formation and adaptation of metabolic networks has been a long-standing question in biology. With recent developments in biotechnology and bioinformatics, the understanding of metabolism is progressively becoming clearer from a network perspective. This review introduces the comprehensive metabolic world that has been revealed by a wide range of data analyses and theoretical studies; in particular, it illustrates the role of evolutionary events, such as gene duplication and horizontal gene transfer, and environmental factors, such as nutrient availability and growth conditions, in evolution of the metabolic network. Furthermore, the mathematical models for the formation and adaptation of metabolic networks have also been described, according to the current understanding from a perspective of metabolic networks. These recent findings are helpful in not only understanding the formation of metabolic networks and their adaptation, but also metabolic engineering.

  12. Understanding

    ERIC Educational Resources Information Center

    Buxkemper, Andra C.; Hartfiel, D. J.

    2003-01-01

    There is no common agreement on the meaning of the word "understand". However, there is agreement on what students should be able to do with material they understand. Bloom et al. discuss kinds of tasks a student should be able to do, provided that the student understands. In a similar way, Biggs and Collis provide a taxonomy intended to evaluate…

  13. Advances in understanding monoclonal gammopathy of undetermined significance as a precursor of multiple myeloma

    PubMed Central

    Weiss, Brendan M; Kuehl, W Michael

    2010-01-01

    Monoclonal gammopathy of undetermined significance (MGUS) affects at least 3% of the population above the age of 50 and is the precursor to multiple myeloma (MM), an incurable malignancy of plasma cells. Recent advances in MGUS include: an improved understanding of the pathogenesis of MGUS and its progression to MM, involving molecular events intrinsic to the malignant plasma cell as well as the microenvironment; novel techniques to assess risk for progression to MM using serum-free light-chain analysis and immunophenotyping; and a renewed interest in chemoprevention of MM. In the future, continued improvement in our understanding of MGUS will lead to the development of better biomarkers for prognosis and therapies for chemoprevention of MM. PMID:20473362

  14. Understanding the current-voltage characteristics of industrial crystalline silicon solar cells by considering inhomogeneous current distributions

    NASA Astrophysics Data System (ADS)

    Breitenstein, O.

    2013-09-01

    Solar cells made from multi- or mono-crystalline silicon wafers are the base of today's photovoltaics industry. These devices are essentially large-area semiconductor p-n junctions. Technically, solar cells have a relatively simple structure, and the theory of p-n junctions was established already decades ago. The generally accepted model for describing them is the so-called two-diode model. However, the current-voltage characteristics of industrial solar cells, particularly of that made from multi-crystalline silicon material, show significant deviations from established diode theory. These deviations regard the forward and the reverse dark characteristics as well as the relation between the illuminated characteristics to the dark ones. In the recent years it has been found that the characteristics of industrial solar cells can only be understood by taking into account local inhomogeneities of the dark current flow. Such inhomogeneities can be investigated by applying lock-in thermography techniques. Based on these and other investigations, meanwhile the basic properties of industrial silicon solar cells are well understood. This contribution reviews the most important experimental results leading to the present state of physical understanding of the dark and illuminated characteristics of multi-crystalline industrial solar cells. This analysis should be helpful for the continuing process of optimizing such cells for further increasing their energy conversion efficiency.

  15. A historical study to understand students’ current difficulties about RMS values

    NASA Astrophysics Data System (ADS)

    Khantine-Langlois, Françoise; Munier, Valérie

    2016-07-01

    Several studies show that students experience more and more difficulties managing the measurements of electrical values in alternating current and that they have trouble making links between theory and practice. They find it difficult to give meaning to root mean square (RMS; or effective) values, which are not understood as average values and are confused with instantaneous values. This shows that students do not clearly differentiate variable and direct currents. In this paper we try, with a historical study and a study of teaching the concept of RMS values, to understand students’ difficulties with this concept. In the first part we present an epistemological analysis of the concept of RMS values, showing that it is multifaceted and can be approached from different points of view. In the second part we analyse the evolution of French secondary school curricula and textbooks from the explicit introduction of variable currents to today, questioning the links between the evolution of the curricula and the evolution of the place of science and technology in our societies. We point out that the evolution of the curricula is linked to the social context and to the connections between science, technology and society, and also to the relationship with mathematics curricula. We show that alternating current is introduced earlier in the curriculum but has gradually lost all phenomenological description. This study allows us to better understand students’ difficulties and to discuss some implications for teaching.

  16. Dynamics of the Earth's Inner Magnetosphere and its Connection to the Ionosphere: Current Understanding and Challenges

    NASA Technical Reports Server (NTRS)

    Zheng, Yihua

    2010-01-01

    The Earth's inner magnetosphere, a vast volume in space spanning from 1.5 Re (Earth radii) to 10 Re, is a host to a variety of plasma populations (with energy from 1 eV to few MeV) and physical processes where most of which involve plasma and field coupling. As a gigantic particle accelerator, the inner magnetosphere includes three overlapping regions: the plasmasphere, the ring current, and the Van Allen radiation belt. The complex structures and dynamics of these regions are externally driven by solar activities and internally modulated by intricate interactions and coupling. As a major constituent of Space Weather, the inner magnetosphere is both scientifically intriguing and practically important to our society. In this presentation, I will discuss our recent results from the Comprehensive Ring Current Model, in the context of our current understanding of the inner magnetosphere in general and challenges ahead in making further progresses.

  17. Dynamics of the Earth's Inner Magnetosphere and Its Connection to the Ionosphere: Current Understanding and Challenges

    NASA Technical Reports Server (NTRS)

    Zheng, Yihua

    2011-01-01

    The Earth's inner magnetosphere, a vast volume in space spanning from 1.5 Re (Earth radii) to 10 Re, is a host to a variety of plasma populations (with energy from 1 eV to few MeV) and physical processes where most of which involve plasma and field coupling. As a gigantic particle accelerator, the inner magnetosphere includes three overlapping regions: the plasmasphere, the ring current, and the Van Allen radiation belt. The complex structures and dynamics of these regions are externally driven by solar activities and internally modulated by intricate interactions and coupling. As a major constituent of Space Weather, the inner magnetosphere is both scientifically intriguing and practically important to our society. In this presentation, I will discuss our recent results from the Comprehensive Ring Current Model, in the context of our current understanding of the inner magnetosphere in general and challenges ahead in making further progresses.

  18. Experimental Investigation and Fundamental Understanding of a Slowed UH-60A Rotor at High Advance Ratios

    NASA Technical Reports Server (NTRS)

    Datta, Anubhav; Yeo, Hyeonsoo; Norman, Thomas R.

    2011-01-01

    This paper describes and analyzes the measurements from a full-scale, slowed RPM, UH-60A rotor tested at the National Full-Scale Aerodynamics Complex 40- by 80- ft wind tunnel up to an advance ratio of 1.0. A comprehensive set of measurements, that includes performance, blade loads, hub loads and pressures/airloads makes this data set unique. The measurements reveal new and rich aeromechanical phenomena that are special to this exotic regime. These include reverse chord dynamic stall, retreating side impulse in pitch-link load, large inboard-outboard elastic twist differential, supersonic flow at low subsonic advancing tip Mach numbers, diminishing rotor forces yet dramatic build up of blade loads, and dramatic blade loads yet benign levels of vibratory hub loads. The objective of this research is the fundamental understanding of these unique aeromechanical phenomena. The intent is to provide useful knowledge for the design of high speed, high efficiency, slowed RPM rotors of the future and a challenging database for advanced analyses validation.

  19. Modeling Interfacial Glass-Water Reactions: Recent Advances and Current Limitations

    SciTech Connect

    Pierce, Eric M.; Frugier, Pierre; Criscenti, Louise J.; Kwon, Kideok D.; Kerisit, Sebastien N.

    2014-07-12

    Describing the reactions that occur at the glass-water interface and control the development of the altered layer constitutes one of the main scientific challenges impeding existing models from providing accurate radionuclide release estimates. Radionuclide release estimates are a critical component of the safety basis for geologic repositories. The altered layer (i.e., amorphous hydrated surface layer and crystalline reaction products) represents a complex region, both physically and chemically, sandwiched between two distinct boundaries pristine glass surface at the inner most interface and aqueous solution at the outer most interface. Computational models, spanning different length and time-scales, are currently being developed to improve our understanding of this complex and dynamic process with the goal of accurately describing the pore-scale changes that occur as the system evolves. These modeling approaches include geochemical simulations [i.e., classical reaction path simulations and glass reactivity in allowance for alteration layer (GRAAL) simulations], Monte Carlo simulations, and Molecular Dynamics methods. Finally, in this manuscript, we discuss the advances and limitations of each modeling approach placed in the context of the glass-water reaction and how collectively these approaches provide insights into the mechanisms that control the formation and evolution of altered layers.

  20. Modeling Interfacial Glass-Water Reactions: Recent Advances and Current Limitations

    SciTech Connect

    Pierce, Eric M.; Frugier, Pierre; Criscenti, Louise J.; Kwon, K. D.; Kerisit, Sebastien N.

    2014-07-12

    The altered layer (i.e., amorphous hydrated surface layer and crystalline reaction products)represents a complex region, both physically and chemically, sandwiched between two distinct boundaries - pristine glass surface at the inner most interface and aqueous solution at the outer most. The physico-chemical processes that control the development of this region have a significant impact on the long-term glass-water reaction. Computational models, spanning different length and time-scales, are currently being developed to improve our understanding of this complex and dynamic process with the goal of accurately describing the pore-scale changes that occur as the system evolves. These modeling approaches include Geochemical Reaction Path simulations, Glass Reactivity in Allowance for Alteration Layer simulations, Monte Carlo simulations, and Molecular Dynamics methods. Discussed in this manuscript are the advances and limitations of each modeling approach placed in the context of the glass water reaction and how collectively these approaches provide insights into the mechanisms that control the formation and evolution of altered layers; thus providing the fundamental data needed to develop pore-scale equations that enable more accurate predictions of nuclear waste glass corrosion in a geologic repository.

  1. Modeling Interfacial Glass-Water Reactions: Recent Advances and Current Limitations

    DOE PAGES

    Pierce, Eric M.; Frugier, Pierre; Criscenti, Louise J.; ...

    2014-07-12

    Describing the reactions that occur at the glass-water interface and control the development of the altered layer constitutes one of the main scientific challenges impeding existing models from providing accurate radionuclide release estimates. Radionuclide release estimates are a critical component of the safety basis for geologic repositories. The altered layer (i.e., amorphous hydrated surface layer and crystalline reaction products) represents a complex region, both physically and chemically, sandwiched between two distinct boundaries pristine glass surface at the inner most interface and aqueous solution at the outer most interface. Computational models, spanning different length and time-scales, are currently being developed tomore » improve our understanding of this complex and dynamic process with the goal of accurately describing the pore-scale changes that occur as the system evolves. These modeling approaches include geochemical simulations [i.e., classical reaction path simulations and glass reactivity in allowance for alteration layer (GRAAL) simulations], Monte Carlo simulations, and Molecular Dynamics methods. Finally, in this manuscript, we discuss the advances and limitations of each modeling approach placed in the context of the glass-water reaction and how collectively these approaches provide insights into the mechanisms that control the formation and evolution of altered layers.« less

  2. Recent advances in understanding the biomolecular basis of chronic beryllium disease: a review.

    PubMed

    McCleskey, T Mark; Buchner, Virginia; Field, R William; Scott, Brian L

    2009-01-01

    In this review we summarize the work conducted over the past decade that has advanced our knowledge of pulmonary diseases associated with exposure to beryllium that has provided a molecular-based understanding of the chemistry, immunopathology, and immunogenetics of beryllium toxicity. Beryllium is a strong and lightweight metal that generates and reflects neutrons, resists corrosion, is transparent to X-rays, and conducts electricity. Beryllium is one of the most toxic elements on the periodic table, eliciting in susceptible humans (a) an allergic immune response known as beryllium sensitization (BeS); (b) acute beryllium disease, an acutely toxic, pneumonitis-like lung condition resulting from exposure to high beryllium concentrations that are rarely seen in modern industry; and (c) chronic beryllium disease (CBD) following either high or very low levels of exposure. Because of its exceptional strength, stability, and heat-absorbing capability, beryllium is used in many important technologies in the modern world. In the early 1940s, beryllium was recognized as posing an occupational hazard in manufacturing and production settings. Although acute beryllium disease is now rare, beryllium is an insidious poison with a latent toxicity and the risk of developing CBD persists. Chronic beryllium disease-a systemic granulomatous lung disorder caused by a specific delayed immune response to beryllium within a few months to several decades after exposure-has been called the "unrecognized epidemic". Although not a disease in itself, BeS, the innate immune response to beryllium identified by an abnormal beryllium lymphocyte proliferation test result, is a population-based predictor of CBD. Genetic susceptibility to CBD is associated with alleles of the major histocompatibility gene, human leukocyte antigen DP (HLA-DP) containing glutamic acid at the 69th position of the beta chain (HLA-DPbeta-E69). Other genes are likely to be involved in the disease process, and research on

  3. Design and fundamental understanding of Minimum Quantity Lubrication (MQL) assisted grinding using advanced nanolubricants

    NASA Astrophysics Data System (ADS)

    Kalita, Parash

    Abrasive grinding is widely used across manufacturing industry for finishing parts and components requiring smooth superficial textures and precise dimensional tolerances and accuracy. Unlike any other machining operations, the complex thermo-mechanical processes during grinding produce excessive friction-induced energy consumption, heat, and intense contact seizures. Lubrication and cooling from grinding fluids is crucial in minimizing the deleterious effects of friction and heat to maximize the output part quality and process efficiency. The conventional flood grinding approach of an uneconomical application of large quantities of chemically active fluids has been found ineffective to provide sufficient lubrication and produces waste streams and pollutants that are hazardous to human health and environment. Application of Minimum Quantity Lubrication (MQL) that cuts the volumetric fluid consumption by 3-4 orders of magnitude have been extensively researched in grinding as a high-productivity and environmentally-sustainable alternative to the conventional flood method. However, the lubrication performance and productivity of MQL technique with current fluids has been critically challenged by the extreme thermo-mechanical conditions of abrasive grinding. In this research, an MQL system based on advanced nanolubricants has been proposed to address the current thermo-mechanical challenges of MQL grinding and improve its productivity. The nanolubricants were composed of inorganic Molybdenum Disulphide nanoparticles (≈ 200 nm) intercalated with organic macromolecules of EP/AW property, dispersed in straight (base) oils---mineral-based paraffin and vegetable-based soybean oil. After feasibility investigations into the grindability of cast iron using MQL with nanolubricants, this research focused on the fundamental understanding of tribological behavior and lubricating mechanisms of nanolubricants as a method to improve the productivity of MQL-assisted surface grinding

  4. Use It or Lose It: Advances in Our Understanding of Terrestrial Nitrogen Retention and Loss (Invited)

    NASA Astrophysics Data System (ADS)

    Silver, W. L.; Yang, W. H.

    2013-12-01

    Understanding of the terrestrial nitrogen (N) cycle has grown over the last decade to include a variety of pathways that have the potential to either retain N in the ecosystem or result in losses to the atmosphere or groundwater. Early work has described the mechanics of these N transformations, but the relevance of these processes to ecosystem, regional, or global scale N cycling has not been well quantified. In this study, we review advances in our understanding of the terrestrial N cycle, and focus on three pathways with particular relevance to N retention and loss: dissimilatory nitrate and nitrite reduction to ammonium (DNRA), anaerobic ammonium oxidation (annamox), and anaerobic ammonium oxidation coupled to iron reduction (Feammox). We discuss the role of these processes in the microbial N economy (sensu Burgin et al. 2011) of the terrestrial N cycle, the environmental and ecological constraints, and relationships with other key biogeochemical cycles. We also discuss recent advances in analytical approaches that have improved our ability to detect these and related N fluxes in terrestrial ecosystems. Finally, we present a scaling exercise that identifies the potential importance of these pathways for N retention and loss across a range of spatial and temporal scales, and discuss their significance in terms of N limitation to net primary productivity, N leaching to groundwater, and the release of reactive N gases to the atmosphere.

  5. Advances in understanding and treating liver diseases during pregnancy: A review.

    PubMed

    Kamimura, Kenya; Abe, Hiroyuki; Kawai, Hirokazu; Kamimura, Hiroteru; Kobayashi, Yuji; Nomoto, Minoru; Aoyagi, Yutaka; Terai, Shuji

    2015-05-07

    Liver disease in pregnancy is rare but pregnancy-related liver diseases may cause threat to fetal and maternal survival. It includes pre-eclampsia; eclampsia; haemolysis, elevated liver enzymes, and low platelets syndrome; acute fatty liver of pregnancy; hyperemesis gravidarum; and intrahepatic cholestasis of pregnancy. Recent basic researches have shown the various etiologies involved in this disease entity. With these advances, rapid diagnosis is essential for severe cases since the decision of immediate delivery is important for maternal and fetal survival. The other therapeutic options have also been shown in recent reports based on the clinical trials and cooperation and information sharing between hepatologist and gynecologist is important for timely therapeutic intervention. Therefore, correct understandings of diseases and differential diagnosis from the pre-existing and co-incidental liver diseases during the pregnancy will help to achieve better prognosis. Therefore, here we review and summarized recent advances in understanding the etiologies, clinical courses and management of liver disease in pregnancy. This information will contribute to physicians for diagnosis of disease and optimum management of patients.

  6. Choroid plexus papillomas: advances in molecular biology and understanding of tumorigenesis.

    PubMed

    Safaee, Michael; Oh, Michael C; Bloch, Orin; Sun, Matthew Z; Kaur, Gurvinder; Auguste, Kurtis I; Tihan, Tarik; Parsa, Andrew T

    2013-03-01

    Choroid plexus papillomas are rare, benign tumors originating from the choroid plexus. Although generally found within the ventricular system, they can arise ectopically in the brain parenchyma or disseminate throughout the neuraxis. We sought to review recent advances in our understanding of the molecular biology and oncogenic pathways associated with this disease. A comprehensive PubMed literature review was conducted to identify manuscripts discussing the clinical, molecular, and genetic features of choroid plexus papillomas. Articles concerning diagnosis, treatment, and long-term patient outcomes were also reviewed. The introduction of atypical choroid plexus papilloma as a distinct entity has increased the need for accurate histopathologic diagnosis. Advances in immunohistochemical staining have improved our ability to differentiate choroid plexus papillomas from other intracranial tumors or metastatic lesions using combinations of key markers and mitotic indices. Recent findings have implicated Notch3 signaling, the transcription factor TWIST1, platelet-derived growth factor receptor, and the tumor necrosis factor-related apoptosis-inducing ligand pathway in choroid plexus papilloma tumorigenesis. A combination of commonly occurring chromosomal duplications and deletions has also been identified. Surgical resection remains the standard of care, although chemotherapy and radiotherapy may be considered for recurrent or metastatic lesions. While generally considered benign, these tumors possess a complex biology that sheds insight into other choroid plexus tumors, particularly malignant choroid plexus carcinomas. Improving our understanding of the molecular biology, genetics, and oncogenic pathways associated with this tumor will allow for the development of targeted therapies and improved outcomes for patients with this disease.

  7. Current Understanding of Metformin Effect on the Control of Hyperglycemia in Diabetes

    PubMed Central

    An, Hongying; He, Ling

    2016-01-01

    Metformin is a first line oral anti-diabetic agent that has been used clinically to treat patients with type 2 diabetes for over 60 years. Due to its efficacy in therapy and affordable price, metformin is taken by over 150 million people each year. Metformin improves hyperglycemia mainly through the suppression of hepatic gluconeogenesis along with the improvement of insulin signaling. However, its mechanism of action remains partially understood and controversial, especially in regards to the role of AMPK in metformin’s action and the mechanism of AMPK activation. In this review, we will discuss recent advances in the understanding of metformin’s suppression of hepatic glucose production and the mechanism related to the improvement of insulin signaling. PMID:26743209

  8. Advancing Capabilities for Understanding the Earth System Through Intelligent Systems, the NSF Perspective

    NASA Astrophysics Data System (ADS)

    Gil, Y.; Zanzerkia, E. E.; Munoz-Avila, H.

    2015-12-01

    The National Science Foundation (NSF) Directorate for Geosciences (GEO) and Directorate for Computer and Information Science (CISE) acknowledge the significant scientific challenges required to understand the fundamental processes of the Earth system, within the atmospheric and geospace, Earth, ocean and polar sciences, and across those boundaries. A broad view of the opportunities and directions for GEO are described in the report "Dynamic Earth: GEO imperative and Frontiers 2015-2020." Many of the aspects of geosciences research, highlighted both in this document and other community grand challenges, pose novel problems for researchers in intelligent systems. Geosciences research will require solutions for data-intensive science, advanced computational capabilities, and transformative concepts for visualizing, using, analyzing and understanding geo phenomena and data. Opportunities for the scientific community to engage in addressing these challenges are available and being developed through NSF's portfolio of investments and activities. The NSF-wide initiative, Cyberinfrastructure Framework for 21st Century Science and Engineering (CIF21), looks to accelerate research and education through new capabilities in data, computation, software and other aspects of cyberinfrastructure. EarthCube, a joint program between GEO and the Advanced Cyberinfrastructure Division, aims to create a well-connected and facile environment to share data and knowledge in an open, transparent, and inclusive manner, thus accelerating our ability to understand and predict the Earth system. EarthCube's mission opens an opportunity for collaborative research on novel information systems enhancing and supporting geosciences research efforts. NSF encourages true, collaborative partnerships between scientists in computer sciences and the geosciences to meet these challenges.

  9. Actuarial senescence in a long-lived orchid challenges our current understanding of ageing.

    PubMed

    Dahlgren, Johan Petter; Colchero, Fernando; Jones, Owen R; Øien, Dag-Inge; Moen, Asbjørn; Sletvold, Nina

    2016-11-16

    The dominant evolutionary theory of actuarial senescence-an increase in death rate with advancing age-is based on the concept of a germ cell line that is separated from the somatic cells early in life. However, such a separation is not clear in all organisms. This has been suggested to explain the paucity of evidence for actuarial senescence in plants. We used a 32 year study of Dactylorhiza lapponica that replaces its organs each growing season, to test whether individuals of this tuberous orchid senesce. We performed a Bayesian survival trajectory analysis accounting for reproductive investment, for individuals under two types of land use, in two climatic regions. The mortality trajectory was best approximated by a Weibull model, showing clear actuarial senescence. Rates of senescence in this model declined with advancing age, but were slightly higher in mown plots and in the more benign climatic region. At older ages, senescence was evident only when accounting for a positive effect of reproductive investment on mortality. Our results demonstrate actuarial senescence as well as a survival-reproduction trade-off in plants, and indicate that environmental context may influence senescence rates. This knowledge is crucial for understanding the evolution of demographic senescence and for models of plant population dynamics.

  10. Impact of off-axis RF current drive on JET advanced scenarios

    NASA Astrophysics Data System (ADS)

    Garcia, J.; Giruzzi, G.; Litaudon, X.; Mailloux, J.; Artaud, J. F.; Basiuk, V.; Decker, J.; Imbeaux, F.; Peysson, Y.; Schneider, M.; JET EFDA contributors, the

    2011-07-01

    The impact of the radio-frequency heating and current drive systems on JET advanced scenarios at high density is analysed by means of the CRONOS suite of codes for integrated tokamak modelling. In particular, the performance of the proposed electron cyclotron heating and current drive system for JET is evaluated. As a first step, the code is applied in the interpretative mode to analyse two high power advanced scenario discharges of JET, in order to validate both the heating and current drive computational modules and the overall simulation procedure. Then, JET advanced scenarios are studied by predictive simulations on the basis of previous results. The simulations show that lower hybrid and electron cyclotron heating and current drive systems can together provide off-axis current in order to create and sustain steady-state scenarios on JET at high density. These results give deeper insight into the future advanced scenarios in ITER, since they establish a clear way to test some key aspects of them in present day devices such as JET.

  11. Performance of current measurement system in poloidal field power supply for Experimental Advanced Superconducting Tokamak

    NASA Astrophysics Data System (ADS)

    Liu, D. M.; Li, J.; Wan, B. N.; Lu, Z.; Wang, L. S.; Jiang, L.; Lu, C. H.; Huang, J.

    2016-11-01

    As one of the core subsystems of the Experimental Advanced Superconducting Tokamak (EAST), the poloidal field power system supplies energy to EAST's superconducting coils. To measure the converter current in the poloidal field power system, a current measurement system has been designed. The proposed measurement system is composed of a Rogowski coil and a newly designed integrator. The results of the resistor-inductor-capacitor discharge test and the converter equal current test show that the current measurement system provides good reliability and stability, and the maximum error of the proposed system is less than 1%.

  12. Performance of current measurement system in poloidal field power supply for Experimental Advanced Superconducting Tokamak.

    PubMed

    Liu, D M; Li, J; Wan, B N; Lu, Z; Wang, L S; Jiang, L; Lu, C H; Huang, J

    2016-11-01

    As one of the core subsystems of the Experimental Advanced Superconducting Tokamak (EAST), the poloidal field power system supplies energy to EAST's superconducting coils. To measure the converter current in the poloidal field power system, a current measurement system has been designed. The proposed measurement system is composed of a Rogowski coil and a newly designed integrator. The results of the resistor-inductor-capacitor discharge test and the converter equal current test show that the current measurement system provides good reliability and stability, and the maximum error of the proposed system is less than 1%.

  13. Advancing our understanding of functional genome organisation through studies in the fission yeast.

    PubMed

    Olsson, Ida; Bjerling, Pernilla

    2011-02-01

    Significant progress has been made in understanding the functional organisation of the cell nucleus. Still many questions remain to be answered about the relationship between the spatial organisation of the nucleus and the regulation of the genome function. There are many conflicting data in the field making it very difficult to merge published results on mammalian cells into one model on subnuclear chromatin organisation. The fission yeast, Schizosaccharomyces pombe, over the last decades has emerged as a valuable model organism in understanding basic biological mechanisms, especially the cell cycle and chromosome biology. In this review we describe and compare the nuclear organisation in mammalian and fission yeast cells. We believe that fission yeast is a good tool to resolve at least some of the contradictions and unanswered questions concerning functional nuclear architecture, since S. pombe has chromosomes structurally similar to that of human. S. pombe also has the advantage over higher eukaryotes in that the genome can easily be manipulated via homologous recombination making it possible to integrate the tools needed for visualisation of chromosomes using live-cell microscopy. Classical genetic experiments can be used to elucidate what factors are involved in a certain mechanism. The knowledge we have gained during the last few years indicates similarities between the genome organisation in fission yeast and mammalian cells. We therefore propose the use of fission yeast for further advancement of our understanding of functional nuclear organisation.

  14. Dhat syndrome: Evolution of concept, current understanding, and need of an integrated approach

    PubMed Central

    Kar, Sujita Kumar; Sarkar, Siddharth

    2015-01-01

    Dhat syndrome has often been construed as a culture-bound sexual neurosis of the Indian subcontinent. Symptoms similar to that of Dhat syndrome has been described in other cultures across different time periods. The present paper looks at the evolution of the concept of Dhat syndrome in India. The review also takes an overview of the current understanding of this syndrome in terms of nosological status as a distinct entity and its “culture-bound” status. The narrative finally attempts to discuss the integrated approach for the treatment of this disorder. PMID:26538854

  15. Advances in understanding the molecular basis of the first steps in color vision

    PubMed Central

    Hofmann, Lukas; Palczewski, Krzysztof

    2015-01-01

    Serving as one of our primary environmental inputs, vision is the most sophisticated sensory system in humans. Here, we present recent findings derived from energetics, genetics and physiology that provide a more advanced understanding of color perception in mammals. Energetics of cis–trans isomerization of 11-cis-retinal accounts for color perception in the narrow region of the electromagnetic spectrum and how human eyes can absorb light in the near infrared (IR) range. Structural homology models of visual pigments reveal complex interactions of the protein moieties with the light sensitive chromophore 11-cis-retinal and that certain color blinding mutations impair secondary structural elements of these G protein-coupled receptors (GPCRs). Finally, we identify unsolved critical aspects of color tuning that require future investigation. PMID:26187035

  16. Understanding requirements of novel healthcare information systems for management of advanced prostate cancer.

    PubMed

    Wagholikar, Amol S; Fung, Maggie; Nelson, Colleen C

    2012-01-01

    Effective management of chronic diseases is a global health priority. A healthcare information system offers opportunities to address challenges of chronic disease management. However, the requirements of health information systems are often not well understood. The accuracy of requirements has a direct impact on the successful design and implementation of a health information system. Our research describes methods used to understand the requirements of health information systems for advanced prostate cancer management. The research conducted a survey to identify heterogeneous sources of clinical records. Our research showed that the General Practitioner was the common source of patient's clinical records (41%) followed by the Urologist (14%) and other clinicians (14%). Our research describes a method to identify diverse data sources and proposes a novel patient journey browser prototype that integrates disparate data sources.

  17. The impact of recent advances in laboratory astrophysics on our understanding of the cosmos.

    PubMed

    Savin, D W; Brickhouse, N S; Cowan, J J; Drake, R P; Federman, S R; Ferland, G J; Frank, A; Gudipati, M S; Haxton, W C; Herbst, E; Profumo, S; Salama, F; Ziurys, L M; Zweibel, E G

    2012-03-01

    An emerging theme in modern astrophysics is the connection between astronomical observations and the underlying physical phenomena that drive our cosmos. Both the mechanisms responsible for the observed astrophysical phenomena and the tools used to probe such phenomena-the radiation and particle spectra we observe-have their roots in atomic, molecular, condensed matter, plasma, nuclear and particle physics. Chemistry is implicitly included in both molecular and condensed matter physics. This connection is the theme of the present report, which provides a broad, though non-exhaustive, overview of progress in our understanding of the cosmos resulting from recent theoretical and experimental advances in what is commonly called laboratory astrophysics. This work, carried out by a diverse community of laboratory astrophysicists, is increasingly important as astrophysics transitions into an era of precise measurement and high fidelity modeling.

  18. Advances in understanding the molecular basis of the first steps in color vision.

    PubMed

    Hofmann, Lukas; Palczewski, Krzysztof

    2015-11-01

    Serving as one of our primary environmental inputs, vision is the most sophisticated sensory system in humans. Here, we present recent findings derived from energetics, genetics and physiology that provide a more advanced understanding of color perception in mammals. Energetics of cis-trans isomerization of 11-cis-retinal accounts for color perception in the narrow region of the electromagnetic spectrum and how human eyes can absorb light in the near infrared (IR) range. Structural homology models of visual pigments reveal complex interactions of the protein moieties with the light sensitive chromophore 11-cis-retinal and that certain color blinding mutations impair secondary structural elements of these G protein-coupled receptors (GPCRs). Finally, we identify unsolved critical aspects of color tuning that require future investigation.

  19. [Advances in understanding Drosophila salivary gland polytene chromosome and its applications in genetics teaching].

    PubMed

    Gang, Li; Fanguo, Chen

    2015-06-01

    Drosophila salivary gland polytene chromosome, one of the three classical chromosomes with remarkable characteristics, has been used as an outstanding model for a variety of genetic studies since 1934. The greatest contribution of this model to genetics has been providing extraordinary angle of view in studying interphase chromosome structure and gene expression regulation. Additionally, it has been extensively used to understand some special genetic phenomena, such as dosage compensation and position-effect variegation. In this paper, we briefly review the advances in the study of Drosophila salivary gland chromosome, and try to systematically and effectively introduce this model system into genetics teaching practice in order to steer and inspire students' interest in genetics.

  20. Advancing understanding of microbial bioenergy conversion processes by activity-based protein profiling

    SciTech Connect

    Liu, Yun; Fredrickson, James K.; Sadler, Natalie C.; Nandhikonda, Premchendar; Smith, Richard D.; Wright, Aaron T.

    2015-09-25

    Here, the development of renewable biofuels is a global priority, but success will require novel technologies that greatly improve our understanding of microbial systems biology. An approach with great promise in enabling functional characterization of microbes is activity-based protein profiling (ABPP), which employs chemical probes to directly measure enzyme function in discrete enzyme classes in vivo and/or in vitro, thereby facilitating the rapid discovery of new biocatalysts and enabling much improved biofuel production platforms. We review general design strategies in ABPP, and highlight recent advances that are or could be pivotal to biofuels processes including applications of ABPP to cellulosic bioethanol, biodiesel, and phototrophic production of hydrocarbons. We also examine the key challenges and opportunities of ABPP in renewable biofuels research. The integration of ABPP with molecular and systems biology approaches will shed new insight on the catalytic and regulatory mechanisms of functional enzymes and their synergistic effects in the field of biofuels production.

  1. Advanced simulation capability for environmental management - current status and future applications

    SciTech Connect

    Freshley, Mark; Scheibe, Timothy; Robinson, Bruce; Moulton, J. David; Dixon, Paul; Marble, Justin; Gerdes, Kurt; Stockton, Tom; Seitz, Roger; Black, Paul

    2013-07-01

    The U.S. Department of Energy (US DOE) Office of Environmental Management (EM), Office of Soil and Groundwater (EM-12), is supporting development of the Advanced Simulation Capability for Environmental Management (ASCEM). ASCEM is a state-of-the-art scientific tool and approach that is currently aimed at understanding and predicting contaminant fate and transport in natural and engineered systems. ASCEM is a modular and open source high-performance computing tool. It will be used to facilitate integrated approaches to modeling and site characterization, and provide robust and standardized assessments of performance and risk for EM cleanup and closure activities. The ASCEM project continues to make significant progress in development of capabilities, with current emphasis on integration of capabilities in FY12. Capability development is occurring for both the Platform and Integrated Tool-sets and High-Performance Computing (HPC) multi-process simulator. The Platform capabilities provide the user interface and tools for end-to-end model development, starting with definition of the conceptual model, management of data for model input, model calibration and uncertainty analysis, and processing of model output, including visualization. The HPC capabilities target increased functionality of process model representations, tool-sets for interaction with Platform, and verification and model confidence testing. The integration of the Platform and HPC capabilities were tested and evaluated for EM applications in a set of demonstrations as part of Site Applications Thrust Area activities in 2012. The current maturity of the ASCEM computational and analysis capabilities has afforded the opportunity for collaborative efforts to develop decision analysis tools to support and optimize radioactive waste disposal. Recent advances in computerized decision analysis frameworks provide the perfect opportunity to bring this capability into ASCEM. This will allow radioactive waste

  2. Investigating animal cognition with the Aesop's Fable paradigm: Current understanding and future directions

    PubMed Central

    Jelbert, Sarah A; Taylor, Alex H; Gray, Russell D

    2015-01-01

    The Aesop's Fable paradigm – in which subjects drop stones into tubes of water to obtain floating out-of-reach rewards – has been used to assess causal understanding in rooks, crows, jays and human children. To date, the performance of corvids suggests that they can recognize the functional properties of a variety of objects including size, weight and solidity, and they seem to be more capable of learning from causal information than arbitrary information. However, 2 alternative explanations for their performance have yet to be ruled out. The perceptual-motor feedback hypothesis suggests that subjects may attend solely to the movement of the reward, repeating actions which bring the reward closer, while the object-bias hypothesis suggests that subjects could pass certain tasks by preferring to handle objects that resemble natural stones. Here we review our current understanding of performance on the Aesop's Fable tasks, and suggest that studies controlling for feedback and object preferences will help us determine exactly what animals understand about the cause and effect of water displacement. PMID:26478777

  3. Earth Observing-1 Advanced Land Imager: Dark Current and Noise Characterization and Anomalous Detectors

    NASA Technical Reports Server (NTRS)

    Mendenhall, J. A.

    2001-01-01

    The dark current and noise characteristics of the Earth Observing-1 Advanced Land Imager measured during ground calibration at MIT Lincoln Laboratory are presented. Data were collected for the nominal focal plane operating temperature of 220 K as well as supplemental operating temperatures (215 and 225 K). Dark current baseline values are provided, and noise characterization includes the evaluation of white, coherent, low frequency, and high frequency components. Finally, anomalous detectors, characterized by unusual dark current, noise, gain, or cross-talk properties are investigated.

  4. Recent advances in understanding hypertension development in sub-Saharan Africa.

    PubMed

    Schutte, A E; Botha, S; Fourie, C M T; Gafane-Matemane, L F; Kruger, R; Lammertyn, L; Malan, L; Mels, C M C; Schutte, R; Smith, W; van Rooyen, J M; Ware, L J; Huisman, H W

    2017-03-23

    Consistent reports indicate that hypertension is a particularly common finding in black populations. Hypertension occurs at younger ages and is often more severe in terms of blood pressure levels and organ damage than in whites, resulting in a higher incidence of cardiovascular disease and mortality. This review provides an outline of recent advances in the pathophysiological understanding of blood pressure elevation and the consequences thereof in black populations in Africa. This is set against the backdrop of populations undergoing demanding and rapid demographic transition, where infection with the human immunodeficiency virus predominates, and where under and over-nutrition coexist. Collectively, recent findings from Africa illustrate an increased lifetime risk to hypertension from foetal life onwards. From young ages black populations display early endothelial dysfunction, increased vascular tone and reactivity, microvascular structural adaptions as well as increased aortic stiffness resulting in elevated central and brachial blood pressures during the day and night, when compared to whites. Together with knowledge on the contributions of sympathetic activation and abnormal renal sodium handling, these pathophysiological adaptations result in subclinical and clinical organ damage at younger ages. This overall enhanced understanding on the determinants of blood pressure elevation in blacks encourages (a) novel approaches to assess and manage hypertension in Africa better, (b) further scientific discovery to develop more effective prevention and treatment strategies and

  5. Advances in understanding tumour evolution through single-cell sequencing.

    PubMed

    Kuipers, Jack; Jahn, Katharina; Beerenwinkel, Niko

    2017-02-11

    The mutational heterogeneity observed within tumours poses additional challenges to the development of effective cancer treatments. A thorough understanding of a tumour's subclonal composition and its mutational history is essential to open up the design of treatments tailored to individual patients. Comparative studies on a large number of tumours permit the identification of mutational patterns which may refine forecasts of cancer progression, response to treatment and metastatic potential. The composition of tumours is shaped by evolutionary processes. Recent advances in next-generation sequencing offer the possibility to analyse the evolutionary history and accompanying heterogeneity of tumours at an unprecedented resolution, by sequencing single cells. New computational challenges arise when moving from bulk to single-cell sequencing data, leading to the development of novel modelling frameworks. In this review, we present the state of the art methods for understanding the phylogeny encoded in bulk or single-cell sequencing data, and highlight future directions for developing more comprehensive and informative pictures of tumour evolution. This article is part of a Special Issue entitled: Evolutionary principles - heterogeneity in cancer?, edited by Dr. Robert A. Gatenby.

  6. Gerontology found me: gaining understanding of advanced practice nurses in geriatrics.

    PubMed

    Campbell-Detrixhe, Dia D; Grassley, Jane S; Zeigler, Vicki L

    2013-10-01

    Examining the meanings of the experiences of advanced practice nurses (APNs) who chose to work with older adults and why they continue to work with this population was the focus of this hermeneutic qualitative research study. Twelve geriatric APNs currently practicing in two South Central states were interviewed using an open-ended interview guide. Using Gadamerian hermeneutics, the researchers identified Gerontology Found Me as the significant expression that reflected the fundamental meaning of the experience as a whole. Four themes emerged that further described the meanings of the participants' personal, educational, and professional experiences: Becoming a Gerontology Nurse, Being a Gerontology Nurse, Belonging to Gerontology, and Bringing Others to Gerontology. This study concluded that APNs' personal and professional experiences were more influential than educational experiences to become geriatric nurses, and having these personal and professional experiences of being in relationship with older individuals further contributed to their choice of gerontology.

  7. Toward understanding of differences in current cloud retrievals of ARM ground-based measurements

    SciTech Connect

    Zhao C.; Dunn M.; Xie, S.; Klein, S. A.; Protat, A.; Shupe, M. D.; McFarlane, S. A.; Comstock, J. M.; Delanoë, J.; Deng, M.; Hogan, R. J.; Huang, D.; Jensen, M. P.; Mace, G. G.; McCoy, R.; O’Connor, E. J.; Turner, D. D.; Wang, Z.

    2012-05-30

    Accurate observations of cloud microphysical properties are needed for evaluating and improving the representation of cloud processes in climate models and better estimate of the Earth radiative budget. However, large differences are found in current cloud products retrieved from ground-based remote sensing measurements using various retrieval algorithms. Understanding the differences is an important step to address uncertainties in the cloud retrievals. In this study, an in-depth analysis of nine existing ground-based cloud retrievals using ARM remote sensing measurements is carried out. We place emphasis on boundary layer overcast clouds and high level ice clouds, which are the focus of many current retrieval development efforts due to their radiative importance and relatively simple structure. Large systematic discrepancies in cloud microphysical properties are found in these two types of clouds among the nine cloud retrieval products, particularly for the cloud liquid and ice particle effective radius. Note that the differences among some retrieval products are even larger than the prescribed uncertainties reported by the retrieval algorithm developers. It is shown that most of these large differences have their roots in the retrieval theoretical bases, assumptions, as well as input and constraint parameters. This study suggests the need to further validate current retrieval theories and assumptions and even the development of new retrieval algorithms with more observations under different cloud regimes.

  8. Toward Understanding of Differences in Current Cloud Retrievals of ARM Ground-based Measurements

    SciTech Connect

    Zhao, Chuanfeng; Xie, Shaocheng; Klein, Stephen A.; Protat, Alain; Shupe, Matthew D.; McFarlane, Sally A.; Comstock, Jennifer M.; Delanoe, Julien; Deng, Min; Dunn, Maureen; Hogan, Robin; Huang, Dong; Jensen, Michael; Mace, Gerald G.; McCoy, Renata; O'Conner, Ewan J.; Turner, Dave; Wang, Zhien

    2012-05-30

    Accurate observations of cloud microphysical properties are needed for evaluating and improving the representation of cloud processes in climate models. However, large differences are found in current cloud products retrieved from ground-based remote sensing measurements using various retrieval algorithms. Understanding the differences is an important step to address uncertainties in the cloud retrievals. In this study, an in-depth analysis of nine existing ground-based cloud retrievals using ARM remote sensing measurements is carried out. We place emphasize on boundary layer overcast clouds and high level ice clouds, which are the focus of many current retrieval development efforts due to their radiative importance and relatively simple structure. Large systematic discrepancies in cloud microphysical properties are found in these two types of clouds among the nine cloud retrieval products, particularly for the cloud liquid and ice effective radius. It is shown that most of these large differences have their roots in the retrieval algorithms used by these cloud products, including the retrieval theoretical bases, assumptions, as well as input and constraint parameters. This study suggests the need to further validate current retrieval theories and assumptions and even the development of new retrieval algorithms with more observations under different cloud regimes.

  9. Health Self-management Among Older Prisoners: Current Understandings and Directions for Policy, Practice, and Research.

    PubMed

    Ruggiano, Nicole; Lukic, Andreja; Blowers, Anita; Doerner, Jill

    The population of aging prisoners has increased significantly over the past several decades, resulting in concerns about the criminal justice system's ability to address the needs of prisoners and parolees with chronic health conditions. This is troubling, given the health disparities among incarcerated populations. Health self-management has become a strategy within the community-based health care industry to improve health services and outcomes while reducing health care costs for nonincarcerated individuals with chronic conditions. However, to date little research has focused on the practice or promotion of health self-management among current and former incarcerated populations. This article highlights current understandings about chronic health self-management among older prisoners and parolees, with an emphasis on the potential benefits and current challenges in promoting their health self-management practices. Finally, specific recommendations are made for promoting health self-management for these populations through social work practice, policy advocacy, and research to achieve goals in improving health outcomes and reducing healthcare costs.

  10. Relationship between Added Sugars Consumption and Chronic Disease Risk Factors: Current Understanding

    PubMed Central

    Rippe, James M.; Angelopoulos, Theodore J.

    2016-01-01

    Added sugars are a controversial and hotly debated topic. Consumption of added sugars has been implicated in increased risk of a variety of chronic diseases including obesity, cardiovascular disease, diabetes and non-alcoholic fatty liver disease (NAFLD) as well as cognitive decline and even some cancers. Support for these putative associations has been challenged, however, on a variety of fronts. The purpose of the current review is to summarize high impact evidence including systematic reviews, meta-analyses, and randomized controlled trials (RCTs), in an attempt to provide an overview of current evidence related to added sugars and health considerations. This paper is an extension of a symposium held at the Experimental Biology 2015 conference entitled “Sweeteners and Health: Current Understandings, Controversies, Recent Research Findings and Directions for Future Research”. We conclude based on high quality evidence from randomized controlled trials (RCT), systematic reviews and meta-analyses of cohort studies that singling out added sugars as unique culprits for metabolically based diseases such as obesity, diabetes and cardiovascular disease appears inconsistent with modern, high quality evidence and is very unlikely to yield health benefits. While it is prudent to consume added sugars in moderation, the reduction of these components of the diet without other reductions of caloric sources seems unlikely to achieve any meaningful benefit. PMID:27827899

  11. Bioremediation and Biodegradation: Current Advances in Reducing Toxicity, Exposure and Environmental Consequences

    SciTech Connect

    Kukor, J. J.; Young, L.

    2003-04-01

    Topics discussed at the conference included Approaches to Overcome Bioavailability Limitations in Bioremediation; New Discoveries in Microbial Degradation of Persistent Environmental Contaminants; Biological Activity and Potential Toxicity of the Products of Biodegradation; New Methods to Monitor and Assess the Effectiveness of Remediation Processes; and Strategies for Remediation of Mixed Contaminants. The United States has thousands of hazardous waste sites, most of which are a legacy of many decades of industrial development, mining, manufacturing and military activities. There is considerable uncertainty about the health risks of these sites, such as a lack of understanding about the spectrum of health effects that could result from exposure to hazardous substances and the unique toxicity of these substances to children or the developing fetus. In addition to these kinds of knowledge gaps, the fate and transport of hazardous wastes in soil, surface water and ground water are poorly understood, making it difficult to predict exposures. Moreover, cleaning up hazardous wastes has proven costly and difficult; thus, there is a need for advanced technologies to decrease or eliminate contamination from soil, surface water, and ground water. Since biodegradative processes and bioremediation solutions form a large part of the current science and technology directed at treatment of environmental contaminants at hazardous waste sites, and since there has been an explosion of cutting-edge basic research in these areas over the past several years, it was an opportune time for a meeting of this type. Representatives from the EPA as well as many of the other Federal agencies that helped fund the conference were also in attendance, providing an opportunity for discussions from the regulatory perspective of hazardous site remediation, as well as from the scientific discovery side.

  12. Recent Advances in Understanding the Molecular Mechanisms Regulating the Root System Response to Phosphate Deficiency in Arabidopsis

    PubMed Central

    Bouain, Nadia; Doumas, Patrick; Rouached, Hatem

    2016-01-01

    Phosphorus (P) is an essential macronutrient for plant growth and development. Inorganic phosphate (Pi) is the major form of P taken up from the soil by plant roots. It is well established that under Pi deficiency condition, plant roots undergo striking morphological changes; mainly a reduction in primary root length while increase in lateral root length as well as root hair length and density. This typical phenotypic change reflects complex interactions with other nutrients such as iron, and involves the activity of a large spectrum of plant hormones. Although, several key proteins involved in the regulation of root growth under Pi-deficiency have been identified in Arabidopsis, how plants adapt roots system architecture in response to Pi availability remains an open question. In the current post-genomic era, state of the art technologies like high-throughput phenotyping and sequencing platforms,“omics” methods, together with the widespread use of system biology and genome-wide association studies will help to elucidate the genetic architectures of root growth on different Pi regimes. It is clear that the large-scale characterization of molecular systems will improve our understanding of nutrient stress phenotype and biology. Herein, we summarize the recent advances and future directions towards a better understanding of Arabidopsis root developmental programs functional under Pi deficiency. Such a progress is necessary to devise strategies to improve the Pi use efficiency in plants that is an important issue for agriculture. PMID:27499680

  13. DARPA Advanced High Current Density Cathodes for Defense Applications: Development Phase

    DTIC Science & Technology

    1993-03-01

    Relevant approximations are applied to these exact solutions in order to extract the general thermodynamic properties without the need for the full...understanding that has been developed in terms of the properties of the advanced cathode materials, the fabrication and optimization processing, and the design...demonstrated that the parameters a and P3 are not constants, and that when a simple account of realistic material properties is included, the variation of a and

  14. Current Understanding of the Correlation of Lignin Structure with Biomass Recalcitrance

    PubMed Central

    Li, Mi; Pu, Yunqiao; Ragauskas, Arthur J.

    2016-01-01

    Lignin, a complex aromatic polymer in terrestrial plants, contributes significantly to biomass recalcitrance to microbial and/or enzymatic deconstruction. To reduce biomass recalcitrance, substantial endeavors have been exerted on pretreatment and lignin engineering in the past few decades. Lignin removal and/or alteration of lignin structure have been shown to result in reduced biomass recalcitrance with improved cell wall digestibility. While high lignin content is usually a barrier to a cost-efficient application of bioresources to biofuels, the direct correlation of lignin structure and its concomitant properties with biomass remains unclear due to the complexity of cell wall and lignin structure. Advancement in application of biorefinery to production of biofuels, chemicals, and bio-derived materials necessitates a fundamental understanding of the relationship of lignin structure and biomass recalcitrance. In this mini-review, we focus on recent investigations on the influence of lignin chemical properties on bioprocessability—pretreatment and enzymatic hydrolysis of biomass. Specifically, lignin-enzyme interactions and the effects of lignin compositional units, hydroxycinnamates, and lignin functional groups on biomass recalcitrance have been highlighted, which will be useful not only in addressing biomass recalcitrance but also in deploying renewable lignocelluloses efficiently. PMID:27917379

  15. Current understanding of the correlation of lignin structure with biomass recalcitrance

    SciTech Connect

    Li, Mi; Pu, Yunqiao; Ragauskas, Arthur J.

    2016-11-18

    Lignin, a complex aromatic polymer in terrestrial plants, contributes significantly to biomass recalcitrance to microbial and/or enzymatic deconstruction. To reduce biomass recalcitrance, substantial endeavors have been exerted on pretreatment and lignin engineering in the past few decades. Lignin removal and/or alteration of lignin structure have been shown to result in reduced biomass recalcitrance with improved cell wall digestibility. While high lignin content is usually a barrier to a cost-efficient application of bioresources to biofuels, the direct correlation of lignin structure and its concomitant properties with biomass remains unclear due to the complexity of cell wall and lignin structure. Advancement in application of biorefinery to production of biofuels, chemicals, and bio-derived materials necessitates a fundamental understanding of the relationship of lignin structure and biomass recalcitrance. In this mini-review, we focus on recent investigations on the influence of lignin chemical properties on bioprocessability—pretreatment and enzymatic hydrolysis of biomass. Furthermore, lignin-enzyme interactions and the effects of lignin compositional units, hydroxycinnamates, and lignin functional groups on biomass recalcitrance have been highlighted, which will be useful not only in addressing biomass recalcitrance but also in deploying renewable lignocelluloses efficiently.

  16. Current understanding of the correlation of lignin structure with biomass recalcitrance

    DOE PAGES

    Li, Mi; Pu, Yunqiao; Ragauskas, Arthur J.

    2016-11-18

    Lignin, a complex aromatic polymer in terrestrial plants, contributes significantly to biomass recalcitrance to microbial and/or enzymatic deconstruction. To reduce biomass recalcitrance, substantial endeavors have been exerted on pretreatment and lignin engineering in the past few decades. Lignin removal and/or alteration of lignin structure have been shown to result in reduced biomass recalcitrance with improved cell wall digestibility. While high lignin content is usually a barrier to a cost-efficient application of bioresources to biofuels, the direct correlation of lignin structure and its concomitant properties with biomass remains unclear due to the complexity of cell wall and lignin structure. Advancement inmore » application of biorefinery to production of biofuels, chemicals, and bio-derived materials necessitates a fundamental understanding of the relationship of lignin structure and biomass recalcitrance. In this mini-review, we focus on recent investigations on the influence of lignin chemical properties on bioprocessability—pretreatment and enzymatic hydrolysis of biomass. Furthermore, lignin-enzyme interactions and the effects of lignin compositional units, hydroxycinnamates, and lignin functional groups on biomass recalcitrance have been highlighted, which will be useful not only in addressing biomass recalcitrance but also in deploying renewable lignocelluloses efficiently.« less

  17. Mini-review: Current Understanding of the Correlation of Lignin Structure with Biomass Recalcitrance

    NASA Astrophysics Data System (ADS)

    Li, Mi; Pu, Yunqiao; Ragauskas, Arthur

    2016-11-01

    Lignin, a complex aromatic polymer in terrestrial plants, contributes significantly to biomass recalcitrance to microbial and/or enzymatic deconstruction. To reduce biomass recalcitrance, substantial endeavors have been exerted on pretreatment and lignin engineering in the past few decades. Lignin removal and/or alteration of lignin structure have been shown to result in reduced biomass recalcitrance with improved cell wall digestibility. While high lignin content is usually a barrier to a cost-efficient application of bioresource to biofuels, the direct correlation of lignin structure and its concomitant properties with biomass remains unclear due to the complexity of cell wall and lignin structure. Advancement in application of biorefinery to production of biofuels, chemicals, and biomaterials necessitates a fundamental understanding of the relationship of lignin structure and biomass recalcitrance. In this mini-review, we focus on recent investigations on the influence of lignin chemical properties on bioprocessability— pretreatment and enzymatic hydrolysis of biomass. Specifically, lignin-enzyme interaction and the effects of lignin compositional units, hydroxycinnamates, and lignin functional groups on biomass recalcitrance have been highlighted, which will be useful not only in addressing biomass recalcitrance but also in deploying renewable lignocelluloses efficiently.

  18. Intra-household allocation of food and health care: current findings and understandings--introduction.

    PubMed

    Messer, E

    1997-06-01

    This work offers an anthropological analysis of intra-household processes underlying gender- and age-specific differences in individual nutritional and health care allocations and outcomes in particular cultures. Based on recent ethnographic studies in India, Nepal, Madagascar, Mexico, and Peru, correspondences are analyzed between local cultural ("emic") and scientist-policy maker practitioner ("etic") understandings of nutrition, health, and human development, and the relative "values" of females, males, and children of different ages. The data and analyses clarify specific epidemiological and demographic findings on age and gender bias in nutrition and health and highlight the multiple cultural, economic, and biological factors that contribute to gender- or age-based discrimination or neglect. Recent advances in nutrition policy have argued for a broader concept of nutritional security, one that incorporates both food quantity and quality, and of nutrition as "food, health and care" (International Conference on Nutrition, World Declaration and Plan of Action for Nutrition, FAO/WHO, Rome, 1992). These ethnographic findings; lend strong support for such broader nutrition concepts and associated nutrition policies. The studies also suggest ways in which anthropological questions, methods, and data and community-based research can help predict or identify the nutritionally vulnerable within households and help other social and medical scientists design more effective interventions.

  19. Analysis of Advanced Fuel Assemblies and Core Designs for the Current and Next Generations of LWRs

    SciTech Connect

    Ragusa, Jean; Vierow, Karen

    2011-09-01

    The objective of the project is to design and analyze advanced fuel assemblies for use in current and future light water reactors and to assess their ability to reduce the inventory of transuranic elements, while preserving operational safety. The reprocessing of spent nuclear fuel can delay or avoid the need for a second geological repository in the US. Current light water reactor fuel assembly designs under investigation could reduce the plutonium inventory of reprocessed fuel. Nevertheless, these designs are not effective in stabilizing or reducing the inventory of minor actinides. In the course of this project, we developed and analyzed advanced fuel assembly designs with improved thermal transmutation capability regarding transuranic elements and especially minor actinides. These designs will be intended for use in thermal spectrum (e.g., current and future fleet of light water reactors in the US). We investigated various fuel types, namely high burn-up advanced mixed oxides and inert matrix fuels, in various geometrical designs that are compliant with the core internals of current and future light water reactors. Neutronic/thermal hydraulic effects were included. Transmutation efficiency and safety parameters were used to rank and down-select the various designs.

  20. Anaerobic fungi (phylum Neocallimastigomycota): advances in understanding their taxonomy, life cycle, ecology, role and biotechnological potential.

    PubMed

    Gruninger, Robert J; Puniya, Anil K; Callaghan, Tony M; Edwards, Joan E; Youssef, Noha; Dagar, Sumit S; Fliegerova, Katerina; Griffith, Gareth W; Forster, Robert; Tsang, Adrian; McAllister, Tim; Elshahed, Mostafa S

    2014-10-01

    Anaerobic fungi (phylum Neocallimastigomycota) inhabit the gastrointestinal tract of mammalian herbivores, where they play an important role in the degradation of plant material. The Neocallimastigomycota represent the earliest diverging lineage of the zoosporic fungi; however, understanding of the relationships of the different taxa (both genera and species) within this phylum is in need of revision. Issues exist with the current approaches used for their identification and classification, and recent evidence suggests the presence of several novel taxa (potential candidate genera) that remain to be characterised. The life cycle and role of anaerobic fungi has been well characterised in the rumen, but not elsewhere in the ruminant alimentary tract. Greater understanding of the 'resistant' phase(s) of their life cycle is needed, as is study of their role and significance in other herbivores. Biotechnological application of anaerobic fungi, and their highly active cellulolytic and hemi-cellulolytic enzymes, has been a rapidly increasing area of research and development in the last decade. The move towards understanding of anaerobic fungi using -omics based (genomic, transcriptomic and proteomic) approaches is starting to yield valuable insights into the unique cellular processes, evolutionary history, metabolic capabilities and adaptations that exist within the Neocallimastigomycota.

  1. NIDDK International Conference Report on Diabetes and Depression: Current Understanding and Future Directions

    PubMed Central

    de Groot, Mary; Lucki, Irwin; Hunter, Christine M.; Sartorius, Norman; Golden, Sherita H.

    2014-01-01

    Comorbid diabetes and depression are a major clinical challenge as the outcomes of each condition are worsened by the other. This article is based on the presentations and discussions during an international meeting on diabetes and depression convened by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in collaboration with the National Institute of Mental Health and the Dialogue on Diabetes and Depression. While the psychological burden of diabetes may contribute to depression in some cases, this explanation does not sufficiently explain the relationship between these two conditions. Shared biological and behavioral mechanisms, such as hypothalamic-pituitary-adrenal axis activation, inflammation, autonomic dysfunction, sleep disturbance, inactive lifestyle, poor dietary habits, and environmental and cultural risk factors, are important to consider in understanding the link between depression and diabetes. Both individual psychological and pharmacological depression treatments are effective in people with diabetes, but the current range of treatment options is limited and has shown mixed effects on glycemic outcomes. More research is needed to understand what factors contribute to individual differences in vulnerability, treatment response, and resilience to depression and metabolic disorders across the life course and how best to provide care for people with comorbid diabetes and depression in different health care settings. Training programs are needed to create a cross-disciplinary workforce that can work in different models of care for comorbid conditions. PMID:25061135

  2. Crucial knowledge gaps in current understanding of climate change impacts on coral reef fishes.

    PubMed

    Wilson, S K; Adjeroud, M; Bellwood, D R; Berumen, M L; Booth, D; Bozec, Y-Marie; Chabanet, P; Cheal, A; Cinner, J; Depczynski, M; Feary, D A; Gagliano, M; Graham, N A J; Halford, A R; Halpern, B S; Harborne, A R; Hoey, A S; Holbrook, S J; Jones, G P; Kulbiki, M; Letourneur, Y; De Loma, T L; McClanahan, T; McCormick, M I; Meekan, M G; Mumby, P J; Munday, P L; Ohman, M C; Pratchett, M S; Riegl, B; Sano, M; Schmitt, R J; Syms, C

    2010-03-15

    Expert opinion was canvassed to identify crucial knowledge gaps in current understanding of climate change impacts on coral reef fishes. Scientists that had published three or more papers on the effects of climate and environmental factors on reef fishes were invited to submit five questions that, if addressed, would improve our understanding of climate change effects on coral reef fishes. Thirty-three scientists provided 155 questions, and 32 scientists scored these questions in terms of: (i) identifying a knowledge gap, (ii) achievability, (iii) applicability to a broad spectrum of species and reef habitats, and (iv) priority. Forty-two per cent of the questions related to habitat associations and community dynamics of fish, reflecting the established effects and immediate concern relating to climate-induced coral loss and habitat degradation. However, there were also questions on fish demographics, physiology, behaviour and management, all of which could be potentially affected by climate change. Irrespective of their individual expertise and background, scientists scored questions from different topics similarly, suggesting limited bias and recognition of a need for greater interdisciplinary and collaborative research. Presented here are the 53 highest-scoring unique questions. These questions should act as a guide for future research, providing a basis for better assessment and management of climate change impacts on coral reefs and associated fish communities.

  3. Current understanding of iberiotoxin-resistant BK channels in the nervous system

    PubMed Central

    Wang, Bin; Jaffe, David B.; Brenner, Robert

    2014-01-01

    While most large-conductance, calcium-, and voltage-activated potassium channels (BK or Maxi-K type) are blocked by the scorpion venom iberiotoxin, the so-called “type II” subtype has the property of toxin resistance. This property is uniquely mediated by channel assembly with one member of the BK accessory β subunit family, the neuron-enriched β4 subunit. This review will focus on current understanding of iberiotoxin-resistant, β4-containing BK channel properties and their function in the CNS. Studies have shown that β4 dramatically promotes BK channel opening by shifting voltage sensor activation to more negative voltage ranges, but also slows activation to timescales that theoretically preclude BK ability to shape action potentials (APs). In addition, β4 membrane trafficking is regulated through an endoplasmic retention signal and palmitoylation. More recently, the challenge has been to understand the functional role of the iberiotoxin-resistant BK subtype utilizing computational modeling of neurons and neurophysiological approaches. Utilizing iberiotoxin-resistance as a footprint for these channels, they have been identified in dentate gyrus granule neurons and in purkinje neurons of the cerebellum. In these neurons, the role of these channels is largely consistent with slow-gated channels that reduce excitability either through an interspike conductance, such as in purkinje neurons, or by replacing fast-gating BK channels that otherwise facilitate high frequency AP firing, such as in dentate gyrus neurons. They are also observed in presynaptic mossy fiber terminals of the dentate gyrus and posterior pituitary terminals. More recent studies suggest that β4 subunits may also be expressed in some neurons lacking iberiotoxin-resistant BK channels, such as in CA3 hippocampus neurons. Ongoing research using novel, specific blockers and agonists of BK/β4, and β4 knockout mice, will continue to move the field forward in understanding the function of these

  4. Current understanding of iberiotoxin-resistant BK channels in the nervous system.

    PubMed

    Wang, Bin; Jaffe, David B; Brenner, Robert

    2014-01-01

    While most large-conductance, calcium-, and voltage-activated potassium channels (BK or Maxi-K type) are blocked by the scorpion venom iberiotoxin, the so-called "type II" subtype has the property of toxin resistance. This property is uniquely mediated by channel assembly with one member of the BK accessory β subunit family, the neuron-enriched β4 subunit. This review will focus on current understanding of iberiotoxin-resistant, β4-containing BK channel properties and their function in the CNS. Studies have shown that β4 dramatically promotes BK channel opening by shifting voltage sensor activation to more negative voltage ranges, but also slows activation to timescales that theoretically preclude BK ability to shape action potentials (APs). In addition, β4 membrane trafficking is regulated through an endoplasmic retention signal and palmitoylation. More recently, the challenge has been to understand the functional role of the iberiotoxin-resistant BK subtype utilizing computational modeling of neurons and neurophysiological approaches. Utilizing iberiotoxin-resistance as a footprint for these channels, they have been identified in dentate gyrus granule neurons and in purkinje neurons of the cerebellum. In these neurons, the role of these channels is largely consistent with slow-gated channels that reduce excitability either through an interspike conductance, such as in purkinje neurons, or by replacing fast-gating BK channels that otherwise facilitate high frequency AP firing, such as in dentate gyrus neurons. They are also observed in presynaptic mossy fiber terminals of the dentate gyrus and posterior pituitary terminals. More recent studies suggest that β4 subunits may also be expressed in some neurons lacking iberiotoxin-resistant BK channels, such as in CA3 hippocampus neurons. Ongoing research using novel, specific blockers and agonists of BK/β4, and β4 knockout mice, will continue to move the field forward in understanding the function of these

  5. Transcription Factors and Plants Response to Drought Stress: Current Understanding and Future Directions

    PubMed Central

    Joshi, Rohit; Wani, Shabir H.; Singh, Balwant; Bohra, Abhishek; Dar, Zahoor A.; Lone, Ajaz A.; Pareek, Ashwani; Singla-Pareek, Sneh L.

    2016-01-01

    Increasing vulnerability of plants to a variety of stresses such as drought, salt and extreme temperatures poses a global threat to sustained growth and productivity of major crops. Of these stresses, drought represents a considerable threat to plant growth and development. In view of this, developing staple food cultivars with improved drought tolerance emerges as the most sustainable solution toward improving crop productivity in a scenario of climate change. In parallel, unraveling the genetic architecture and the targeted identification of molecular networks using modern “OMICS” analyses, that can underpin drought tolerance mechanisms, is urgently required. Importantly, integrated studies intending to elucidate complex mechanisms can bridge the gap existing in our current knowledge about drought stress tolerance in plants. It is now well established that drought tolerance is regulated by several genes, including transcription factors (TFs) that enable plants to withstand unfavorable conditions, and these remain potential genomic candidates for their wide application in crop breeding. These TFs represent the key molecular switches orchestrating the regulation of plant developmental processes in response to a variety of stresses. The current review aims to offer a deeper understanding of TFs engaged in regulating plant’s response under drought stress and to devise potential strategies to improve plant tolerance against drought. PMID:27471513

  6. Current multiple sclerosis treatments have improved our understanding of MS autoimmune pathogenesis.

    PubMed

    Martin, Roland; Sospedra, Mireia; Rosito, Maria; Engelhardt, Britta

    2016-09-01

    Multiple sclerosis (MS) is the most common inflammatory disorder of the central nervous system (CNS) in young adults. When MS is not treated, it leads to irreversible and severe disability. The etiology of MS and its pathogenesis are not fully understood. The recent discovery that MS-associated genetic variants code for molecules related to the function of specific immune cell subsets is consistent with the concept of MS as a prototypic, T-cell-mediated autoimmune disease targeting the CNS. While the therapeutic efficacy of the currently available immunomodulatory therapies further strengthen this concept, differences observed in responses to MS treatment as well as additional clinical and imaging observations have also shown that the autoimmune pathogenesis underlying MS is much more complex than previously thought. There is therefore an unmet need for continued detailed phenotypic and functional analysis of disease-relevant adaptive immune cells and tissues directly derived from MS patients to unravel the immune etiology of MS in its entire complexity. In this review, we will discuss the currently available MS treatment options and approved drugs, including how they have contributed to the understanding of the immune pathology of this autoimmune disease.

  7. Current Understanding of HSP90 as a Novel Therapeutic Target: An Emerging Approach for the Treatment of Cancer.

    PubMed

    Haque, Absarul; Alam, Qamre; Alam, Mohammad Zubair; Azhar, Esam I; Sait, Khalid Hussain Wali; Anfinan, Nisrin; Mushtaq, Gohar; Kamal, Mohammad Amjad; Rasool, Mahmood

    2016-01-01

    Heat Shock Protein 90 (HSP90) is a ubiquitous molecular chaperone that is considered to be the most abundantly expressed protein in various human cancers such as breast, lung, colon, prostate, leukemia and skin. The master regulator, HSP90 plays a pivotal role in the conformational stabilization, maturation and activity of its various labile oncogenic client proteins such as p53, ErbB2, Bcr-Abl, Akt, Her-2, Cdk4, Cdk6, Raf-1 and v-Src in altered cells. Hence, making a guaranteed attempt to inhibit such a master regulator for cancer therapy appears to be a potential approach for combinatorial inhibition of numerous oncogenic signaling pathways simultaneously. Considerable efforts are being under way to develop novel molecular targets and its inhibitors that may block key signaling pathways involved in the process of tumorigenesis and metastasis. In this regards, HSP90 has acquired immense interest as a potent anticancer drug-target due to its key functional link with multiple signaling pathways involved in the process of cell proliferation and cell survival. Notably, geldanamycin and its derivatives (17-AAG, 17-DMAG) have shown quite encouraging results in inhibiting HSP90 function in several cancers and currently almost 17 drug candidates known to be target HSP90 are being under clinical trials either as single agents or combinatorial therapy. Hence, this review is an attempt to get new insight into novel drug target therapy by focusing on recent advances made in understanding HSP90 chaperone structure-function relationships, identification of new HSP90 client proteins and, more importantly, on the advancements of HSP90 targeted therapy based on various existing and emerging classical inhibitors.

  8. Regeneration of tissues of the oral complex: current clinical trends and research advances.

    PubMed

    Nguyen, Thomas T; Mui, Brennan; Mehrabzadeh, Mahsa; Chea, Yannie; Chaudhry, Zoya; Chaudhry, Kamran; Tran, Simon D

    2013-01-01

    Regenerative therapy in oral health care is limited by both the body's natural capacity for regeneration and the materials and methods currently available. Research on various aspects of regenerative therapy, such as tissue engineering and stem cell and gene therapy, has produced promising results. Compelling advances, ranging from the discovery and characterization of stem cell populations in oral tissue to the engineering and transplantation of whole tooth structures, could result in exciting new treatment methods for clinicians in the near future. In this review, we discuss the limitations of natural healing and regeneration of various tissues of the oral complex, including teeth, periodontium and salivary glands, and summarize current treatment methods for tissue damage as well as research advances in oral tissue regeneration.

  9. Neurogenic thoracic outlet syndrome: current diagnostic criteria and advances in MRI diagnostics.

    PubMed

    Magill, Stephen T; Brus-Ramer, Marcel; Weinstein, Philip R; Chin, Cynthia T; Jacques, Line

    2015-09-01

    Neurogenic thoracic outlet syndrome (nTOS) is caused by compression of the brachial plexus as it traverses from the thoracic outlet to the axilla. Diagnosing nTOS can be difficult because of overlap with other complex pain and entrapment syndromes. An nTOS diagnosis is made based on patient history, physical exam, electrodiagnostic studies, and, more recently, interpretation of MR neurograms with tractography. Advances in high-resolution MRI and tractography can confirm an nTOS diagnosis and identify the location of nerve compression, allowing tailored surgical decompression. In this report, the authors review the current diagnostic criteria, present an update on advances in MRI, and provide case examples demonstrating how MR neurography (MRN) can aid in diagnosing nTOS. The authors conclude that improved high-resolution MRN and tractography are valuable tools for identifying the source of nerve compression in patients with nTOS and can augment current diagnostic modalities for this syndrome.

  10. Some inadequacies of the current human factors certification process of advanced aircraft technologies

    NASA Technical Reports Server (NTRS)

    Paries, Jean

    1994-01-01

    Automation related accidents or serious incidents are not limited to advanced technology aircraft. There is a full history of such accidents with conventional technology aircraft. However, this type of occurrence is far from sparing the newest 'glass cockpit' generation, and it even seems to be a growing contributor to its accident rate. Nevertheless, all these aircraft have been properly certificated according to the relevant airworthiness regulations. Therefore, there is a growing concern that with the technological advancement of air transport aircraft cockpits, the current airworthiness regulations addressing cockpit design and human factors may have reached some level of inadequacy. This paper reviews some aspects of the current airworthiness regulations and certification process related to human factors of cockpit design and focuses on questioning their ability to guarantee the intended safety objectives.

  11. Advanced practice clinicians as abortion providers: current developments in the United States.

    PubMed

    Joffe, Carole; Yanow, Susan

    2004-11-01

    A hopeful note in the contemporary abortion environment in the United States is the expanding role of advanced practice clinicians--nurse practitioners, physician assistants and nurse-midwives--in first trimester abortion provision. A large percentage of primary health care in the U.S. is currently provided by these non-physicians but their involvement in abortion care is promising, especially in light of the shortage of physician providers. Two national symposia in 1990 and 1996 approved the expansion of early abortion care to non-physicians. As of January 2004, trained advanced practice clinicians were providing medical, and in some cases, early surgical abortion in 14 states. This has required not only medical training but also political organising to achieve the necessary legal and regulatory changes, state by state, by groups such as Clinicians for Choice and the Abortion Access Project, described here in examples in two states and the reflections of three advanced practice clinicians. Recent surveys in three states show a substantial interest among advanced practice clinicians in abortion training, leading to cautious optimism about the possibility of increased abortion access for women. Most encouraging, advanced practice clinicians, like their physician counterparts, show a level of passionate commitment to the work that is rare elsewhere in health care in the U.S. today.

  12. Advances in understanding mineral dust and boundary layer processes over the Sahara from Fennec aircraft observations

    NASA Astrophysics Data System (ADS)

    Ryder, C. L.; McQuaid, J. B.; Flamant, C.; Washington, R.; Brindley, H. E.; Highwood, E. J.; Marsham, J. H.; Parker, D. J.; Todd, M. C.; Banks, J. R.; Brooke, J. K.; Engelstaedter, S.; Estellés, V.; Formenti, P.; Garcia-Carreras, L.; Kocha, C.; Marenco, F.; Rosenberg, P.; Sodemann, H.; Allen, C. J. T.; Bourdon, A.; Bart, M.; Cavazos-Guerra, C.; Chevaillier, S.; Crosier, J.; Darbyshire, E.; Dean, A. R.; Dorsey, J. R.; Kent, J.; O'Sullivan, D.; Schepanski, K.; Szpek, K.; Woolley, A.

    2015-01-01

    The Fennec climate program aims to improve understanding of the Saharan climate system through a synergy of observations and modelling. We present a description of the Fennec airborne observations during 2011 and 2012 over the remote Sahara (Mauritania and Mali) and the advances in the understanding of mineral dust and boundary layer processes they have provided. Aircraft instrumentation aboard the UK FAAM BAe146 and French SAFIRE Falcon 20 is described, with specific focus on instrumentation specially developed and relevant to Saharan meteorology and dust. Flight locations, aims and associated meteorology are described. Examples and applications of aircraft measurements from the Fennec flights are presented, highlighting new scientific results delivered using a synergy of different instruments and aircraft. These include: (1) the first airborne measurement of dust particles sized up to 300 microns and associated dust fluxes in the Saharan atmospheric boundary layer (SABL), (2) dust uplift from the breakdown of the nocturnal low-level jet before becoming visible in SEVIRI satellite imagery, (3) vertical profiles of the unique vertical structure of turbulent fluxes in the SABL, (4) in-situ observations of processes in SABL clouds showing dust acting as CCN and IN at -15 °C, (5) dual-aircraft observations of the SABL dynamics, thermodynamics and composition in the Saharan heat low region (SHL), (6) airborne observations of a dust storm associated with a cold-pool (haboob) issued from deep convection over the Atlas, (7) the first airborne chemical composition measurements of dust in the SHL region with differing composition, sources (determined using Lagrangian backward trajectory calculations) and absorption properties between 2011 and 2012, (8) coincident ozone and dust surface area measurements suggest coarser particles provide a route for ozone depletion, (9) discrepancies between airborne coarse mode size distributions and AERONET sunphotometer retrievals under

  13. Advances in understanding societal vulnerability to tsunamis in the United States

    NASA Astrophysics Data System (ADS)

    Wood, N. J.

    2009-12-01

    Loss of life and property damage from future tsunamis can be reduced if officials develop risk-reduction strategies and education programs that address how at-risk populations and communities are specifically vulnerable to tsunamis. Prior to the 2004 Indian Ocean tsunami, information concerning societal vulnerability to tsunamis in the U.S. was largely limited to state-level summaries of the number of residents within one kilometer of the coast. Since 2004, the U.S. Geological Survey has furthered the Nation’s understanding of societal vulnerability to tsunamis with several studies that describe the exposure, sensitivity, and adaptive capacity of at-risk populations in tsunami-hazard zones. Community-level assessments have been completed in Hawaii, Oregon, and Washington to document variations in the number and types of people, businesses, and critical facilities in tsunami-prone areas. A method using midresolution satellite imagery was developed to identify community variations in the amount of developed land in tsunami-prone areas. Factor analysis and geospatial analysis were integrated to model variations in demographic sensitivity to tsunamis. Public workshops have been held to examine community sensitivity, adaptive capacity and post-tsunami recovery. Results demonstrate that social vulnerability to tsunamis varies throughout a community or region and that certain areas are likely to suffer disproportionately due to differences in pre-tsunami socioeconomic conditions and other demographic attributes. This presentation will summarize advances in understanding societal vulnerability in the U.S. to tsunamis since the 2004 Indian Ocean tsunami, as well as discuss opportunities and needs for further work.

  14. COLLABORATIVE RESEARCH: TOWARDS ADVANCED UNDERSTANDING AND PREDICTIVE CAPABILITY OF CLIMATE CHANGE IN THE ARCTIC USING A HIGH-RESOLUTION REGIONAL ARCTIC CLIMATE SYSTEM MODEL

    SciTech Connect

    Gutowski, William J.

    2013-02-07

    The motivation for this project was to advance the science of climate change and prediction in the Arctic region. Its primary goals were to (i) develop a state-of-the-art Regional Arctic Climate system Model (RACM) including high-resolution atmosphere, land, ocean, sea ice and land hydrology components and (ii) to perform extended numerical experiments using high performance computers to minimize uncertainties and fundamentally improve current predictions of climate change in the northern polar regions. These goals were realized first through evaluation studies of climate system components via one-way coupling experiments. Simulations were then used to examine the effects of advancements in climate component systems on their representation of main physics, time-mean fields and to understand variability signals at scales over many years. As such this research directly addressed some of the major science objectives of the BER Climate Change Research Division (CCRD) regarding the advancement of long-term climate prediction.

  15. Bovine viral diarrhea virus infections: manifestations of infection and recent advances in understanding pathogenesis and control.

    PubMed

    Brodersen, B W

    2014-03-01

    Bovine viral diarrhea virus (BVDV) continues to be of economic significance to the livestock industry in terms of acute disease and fetal loss. Many of the lesions relating to BVDV infection have been well described previously. The virus is perpetuated in herds through the presence of calves that are persistently infected. Relationships between various species and biotypes of BVDV and host defenses are increasingly understood. Understanding of the host defense mechanisms of innate immunity and adaptive immunity continues to improve, and the effects of the virus on these immune mechanisms are being used to explain how persistent infection develops. The noncytopathic biotype of BVDV plays the major role in its effects on the host defenses by inhibiting various aspects of the innate immune system and creation of immunotolerance in the fetus during early gestation. Recent advances have allowed for development of affordable test strategies to identify and remove persistently infected animals. With these improved tests and removal strategies, the livestock industry can begin more widespread effective control programs.

  16. Advancing understanding of microbial bioenergy conversion processes by activity-based protein profiling

    DOE PAGES

    Liu, Yun; Fredrickson, James K.; Sadler, Natalie C.; ...

    2015-09-25

    Here, the development of renewable biofuels is a global priority, but success will require novel technologies that greatly improve our understanding of microbial systems biology. An approach with great promise in enabling functional characterization of microbes is activity-based protein profiling (ABPP), which employs chemical probes to directly measure enzyme function in discrete enzyme classes in vivo and/or in vitro, thereby facilitating the rapid discovery of new biocatalysts and enabling much improved biofuel production platforms. We review general design strategies in ABPP, and highlight recent advances that are or could be pivotal to biofuels processes including applications of ABPP to cellulosicmore » bioethanol, biodiesel, and phototrophic production of hydrocarbons. We also examine the key challenges and opportunities of ABPP in renewable biofuels research. The integration of ABPP with molecular and systems biology approaches will shed new insight on the catalytic and regulatory mechanisms of functional enzymes and their synergistic effects in the field of biofuels production.« less

  17. Recent advances in the understanding of Quaternary periglacial features of the English Channel coastlands

    NASA Astrophysics Data System (ADS)

    Murton, Julian B.; Lautridou, Jean-Pierre

    2003-02-01

    Recent advances in the understanding of Quaternary periglaciation of the English Channel coastlands concern laboratory modelling of periglacial processes, dating of periglacial sediments and the distribution of permafrost during marine oxygen isotope stage (MOIS) 2. Modelling studies have successfully simulated (i) ice segregation in chalk in artificial permafrost, (ii) periglacial solifluction of natural slope sediments, and (iii) soft-sediment deformation during thaw of ice-rich soil. The resultant structures and deposits in these experiments have similarities with naturally brecciated chalk, solifluction deposits and involutions, respectively, along the English Channel coastlands, providing insights into their genesis and palaeoenvironmental significance.Dating of periglacial sediments is based on radiocarbon assays of organic material in head deposits, luminescence measurements of loess and coversand, and mammalian biostratigraphy in raised-beach and associated slope deposits. Most age estimates fall within MOIS 2, although some are within MOIS 6 and possibly other cold stages.Maps reconstructing the distribution of permafrost during MOIS 2 vary in detail. The precise distribution of permafrost remains to be established owing to problems of (i) imprecise dating in the context of climatic instability, (ii) uncertain palaeoclimatic significance of particular periglacial structures and (iii) sparse data on the age and distribution of relict periglacial features.The wider significance of periglacial processes to the evolution of the Channel coastlands is speculated to involve rapid valley development by flowing water in areas of moist, frost-susceptible bedrock that has been brecciated by ice segregation.

  18. Recent advances in understanding the role of lamins in health and disease

    PubMed Central

    Reddy, Sita; Comai, Lucio

    2016-01-01

    Lamins are major components of the nuclear lamina, a network of proteins that supports the nuclear envelope in metazoan cells. Over the past decade, biochemical studies have provided support for the view that lamins are not passive bystanders providing mechanical stability to the nucleus but play an active role in the organization of the genome and the function of fundamental nuclear processes. It has also become apparent that lamins are critical for human health, as a large number of mutations identified in the gene that encodes for A-type lamins are associated with tissue-specific and systemic genetic diseases, including the accelerated aging disorder known as Hutchinson-Gilford progeria syndrome. Recent years have witnessed great advances in our understanding of the role of lamins in the nucleus and the functional consequences of disease-associated A-type lamin mutations. Many of these findings have been presented in comprehensive reviews. In this mini-review, we discuss recent breakthroughs in the role of lamins in health and disease and what lies ahead in lamin research. PMID:27803806

  19. Guard Cell Signal Transduction Network: Advances in Understanding Abscisic Acid, CO2, and Ca2+ Signaling

    PubMed Central

    Kim, Tae-Houn; Böhmer, Maik; Hu, Honghong; Nishimura, Noriyuki; Schroeder, Julian I.

    2011-01-01

    Stomatal pores are formed by pairs of specialized epidermal guard cells and serve as major gateways for both CO2 influx into plants from the atmosphere and transpirational water loss of plants. Because they regulate stomatal pore apertures via integration of both endogenous hormonal stimuli and environmental signals, guard cells have been highly developed as a model system to dissect the dynamics and mechanisms of plant-cell signaling. The stress hormone ABA and elevated levels of CO2 activate complex signaling pathways in guard cells that are mediated by kinases/phosphatases, secondary messengers, and ion channel regulation. Recent research in guard cells has led to a new hypothesis for how plants achieve specificity in intracellular calcium signaling: CO2 and ABA enhance (prime) the calcium sensitivity of downstream calcium-signaling mechanisms. Recent progress in identification of early stomatal signaling components are reviewed here, including ABA receptors and CO2-binding response proteins, as well as systems approaches that advance our understanding of guard cell-signaling mechanisms. PMID:20192751

  20. Current understanding of the driving mechanisms for spatiotemporal variations of atmospheric speciated mercury: a review

    NASA Astrophysics Data System (ADS)

    Mao, Huiting; Cheng, Irene; Zhang, Leiming

    2016-10-01

    Atmospheric mercury (Hg) is a global pollutant and thought to be the main source of mercury in oceanic and remote terrestrial systems, where it becomes methylated and bioavailable; hence, atmospheric mercury pollution has global consequences for both human and ecosystem health. Understanding of spatial and temporal variations of atmospheric speciated mercury can advance our knowledge of mercury cycling in various environments. This review summarized spatiotemporal variations of total gaseous mercury or gaseous elemental mercury (TGM/GEM), gaseous oxidized mercury (GOM), and particulate-bound mercury (PBM) in various environments including oceans, continents, high elevation, the free troposphere, and low to high latitudes. In the marine boundary layer (MBL), the oxidation of GEM was generally thought to drive the diurnal and seasonal variations of TGM/GEM and GOM in most oceanic regions, leading to lower GEM and higher GOM from noon to afternoon and higher GEM during winter and higher GOM during spring-summer. At continental sites, the driving mechanisms of TGM/GEM diurnal patterns included surface and local emissions, boundary layer dynamics, GEM oxidation, and for high-elevation sites mountain-valley winds, while oxidation of GEM and entrainment of free tropospheric air appeared to control the diurnal patterns of GOM. No pronounced diurnal variation was found for Tekran measured PBM at MBL and continental sites. Seasonal variations in TGM/GEM at continental sites were attributed to increased winter combustion and summertime surface emissions, and monsoons in Asia, while those in GOM were controlled by GEM oxidation, free tropospheric transport, anthropogenic emissions, and wet deposition. Increased PBM at continental sites during winter was primarily due to local/regional coal and wood combustion emissions. Long-term TGM measurements from the MBL and continental sites indicated an overall declining trend. Limited measurements suggested TGM/GEM increasing from the

  1. Advances in the understanding of mitochondrial DNA as a pathogenic factor in inflammatory diseases

    PubMed Central

    Boyapati, Ray K.; Tamborska, Arina; Dorward, David A.; Ho, Gwo-Tzer

    2017-01-01

    Mitochondrial DNA (mtDNA) has many similarities with bacterial DNA because of their shared common ancestry. Increasing evidence demonstrates mtDNA to be a potent danger signal that is recognised by the innate immune system and can directly modulate the inflammatory response. In humans, elevated circulating mtDNA is found in conditions with significant tissue injury such as trauma and sepsis and increasingly in chronic organ-specific and systemic illnesses such as steatohepatitis and systemic lupus erythematosus. In this review, we examine our current understanding of mtDNA-mediated inflammation and how the mechanisms regulating mitochondrial homeostasis and mtDNA release represent exciting and previously under-recognised important factors in many human inflammatory diseases, offering many new translational opportunities. PMID:28299196

  2. From endocrine disruptors to nanomaterials: advancing our understanding of environmental health to protect public health.

    PubMed

    Birnbaum, Linda S; Jung, Paul

    2011-05-01

    Environmental health science is the study of the impact of the environment on human health. This paper introduces basic topics in environmental health, including clean air, clean water, and healthful food, as well as a range of current issues and controversies in environmental health. Conceptual shifts in modern toxicology have changed the field. There is a new understanding of the effects of exposure to chemicals at low doses, and in combination, and the impact on human growth and development. Other emerging topics include the role of epigenetics, or changes in genes and gene expression that can be brought about by chemical exposure; environmental justice; and potential effects of engineered nanomaterials and climate change. We review the important implications for public health policy and recommend a broad environmental health research strategy aimed at protecting and improving human health.

  3. Recent advances in understanding the role of cellulose accessibility in enzymatic hydrolysis of lignocellulosic substrates.

    PubMed

    Meng, Xianzhi; Ragauskas, Arthur Jonas

    2014-06-01

    Cellulose accessibility has been proposed as a key factor in the efficient bio-conversion of lignocellulosic biomass to fermentable sugars. Factors affecting cellulose accessibility can be divided into direct factors that refer to accessible surface area of cellulose, and indirect factors referring to chemical composition such as lignin/hemicellulose content, and biomass structure-relevant factors (i.e. particle size, porosity). An overview of the current pretreatment technologies special focus on the major mode of action to increase cellulose accessibility as well as multiple techniques that could be used to assess the cellulose accessibility are presented in this review. The appropriate determination of cellulose accessibility before and after pretreatment can assist to understand the effectiveness of a particular pretreatment in overcoming lignocellulosic recalcitrance to improve substrate enzymatic digestibility.

  4. Direction of R&D and Current Status of Understanding of Advanced Gear Steels

    DTIC Science & Technology

    1986-02-01

    will be compared. Three additional alloys ( M50NiL , CBS1000M, and AMAX B) will be discussed in less detail. Most of the information contained in this...40 MPa6 frac:,are toughness, makes it a poor last of the materials being considered. M50NiL , however, c,.n be readily vacuum carburized and in the...coeparable fracture toughness to M50NiL and can be carburized as readily as AlSl 9310. At this time, it would not appear to be a strong candidate for

  5. Advances in the understanding of the pathogenesis and epidemiology of herpes zoster

    PubMed Central

    Gershon, Anne A.; Gershon, Michael D.; Breuer, Judith; Levin, Myron J.; Oaklander, Anne Louise; Griffiths, Paul D.

    2017-01-01

    SUMMARY The primary varicella zoster virus (VZV) infection results in chickenpox (varicella), which is transmitted via the airborne route. VZV is highly infectious, but in the USA the incidence of varicella has been reduced by 76–87% as a result of the varicella vaccine. The virus establishes latency in the dorsal root ganglia during varicella and, when reactivated, travels along the sensory nerve axons to cause shingles (herpes zoster [HZ]). There are over 1 million cases of HZ in the USA each year, with an estimated lifetime attack rate of 30%. The incidence of HZ, which causes significant morbidity, increases with age and reaches approximately 10 cases per 1,000 patient-years by age 80. Cell-mediated immunity (CMI) is known to decline with age as part of immunosenescence, and decreased CMI is associated with reactivation of VZV. This article provides an overview of our emerging understanding of the epidemiology and pathogenesis of varicella and HZ, in addition to exploring the current theories on latency and reactivation. Understanding the risk factors for developing HZ and the complications associated with infection, particularly in older people, is important for prompt diagnosis and management of HZ in primary care, and they are therefore also reviewed. PMID:20510263

  6. Recent advances in understanding of meiosis initiation and the apomictic pathway in plants.

    PubMed

    Wang, Chung-Ju R; Tseng, Ching-Chih

    2014-01-01

    Meiosis, a specialized cell division to produce haploid cells, marks the transition from a sporophytic to a gametophytic generation in the life cycle of plants. In angiosperms, meiosis takes place in sporogenous cells that develop de novo from somatic cells in anthers or ovules. A successful transition from the mitotic cycle to the meiotic program in sporogenous cells is crucial for sexual reproduction. By contrast, when meiosis is bypassed or a mitosis-like division occurs to produce unreduced cells, followed by the development of an embryo sac, clonal seeds can be produced by apomixis, an asexual reproduction pathway found in 400 species of flowering plants. An understanding of the regulation of entry into meiosis and molecular mechanisms of apomictic pathway will provide vital insight into reproduction for plant breeding. Recent findings suggest that AM1/SWI1 may be the key gene for entry into meiosis, and increasing evidence has shown that the apomictic pathway is epigenetically controlled. However, the mechanism for the initiation of meiosis during sexual reproduction or for its omission in the apomictic pathway still remains largely unknown. Here we review the current understanding of meiosis initiation and the apomictic pathway and raised several questions that are awaiting further investigation.

  7. Advances in Understanding Global Water Cycle with Advent of Global Precipitation Measurement (GPM) Mission

    NASA Technical Reports Server (NTRS)

    Smith, Eric A.; Starr, David (Technical Monitor)

    2002-01-01

    Within this decade the internationally organized Global Precipitation Measurement (GPM) Mission will take an important step in creating a global precipitation observing system from space. One perspective for understanding the nature of GPM is that it will be a hierarchical system of datastreams beginning with very high caliber combined dual frequency radar/passive microwave (PMW) rain-radiometer retrievals, to high caliber PMW rain-radiometer only retrievals, and then on to blends of the former datastreams with additional lower-caliber PMW-based and IR-based rain retrievals. Within the context of the now emerging global water & energy cycle (GWEC) programs of a number of research agencies throughout the world, GPM serves as a centerpiece space mission for improving our understanding of the global water cycle from a global measurement perspective. One of the salient problems within our current understanding of the global water and energy cycle is determining whether a change in the rate of the water cycle is accompanying changes in climate, e.g., climate warming. As there are a number of ways in which to define a rate-change of the global water cycle, it is not entirely clear as to what constitutes such a determination. This paper presents an overview of the GPM Mission and how its observations can be used within the framework of the oceanic and continental water budget equations to determine whether a given perturbation in precipitation is indicative of an actual rate change in the global water cycle, consistent with required responses in water storage and/or water flux transport processes, or whether it is the natural variability of a fixed rate cycle.

  8. Advances In Understanding Global Water Cycle With Advent of GPM Mission

    NASA Technical Reports Server (NTRS)

    Smith, Eric A.

    2002-01-01

    During the coming decade, the internationally organized Global Precipitation Measurement (GPM) Mission will take an important step in creating a global precipitation observing system from space based on an international fleet of satellites operated as a constellation. One perspective for understanding the nature of GPM is that it will be a hierarchical system of datastreams beginning with very high caliber combined dual frequency radar/passive microwave (PMW) rain-radiometer retrievals, to high caliber PMW rain-radiometer only retrievals, and then on to blends of the former datastreams with additional lower-caliber PMW-based and IR-based rain retrievals. Within the context of the now emerging global water & energy cycle (GWEC) programs of a number of research agencies throughout the world, GPM serves as a centerpiece space mission for improving our understanding of the Earth's water cycle from a global measurement perspective and on down to regional scales and below. One of the salient problems within our current understanding of the global water and energy cycle is determining whether a change in the rate of the water cycle is accompanying changes in climate, e.g., climate warming. As there are a number of ways in which to define a rate-change of the global water cycle, it is not entirely clear as to what constitutes such a determination. This paper first presents an overview of the GPM Mission and how its overriding scientific objectives for climate, weather, and hydrology flow from the anticipated improvements that are being planned for the constellation-based measuring system. Next, the paper shows how the GPM observations can be used within the framework of the oceanic and continental water budget equations to determine whether a given perturbation in precipitation is indicative of an actual rate change in the water cycle, consistent with required responses in water storage and/or water flux transport processes, or whether it is simply part of the natural

  9. Managing in the trenches of consumer care: the challenges of understanding and initiating the advance care planning process.

    PubMed

    Baughman, Kristin R; Aultman, Julie; Hazelett, Susan; Palmisano, Barbara; O'Neill, Anne; Ludwick, Ruth; Sanders, Margaret

    2012-01-01

    To better understand how community-based long-term care providers define advance care planning and their role in the process, we conducted 8 focus groups with 62 care managers (social workers and registered nurses) providing care for Ohio's Medicaid waiver program. Care managers shared that most consumers had little understanding of advance care planning. The care managers defined it broadly, including legal documentation, social aspects, medical considerations, ongoing communication, and consumer education. Care managers saw their roles as information providers, healthcare team members, and educators/coaches. Better education, resources, and coordination are needed to ensure that consumer preferences are realized.

  10. Recent Advances in Understanding and Mitigating Adipogenic and Metabolic Effects of Antipsychotic Drugs

    PubMed Central

    Gohlke, Julia M.; Dhurandhar, Emily J.; Correll, Christoph U.; Morrato, Elaine H.; Newcomer, John W.; Remington, Gary; Nasrallah, Henry A.; Crystal, Stephen; Nicol, Ginger; Allison, David B.

    2012-01-01

    Although offering many benefits for several psychiatric disorders, antipsychotic drugs (APDs) as a class have a major liability in their tendency to promote adiposity, obesity, and metabolic dysregulation in an already metabolically vulnerable population. The past decade has witnessed substantial research aimed at investigating the mechanisms of these adverse effects and mitigating them. On July 11 and 12, 2011, with support from 2 NIH institutes, leading experts convened to discuss current research findings and to consider future research strategies. Five areas where significant advances are being made emerged from the conference: (1) methodological issues in the study of APD effects; (2) unique characteristics and needs of pediatric patients; (3) genetic components underlying susceptibility to APD-induced metabolic effects; (4) APD effects on weight gain and adiposity in relation to their acute effects on glucose regulation and diabetes risk; and (5) the utility of behavioral, dietary, and pharmacological interventions in mitigating APD-induced metabolic side effects. This paper summarizes the major conclusions and important supporting data from the meeting. PMID:22754543

  11. Understanding the Dynamics of the Coupled Ring Current Radiation Belt System Using 4D VERB Simulations

    NASA Astrophysics Data System (ADS)

    Shprits, Y.; Kellerman, A. C.; Drozdov, A.; Orlova, K.; Spasojevic, M.

    2014-12-01

    Predicting and understanding the non-linear response of different electron populations in the inner magnetosphere, including ring current and higher energy radiation belts, has been a grand challenge since the beginning of the space age. During this past decade, there have been a number of long-term simulations that used lower energy boundary condition observations around geosynchronous orbit. In this study, we set up observations at around 15 RE and study how the combined convective-diffusive transport can result in the acceleration of keV to relativistic and ultra-relativistic energies. We show that while lower energy radial transport is dominated by the convection, higher energy transport is dominated by the diffusive radial transport. MLT dependent diffusion confidents allow us to study how difference in wave properties at different MLT can influence the dynamics of the particles. Inclusion of adiabatic changes also allows us to study the radial transport that results from pitch-angle scattering and adiabatic changes. We also show that there exists an intermediate range of energies for electrons for which both processes work simultaneously. We show the comparison of the 4D VERB simulations with the Van Allen Probes measurements.

  12. Current ecological understanding of fungal-like pathogens of fish: what lies beneath?

    PubMed

    Gozlan, Rodolphe E; Marshall, Wyth L; Lilje, Osu; Jessop, Casey N; Gleason, Frank H; Andreou, Demetra

    2014-01-01

    Despite increasingly sophisticated microbiological techniques, and long after the first discovery of microbes, basic knowledge is still lacking to fully appreciate the ecological importance of microbial parasites in fish. This is likely due to the nature of their habitats as many species of fish suffer from living beneath turbid water away from easy recording. However, fishes represent key ecosystem services for millions of people around the world and the absence of a functional ecological understanding of viruses, prokaryotes, and small eukaryotes in the maintenance of fish populations and of their diversity represents an inherent barrier to aquatic conservation and food security. Among recent emerging infectious diseases responsible for severe population declines in plant and animal taxa, fungal and fungal-like microbes have emerged as significant contributors. Here, we review the current knowledge gaps of fungal and fungal-like parasites and pathogens in fish and put them into an ecological perspective with direct implications for the monitoring of fungal fish pathogens in the wild, their phylogeography as well as their associated ecological impact on fish populations. With increasing fish movement around the world for farming, releases into the wild for sport fishing and human-driven habitat changes, it is expected, along with improved environmental monitoring of fungal and fungal-like infections, that the full extent of the impact of these pathogens on wild fish populations will soon emerge as a major threat to freshwater biodiversity.

  13. Current ecological understanding of fungal-like pathogens of fish: what lies beneath?

    PubMed Central

    Gozlan, Rodolphe E.; Marshall, Wyth L.; Lilje, Osu; Jessop, Casey N.; Gleason, Frank H.; Andreou, Demetra

    2014-01-01

    Despite increasingly sophisticated microbiological techniques, and long after the first discovery of microbes, basic knowledge is still lacking to fully appreciate the ecological importance of microbial parasites in fish. This is likely due to the nature of their habitats as many species of fish suffer from living beneath turbid water away from easy recording. However, fishes represent key ecosystem services for millions of people around the world and the absence of a functional ecological understanding of viruses, prokaryotes, and small eukaryotes in the maintenance of fish populations and of their diversity represents an inherent barrier to aquatic conservation and food security. Among recent emerging infectious diseases responsible for severe population declines in plant and animal taxa, fungal and fungal-like microbes have emerged as significant contributors. Here, we review the current knowledge gaps of fungal and fungal-like parasites and pathogens in fish and put them into an ecological perspective with direct implications for the monitoring of fungal fish pathogens in the wild, their phylogeography as well as their associated ecological impact on fish populations. With increasing fish movement around the world for farming, releases into the wild for sport fishing and human-driven habitat changes, it is expected, along with improved environmental monitoring of fungal and fungal-like infections, that the full extent of the impact of these pathogens on wild fish populations will soon emerge as a major threat to freshwater biodiversity. PMID:24600442

  14. Understanding the Dynamical Evolution of the Earth Radiation Belt and Ring Current Coupled System

    NASA Astrophysics Data System (ADS)

    Shprits, Yuri; Usanova, Maria; Kellerman, Adam; Drozdov, Alexander

    2016-07-01

    Modeling and understanding the ring current and radiation belt-coupled system has been a grand challenge since the beginning of the space age. In this study we show long-term simulations with a 3D Versatile Electron Radiation Belt (VERB) code of modeling the radiation belts with boundary conditions derived from observations around geosynchronous orbit. Simulations can reproduce long term variations of the electron radiation belt fluxes and show the importance of local acceleration, radial diffusion, loss to the atmosphere and loss to the magnetopause. We also present 4D VERB simulations that include convective transport, radial diffusion, pitch angle scattering and local acceleration. VERB simulations show that the lower energy inward transport is dominated by the convection and higher energy transport is dominated by the diffusive radial transport. We also show that at energies of 100s of keV, a number of processes work simultaneously, including convective transport, radial diffusion, local acceleration, loss to the loss cone and loss to the magnetopause. The results of the simulation of the March 2013 storm are compared with Van Allen Probes observations.

  15. Review: Animal model and the current understanding of molecule dynamics of adipogenesis.

    PubMed

    Campos, C F; Duarte, M S; Guimarães, S E F; Verardo, L L; Wei, S; Du, M; Jiang, Z; Bergen, W G; Hausman, G J; Fernyhough-Culver, M; Albrecht, E; Dodson, M V

    2016-06-01

    Among several potential animal models that can be used for adipogenic studies, Wagyu cattle is the one that presents unique molecular mechanisms underlying the deposit of substantial amounts of intramuscular fat. As such, this review is focused on current knowledge of such mechanisms related to adipose tissue deposition using Wagyu cattle as model. So abundant is the lipid accumulation in the skeletal muscles of these animals that in many cases, the muscle cross-sectional area appears more white (adipose tissue) than red (muscle fibers). This enhanced marbling accumulation is morphologically similar to that seen in numerous skeletal muscle dysfunctions, disease states and myopathies; this might indicate cross-similar mechanisms between such dysfunctions and fat deposition in Wagyu breed. Animal models can be used not only for a better understanding of fat deposition in livestock, but also as models to an increased comprehension on molecular mechanisms behind human conditions. This revision underlies some of the complex molecular processes of fat deposition in animals.

  16. Danger Signals and Graft-versus-host Disease: Current Understanding and Future Perspectives

    PubMed Central

    Toubai, Tomomi; Mathewson, Nathan D.; Magenau, John; Reddy, Pavan

    2016-01-01

    Graft-versus-host response after allogeneic hematopoietic stem cell transplantation (allo-HCT) represents one of the most intense inflammatory responses observed in humans. Host conditioning facilitates engraftment of donor cells, but the tissue injury caused from it primes the critical first steps in the development of acute graft-versus-host disease (GVHD). Tissue injuries release pro-inflammatory cytokines (such as TNF-α, IL-1β, and IL-6) through widespread stimulation of pattern recognition receptors (PRRs) by the release of danger stimuli, such as damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs). DAMPs and PAMPs function as potent stimulators for host and donor-derived antigen presenting cells (APCs) that in turn activate and amplify the responses of alloreactive donor T cells. Emerging data also point towards a role for suppression of DAMP induced inflammation by the APCs and donor T cells in mitigating GVHD severity. In this review, we summarize the current understanding on the role of danger stimuli, such as the DAMPs and PAMPs, in GVHD. PMID:27965667

  17. Current Understanding of the Interplay between Phytohormones and Photosynthesis under Environmental Stress

    PubMed Central

    Gururani, Mayank Anand; Mohanta, Tapan Kumar; Bae, Hanhong

    2015-01-01

    Abiotic stress accounts for huge crop losses every year across the globe. In plants, the photosynthetic machinery gets severely damaged at various levels due to adverse environmental conditions. Moreover, the reactive oxygen species (ROS) generated as a result of stress further promote the photosynthetic damage by inhibiting the repair system of photosystem II. Earlier studies have suggested that phytohormones are not only required for plant growth and development, but they also play a pivotal role in regulating plants’ responses to different abiotic stress conditions. Although, phytohormones have been studied in great detail in the past, their influence on the photosynthetic machinery under abiotic stress has not been studied. One of the major factors that limits researchers fromelucidating the precise roles of phytohormones is the highly complex nature of hormonal crosstalk in plants. Another factor that needs to be elucidated is the method used for assessing photosynthetic damage in plants that are subjected to abiotic stress. Here, we review the current understanding on the role of phytohormones in the photosynthetic machinery under various abiotic stress conditions and discuss the potential areas for further research. PMID:26287167

  18. Mesenchymal Stem Cells and Metabolic Syndrome: Current Understanding and Potential Clinical Implications

    PubMed Central

    2016-01-01

    Metabolic syndrome is an obesity-based, complicated clinical condition that has become a global epidemic problem with a high associated risk for cardiovascular disease and mortality. Dyslipidemia, hypertension, and diabetes or glucose dysmetabolism are the major factors constituting metabolic syndrome, and these factors are interrelated and share underlying pathophysiological mechanisms. Severe obesity predisposes individuals to metabolic syndrome, and recent data suggest that mesenchymal stem cells (MSCs) contribute significantly to adipocyte generation by increasing the number of adipocytes. Accordingly, an increasing number of studies have examined the potential roles of MSCs in managing obesity and metabolic syndrome. However, despite the growing bank of experimental and clinical data, the efficacy and the safety of MSCs in the clinical setting are still to be optimized. It is thus hoped that ongoing and future studies can elucidate the roles of MSCs in metabolic syndrome and lead to MSC-based therapeutic options for affected patients. This review discusses current understanding of the relationship between MSCs and metabolic syndrome and its potential implications for patient management. PMID:27313625

  19. Advances in the Classification and Treatment of Mastocytosis: Current Status and Outlook toward the Future.

    PubMed

    Valent, Peter; Akin, Cem; Hartmann, Karin; Nilsson, Gunnar; Reiter, Andreas; Hermine, Olivier; Sotlar, Karl; Sperr, Wolfgang R; Escribano, Luis; George, Tracy I; Kluin-Nelemans, Hanneke C; Ustun, Celalettin; Triggiani, Massimo; Brockow, Knut; Gotlib, Jason; Orfao, Alberto; Schwartz, Lawrence B; Broesby-Olsen, Sigurd; Bindslev-Jensen, Carsten; Kovanen, Petri T; Galli, Stephen J; Austen, K Frank; Arber, Daniel A; Horny, Hans-Peter; Arock, Michel; Metcalfe, Dean D

    2017-03-02

    Mastocytosis is a term used to denote a heterogeneous group of conditions defined by the expansion and accumulation of clonal (neoplastic) tissue mast cells in various organs. The classification of the World Health Organization (WHO) divides the disease into cutaneous mastocytosis, systemic mastocytosis, and localized mast cell tumors. On the basis of histomorphologic criteria, clinical parameters, and organ involvement, systemic mastocytosis is further divided into indolent systemic mastocytosis and advanced systemic mastocytosis variants, including aggressive systemic mastocytosis and mast cell leukemia. The clinical impact and prognostic value of this classification has been confirmed in numerous studies, and its basic concept remains valid. However, refinements have recently been proposed by the consensus group, the WHO, and the European Competence Network on Mastocytosis. In addition, new treatment options are available for patients with advanced systemic mastocytosis, including allogeneic hematopoietic stem cell transplantation and multikinase inhibitors directed against KIT D816V and other key signaling molecules. Our current article provides an overview of recent advances in the field of mastocytosis, with emphasis on classification, prognostication, and emerging new treatment options in advanced systemic mastocytosis. Cancer Res; 77(6); 1-10. ©2017 AACR.

  20. Current status of environmental, health, and safety issues of electrochemical capacitors for advanced vehicle applications

    SciTech Connect

    Vimmerstedt, L J; Hammel, C J

    1997-04-01

    Electrochemical capacitors are a candidate for traction power assists in hybrid electric vehicles (HEVs). Other advanced automotive applications, while not the primary focus of current development efforts, are also possible. These include load leveling high-energy batteries, power conditioning electronics, electrically hated catalysts, electric power steering, and engine starter power. Higher power and longer cycle life are expected for electrochemical capacitors than for batteries. Evaluation of environmental, health, and safety (EH and S) issues of electrochemical capacitors is an essential part of the development and commercialization of electrochemical capacitors for advanced vehicles. This report provides an initial EH and S assessment. This report presents electrochemical capacitor electrochemistry, materials selection, intrinsic material hazards, mitigation of those hazards, environmental requirements, pollution control options, and shipping requirements. Most of the information available for this assessment pertains to commercial devices intended for application outside the advanced vehicle market and to experiment or prototype devices. Electrochemical capacitors for power assists in HEVs are not produced commercially now. Therefore, materials for advanced vehicle electrochemical capacitors may change, and so would the corresponding EH and S issues. Although changes are possible, this report describes issues for likely electrochemical capacitor designs.

  1. Interfaces in Heterogeneous Catalysts: Advancing Mechanistic Understanding through Atomic-Scale Measurements.

    PubMed

    Gao, Wenpei; Hood, Zachary D; Chi, Miaofang

    2017-02-16

    interfaces and providing deeper insight for fine-tuning and optimizing catalyst properties. Scanning transmission electron microscopy (STEM) has long been a primary characterization technique used for studying nanomaterials because of its exceptional imaging resolution and simultaneous chemical analysis. Over the past decade, advances in STEM, that is, the commercialization of both aberration correctors and monochromators, have significantly improved the spatial and energy resolution. Imaging atomic structures with subangstrom resolution and identifying chemical species with single-atom sensitivity are now routine for STEM. These advancements have greatly benefitted catalytic research. For example, the roles of lattice strain and surface elemental distribution and their effect on catalytic stability and reactivity have been well documented in bimetallic catalysts. In addition, three-dimensional atomic structures revealed by STEM tomography have been integrated in theoretical modeling for predictive catalyst NP design. Recent developments in stable electronic and mechanical devices have opened opportunities to monitor the evolution of catalysts in operando under synthesis and reaction conditions; high-speed direct electron detectors have achieved sub-millisecond time resolutions and allow for rapid structural and chemical changes to be captured. Investigations of catalysts using these latest microscopy techniques have provided new insights into atomic-level catalytic mechanisms. Further integration of new microscopy methods is expected to provide multidimensional descriptions of interfaces under relevant synthesis and reaction conditions. In this Account, we discuss recent insights on understanding catalyst activity, selectivity, and stability using advanced STEM techniques, with an emphasis on how critical interfaces dictate the performance of precious metal-based heterogeneous catalysts. The role of extended interfacial structures, including those between core and shell

  2. RNAi therapeutics for brain cancer: current advancements in RNAi delivery strategies.

    PubMed

    Malhotra, Meenakshi; Toulouse, André; Godinho, Bruno M D C; Mc Carthy, David John; Cryan, John F; O'Driscoll, Caitriona M

    2015-10-01

    Malignant primary brain tumors are aggressive cancerous cells that invade the surrounding tissues of the central nervous system. The current treatment options for malignant brain tumors are limited due to the inability to cross the blood-brain barrier. The advancements in current research has identified and characterized certain molecular markers that are essential for tumor survival, progression, metastasis and angiogenesis. These molecular markers have served as therapeutic targets for the RNAi based therapies, which enable site-specific silencing of the gene responsible for tumor proliferation. However, to bring about therapeutic success, an efficient delivery carrier that can cross the blood-brain barrier and reach the targeted site is essential. The current review focuses on the potential of targeted, non-viral and viral particles containing RNAi therapeutic molecules as delivery strategies specifically for brain tumors.

  3. Hydrological partitioning in the critical zone: Recent advances and opportunities for developing transferable understanding of water cycle dynamics

    NASA Astrophysics Data System (ADS)

    Brooks, Paul D.; Chorover, Jon; Fan, Ying; Godsey, Sarah E.; Maxwell, Reed M.; McNamara, James P.; Tague, Christina

    2015-09-01

    Hydrology is an integrative discipline linking the broad array of water-related research with physical, ecological, and social sciences. The increasing breadth of hydrological research, often where subdisciplines of hydrology partner with related sciences, reflects the central importance of water to environmental science, while highlighting the fractured nature of the discipline itself. This lack of coordination among hydrologic subdisciplines has hindered the development of hydrologic theory and integrated models capable of predicting hydrologic partitioning across time and space. The recent development of the concept of the critical zone (CZ), an open system extending from the top of the canopy to the base of groundwater, brings together multiple hydrological subdisciplines with related physical and ecological sciences. Observations obtained by CZ researchers provide a diverse range of complementary process and structural data to evaluate both conceptual and numerical models. Consequently, a cross-site focus on "critical zone hydrology" has potential to advance the discipline of hydrology and to facilitate the transition of CZ observatories into a research network with immediate societal relevance. Here we review recent work in catchment hydrology and hydrochemistry, hydrogeology, and ecohydrology that highlights a common knowledge gap in how precipitation is partitioned in the critical zone: "how is the amount, routing, and residence time of water in the subsurface related to the biogeophysical structure of the CZ?" Addressing this question will require coordination among hydrologic subdisciplines and interfacing sciences, and catalyze rapid progress in understanding current CZ structure and predicting how climate and land cover changes will affect hydrologic partitioning.

  4. Advances in understanding mineral dust and boundary layer processes over the Sahara from Fennec aircraft observations

    NASA Astrophysics Data System (ADS)

    Ryder, C. L.; McQuaid, J. B.; Flamant, C.; Rosenberg, P. D.; Washington, R.; Brindley, H. E.; Highwood, E. J.; Marsham, J. H.; Parker, D. J.; Todd, M. C.; Banks, J. R.; Brooke, J. K.; Engelstaedter, S.; Estelles, V.; Formenti, P.; Garcia-Carreras, L.; Kocha, C.; Marenco, F.; Sodemann, H.; Allen, C. J. T.; Bourdon, A.; Bart, M.; Cavazos-Guerra, C.; Chevaillier, S.; Crosier, J.; Darbyshire, E.; Dean, A. R.; Dorsey, J. R.; Kent, J.; O'Sullivan, D.; Schepanski, K.; Szpek, K.; Trembath, J.; Woolley, A.

    2015-07-01

    The Fennec climate programme aims to improve understanding of the Saharan climate system through a synergy of observations and modelling. We present a description of the Fennec airborne observations during 2011 and 2012 over the remote Sahara (Mauritania and Mali) and the advances in the understanding of mineral dust and boundary layer processes they have provided. Aircraft instrumentation aboard the UK FAAM BAe146 and French SAFIRE (Service des Avions Français Instrumentés pour la Recherche en Environnement) Falcon 20 is described, with specific focus on instrumentation specially developed for and relevant to Saharan meteorology and dust. Flight locations, aims and associated meteorology are described. Examples and applications of aircraft measurements from the Fennec flights are presented, highlighting new scientific results delivered using a synergy of different instruments and aircraft. These include (1) the first airborne measurement of dust particles sizes of up to 300 microns and associated dust fluxes in the Saharan atmospheric boundary layer (SABL), (2) dust uplift from the breakdown of the nocturnal low-level jet before becoming visible in SEVIRI (Spinning Enhanced Visible Infra-Red Imager) satellite imagery, (3) vertical profiles of the unique vertical structure of turbulent fluxes in the SABL, (4) in situ observations of processes in SABL clouds showing dust acting as cloud condensation nuclei (CCN) and ice nuclei (IN) at -15 °C, (5) dual-aircraft observations of the SABL dynamics, thermodynamics and composition in the Saharan heat low region (SHL), (6) airborne observations of a dust storm associated with a cold pool (haboob) issued from deep convection over the Atlas Mountains, (7) the first airborne chemical composition measurements of dust in the SHL region with differing composition, sources (determined using Lagrangian backward trajectory calculations) and absorption properties between 2011 and 2012, (8) coincident ozone and dust surface area

  5. Recent advances in the understanding and management of atrial fibrillation: a focus on stroke prevention

    PubMed Central

    Shahid, Farhan; Shantsila, Eduard; Lip, Gregory Y. H.

    2016-01-01

    Atrial fibrillation (AF) is associated with an increased risk of stroke compared with the general population. It is anticipated that by 2030 an estimated 14–17 million patients will be diagnosed with this most prevalent arrhythmia within the European Union. AF-related stroke confers a higher mortality and morbidity risk, and thus early detection and assessment for the initiation of effective stroke prevention with oral anticoagulation (OAC) is crucial. Recent guidelines point to the use of non-vitamin K antagonist OACs (NOACs) where appropriate in stroke prevention of patients with non-valvular AF. At present, there are four NOACS available, with no direct head-to-head comparisons to suggest the superiority of one drug over another. Simple and practical risk assessment tools have evolved over the years to facilitate stroke and bleeding risk assessment in busy clinics and wards to aid decision-making. At present, the CHA 2DS 2VASc (congestive heart failure, hypertension, age 65–74/>75, diabetes mellitus, stroke/transient ischemic attack/thromboembolism, vascular disease, female sex) score is recommended by many international guidelines as a simple and practical method of assessing stroke risk in such patients. Alongside this, use of the HAS BLED (hypertension systolic blood pressure >160 mmHg, abnormal liver/renal function [with creatinine ≥200 μmol/L], stroke, bleeding history or predisposition, labile international normalized ratio [range <60% of the time], elderly [>65], concomitant drugs/alcohol) score aims to identify patients at high risk of bleeding for more regular review and follow-up and draws attention to potentially reversible bleeding risk factors. The aim of this review article is to provide an overview of recent advances in the understanding and management of AF with a focus on stroke prevention. PMID:28105320

  6. Experimental alluvial fans: Advances in understanding of fan dynamics and processes

    NASA Astrophysics Data System (ADS)

    Clarke, Lucy E.

    2015-09-01

    Alluvial fans are depositional systems that develop because of a disparity between the upstream and downstream sediment transport capacity of a system, usually at the base of mountain fronts as rivers emerge from the constrained mountain area onto the plain. They are dynamic landforms that are prone to abrupt changes on a geomorphological (decades to centuries) time scale, while also being long-term deposition features that preserve sedimentary strata and are sensitive indictors of environmental change. The complexity of interactions between catchment characteristics, climate, tectonics, internal system feedbacks, and environmental processes on field alluvial fans means that it is difficult to isolate individual variables in a field setting; therefore, the controlled conditions afforded by experimental models has provided a novel technique to overcome some of these complexities. The use of experimental models of alluvial fans has a long history and these have been implemented over a range of different research areas utilising various experimental designs. Using this technique, important advances have been made in determining the primary factors influencing fan slope, understanding of avulsion dynamics, identifying autogenic processes driving change on fan systems independent of any change in external conditions, and the mechanics of flow and flood risk on alluvial fans, to name a few. However, experiments cannot be carried out in isolation. Thus, combining the findings from experimental alluvial fans with field research and numerical modelling is important and, likewise, using these techniques to inform experimental design. If this can be achieved, there is potential for future experimental developments to explore key alluvial fan issues such as stratigraphic preservation potential and simulating extra terrestrial fan systems.

  7. High-grade glioma management and response assessment—recent advances and current challenges

    PubMed Central

    Khan, M.N.; Sharma, A.M.; Pitz, M.; Loewen, S.K.; Quon, H.; Poulin, A.; Essig, M.

    2016-01-01

    The management of high-grade gliomas (hggs) is complex and ever-evolving. The standard of care for the treatment of hggs consists of surgery, chemotherapy, and radiotherapy. However, treatment options are influenced by multiple factors such as patient age and performance status, extent of tumour resection, biomarker profile, and tumour histology and grade. Follow-up cranial magnetic resonance imaging (mri) to differentiate treatment response from treatment effect can be challenging and affects clinical decision-making. An assortment of advanced radiologic techniques—including perfusion imaging with dynamic susceptibility contrast mri, dynamic contrast-enhanced mri, diffusion-weighted imaging, proton spectroscopy, mri subtraction imaging, and amino acid radiotracer imaging—can now incorporate novel physiologic data, providing new methods to help characterize tumour progression, pseudoprogression, and pseudoresponse. In the present review, we provide an overview of current treatment options for hgg and summarize recent advances and challenges in imaging technology. PMID:27536188

  8. Advances in Our Understanding of Oxylipins Derived from Dietary PUFAs12

    PubMed Central

    Gabbs, Melissa; Leng, Shan; Devassy, Jessay G; Monirujjaman, Md; Aukema, Harold M

    2015-01-01

    Oxylipins formed from polyunsaturated fatty acids (PUFAs) are the main mediators of PUFA effects in the body. They are formed via cyclooxygenase, lipoxygenase, and cytochrome P450 pathways, resulting in the formation of prostaglandins, thromboxanes, mono-, di-, and tri-hydroxy fatty acids (FAs), epoxy FAs, lipoxins, eoxins, hepoxilins, resolvins, protectins (also called neuroprotectins in the brain), and maresins. In addition to the well-known eicosanoids derived from arachidonic acid, recent developments in lipidomic methodologies have raised awareness of and interest in the large number of oxylipins formed from other PUFAs, including those from the essential FAs and the longer-chain n–3 (ω-3) PUFAs. Oxylipins have essential roles in normal physiology and function, but can also have detrimental effects. Compared with the oxylipins derived from n–3 PUFAs, oxylipins from n–6 PUFAs generally have greater activity and more inflammatory, vasoconstrictory, and proliferative effects, although there are notable exceptions. Because PUFA composition does not necessarily reflect oxylipin composition, comprehensive analysis of the oxylipin profile is necessary to understand the overall physiologic effects of PUFAs mediated through their oxylipins. These analyses should include oxylipins derived from linoleic and α-linolenic acids, because these largely unexplored bioactive oxylipins constitute more than one-half of oxylipins present in tissues. Because collated information on oxylipins formed from different PUFAs is currently unavailable, this review provides a detailed compilation of the main oxylipins formed from PUFAs and describes their functions. Much remains to be elucidated in this emerging field, including the discovery of more oxylipins, and the understanding of the differing biological potencies, kinetics, and isomer-specific activities of these novel PUFA metabolites. PMID:26374175

  9. APPLICATION OF ADVANCED IN VITRO TECHNIQUES TO MEASURE, UNDERSTAND AND PREDICT THE KINETICS AND MECHANISMS OF XENOBIOTIC METABOLISM

    EPA Science Inventory

    We have developed a research program in metabolism that involves numerous collaborators across EPA as well as other federal and academic labs. A primary goal is to develop and apply advanced in vitro techniques to measure, understand and predict the kinetics and mechanisms of xen...

  10. Advances in understanding the cell types and approaches used for generating induced pluripotent stem cells.

    PubMed

    Li, Jun; Song, Wei; Pan, Guangjin; Zhou, Jun

    2014-07-19

    Successfully reprogramming somatic cells to a pluripotent state generates induced pluripotent stem (iPS) cells (or iPSCs), which have extensive self-renewal capacity like embryonic stem cells (ESCs). iPSCs can also generate daughter cells that can further undergo differentiation into various lineages or terminally differentiate to reach their final functional state. The discovery of how to produce iPSCs opened a new field of stem cell research with both intellectual and therapeutic benefits. The huge potential implications of disease-specific or patient-specific iPSCs have impelled scientists to solve problems hindering their applications in clinical medicine, especially the issues of convenience and safety. To determine the range of tissue types amenable to reprogramming as well as their particular characteristics, cells from three embryonic germ layers have been assessed, and the advantages that some tissue origins have over fibroblast origins concerning efficiency and accessibility have been elucidated. To provide safe iPSCs in an efficient and convenient way, the delivery systems and combinations of inducing factors as well as the chemicals used to generate iPSCs have also been significantly improved in addition to the efforts on finding better donor cells. Currently, iPSCs can be generated without c-Myc and Klf4 oncogenes, and non-viral delivery integration-free chemically mediated reprogramming methods have been successfully employed with relatively satisfactory efficiency. This paper will review recent advances in iPS technology by highlighting tissue origin and generation of iPSCs. The obstacles that need to be overcome for clinical applications of iPSCs are also discussed.

  11. Advancement Information Resources Management: An Information Understanding Profession in Support of Philanthropy.

    ERIC Educational Resources Information Center

    Mayer, Anne E.

    Professional fundraising has given rise to a new information specialist profession. This career path, which has been known as prospect research or advancement research, should be more accurately characterized as information resources management for advancement. With primary emphasis on value-added information processes that involve analysis and…

  12. Current developments in understanding of West Nile virus central nervous system disease

    PubMed Central

    Tyler, Kenneth L.

    2014-01-01

    Purpose of review West Nile virus (WNV) is the most important cause of epidemic encephalitis in the United States. We review articles published in the last 18 months related to the epidemiology, immunology, clinical features, and treatment of this disease. Recent findings There was a resurgence in WNV disease in the United States in 2012. The WNV strain now predominant in the United States (NA/WN02) differs from the initial emergent isolate in 1999 (NY99). However, differences in the genetics of currently circulating United States WNV strains do not explain variations in epidemic magnitude or disease severity. Innate and acquired immunity are critical in control of WNV, and in some cases pathways are central nervous system specific. The clinical features of infection are now well understood, although nonconfirmed observations of chronic viral excretion in urine remain controversial. There is no specific antiviral therapy for WNV, but studies of antivirals specific for other flaviviruses may identify agents with promise against WNV. Phase I and II human WNV vaccine clinical trials have established that well tolerated and immunogenic WNV vaccines can be developed. Summary WNV remains an important public health problem. Although recent studies have significantly increased our understanding of host immune and genetic factors involved in control of WNV infection, no specific therapy is yet available. Development of a well tolerated, immunogenic, and effective vaccine against WNV is almost certainly feasible, but economic factors and the lack of predictability of the magnitude and location of outbreaks are problematic for designing phase III trials and ultimate licensure. PMID:24722324

  13. Advanced computer techniques for inverse modeling of electric current in cardiac tissue

    SciTech Connect

    Hutchinson, S.A.; Romero, L.A.; Diegert, C.F.

    1996-08-01

    For many years, ECG`s and vector cardiograms have been the tools of choice for non-invasive diagnosis of cardiac conduction problems, such as found in reentrant tachycardia or Wolff-Parkinson-White (WPW) syndrome. Through skillful analysis of these skin-surface measurements of cardiac generated electric currents, a physician can deduce the general location of heart conduction irregularities. Using a combination of high-fidelity geometry modeling, advanced mathematical algorithms and massively parallel computing, Sandia`s approach would provide much more accurate information and thus allow the physician to pinpoint the source of an arrhythmia or abnormal conduction pathway.

  14. Design of the beam shut-off current monitor upgrade for the Advanced Photon Source

    SciTech Connect

    Pietryla, A.; Decker, G.

    2000-05-05

    Plans to eliminate the positron accumulator ring (PAR) from the Advanced Photon Source (APS) injector complex have created the need for a device to limit the allowable beam charge injected into the APS injector synchrotrons. The beam shut-off current monitor (BESOCM) was chosen to provide this function. This new application of the BESOCM provided the opportunity to explore new design philosophies. Two design goals were to de-emphasize reliance on external signals and to become insensitive to timing variations. Both of these goals were accomplished by deriving the trigger directly from the beam. This paper will discuss the features of the new BESOCM design and present data demonstrating its function.

  15. Monitoring for opioid-induced advancing sedation and respiratory depression: ASPMN membership survey of current practice.

    PubMed

    Jungquist, Carla R; Willens, Joyce S; Dunwoody, Danielle R; Klingman, Karen J; Polomano, Rosemary C

    2014-09-01

    Adverse events secondary to opioid-induced advancing sedation and respiratory depression continue to occur during hospitalizations despite efforts to increase awareness and clinical practice guidelines to address prevention strategies. In 2009, ASPMN surveyed membership on current practices surrounding this topic. ASPMN clinical practice guidelines were then published in 2011. In winter of 2013, ASPMN membership was again surveyed to assess progress in preventing adverse events. This is a report of the follow-up membership survey. In general, monitoring practices are slowly improving over time, but there are many facilities that have not instituted best practices for avoiding adverse events.

  16. Development of processing procedures for advanced silicon solar cells. [antireflection coatings and short circuit currents

    NASA Technical Reports Server (NTRS)

    Scott-Monck, J. A.; Stella, P. M.; Avery, J. E.

    1975-01-01

    Ten ohm-cm silicon solar cells, 0.2 mm thick, were produced with short circuit current efficiencies up to thirteen percent and using a combination of recent technical advances. The cells were fabricated in conventional and wraparound contact configurations. Improvement in cell collection efficiency from both the short and long wavelengths region of the solar spectrum was obtained by coupling a shallow junction and an optically transparent antireflection coating with back surface field technology. Both boron diffusion and aluminum alloying techniques were evaluated for forming back surface field cells. The latter method is less complicated and is compatible with wraparound cell processing.

  17. Recent advances and current issues in single-cell sequencing of tumors.

    PubMed

    Sun, Hai-Jian; Chen, Jian; Ni, Bing; Yang, Xia; Wu, Yu-Zhang

    2015-08-28

    Intratumoral heterogeneity is a recently recognized but important feature of cancer that underlies the various biocharacteristics of cancer tissues. The advent of next-generation sequencing technologies has facilitated large scale capture of genomic data, while the recent development of single-cell sequencing has allowed for more in-depth studies into the complex molecular mechanisms of intratumoral heterogeneity. In this review, the recent advances and current challenges in single-cell sequencing methodologies are discussed, highlighting the potential power of these data to provide insights into oncological processes, from tumorigenesis through progression to metastasis and therapy resistance.

  18. The Radiation Belt Storm Probes Mission: Advancing Our Understanding of the Earth's Radiation Belts

    NASA Technical Reports Server (NTRS)

    Sibeck, David; Kanekal, Shrikanth; Kessel, Ramona; Fox, Nicola; Mauk, Barry

    2012-01-01

    We describe NASA's Radiation Belt Storm Probe (RBSP) mission, whose primary science objective is to understand, ideally to the point of predictability, the dynamics of relativistic electrons and penetrating ions in the Earth's radiation belts resulting from variable solar activity. The overarching scientific questions addressed include: 1. the physical processes that produce radiation belt enhancement events, 2. the dominant mechanisms for relativistic electron loss, and 3. how the ring current and other geomagnetic processes affect radiation belt behavior. The RBSP mission comprises two spacecraft which will be launched during Fall 2012 into low inclination lapping equatorial orbits. The orbit periods are about 9 hours, with perigee altitudes and apogee radial distances of 600 km and 5.8 RE respectively. During the two-year primary mission, the spacecraft orbits precess once around the Earth and lap each other twice in each local time quadrant. The spacecraft are each equipped with identical comprehensive instrumentation packages to measure, electrons, ions and wave electric and magnetic fields. We provide an overview of the RBSP mission, onboard instrumentation and science prospects and invite scientific collaboration.

  19. Advances in the understanding of mineral and bone metabolism in inflammatory bowel diseases

    PubMed Central

    Ghishan, Fayez K.

    2011-01-01

    Chronic inflammatory disorders such as inflammatory bowel diseases (IBDs) affect bone metabolism and are frequently associated with the presence of osteopenia, osteoporosis, and increased risk of fractures. Although several mechanisms may contribute to skeletal abnormalities in IBD patients, inflammation and inflammatory mediators such as TNF, IL-1β, and IL-6 may be the most critical. It is not clear whether the changes in bone metabolism leading to decreased mineral density are the result of decreased bone formation, increased bone resorption, or both, with varying results reported in experimental models of IBD and in pediatric and adult IBD patients. New data, including our own, challenge the conventional views, and contributes to the unraveling of an increasingly complex network of interactions leading to the inflammation-associated bone loss. Since nutritional interventions (dietary calcium and vitamin D supplementation) are of limited efficacy in IBD patients, understanding the pathophysiology of osteopenia and osteoporosis in Crohn's disease and ulcerative colitis is critical for the correct choice of available treatments or the development of new targeted therapies. In this review, we discuss current concepts explaining the effects of inflammation, inflammatory mediators and their signaling effectors on calcium and phosphate homeostasis, osteoblast and osteoclast function, and the potential limitations of vitamin D used as an immunomodulator and anabolic hormone in IBD. PMID:21088237

  20. Understanding of the Dynamics of the Stirling Convertor Advanced by Structural Testing

    NASA Technical Reports Server (NTRS)

    Hughes, William O.

    2003-01-01

    associated harmonics. Therefore, Stirling power systems will not disturb spacecraft science experiments if minimal appropriate mounting efforts are made. The third test program, performed in February and May 2001, resulted in a modal characterization of a Stirling convertor. Since the deflection of the TDC piston rod, under vibration excitation, was of particular interest, the outer pressure shell was removed to allow access to the rod. Through this testing, the Stirling TDC's natural frequencies and modes were identified. This knowledge advanced our understanding of the successful 1999 vibration test and may be utilized to optimize the output power of future Stirling designs. The fourth test program, in April 2001, was conducted to characterize the structural response of a pair of Stirling convertors, as a function of their mounting interface stiffness. The test results provide guidance for the Stirling power package interface design. Properly designed, the interface may lead to increased structural capability and power performance beyond what was demonstrated in the successful 1999 vibration test. Dynamic testing performed to date at Glenn has shown that the Stirling convertors can withstand liftoff random vibration environments and meet "good neighbor" vibratory emission requirements. Furthermore, the future utilization of the information obtained during the tests will allow the corporation selected to be the Stirling system integrator to optimize their convertor and system interfaces designs. Glenn's Thermo-Mechanical Systems Branch provides Stirling technology expertise under a Space Act Agreement with the Department of Energy. Additional vibration testing by Glenn's Structural Systems Dynamics Branch is planned to continue to demonstrate the Stirling power system's vibration capability as its technology and flight system designs progress.

  1. Advances in Frozen Ground Studies and Understanding its Role in the Hydrological Cycle

    NASA Astrophysics Data System (ADS)

    Zhang, T.

    2004-05-01

    Significant advances in frozen ground studies have been achieved over the past several decades. Knowledge and information on frozen ground would improve our understanding in local, regional, and global water cycle over the cold regions/cold seasons. Permafrost regions occupy approximately 24 percent of the land area in the Northern Hemisphere. The total volume of the excess ground ice contained in the ice-rich permafrost ranges from about 10,800 to 35,460 cubic kilometers or about 2.7 to 8.8 cm sea-level equivalent. Permafrost limits the amount of subsurface water storage and infiltration that can occur, leading to wet soils and standing surface water, unusual for a region with limited precipitation. Observational evidence indicates that permafrost warming and thawing in the Northern Hemisphere have occurred over the past several decades. Active layer thickness has increased and depth of seasonally frozen ground has decreased significantly in the Russian Arctic and Subarctic. Thickening of the active layer and melting of the excess ground ice may partly contribute to the increase of runoff over the Russian Arctic drainage basin. Increase in active layer thickness may also delay the active layer freeze-up date, possibly leading to the increase in winter river runoff. On average, nearly 50 percent of the land surface in the Northern Hemisphere experiences freeze/thaw cycles that last from a few days to several months with thickness up to several meters. The existence of a thin frozen layer near the surface essentially decouples moisture exchange between the atmosphere and deeper soils. Knowing whether the soil is frozen is important in predicting spring surface runoff and soil moisture reserve in northern United States. Coupling of soil freezing and thawing processes into the hydrological model improves the model prediction on river runoff significantly. The timing, duration, areal extent,frequency, and thickness of the near-surface soil freeze/thaw cycle have

  2. Advanced Practice Registered Nurses and Physician Assistants in Sleep Centers and Clinics: A Survey of Current Roles and Educational Background

    PubMed Central

    Colvin, Loretta; Cartwright, Ann; Collop, Nancy; Freedman, Neil; McLeod, Don; Weaver, Terri E.; Rogers, Ann E.

    2014-01-01

    Study Objectives: To survey Advanced Practice Registered Nurse (APRN) and Physician Assistant (PA) utilization, roles and educational background within the field of sleep medicine. Methods: Electronic surveys distributed to American Academy of Sleep Medicine (AASM) member centers and APRNs and PAs working within sleep centers and clinics. Results: Approximately 40% of responding AASM sleep centers reported utilizing APRNs or PAs in predominantly clinical roles. Of the APRNs and PAs surveyed, 95% reported responsibilities in sleep disordered breathing and more than 50% in insomnia and movement disorders. Most APRNs and PAs were prepared at the graduate level (89%), with sleep-specific education primarily through “on the job” training (86%). All APRNs surveyed were Nurse Practitioners (NPs), with approximately double the number of NPs compared to PAs. Conclusions: APRNs and PAs were reported in sleep centers at proportions similar to national estimates of NPs and PAs in physicians' offices. They report predominantly clinical roles, involving common sleep disorders. Given current predictions that the outpatient healthcare structure will change and the number of APRNs and PAs will increase, understanding the role and utilization of these professionals is necessary to plan for the future care of patients with sleep disorders. Surveyed APRNs and PAs reported a significant deficiency in formal and standardized sleep-specific education. Efforts to provide formal and standardized educational opportunities for APRNs and PAs that focus on their clinical roles within sleep centers could help fill a current educational gap. Citation: Colvin L, Cartwright Ann, Collop N, Freedman N, McLeod D, Weaver TE, Rogers AE. Advanced practice registered nurses and physician assistants in sleep centers and clinics: a survey of current roles and educational background. J Clin Sleep Med 2014;10(5):581-587. PMID:24812545

  3. Current advancements and potential strategies in the development of MERS-CoV vaccines.

    PubMed

    Zhang, Naru; Jiang, Shibo; Du, Lanying

    2014-06-01

    Middle East respiratory syndrome (MERS) is a newly emerging infectious disease caused by a novel coronavirus, MERS-coronavirus (MERS-CoV), a new member in the lineage C of β-coronavirus (β-CoV). The increased human cases and high mortality rate of MERS-CoV infection make it essential to develop safe and effective vaccines. In this review, the current advancements and potential strategies in the development of MERS vaccines, particularly subunit vaccines based on MERS-CoV spike (S) protein and its receptor-binding domain (RBD), are discussed. How to improve the efficacy of subunit vaccines through novel adjuvant formulations and routes of administration as well as currently available animal models for evaluating the in vivo efficacy of MERS-CoV vaccines are also addressed. Overall, these strategies may have important implications for the development of effective and safe vaccines for MERS-CoV in the future.

  4. Current advancements and potential strategies in the development of MERS-CoV vaccines

    PubMed Central

    Zhang, Naru; Jiang, Shibo; Du, Lanying

    2014-01-01

    Middle East respiratory syndrome (MERS) is a newly emerging infectious disease caused by a novel coronavirus, MERS-coronavirus (MERS-CoV), a new member in the lineage C of β-coronavirus (β-CoV). The increased human cases and high mortality rate of MERS-CoV infection make it essential to develop safe and effective vaccines. In this review, the current advancements and potential strategies in the development of MERS vaccines, particularly subunit vaccines based on MERS-CoV spike (S) protein and its receptor-binding domain (RBD), are discussed. How to improve the efficacy of subunit vaccines through novel adjuvant formulations and routes of administration as well as currently available animal models for evaluating the in vivo efficacy of MERS-CoV vaccines are also addressed. Overall, these strategies may have important implications for the development of effective and safe vaccines for MERS-CoV in the future. PMID:24766432

  5. The Blue LED Nobel Prize: Historical context, current scientific understanding, human benefit

    SciTech Connect

    Tsao, Jeffrey Y.; Han, Jung; Haitz, Roland H.; Pattison, P. Morgan

    2015-06-19

    Here, the paths that connect scientific understanding with tools and technology are rarely linear. Sometimes scientific understanding leads and enables, sometimes tools and technologies lead and enable. But by feeding on each other, they create virtuous spirals of forward and backward innovation.

  6. Current status of selected oral peptide technologies in advanced preclinical development and in clinical trials.

    PubMed

    Aguirre, T A S; Teijeiro-Osorio, D; Rosa, M; Coulter, I S; Alonso, M J; Brayden, D J

    2016-11-15

    The development of oral dosage forms that allows absorption of therapeutic peptides to the systemic circulation is one of the greatest challenges for the pharmaceutical industry. Currently, a number of technologies including either mixtures of penetration enhancers or protease inhibitors and/or nanotechnology-based products are under clinical development. Typically, these formulations are presented in the form of enteric-coated tablets or capsules. Systems undergoing preclinical investigation include further advances in nanotechnology, including intestinal microneedle patches, as well as their combination with regional delivery to the colon. This review critically examines four selected promising oral peptide technologies at preclinical stage and the twelve that have progressed to clinical trials, as indicated in www.clinicaltrials.gov. We examined these technologies under the criteria of peptide selection, formulation design, system components and excipients, intestinal mechanism of action, efficacy in man, and safety issues. The conclusion is that most of the technologies in clinical trials are incremental rather than paradigm-shifting and that even the more clinically advanced oral peptide drugs examples of oral bioavailability appear to yield oral bioavailability values of only 1-2% and are, therefore, only currently suitable for a limited range of peptides.

  7. JSC Advanced Curation: Research and Development for Current Collections and Future Sample Return Mission Demands

    NASA Technical Reports Server (NTRS)

    Fries, M. D.; Allen, C. C.; Calaway, M. J.; Evans, C. A.; Stansbery, E. K.

    2015-01-01

    Curation of NASA's astromaterials sample collections is a demanding and evolving activity that supports valuable science from NASA missions for generations, long after the samples are returned to Earth. For example, NASA continues to loan hundreds of Apollo program samples to investigators every year and those samples are often analyzed using instruments that did not exist at the time of the Apollo missions themselves. The samples are curated in a manner that minimizes overall contamination, enabling clean, new high-sensitivity measurements and new science results over 40 years after their return to Earth. As our exploration of the Solar System progresses, upcoming and future NASA sample return missions will return new samples with stringent contamination control, sample environmental control, and Planetary Protection requirements. Therefore, an essential element of a healthy astromaterials curation program is a research and development (R&D) effort that characterizes and employs new technologies to maintain current collections and enable new missions - an Advanced Curation effort. JSC's Astromaterials Acquisition & Curation Office is continually performing Advanced Curation research, identifying and defining knowledge gaps about research, development, and validation/verification topics that are critical to support current and future NASA astromaterials sample collections. The following are highlighted knowledge gaps and research opportunities.

  8. A survey to determine current practice patterns in the surgical treatment of advanced thumb carpometacarpal osteoarthrosis

    PubMed Central

    Brunton, Lance M.

    2010-01-01

    Background The purpose of this study was to determine current practice patterns and examine the influence of recent evidence in the surgical treatment of advanced thumb carpometacarpal (CMC) osteoarthrosis. Methods A survey was sent to 2,536 American Society for Surgery of the Hand members. Information regarding specialty training, years of experience, annual cases performed, treatment of choice, technique, and postoperative immobilization was collected. Respondents were asked whether their current treatment of choice differs from what they performed 5 years ago and about the importance of ligament reconstruction and “interposition” to thumb CMC arthroplasty success. Results One thousand twenty-four respondents completed the survey (40% response rate). Treatment of choice was trapeziectomy with ligament reconstruction and tendon interposition (68%), regardless of specialty training, years of experience, and annual cases performed. Over 70% favored treatment that was not different from what they performed 5 years ago. Less than 3% of respondents perform a trapeziectomy alone; only 14 surgeons have changed to this procedure in the last 5 years. Only 35% of the 822 respondents who perform a ligament reconstruction and 14% of the 764 respondents who perform an interposition believe those techniques are “extremely important” to thumb CMC arthroplasty success. Conclusions Despite recent evidence that suggests neither ligament reconstruction nor tendon interposition confers any additional benefit over trapeziectomy alone, few respondents have converted to the simpler procedure. Either the current evidence is not convincing enough to drastically change practice patterns, or other factors apart from this evidence have a greater influence on surgical decision-making for advanced thumb CMC osteoarthrosis. Electronic supplementary material The online version of this article (doi:10.1007/s11552-010-9275-7) contains supplementary material, which is available to

  9. Current status of understanding quasi-permanent fields associated with earthquakes. [including geological faults and tectonics

    NASA Technical Reports Server (NTRS)

    Brune, J. N.

    1975-01-01

    The basic concepts relating to displacement fields associated with earthquakes are described. Factors discussed include: understanding the geologic and tectonic setting, the discovery of fault creep, and an extended range of possible models of strain buildup. Problems in tectonic modeling reviewed relate to understanding (1) frictional heat generation on faults, (2) the character of stress and strain on faults below the depth of earthquakes, and (3) the predictability of major earthquakes.

  10. Towards integrated approaches to advance understanding of ecohydrological systems across scales

    NASA Astrophysics Data System (ADS)

    Tetzlaff, Doerthe; Soulsby, Chris

    2016-04-01

    It is increasingly recognised that the processes and connections in our landscapes are influencing the functioning of aquatic ecosystems. Fundamental scientific understanding of the functioning of both aquatic and terrestrial ecosystems is required for an integrated and sustainable management of landscapes and riverscapes to maintain their ecosystem services and biological integrity at multiple scales. This talk will show how the interactions and feedbacks in ecohydrological systems can be quantitatively assessed through a number of novel, integrated approaches. Importantly, this talk will discuss the need to understand the role of vegetation on water partitioning at the terrestrial and aquatic interface. Terrestrial and aquatic ecosystems are interacting at every scale level and cross-scale investigations are extremely useful to gain an integrated understanding of ecohydrological systems. Environmental tracers are valuable tools to understand the functioning of ecohydrological systems at the landscape scale in terms of understand flow paths, sources of water and associated biogeochemical interactions. Extensive empirical studies were conducted at the plot and hillslope scale to understand ecohydrological systems, and in particular, soil-vegetation-water interlinkages. This empirically based understanding was then integrated into spatially distributed, tracer-aided models to understand mixing of water, flows to the stream and water age distribution at the catchment scale. Finally, remote sensing techniques were used to integrate empirically based findings and to extrapolate system understanding to cross-regional scales, specifically in terms of studying hydroclimatic variability, vegetation dynamics and consequent changes of plant water use and water partitioning.

  11. Recent advances in bio-logging science: Technologies and methods for understanding animal behaviour and physiology and their environments

    NASA Astrophysics Data System (ADS)

    Evans, K.; Lea, M.-A.; Patterson, T. A.

    2013-04-01

    The deployment of an ever-evolving array of animal-borne telemetry and data logging devices is rapidly increasing our understanding of the movement, behaviour and physiology of a variety species and the complex, and often highly dynamic, environments they use and respond to. The rapid rate at which new technologies, improvements to current technologies and new analytical techniques are being developed has meant that movements, behaviour and physiological processes are being quantified at finer spatial and temporal scales than ever before. The Fourth International Symposium on Bio-logging Science, held on 14-18 March in Hobart, Australia, brought together scientists across multiple disciplines to discuss the latest innovations in technology, applications and analytical techniques in bio-logging science, building on research presented at three previous conferences. Here we present an update on the state of bio-logging research and provide some views on the future of this field of research. Papers were grouped into five theme areas: (i) Southern Ocean ecosystems; (ii) fishery and biodiversity management applications; (iii) from individuals to populations—inferences of population dynamics from individuals; (iv) conservation biology and (v) habitat modelling. Papers reflected wider uptake of newer technologies, with a greater proportion of studies utilising accelerometry and incorporating advances in statistical modelling of behaviour and habitats, especially via state space modelling methods. Environmental data collected by tags at increasing accuracies are now having wider application beyond the bio-logging community, providing important oceanographic data from regions difficult to sample using traditional methodologies. Partnerships between multiple organisations are also now enabling regional assessments of species movements, behaviour and physiology at population scales and will continue to be important for applying bio-logging technologies to species

  12. Recent advances in understanding/management of non-alcoholic steatohepatitis

    PubMed Central

    Pacana, Tommy

    2015-01-01

    Non-alcoholic steatohepatitis (NASH) can lead to advanced fibrosis, hepatocellular carcinoma, and end-stage liver disease requiring liver transplantation. A myriad of pathways and genetic influence contribute to NASH pathogenesis and liver disease progression. Diagnosing patients with NASH and advanced fibrosis is critical prior to treatment and prognostication. There has been ongoing interest in developing non-invasive biomarkers and tools for identifying NASH and advanced fibrosis. To date, there has been no approved therapy for NASH. Recently, the FLINT (Farnesoid X Receptor [FXR] Ligand Obeticholic Acid in NASH Treatment) trial provided promising results of the efficacy of obeticholic acid, a farnesoid X receptor agonist, in improving histological features of NASH and fibrosis. Long-term studies are needed to assess the safety of obeticholic acid and its effects on liver- and cardiovascular-related outcomes. PMID:25926979

  13. Advancing Understanding Using Nonaka's Model of Knowledge Creation and Problem-Based Learning

    ERIC Educational Resources Information Center

    Tee, Meng Yew; Lee, Shuh Shing

    2013-01-01

    Nonaka's model of knowledge creation can provide guidance for designing learning environments and activities. However, Bereiter is critical of the model because it does not address whether understanding is deepened in the process of socialization, externalization, combination and internalization. To address this issue of understanding, this…

  14. Caustic-based approach to understanding bunching dynamics and current spike formation in particle bunches

    NASA Astrophysics Data System (ADS)

    Charles, T. K.; Paganin, D. M.; Dowd, R. T.

    2016-10-01

    Current modulations, current spikes, and current horns, are observed in a range of accelerator physics applications including strong bunch compression in Free Electron Lasers and linear colliders, trains of microbunching for terahertz radiation, microbunching instability and many others. This paper considers the fundamental mechanism that drives intense current modulations in dispersive regions, beyond the common explanation of nonlinear and higher-order effects. Under certain conditions, neighboring electron trajectories merge to form caustics, and often result in characteristic current spikes. Caustic lines and surfaces are regions of maximum electron density, and are witnessed in accelerator physics as folds in phase space of accelerated bunches. We identify the caustic phenomenon resulting in cusplike current profiles and derive an expression which describes the conditions needed for particle-bunch caustic formation in dispersive regions. The caustic expression not only reveals the conditions necessary for caustics to form but also where in longitudinal space the caustics will form. Particle-tracking simulations are used to verify these findings. We discuss the broader implications of this work including how to utilize the caustic expression for manipulation of the longitudinal phase space to achieve a desired current profile shape.

  15. Advances in Telescope and Detector Technologies - Impacts on the Study and Understanding of Binary Star and Exoplanet Systems

    NASA Astrophysics Data System (ADS)

    Guinan, Edward F.; Engle, Scott; Devinney, Edward J.

    2012-04-01

    Current and planned telescope systems (both on the ground and in space) as well as new technologies will be discussed with emphasis on their impact on the studies of binary star and exoplanet systems. Although no telescopes or space missions are primarily designed to study binary stars (what a pity!), several are available (or will be shortly) to study exoplanet systems. Nonetheless those telescopes and instruments can also be powerful tools for studying binary and variable stars. For example, early microlensing missions (mid-1990s) such as EROS, MACHO and OGLE were initially designed for probing dark matter in the halos of galaxies but, serendipitously, these programs turned out to be a bonanza for the studies of eclipsing binaries and variable stars in the Magellanic Clouds and in the Galactic Bulge. A more recent example of this kind of serendipity is the Kepler Mission. Although Kepler was designed to discover exoplanet transits (and so far has been very successful, returning many planetary candidates), Kepler is turning out to be a ``stealth'' stellar astrophysics mission returning fundamentally important and new information on eclipsing binaries, variable stars and, in particular, providing a treasure trove of data of all types of pulsating stars suitable for detailed Asteroseismology studies. With this in mind, current and planned telescopes and networks, new instruments and techniques (including interferometers) are discussed that can play important roles in our understanding of both binary star and exoplanet systems. Recent advances in detectors (e.g. laser frequency comb spectrographs), telescope networks (both small and large - e.g. Super-WASP, HAT-net, RoboNet, Las Combres Observatory Global Telescope (LCOGT) Network), wide field (panoramic) telescope systems (e.g. Large Synoptic Survey Telescope (LSST) and Pan-Starrs), huge telescopes (e.g. the Thirty Meter Telescope (TMT), the Overwhelming Large Telescope (OWL) and the Extremely Large Telescope (ELT

  16. 48 CFR 1552.215-74 - Advanced understanding-uncompensated time.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... hours delivered during the contract. In the event there is a shortage of uncompensated time hours...-uncompensated time. 1552.215-74 Section 1552.215-74 Federal Acquisition Regulations System ENVIRONMENTAL... Clauses 1552.215-74 Advanced understanding—uncompensated time. As prescribed in 1515.408(b), insert...

  17. Understanding Fluorescence Measurements through a Guided-Inquiry and Discovery Experiment in Advanced Analytical Laboratory

    ERIC Educational Resources Information Center

    Wilczek-Vera, Grazyna; Salin, Eric Dunbar

    2011-01-01

    An experiment on fluorescence spectroscopy suitable for an advanced analytical laboratory is presented. Its conceptual development used a combination of the expository and discovery styles. The "learn-as-you-go" and direct "hands-on" methodology applied ensures an active role for a student in the process of visualization and discovery of concepts.…

  18. Annual Research Review: Impact of Advances in Genetics in Understanding Developmental Psychopathology

    ERIC Educational Resources Information Center

    Addington, Anjene M.; Rapoport, Judith L.

    2012-01-01

    It was hoped that diagnostic guidelines for, and treatment of, child psychiatric disorders in DSM-5 would be informed by the wealth of clinical genetic research related to neurodevelopmental disorders. In spite of remarkable advances in genetic technology, this has not been the case. Candidate gene, genome-wide association, and rare copy number…

  19. Advances in Modern Botnet Understanding and the Accurate Enumeration of Infected Hosts

    ERIC Educational Resources Information Center

    Nunnery, Christopher Edward

    2011-01-01

    Botnets remain a potent threat due to evolving modern architectures, inadequate remediation methods, and inaccurate measurement techniques. In response, this research exposes the architectures and operations of two advanced botnets, techniques to enumerate infected hosts, and pursues the scientific refinement of infected-host enumeration data by…

  20. The current format and ongoing advances of medical education in the United States.

    PubMed

    Gishen, Kriya; Ovadia, Steven; Arzillo, Samantha; Avashia, Yash; Thaller, Seth R

    2014-01-01

    The objective of this study was to examine the current system of medical education along with the advances that are being made to support the demands of a changing health care system. American medical education must reform to anticipate the future needs of a changing health care system. Since the dramatic transformations to medical education that followed the publication of the Flexner report in 1910, medical education in the United States has largely remained unaltered. Today, the education of future physicians is undergoing modifications at all levels: premedical education, medical school, and residency training. Advances are being made with respect to curriculum design and content, standardized testing, and accreditation milestones. Fields such as plastic surgery are taking strides toward improving resident training as the next accreditation system is established. To promote more efficacious medical education, the American Medical Association has provided grants for innovations in education. Likewise, the Accreditation Council for Graduate Medical Education outlined 6 core competencies to standardize the educational goals of residency training. Such efforts are likely to improve the education of future physicians so that they are able to meet the future needs of American health care.

  1. Current therapeutic strategies of anti-HER2 treatment in advanced breast cancer patients

    PubMed Central

    Nowara, Elżbieta

    2016-01-01

    The HER2/neu (ERBB2) oncogene is amplified and/or overexpressed in approximately 20% of breast cancers, and is a strong prognostic factor for relapse and poor overall survival, particularly in node-positive patients. It is also an important predictor for response to trastuzumab, which has established efficacy against breast cancer with overexpression or amplification of the HER2 oncogene. Treatment with the anti-HER2 humanized monoclonal antibody – trastuzumab significantly improves progression-free and overall survival among patients with HER2-positive breast cancer. However, in most patients with HER2-positive metastatic breast cancer, the disease progresses occurred, what cause the need for new targeted therapies for advanced disease. In clinical trials, there are tested new drugs to improve the results of treatment for this group of patients. This paper presents new drugs introduced into clinical practice for treatment of advanced breast cancer, whose molecular target are receptors of the HER2 family. In addition, new therapeutic strategies and drugs that are currently in clinical researches are discussed. PMID:27095932

  2. Current Advances in Lanthanide‐Doped Upconversion Nanostructures for Detection and Bioapplication

    PubMed Central

    Chen, Cailing

    2016-01-01

    Along with the development of science and technology, lanthanide‐doped upconversion nanostructures as a new type of materials have taken their place in the field of nanomaterials. Upconversion luminescence is a nonlinear optical phenomenon, which absorbs two or more photons and emits one photon. Compared with traditional luminescence materials, upconversion nanostructures have many advantages, such as weak background interference, long lifetime, low excitation energy, and strong tissue penetration. These interesting nanostructures can be applied in anticounterfeit, solar cell, detection, bioimaging, therapy, and so on. This review is focused on the current advances in lanthanide‐doped upconversion nanostructures, covering not only basic luminescence mechanism, synthesis, and modification methods but also the design and fabrication of upconversion nanostructures, like core–shell nanoparticles or nanocomposites. At last, this review emphasizes the application of upconversion nanostructure in detection and bioimaging and therapy. Learning more about the advances of upconversion nanostructures can help us better exploit their excellent performance and use them in practice. PMID:27840794

  3. Cancer of the Pancreas: Molecular Pathways and Current Advancement in Treatment

    PubMed Central

    Polireddy, Kishore; Chen, Qi

    2016-01-01

    Pancreatic cancer is one of the most lethal cancers among all malignances, with a median overall survival of <1 year and a 5-year survival of ~5%. The dismal survival rate and prognosis are likely due to lack of early diagnosis, fulminant disease course, high metastasis rate, and disappointing treatment outcome. Pancreatic cancers harbor a variety of genetic alternations that render it difficult to treat even with targeted therapy. Recent studies revealed that pancreatic cancers are highly enriched with a cancer stem cell (CSC) population, which is resistant to chemotherapeutic drugs, and therefore escapes chemotherapy and promotes tumor recurrence. Cancer cell epithelial to mesenchymal transition (EMT) is highly associated with metastasis, generation of CSCs, and treatment resistance in pancreatic cancer. Reviewed here are the molecular biology of pancreatic cancer, the major signaling pathways regulating pancreatic cancer EMT and CSCs, and the advancement in current clinical and experimental treatments for pancreatic cancer. PMID:27471566

  4. The kinetoplastid chemotherapy revisited: current drugs, recent advances and future perspectives.

    PubMed

    Castillo, E; Dea-Ayuela, M A; Bolás-Fernández, F; Rangel, M; González-Rosende, M E

    2010-01-01

    Leishmaniasis, African sleeping sickness and Chagas disease, caused by the kinetoplastid parasites Leishmania spp, Trypanosoma brucei and Trypanosoma cruzi, respectively, are among the most important parasitic diseases, affecting millions of people and considered to be within the most relevant group of neglected tropical diseases. The main alternative to control such parasitosis is chemotherapy. Nevertheless, the current chemotherapeutic treatments are far from being satisfactory. This review outlines the current understanding of different drugs against leishmaniasis, African sleeping sickness and Chagas disease, their mechanism of action and resistance. Recent approaches in the area of anti-leishmanial and trypanocidal therapies are also enumerated, new modulators from the mode of action, development of new formulations of old drugs, therapeutic switching and "in silico" drug design.

  5. Trying to Get Ahead of the Curve: Raising and Understanding Current Themes in New Literacies Practices

    ERIC Educational Resources Information Center

    Wilber, Dana

    2012-01-01

    This article addresses the following questions: What impact does using the theoretical framework of new literacies have on understanding language, literacy, and learning practices today as technologies are constantly being developed and used? What is the state of research in this area? What are some new directions the field might take in order to…

  6. Promoting Fourth Graders' Conceptual Change of Their Understanding of Electric Current via Multiple Analogies

    ERIC Educational Resources Information Center

    Chiu, Mei-Hung; Lin, Jing-Wen

    2005-01-01

    For the past two decades, a growing amount of research has shown that the use of analogies in science teaching and learning promotes meaningful understanding of complex scientific concepts (Gentner, [1983]; Glynn, [1989]; Harrison & Treagust, [1993]; Wong, [1993]). This article presents a study in which multiple analogies were used as scaffolding…

  7. Promoting fourth graders' conceptual change of their understanding of electric current via multiple analogies

    NASA Astrophysics Data System (ADS)

    Chiu, Mei-Hung; Lin, Jing-Wen

    2005-04-01

    For the past two decades, a growing amount of research has shown that the use of analogies in science teaching and learning promotes meaningful understanding of complex scientific concepts (Gentner, [1983]; Glynn, [1989]; Harrison & Treagust, [1993]; Wong, [1993]). This article presents a study in which multiple analogies were used as scaffolding to link students' prior understanding of daily life events to knowledge of the scientific domain. The study was designed to investigate how multiple analogies influence student learning of a complex scientific concept: the electric circuit. We used several analogies in a set of learning materials to present the concepts of parallel and series circuits. Thirty-two fourth graders participated in this study and were randomly assigned to four groups. The four groups were named nonanalogy (control), single analogy, similar analogies, and complementary analogies, according to the materials they used in this study. The results demonstrated that using analogies not only promoted profound understanding of complex scientific concepts (such as electricity), but it also helped students overcome their misconceptions of these concepts. In particular, we found that the reason the students had difficulty understanding the concept of electricity was because of their ontological presupposition of the concept. Implications for teaching and learning are discussed.

  8. Current as the Key Concept of Taiwanese Students' Understandings of Electric Circuits

    ERIC Educational Resources Information Center

    Tsai, Chia-Hsing; Chen, Hsueh-Yu; Chou, Ching-Yang; Lain, Kuen-Der

    2007-01-01

    The purpose of this study was to report the results of a nationwide survey of Taiwanese high schools students' understandings about electric circuits. The study involved two stratified random samples consisting of 7,145 students in Grades 8 and 9, and 2,857 students in Grade 11, accounting for about 2.3% of the total enrolment in the corresponding…

  9. Off-axis Neutral Beam Current Drive for Advanced Scenario Development in DIII-D

    SciTech Connect

    Murakami, M; Park, J; Petty, C; Luce, T; Heidbrink, W; Osborne, T; Wade, M; Austin, M; Brooks, N; Budny, R; Challis, C; DeBoo, J; deGrassie, J; Ferron, J; Gohil, P; Hobirk, J; Holcomb, C; Hollmann, E; Hong, R; Hyatt, A; Lohr, J; Lanctot, M; Makowski, M; McCune, D; Politzer, P; Prater, R; John, H S; Suzuki, T; West, W; Unterberg, E; Van Zeeland, M; Yu, J

    2008-10-13

    Modification of the two existing DIII-D neutral beam lines is proposed to allow vertical steering to provide off-axis neutral beam current drive (NBCD) as far off-axis as half the plasma radius. New calculations indicate very good current drive with good localization off-axis as long as the toroidal magnetic field, B{sub T}, and the plasma current, I{sub p}, are in the same direction (for a beam steered downward). The effects of helicity can be large: e.g., ITER off-axis NBCD can be increased by more than 20% if the B{sub T} direction is reversed. This prediction has been tested by an off-axis NBCD experiment using reduced size plasmas that are vertically shifted with the existing NBI on DIII-D. The existence of off-axis NBCD is evident in sawtooth and internal inductance behavior. By shifting the plasma upward or downward, or by changing the sign of the toroidal field, measured off-axis NBCD profiles, determined from MSE data, are consistent with predicted differences (40%-45%) arising from the NBI orientation with respect to the magnetic field lines. Modification of the DIII-D NB system will strongly support scenario development for ITER and future tokamaks as well as providing flexible scientific tools for understanding transport, energetic particles and heating and current drive.

  10. Recent advances in understanding the role of adipocytokines during non-alcoholic fatty liver disease pathogenesis and their link with hepatokines.

    PubMed

    Panera, Nadia; Della Corte, Claudia; Crudele, Annalisa; Stronati, Laura; Nobili, Valerio; Alisi, Anna

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is currently considered the main cause of chronic liver disease worldwide. Mechanisms leading to the development and progression of this disease are topics of great interest for researchers and clinicians. The current multi-hit hypothesis has thrown the crosstalk between liver and adipose tissue into sharp focus. It is well known that adipose tissue produces circulating factors, known as adipocytokines, which exert several effects on liver cells, promoting the onset of NAFLD and its progression to non-alcoholic steatohepatitis in obese subjects. In a similar way, hepatocytes may also respond to obesogenic stimuli by producing and releasing hepatokines into the circulation. Here, the authors provide an overview of recent advances in our understanding of the role of the most relevant adipocytokines and hepatokines in NAFLD pathogenesis, highlighting their possible molecular and functional interactions.

  11. Greek Primary School Teachers' Understanding of Current Environmental Issues: An Exploration of Their Environmental Knowledge and Images of Nature

    ERIC Educational Resources Information Center

    Michail, Sirmo; Stamou, Anastasia G.; Stamou, George P.

    2007-01-01

    In this article, the Greek primary school teachers' understanding of three current environmental issues (acid rain, the ozone layer depletion, and the greenhouse effect) as well as the emerging images of nature were examined. The study revealed that teachers held several environmental knowledge gaps and misconceptions about the three phenomena.…

  12. Effects of Conceptual Change and Traditional Confirmatory Simulations on Pre-Service Teachers' Understanding of Direct Current Circuits

    ERIC Educational Resources Information Center

    Baser, Mustafa

    2006-01-01

    The objective of this research is to investigate the effects of simulations based on conceptual change conditions (CCS) and traditional confirmatory simulations (TCS) on pre-service elementary school teachers' understanding of direct current electric circuits. The data was collected from a sample consisting of 89 students; 48 students in the…

  13. Satellite soil moisture for advancing our understanding of earth system processes and climate change

    NASA Astrophysics Data System (ADS)

    Dorigo, Wouter; de Jeu, Richard

    2016-06-01

    Soil moisture products obtained from active and passive microwave satellites have reached maturity during the last decade (De Jeu and Dorigo, 2016): On the one hand, research algorithms that were initially applied to sensors designed for other purposes, e.g., for measuring wind speed (e.g. the Advanced Scatterometer (ASCAT)), sea ice, or atmospheric parameters (e.g. the TRMM Microwave Imager (TMI) and the Advanced Microwave Scanning Radiometer - Earth Observing System AMSR-E), have developed into fully operational products. On the other hand, dedicated soil moisture satellite missions were designed and launched by ESA (the Soil Moisture Ocean Salinity (SMOS) mission) and NASA (the Soil Moisture Active Passive (SMAP) mission).

  14. Understanding advanced theory of mind and empathy in high-functioning adults with autism spectrum disorder.

    PubMed

    Mathersul, Danielle; McDonald, Skye; Rushby, Jacqueline A

    2013-01-01

    It has been argued that higher functioning individuals with autism spectrum disorders (ASDs) have specific deficits in advanced but not simple theory of mind (ToM), yet the questionable ecological validity of some tasks reduces the strength of this assumption. The present study employed The Awareness of Social Inference Test (TASIT), which uses video vignettes to assess comprehension of subtle conversational inferences (sarcasm, lies/deception). Given the proposed relationships between advanced ToM and cognitive and affective empathy, these associations were also investigated. As expected, the high-functioning adults with ASDs demonstrated specific deficits in comprehending the beliefs, intentions, and meaning of nonliteral expressions. They also had significantly lower cognitive and affective empathy. Cognitive empathy was related to ToM and group membership whereas affective empathy was only related to group membership.

  15. Understanding the Josephson current through a Kondo-correlated quantum dot.

    PubMed

    Luitz, D J; Assaad, F F; Novotný, T; Karrasch, C; Meden, V

    2012-06-01

    We study the Josephson current 0-π transition of a quantum dot tuned to the Kondo regime. The physics can be quantitatively captured by the numerically exact continuous time quantum Monte Carlo method applied to the single-impurity Anderson model with Bardeen-Cooper-Schrieffer superconducting leads. For a comparison to an experiment, the tunnel couplings are determined by fitting the normal-state linear conductance. Excellent agreement for the dependence of the critical Josephson current on the level energy is achieved. For increased tunnel couplings the Kondo scale becomes comparable to the superconducting gap, and the regime of the strongest competition between superconductivity and Kondo correlations is reached; we predict the gate voltage dependence of the critical current in this regime.

  16. A Changing Landscape of Advanced Prostate Cancer: Understanding Mechanisms of Resistance to Potent Hormonal Therapies

    DTIC Science & Technology

    2015-10-01

    and CpG DNA methylation integrative analyses point to key drivers of NEPC including loss of RB1 and TP53 and primarily epigenetic changes...sequencing (WES) and other molecular analyses of tumor and germline DNA from patients with advanced disease and to follow patients prospectively to...protein expression alterations involving DNA mismatch repair genes consistent with prior studies. The significant overlap between CRPC-Adeno and CRPC

  17. Advances in understanding ventromedial prefrontal function: the accountant joins the executive.

    PubMed

    Fellows, Lesley K

    2007-03-27

    Studies of the brain basis of decision-making and economic behavior are providing a new perspective on the organization and functions of human prefrontal cortex. This line of inquiry has focused particularly on the ventral and medial portions of prefrontal cortex, arguably the most enigmatic regions of the "enigmatic frontal lobes." This review highlights recent advances in the cognitive neuroscience of decision making and neuroeconomics and discusses how these findings can inform clinical thinking about frontal lobe dysfunction.

  18. Pilot Study to Assess Current Understanding of Lateral Mixing in the Ocean

    DTIC Science & Technology

    2016-06-07

    the Navy and society in general, from submarine detection to the development of operational parameterizations of small-scale lateral dispersion based...COMMUNITY’S UNDERSTANDING Significant lateral mixing on scales of 10 m – 10 km is observed in coastal and estuarine environments , at sites close to and...under ocean conditions ranging from relatively quiescent environments such as the inlets of Puget Sound or the New England Shelf to more energetic

  19. Understanding the Effects of Infrastructure Changes on Subpopulations: Survey of Current Methods, Models, and Tools

    DTIC Science & Technology

    2016-04-01

    and services are produced, distributed, and consumed . A formal, western economic approach is to assume that economic decision making is driven by the... decision making . A task assigned to an Engineer Warrant Officer to perform an IR survey simultaneously requires an assessment of social and cultural...operational environment (OE), to form an understanding that is shared by commander and staff and is used by both to support sound decision making

  20. Understanding Thermohaline Mixing in the Agulhas Return Current from Seismic and Finestructure Observations

    DTIC Science & Technology

    2014-07-01

    interleaving thermohaline intrusions at submesoscales . Indian Ocean; Agulhas Current System; seismic observations Unclassified Unclassified...zone that is characterized by the presence of a strong temperature front and is manifested by interleaving thermohaline intrusions at submesoscales ...to elucidate submesoscale and fine scale frontal zone mixing processes by assessing how mesoscale and fine-scale features influence thermohaline

  1. A Historical Study to Understand Students' Current Difficulties about RMS Values

    ERIC Educational Resources Information Center

    Khantine-Langlois, Françoise; Munier, Valérie

    2016-01-01

    Several studies show that students experience more and more difficulties managing the measurements of electrical values in alternating current and that they have trouble making links between theory and practice. They find it difficult to give meaning to root mean square (RMS; or effective) values, which are not understood as average values and are…

  2. Sailing toward Understanding Surface Currents: A Science and Geography Integration Activity for Upper-Elementary Students

    ERIC Educational Resources Information Center

    Eidietis, Laura; Rutherford, Sandra

    2009-01-01

    In the activities presented in this article, students mimic real scientists while constructing predictions and scientific explanations about surface currents. The activities are inspired by and couched within true scientific inquiries regarding the ocean and the North American Great Lakes. Students engage in a classroom inquiry and use map-reading…

  3. Current Advance and Future Prospects of Tissue Engineering Approach to Dentin/Pulp Regenerative Therapy

    PubMed Central

    Gong, Ting; Heng, Boon Chin; Lo, Edward Chin Man; Zhang, Chengfei

    2016-01-01

    Recent advances in biomaterial science and tissue engineering technology have greatly spurred the development of regenerative endodontics. This has led to a paradigm shift in endodontic treatment from simply filling the root canal systems with biologically inert materials to restoring the infected dental pulp with functional replacement tissues. Currently, cell transplantation has gained increasing attention as a scientifically valid method for dentin-pulp complex regeneration. This multidisciplinary approach which involves the interplay of three key elements of tissue engineering—stem cells, scaffolds, and signaling molecules—has produced an impressive number of favorable outcomes in preclinical animal studies. Nevertheless, many practical hurdles need to be overcome prior to its application in clinical settings. Apart from the potential health risks of immunological rejection and pathogenic transmission, the lack of a well-established banking system for the isolation and storage of dental-derived stem cells is the most pressing issue that awaits resolution and the properties of supportive scaffold materials vary across different studies and remain inconsistent. This review critically examines the classic triad of tissue engineering utilized in current regenerative endodontics and summarizes the possible techniques developed for dentin/pulp regeneration. PMID:27069484

  4. High Current ESD Test of Advanced Triple Junction Solar Array Coupon

    NASA Technical Reports Server (NTRS)

    Wright, Kenneth H., Jr.; Schneider, Todd A.; Vaughn, Jason A.; Hoang, Bao; Wong, Frankie

    2014-01-01

    Testing was conducted on an Advanced Triple Junction (ATJ) coupon that was part of a risk reduction effort in the development of a high-powered solar array design by Space Systems Loral, LLC (SSL). The ATJ coupon was a small, 4-cell, two-string configuration of flight-type design that has served as the basic test coupon design used in previous SSL environmental aging campaigns. The objective of the present test was to evaluate the performance of the coupon after being subjected to induced electrostatic discharge (ESD) testing at two string voltages (100 V, 150 V) and four string currents (1.65 A, 2.0 A, 2.475 A, and 3.3 A). An ESD test circuit, unique to SSL solar array design, was built that simulates the effect of missing cells and strings in a full solar panel with special primary arc flashover circuitry. A total of 73 primary arcs were obtained that included 7 temporary sustained arcs (TSA) events. The durations of the TSAs ranged from 50 micro-seconds to 2.75 milli-seconds. All TSAs occurred at a string voltage of 150 V. Post-ESD functional testing showed that no degradation occurred due to the TSA events. These test results point to a robust design for application to a high-current, high-power mission.

  5. Pulmonary hypertension in adults with congenital heart disease and Eisenmenger syndrome: current advanced management strategies.

    PubMed

    D'Alto, Michele; Diller, Gerhard-Paul

    2014-09-01

    The presence of pulmonary arterial hypertension (PAH) increases morbidity and reduces survival in patients with congenital heart disease (CHD). PAH-CHD is a heterogeneous condition, depending on the type of the underlying defect and previous repair strategies. There is growing evidence of the benefits of PAH-specific therapy in the PAH-CHD population, but despite recent advances mortality rates remain relatively high. In the last years, an increasing focus has been placed on patients with PAH-CHD and net left-to-right shunt. Currently, there are limited data to guide the management of these patients and uncertainty on the cut-off values for eventual defect closure. Pregnancy conveys significant risks in PAH-CHD patients: appropriate counselling and care, including psychological support and a multidisciplinary team, should be part of the routine management of women with PAH-CHD of reproductive age. Some subgroups, such as patients with Down's syndrome, Fontan circulation and 'segmental' pulmonary hypertension, present particular challenges in terms of management and therapy. The current review focuses on contemporary treatment strategies in PAH-CHD patients with particular emphasis on challenging patient groups and conditions.

  6. Current advances in diagnosis and surgical treatment of lymph node metastasis in head and neck cancer

    PubMed Central

    Teymoortash, A.; Werner, J. A.

    2012-01-01

    Still today, the status of the cervical lymph nodes is the most important prognostic factor for head and neck cancer. So the individual treatment concept of the lymphatic drainage depends on the treatment of the primary tumor as well as on the presence or absence of suspect lymph nodes in the imaging diagnosis. Neck dissection may have either a therapeutic objective or a diagnostic one. The selective neck dissection is currently the method of choice for the treatment of patients with advanced head and neck cancers and clinical N0 neck. For oncologic reasons, this procedure is generally recommended with acceptable functional and aesthetic results, especially under the aspect of the mentioned staging procedure. In this review article, current aspects on pre- and posttherapeutic staging of the cervical lymph nodes are described and the indication and the necessary extent of neck dissection for head and neck cancer is discussed. Additionally the critical question is discussed if the lymph node metastasis bears an intrinsic risk of metastatic development and thus its removal in a most possible early stage plays an important role. PMID:23320056

  7. Current Advances in the Computational Simulation of the Formation of Low-Mass Stars

    SciTech Connect

    Klein, R I; Inutsuka, S; Padoan, P; Tomisaka, K

    2005-10-24

    Developing a theory of low-mass star formation ({approx} 0.1 to 3 M{sub {circle_dot}}) remains one of the most elusive and important goals of theoretical astrophysics. The star-formation process is the outcome of the complex dynamics of interstellar gas involving non-linear interactions of turbulence, gravity, magnetic field and radiation. The evolution of protostellar condensations, from the moment they are assembled by turbulent flows to the time they reach stellar densities, spans an enormous range of scales, resulting in a major computational challenge for simulations. Since the previous Protostars and Planets conference, dramatic advances in the development of new numerical algorithmic techniques have been successfully implemented on large scale parallel supercomputers. Among such techniques, Adaptive Mesh Refinement and Smooth Particle Hydrodynamics have provided frameworks to simulate the process of low-mass star formation with a very large dynamic range. It is now feasible to explore the turbulent fragmentation of molecular clouds and the gravitational collapse of cores into stars self-consistently within the same calculation. The increased sophistication of these powerful methods comes with substantial caveats associated with the use of the techniques and the interpretation of the numerical results. In this review, we examine what has been accomplished in the field and present a critique of both numerical methods and scientific results. We stress that computational simulations should obey the available observational constraints and demonstrate numerical convergence. Failing this, results of large scale simulations do not advance our understanding of low-mass star formation.

  8. Korean preschoolers' advanced inhibitory control and its relation to other executive skills and mental state understanding.

    PubMed

    Oh, Seungmi; Lewis, Charlie

    2008-01-01

    This study assessed executive function and mental state understanding in Korean preschoolers. In Experiment 1, forty 3.5- and 4-year-old Koreans showed ceiling performance on inhibition and switching measures, although their performance on working memory and false belief was comparable to that of Western children. Experiment 2 revealed a similar advantage in a sample of seventy-six 3- and 4-year-old Koreans compared with sixty-four age-matched British children. Korean children younger than 3.5 years of age showed ceiling effects on some inhibition measures despite more stringent protocols and the link between executive function and mental state understanding was not as strong as in the British sample. The results raise key questions about the nature and development of the executive system and its relation to social understanding.

  9. Age-Related Vestibular Loss: Current Understanding and Future Research Directions

    PubMed Central

    Arshad, Qadeer; Seemungal, Barry M.

    2016-01-01

    The vestibular system sub-serves a number of reflex and perceptual functions, comprising the peripheral apparatus, the vestibular nerve, the brainstem and cerebellar processing circuits, the thalamic relays, and the vestibular cerebral cortical network. This system provides signals of self-motion, important for gaze and postural control, and signals of traveled distance, for spatial orientation, especially in the dark. Current evidence suggests that certain aspects of this multi-faceted system may deteriorate with age and sometimes with severe consequences, such as falls. Often the deterioration in vestibular functioning relates to how the signal is processed by brain circuits rather than an impairment in the sensory transduction process. We review current data concerning age-related changes in the vestibular system, and how this may be important for clinicians dealing with balance disorders. PMID:28066316

  10. Gold deposits in metamorphic belts: Overview of current understanding, outstanding problems, future research, and exploration significance

    USGS Publications Warehouse

    Groves, D.I.; Goldfarb, R.J.; Robert, F.; Hart, C.J.R.

    2003-01-01

    Metamorphic belts are complex regions where accretion or collision has added to, or thickened, continental crust. Gold-rich deposits can be formed at all stages of orogen evolution, so that evolving metamorphic belts contain diverse gold deposit types that may be juxtaposed or overprint each other. This partly explains the high level of controversy on the origin of some deposit types, particularly those formed or overprinted/remobilized during the major compressional orogeny that shaped the final geometry of the hosting metamorphic belts. These include gold-dominated orogenic and intrusion-related deposits, but also particularly controversial gold deposits with atypical metal associations. There are a number of outstanding problems for all types of gold deposits in metamorphc belts. These include the following: (1) definitive classifications, (2) unequivocal recognition of fluid and metal sources, (3) understanding of fluid migration and focusing at all scales, (4) resolution of the precise role of granitoid magmatism, (5) precise gold-depositional mechanisms, particularly those producing high gold grades, and (6) understanding of the release of CO2-rich fluids from subducting slabs and subcreted oceanic crust and granitoid magmas at different crustal levels. Research needs to be better coordinated and more integrated, such that detailed fluid-inclusion, trace-element, and isotopic studies of both gold deposits and potential source rocks, using cutting-edge technology, are embedded in a firm geological framework at terrane to deposit scales. Ultimately, four-dimensional models need to be developed, involving high-quality, three-dimensional geological data combined with integrated chemical and fluid-flow modeling, to understand the total history of the hydrothermal systems involved. Such research, particularly that which can predict superior targets visible in data sets available to exploration companies before discovery, has obvious spin-offs for global- to deposit

  11. A Field Study to Understand the Currents and Loads of a Near Shore Finfish Farm

    DTIC Science & Technology

    2006-09-01

    the flow distur- bance from the sensor housing and mooring. The AQUADOPP also recorded temperature, pressure (for depth), roll , pitch and heading...7 10 14 13 1112 1516 20 19 18 17 North S4 MAVS AQUADOPP ADCP Figure 2: The net-pens are numbered from 1 to 20, the anchors, mooring grid and the...Southwest corner. An RD Instruments ADCP (Acoustic Doppler Current Pro- filer) was deployed ~75 m to the Southwest (seaward) side of net pen #4. It

  12. New test techniques and analytical procedures for understanding the behavior of advanced propellers

    NASA Technical Reports Server (NTRS)

    Stefko, G. L.; Bober, L. J.; Neumann, H. E.

    1983-01-01

    Analytical procedures and experimental techniques were developed to improve the capability to design advanced high speed propellers. Some results from the propeller lifting line and lifting surface aerodynamic analysis codes are compared with propeller force data, probe data and laser velocimeter data. In general, the code comparisons with data indicate good qualitative agreement. A rotating propeller force balance demonstrated good accuracy and reduced test time by 50 percent. Results from three propeller flow visualization techniques are shown which illustrate some of the physical phenomena occurring on these propellers.

  13. Advances in the management and understanding of autoimmune lymphoproliferative syndrome (ALPS).

    PubMed

    Teachey, David T; Seif, Alix E; Grupp, Stephan A

    2010-01-01

    Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of T cell dysregulation caused by defective Fas-mediated apoptosis. Patients with ALPS can develop a myriad of clinical manifestations including lymphadenopathy, hepatosplenomegaly, autoimmunity and increased rates of malignancy. ALPS may be more common that originally thought, and testing for ALPS should be considered in patients with unexplained lymphadenopathy, hepatosplenomegaly, and/or autoimmunity. As the pathophysiology of ALPS is better characterized, a number of targeted therapies are in preclinical development and clinical trials with promising early results. This review describes the clinical and laboratory manifestations found in ALPS patients, as well as the molecular basis for the disease and new advances in treatment.

  14. Disaster health education and training: a pilot questionnaire to understand current status.

    PubMed

    Murray, Virginia; Clifford, Janet; Seynaeve, Geert; Fisher, Judith M

    2006-01-01

    In October 2004, a World Association for Disaster and Emergency Medicine (WADEM) Seminar was convened in Brusselsby the Education Committee to discuss Disaster Education and Training. During this seminar, it became apparent that there was no single tool available to assess knowledge, skills, and resources within this field. Therefore, a tool was administered to 50 of the delegates to assess if the tool would facilitate information-sharing and curriculum development in disaster health education. The WADEM Education Committee devised a reference scheme for disaster health training and education based on seven educational levels within a framework based on the Bradt model. A questionnaire was developed to answer questions regarding current practices in disaster health education and training, and the perceived barriers to creating an international system of standards, guidelines, and accreditation. The questionnaire was sent to all of the delegates and the responses were analyzed. The questionnaire was useful for information-sharing and curriculum development. Based on the respondents' experience, strategies were put forward for adopting better coordinated framework for disaster health education and training. This questionnaire should be updated and repeated annually within the WADEM. Wider use of the tool is recommended to help evaluate current educational resources in disaster health and in the wider educational field. It could facilitate the development and audit of current and future courses. An international system for education and training should lead to more efficient and coordinated health responses to disasters.

  15. Issues In-Depth: Advancing Understanding of Drug Addiction and Treatment

    ERIC Educational Resources Information Center

    Miller, Roxanne Greitz

    2009-01-01

    While most school districts utilize a drug abuse resistance curriculum, as science teachers, it is our responsibility to understand the science behind drug addiction in order to most effectively educate our students against drug abuse. In the last two decades, increases in scientific technology have permitted significant discoveries surrounding…

  16. Plastic debris and policy: Using current scientific understanding to invoke positive change.

    PubMed

    Rochman, Chelsea M; Cook, Anna-Marie; Koelmans, Albert A

    2016-07-01

    Captain Charles Moore introduced the world to the "Great Pacific Garbage Patch" in the mid-1990s, and images of plastic debris in the oceans began to sweep the media. Since then, there has been increasing interest from scientists, the public, and policy makers regarding plastic debris in the environment. Today, there remains no doubt that plastic debris contaminates aquatic (marine and freshwater) habitats and animals globally. The growing scientific evidence demonstrates widespread contamination from plastic debris, and researchers are beginning to understand the sources, fate, and effects of the material. As new scientific understanding breeds new questions, scientists are working to fill data gaps regarding the fate and effects of plastic debris and the mechanisms that drive these processes. In parallel, policy makers are working to mitigate this contamination. The authors focus on what is known about plastic debris that is relevant to policy by reviewing some of the weight of evidence regarding contamination, fate, and effects of the material. Moreover, they highlight some examples of how science has already been used to inform policy change and mitigation and discuss opportunities for future linkages between science and policy to continue the relationship and contribute to effective solutions for plastic debris. Environ Toxicol Chem 2016;35:1617-1626. © 2016 SETAC.

  17. The Next Generation Advanced Video Guidance Sensor: Flight Heritage and Current Development

    NASA Technical Reports Server (NTRS)

    Howard, Richard T.; Bryan, Thomas C.

    2009-01-01

    The Next Generation Advanced Video Guidance Sensor (NGAVGS) is the latest in a line of sensors that have flown four times in the last 10 years. The NGAVGS has been under development for the last two years as a long-range proximity operations and docking sensor for use in an Automated Rendezvous and Docking (AR&D) system. The first autonomous rendezvous and docking in the history of the U.S. Space Program was successfully accomplished by Orbital Express, using the Advanced Video Guidance Sensor (AVGS) as the primary docking sensor. That flight proved that the United States now has a mature and flight proven sensor technology for supporting Crew Exploration Vehicles (CEV) and Commercial Orbital Transport Systems (COTS) Automated Rendezvous and Docking (AR&D). NASA video sensors have worked well in the past: the AVGS used on the Demonstration of Autonomous Rendezvous Technology (DART) mission operated successfully in "spot mode" out to 2 km, and the first generation rendezvous and docking sensor, the Video Guidance Sensor (VGS), was developed and successfully flown on Space Shuttle flights in 1997 and 1998. This paper presents the flight heritage and results of the sensor technology, some hardware trades for the current sensor, and discusses the needs of future vehicles that may rendezvous and dock with the International Space Station (ISS) and other Constellation vehicles. It also discusses approaches for upgrading AVGS to address parts obsolescence, and concepts for minimizing the sensor footprint, weight, and power requirements. In addition, the testing of the various NGAVGS development units will be discussed along with the use of the NGAVGS as a proximity operations and docking sensor.

  18. Recent advances in understanding and preventing human papillomavirus-related disease

    PubMed Central

    Hellner, Karin; Dorrell, Lucy

    2017-01-01

    High-risk human papillomaviruses (hrHPV) are responsible for anogenital and oropharyngeal cancers, which together account for at least 5% of cancers worldwide. Industrialised nations have benefitted from highly effective screening for the prevention of cervical cancer in recent decades, yet this vital intervention remains inaccessible to millions of women in low- and middle-income countries (LMICs), who bear the greatest burden of HPV disease. While there is an urgent need to increase investment in basic health infrastructure and rollout of prophylactic vaccination, there are now unprecedented opportunities to exploit recent scientific and technological advances in screening and treatment of pre-invasive hrHPV lesions and to adapt them for delivery at scale in resource-limited settings. In addition, non-surgical approaches to the treatment of cervical intraepithelial neoplasia and other hrHPV lesions are showing encouraging results in clinical trials of therapeutic vaccines and antiviral agents. Finally, the use of next-generation sequencing to characterise the vaginal microbial environment is beginning to shed light on host factors that may influence the natural history of HPV infections. In this article, we focus on recent advances in these areas and discuss their potential for impact on HPV disease. PMID:28357043

  19. Current scientific understanding of the environmental biosafety of transgenic fish and shellfish.

    PubMed

    Kapuscinski, A R

    2005-04-01

    A fluorescent zebrafish was the first genetically engineered animal to be marketed, and biotechnologists are developing many transgenic fish and shellfish. Biosafety science is not sufficiently advanced to be able to draw scientifically reliable and broadly trusted conclusions about the environmental effects of these animals. The science is best developed for identifying hazards posed by environmental spread of a transgenic fish or shellfish and least developed for assessing potential ecological harms of spread. Environmental spread of certain transgenic fish or shellfish could be an indirect route of entry into the human food supply. The management of predicted environmental risks is in its infancy and has thus far focused on the first step of the risk management process, i.e. risk reduction, via a few confinement methods. There is a critical need to improve scientific methods of environmental safety assessment and management and to gather empirical data needed to substantiate biosafety conclusions and to effectively manage transgenic fish and shellfish. Scientists and potentially affected parties should participate in prioritising the knowledge gaps to be addressed.

  20. Current understanding on ethylene signaling in plants: the influence of nutrient availability.

    PubMed

    Iqbal, Noushina; Trivellini, Alice; Masood, Asim; Ferrante, Antonio; Khan, Nafees A

    2013-12-01

    The plant hormone ethylene is involved in many physiological processes, including plant growth, development and senescence. Ethylene also plays a pivotal role in plant response or adaptation under biotic and abiotic stress conditions. In plants, ethylene production often enhances the tolerance to sub-optimal environmental conditions. This role is particularly important from both ecological and agricultural point of views. Among the abiotic stresses, the role of ethylene in plants under nutrient stress conditions has not been completely investigated. In literature few reports are available on the interaction among ethylene and macro- or micro-nutrients. However, the published works clearly demonstrated that several mineral nutrients largely affect ethylene biosynthesis and perception with a strong influence on plant physiology. The aim of this review is to revisit the old findings and recent advances of knowledge regarding the sub-optimal nutrient conditions on the effect of ethylene biosynthesis and perception in plants. The effect of deficiency or excess of the single macronutrient or micronutrient on the ethylene pathway and plant responses are reviewed and discussed. The synergistic and antagonist effect of the different mineral nutrients on ethylene plant responses is critically analyzed. Moreover, this review highlights the status of information between nutritional stresses and plant response, emphasizing the topics that should be further investigated.

  1. Effects of Conceptual Change and Traditional Confirmatory Simulations on Pre-Service Teachers' Understanding of Direct Current Circuits

    NASA Astrophysics Data System (ADS)

    Baser, Mustafa

    2006-12-01

    The objective of this research is to investigate the effects of simulations based on conceptual change conditions (CCS) and traditional confirmatory simulations (TCS) on pre-service elementary school teachers' understanding of direct current electric circuits. The data was collected from a sample consisting of 89 students; 48 students in the experimental group who were taught simulations based on CCS, and 41 students in control group who followed the TCS. Subjects in both groups used open source software (Qucs) to simulate electric circuits. All students were administered Electric Circuits Concepts Test (DIRECT), Science Process Skills Test, Physics Attitude Scale, and Computer Attitude Scale before the treatment. Pre-test analyses revealed that there is no significant difference between experimental and control groups in terms of understanding of direct current electricity. After completing 3 weeks treatment, all students received the DIRECT again as a post-test. Analysis of covariance was used. Science process skills and attitudes toward computers were taken as covariates. The results showed that the conceptual change based simulations caused significantly better acquisition of conceptual change of direct current electricity concepts than the confirmatory simulation. While science process skills and attitudes towards computer made significant contributions to the variations in achievement, gender differences and interactions between gender and treatment did not. Eleven weeks later, the DIRECT was reapplied to the students in both groups. Eleven weeks delayed post-test results showed that the experimental group outperformed the control group in understanding of direct current electric concepts.

  2. Understanding exposure from natural gas drilling puts current air standards to the test.

    PubMed

    Brown, David; Weinberger, Beth; Lewis, Celia; Bonaparte, Heather

    2014-01-01

    Case study descriptions of acute onset of respiratory, neurologic, dermal, vascular, abdominal, and gastrointestinal sequelae near natural gas facilities contrast with a subset of emissions research, which suggests that there is limited risk posed by unconventional natural gas development (UNGD). An inspection of the pathophysiological effects of acute toxic actions reveals that current environmental monitoring protocols are incompatible with the goal of protecting the health of those living and working near UNGD activities. The intensity, frequency, and duration of exposures to toxic materials in air and water determine the health risks to individuals within a population. Currently, human health risks near UNGD sites are derived from average population risks without adequate attention to the processes of toxicity to the body. The objective of this paper is to illustrate that current methods of collecting emissions data, as well as the analyses of these data, are not sufficient for accurately assessing risks to individuals or protecting the health of those near UNGD sites. Focusing on air pollution impacts, we examined data from public sources and from the published literature. We compared the methods commonly used to evaluate health safety near UNGD sites with the information that would be reasonably needed to determine plausible outcomes of actual exposures. Such outcomes must be based on the pathophysiological effects of the agents present and the susceptibility of residents near these sites. Our study has several findings. First, current protocols used for assessing compliance with ambient air standards do not adequately determine the intensity, frequency or durations of the actual human exposures to the mixtures of toxic materials released regularly at UNGD sites. Second, the typically used periodic 24-h average measures can underestimate actual exposures by an order of magnitude. Third, reference standards are set in a form that inaccurately determines health

  3. Does Titan have an ocean? A review of current understanding of Titan's surface

    NASA Astrophysics Data System (ADS)

    Lunine, J. I.

    1993-05-01

    An attempt is made to provide a balanced perspective regarding the knowledge of Titan's surface and how well current models address the various sets of data. Topics discussed include the Voyager data that led to the notion of a massive, global-scale hydrocarbon ocean; recent data sets including radar, radiometry, and NIR photometry that bear on the nature of the surface. Attention is also given to models of the surface that attempt to fit all of the constraints; and the Cassini investigations of Titan's surface. The surface and regolith of Titan are considered to be most likely a repository of liquid methane, other hydrocarbons, and dissolved nitrogen.

  4. Current Understanding on Antihepatocarcinoma Effects of Xiao Chai Hu Tang and Its Constituents

    PubMed Central

    Zheng, Ningning; Dai, Jianye; Cao, Huijuan; Sun, Shujun; Fang, Junwei; Li, Qianhua; Su, Shibing; Zhang, Yongyu; Qiu, Mingfeng; Huang, Shuang

    2013-01-01

    Xiao Chai Hu Tang (XCHT), a compound formula originally recorded in an ancient Chinese medical book Shanghanlun, has been used to treat chronic liver diseases for a long period of time in China. Although extensive studies have been demonstrated the efficacy of this formula to treat chronic hepatitis, hepatic fibrosis, and hepatocarcinoma, how it works against these diseases still awaits full understanding. Here, we firstly present an overview arranging from the entire formula to mechanism studies of single herb in XCHT and their active components, from a new perspective of “separation study,” and we tried our best to both detailedly and systematically organize the antihepatocarcinoma effects of it, hoping that the review will facilitate the strive on elucidating how XCHT elicits its antihepatocarcinoma role. PMID:23853661

  5. Current understanding of the neurobiology and longitudinal course of geriatric depression.

    PubMed

    Weisenbach, Sara L; Kumar, Anand

    2014-09-01

    Late life depression is a complex disease associated with a number of contributing neurobiological factors, including cerebrovascular disease, neurodegeneration, and inflammation, which also contribute to its longitudinal prognosis and course. These factors create a context in which the brain is more vulnerable to the impact of stress, and thus, to depression. At the same time, some individuals are protected from late life depression and its consequences, even in the face of neurobiological vulnerability, through benefitting from one or more attributes associated with resilience, including social support, engagement in physical and cognitive activities, and brain reserve. Enhanced understanding of how neurobiological and environmental factors interact in predicting vulnerability and resilience is needed to predict onset and course of depression in late life and develop more effective interventions.

  6. Chemotherapy-induced peripheral neuropathy: an update on the current understanding.

    PubMed

    Addington, James; Freimer, Miriam

    2016-01-01

    Chemotherapy-induced peripheral neuropathy is a common side effect of selected chemotherapeutic agents. Previous work has suggested that patients often under report the symptoms of chemotherapy-induced peripheral neuropathy and physicians fail to recognize the presence of such symptoms in a timely fashion. The precise pathophysiology that underlies chemotherapy-induced peripheral neuropathy, in both the acute and the chronic phase, remains complex and appears to be medication specific. Recent work has begun to demonstrate and further clarify potential pathophysiological processes that predispose and, ultimately, lead to the development of chemotherapy-induced peripheral neuropathy. There is increasing evidence that the pathway to neuropathy varies with each agent. With a clearer understanding of how these agents affect the peripheral nervous system, more targeted treatments can be developed in order to optimize treatment and prevent long-term side effects.

  7. Chemotherapy-induced peripheral neuropathy: an update on the current understanding

    PubMed Central

    Addington, James; Freimer, Miriam

    2016-01-01

    Chemotherapy-induced peripheral neuropathy is a common side effect of selected chemotherapeutic agents. Previous work has suggested that patients often under report the symptoms of chemotherapy-induced peripheral neuropathy and physicians fail to recognize the presence of such symptoms in a timely fashion. The precise pathophysiology that underlies chemotherapy-induced peripheral neuropathy, in both the acute and the chronic phase, remains complex and appears to be medication specific. Recent work has begun to demonstrate and further clarify potential pathophysiological processes that predispose and, ultimately, lead to the development of chemotherapy-induced peripheral neuropathy. There is increasing evidence that the pathway to neuropathy varies with each agent. With a clearer understanding of how these agents affect the peripheral nervous system, more targeted treatments can be developed in order to optimize treatment and prevent long-term side effects. PMID:27408692

  8. Current advances in tissue repair and regeneration: the future is bright

    PubMed Central

    2015-01-01

    Abstract The fifth EMBO conference on ‘The Molecular and Cellular Basis of Regeneration and Repair’ took place in the peaceful coastal town of Sant Feliu de Guixols (Spain) on September 2014. The meeting was organised by Emili Saló (U. Barcelona, Spain), Kimberly Mace (U. Manchester, UK), Patrizia Ferretti (University College London, UK) and Michael Brand (Centre for Regenerative Therapies Dresden, Germany) and received the generous support of Society for Developmental Biology, The Company of Biologists, Centre for Regenerative Therapies Dresden, Garland Science and the journals Regeneration and Cell Signalling. The natural surroundings provided an inspiring setting for 185 researchers from all over the world to share their latest findings and views on the field. The conference showcased the great diversity of model organisms used for studying regeneration and tissue repair, including invertebrate and vertebrate species (Fig. 1). Importantly, this diversity in animal models allowed for a global overview of the mechanisms that promote regeneration. In addition, it highlighted some of the unique aspects that confer differences in regenerative capacities among different species. These differences might lie in each of the different steps involved in performing regeneration, including triggering the regenerative response, controlling cellular plasticity, re‐stablishing the correct tissue patterns, as well as determining the roles of extrinsic factors, such as the role of inflammation in regeneration. A deeper understanding of these processes in the naturally regenerating species is a prerequisite for advancing the field of regenerative medicine and tissue repair in humans. PMID:27499870

  9. Research on outcomes of pediatric traumatic brain injury: current advances and future directions.

    PubMed

    Taylor, H Gerry

    2004-01-01

    The articles in this series demonstrate the diversity of research approaches needed to enhance understanding of the sequelae of traumatic brain injury (TBI) in children. Methods ranged from assessment of information processing deficits to evaluation of the construct validity of cognitive tests, tracking of changes in academic achievement after injury, and measurement of behavior and social outcomes. Several articles considered multiple influences on sequelae, including TBI severity, age at injury, time since injury, and preinjury child characteristics. The findings provide new information on injury consequences and the cognitive correlates of postinjury problems in behavior, achievement, and discourse processing. Continued progress requires additional study of relations between specific forms of neuropathology and outcomes, more comprehensive assessments of environmental influences, and greater efforts to monitor postinjury developmental changes. Other needs include more probing assessments of the effects of TBI on daily functioning and social-emotional outcomes, investigation of the specificity of sequelae and of sources of variability in outcome, and application of models that examine mechanisms of effect. This research will benefit clinical practice, clarify processes underlying children's behavior and learning problems, and advance knowledge of normal development.

  10. Special issue on the advances in understanding of the North Pacific subtropical front ecosystem

    NASA Astrophysics Data System (ADS)

    McKinnell, Skip; Seki, Michael P.; Ichii, Taro

    2017-01-01

    Subtropical, oligotrophic oceanic gyres are the largest marine ecosystems in the world. They provide important habitat for many higher trophic level species of fish, squid, seabirds, and marine mammals, with some taxa undergoing extensive seasonal migrations between the subtropical frontal region and summer feeding grounds in the subarctic. Knowledge of the structure, variability, and trends of these regions has developed slowly because of their immense size, remote location, and cost of sampling. The first consolidation of the general understanding of the physical nature of the subtropical North Pacific Ocean (and subarctic transition) was published 25 years ago (Roden, 1991) with important information on its relationship to biota added by the now defunct International North Pacific Fisheries Commission (INPFC, 1992; Ito et al., 1993). At that time, a research imperative had arisen from a need by governments to understand the effects of large-scale pelagic driftnet fishing on marine ecosystems (Wetherall, 1991).

  11. Demystifying Immunotherapy in Prostate Cancer: Understanding Current and Future Treatment Strategies

    PubMed Central

    Madan, Ravi A.; Gulley, James L.; Kantoff, Philip W.

    2013-01-01

    Immunotherapy has emerged as a viable therapeutic option for patients with prostate cancer. There are multiple potential strategies that employ the immune system including therapeutic cancer vaccines that are designed to stimulate immune cells to target antigens expressed by cancer cells. Sipuleucel-T is a vaccine currently approved for the treatment of minimally symptomatic metastatic prostate cancer, while the vaccine PSA-TRICOM and the immune checkpoint inhibitor ipilimumab are in phase III testing. Although there are no short term changes in disease progression or available biomarkers to assess response, these agents appear to improve survival. One hypothesis suggests that this apparent paradox can be explained by the growth moderating effects of these treatments which do not cause tumor size to diminish, but rather stall or slow their growth rate over time. For this reason the use of immunotherapy earlier in the disease process is being investigated. Another approach is to block immune regulatory mechanisms mediated by the molecules CTLA-4 and PD-1. Additional future strategies will combine immunotherapy with other standard therapies, potentially enhancing the latter’s clinical impact and thereby improving both time to progression and overall survival due to the combined effects of both treatments. Prospective trials are currently evaluating these hypotheses and will ultimately serve to optimize immunotherapy in the treatment of prostate cancer. PMID:23337757

  12. Understanding the current status and exploring the potential for distance education in public health in India.

    PubMed

    Sharma, Kavya; George, Sunil; Zodpey, Sanjay

    2011-01-01

    Continuing education of health care providers plays an important role in producing a health work force that is efficient and effective. In India public health education has primarily relied on conventional methods of training. However, such methods have limitations in equipping the health workforce of a vast and varied country like India. This paper analyzes the current status of distance education in public health and lists the various courses that are presently available in India through the distance education mode. Presently 25 institutions in India are offering 69 courses in various domains of public health through distance education. The providers of these programs comprised both government and private educational institutions. This paper also points out the role and importance of various stakeholders in the design and delivery of distance education programs in public health and raises key areas that need attention in the governance of such programs. It urges the use of digital technology in the delivery of distance education programs and points out how distance education that is designed and delivered using the latest technology could address the current gap in training human resources for health in India.

  13. Recent advances in improvement of forecast skill and understanding climate processes using AIRS Version-5 products

    NASA Astrophysics Data System (ADS)

    Susskind, Joel; Molnar, Gyula; Iredell, Lena; Rosenberg, Robert

    2012-10-01

    The NASA Goddard Earth Sciences (GES) Data and Information Services Center (DISC) generates products derived from AIRS/AMSU-A observations, starting from September 2002 when the AIRS instrument became stable, using the AIRS Science Team Version-5 retrieval algorithm. This paper shows results of some of our research using Version-5 products from the points of view of improving forecast skill as well as aiding in the understanding of climate processes.

  14. Recent Advances in Understanding the Reactivity of Energetic Ionic Liquids in Propulsion Applications

    DTIC Science & Technology

    2014-08-12

    enabled the investigation of anion properties such as basicity and nucleophilicity in the condensed phase. Both the basicity and nucleophilicity of the... anion influence the thermal decomposition of ionic liquids and understanding basicity of the anion is important in interpreting hypergolic ignition...Low flammability. – C+A- : 1018 possible combinations of cations and anions . • Hypergolic Ignition involves: – Pre-ignition chemistry- “chemical

  15. The Understanding by Design Guide to Advanced Concepts in Creating and Reviewing Units

    ERIC Educational Resources Information Center

    McTighe, Jay; Wiggins, Grant

    2012-01-01

    Regardless of your stage at implementing the design tools and using the improved template for Understanding by Design[R] (UbD), this companion to "The UbD Guide to Creating High-Quality Units" is essential for taking your work to a higher plane. This volume features a set of hands-on modules containing worksheets, models, and self-assessments that…

  16. Integrating Syntax, Semantics, and Discourse DARPA (Defense Advanced Research Projects Agency) Natural Language Understanding Program.

    DTIC Science & Technology

    1987-08-12

    efforts. At the Workshop, Rebecca Passonneau and Francois Lang gave demos of the PUNDIT system doing message processing and demonstrating acquisition of...conference was attended under NSF funding.) Lynette Hirschman and Rebecca Passonneau attended the Message Understanding Conference at NOSC (Naval Ocean...papers. Deborah Dahl presented the paper she co-authored with Martha Palmer and Rebecca Passonneau entitled "Nominalizations in PUNDIT" Rebecca

  17. Recent advances in understanding and managing cystic fibrosis transmembrane conductance regulator dysfunction

    PubMed Central

    Alton, Eric W.F.W.

    2015-01-01

    Cystic fibrosis is the most common autosomal recessive genetic disease in Caucasians and has been extensively studied for many decades. The cystic fibrosis transmembrane conductance regulator gene was identified in 1989. It encodes a complex protein which has numerous cellular functions. Our understanding of cystic fibrosis pathophysiology and genetics is constantly expanding and being refined, leading to improved management of the disease and increased life expectancy in affected individuals. PMID:26097737

  18. Leveraging Small Aquarium Fishes to Advance Understanding of Environmentally Influenced Human Disorders and Diseases

    EPA Science Inventory

    Small aquarium fishes provide a model organism that recapitulates the development, physiology and specific disease processes present in humans without the many limitations of rodent-based models currently in use. Fish models offer advantages in cost, rapid life-cycles, and extern...

  19. Sarcasm and advanced theory of mind understanding in children and adults with prelingual deafness.

    PubMed

    O'Reilly, Karin; Peterson, Candida C; Wellman, Henry M

    2014-07-01

    Two studies addressed key theoretical debates in theory of mind (ToM) development by comparing (a) deaf native signers (n = 18), (b) deaf late signers (n = 59), and (c) age-matched hearing persons (n = 74) in childhood (Study 1: n = 81) and adulthood (Study 2: n = 70) on tests of first- and second-order false belief and conversational sarcasm. Results showed ToM development to be a life span phenomenon for deaf and hearing people alike. Native and late signers were outperformed by hearing peers on advanced ToM in childhood (M = 9 years), but in adulthood (M = 40 years), native signers had caught up, whereas late signers had not. Findings highlight the extended importance of conversational interaction for ToM growth.

  20. Advances in understanding cis regulation of the plant gene with an emphasis on comparative genomics.

    PubMed

    Burgess, Diane G; Xu, Jie; Freeling, Michael

    2015-10-01

    The plant gene model remains largely an extrapolation from animals, with the cis functional unit, the gene, cast as a dynamic looping structure. Molecular genetics with model plants continues to make advances; highlighted here are quantitative-occupancy results from the Arabidopsis thaliana (Arabidopsis) Phytochrome-Interacting bHLH transcription Factors (PIF) quartet. Compared to this complex snapshot, results from chromatin occupancy and other Encyclopedia of DNA Elements (ENCODE)-like approaches increase our transcription factor-motif cognate library, but regulation cannot by itself be inferred from binding. Complementary published Arabidopsis conserved noncoding sequence lists are compared, evaluated, merged, and released. Comparative genomic approaches have identified a cis modifier of a gene's expression-hypothetically, a transposon-based 'rheostat'-that works in all cells, times and places.

  1. Current advances in the phylogenetic reconstruction of metazoan evolution. A new paradigm for the Cambrian explosion?

    PubMed

    Giribet, Gonzalo

    2002-09-01

    The study of metazoan evolution has fascinated biologists for centuries, and it will certainly keep doing so. Recent interest on the origin of metazoan body plans, early metazoan evolution, genetic mechanisms generating disparity and diversity, molecular clock information, paleontology, and biogeochemistry is contributing to a better understanding of the current phyletic diversity. Unfortunately, the pattern of the metazoan tree of life still shows some important gaps in knowledge. It is the aim of this article to review some of the most important issues related to the inference of the metazoan tree, and point towards possible ways of solving certain obscure aspects in the history of animal evolution. A new hypothesis of the metazoan diversification during the Cambrian explosion is proposed by synthesizing ideas from phylogenetics, molecular evolution, paleontology, and developmental biology.

  2. Understanding the impact of deep brain stimulation on ambulatory activity in advanced Parkinson's disease.

    PubMed

    Rochester, Lynn; Chastin, Sebastien Francois Martin; Lord, Sue; Baker, Katherine; Burn, David John

    2012-06-01

    Whilst deep brain stimulation of the subthalamic nucleus (DBS-STN) improves the motor symptoms of Parkinson's disease (PD), its effect on daily activity is unknown. We aimed to quantify changes in ambulatory activity following DBS-STN in advanced PD using novel accelerometry based measures that describe changes to the volume and pattern of walking. Seventeen participants with advanced PD were measured over a 7-day period using an activPAL (™) activity monitor. Data were collected 6 weeks before and 6 months after surgery and included measures that describe the volume and pattern of ambulatory activity (number of steps per day, accumulation, diversity and variability of walking time), alongside standard measures for disease severity, freezing of gait, gait speed, and extended activities of daily living. Activity outcomes were compared pre- and 6 months post-surgery using linear mixed models and correlated with standard outcomes. The results of this study are despite significant improvements in motor symptoms after surgery, the volume of ambulatory activity (total number of steps per day) did not change (P = 0.468). However, significant increases in length and variability of walking bouts emerged, suggesting improvements in diversity and flexibility of walking patterns. Motor severity and extended activities of daily living scores were significantly correlated with walking bout variability but not with volume of walking. Thus, the conclusions are reduction in motor symptom severity after DBS-STN translated into selective improvements in daily activity. Novel measures derived from accelerometry provide a discrete measure of performance and allow closer interpretation of the impact of DBS-STN on real-world activity.

  3. Prenatal Programming of Mental Illness: Current Understanding of Relationship and Mechanisms

    PubMed Central

    Bale, Tracy L.; Epperson, C. Neill

    2015-01-01

    The British epidemiologist Dr. David J. Barker documented the relationship between infant birth weight and later onset of hypertension, coronary heart disease, insulin resistance, and type II diabetes. A stressful in utero environment can cause long-term consequences for offspring through prenatal programming. Prenatal programming most commonly occurs through epigenetic mechanisms and can be dependent on the type and timing of exposure as well as the sex of the fetus. In this review, we highlight the most recent evidence that prenatal programming is implicated in the development of psychiatric disorders in offspring exposed to maternal stress during pregnancy. Methodological differences between studies contribute to unavoidable heterogeneity in study findings. Current data suggest that fetal exposure to maternal hypothalamic-pituitary-adrenal axis dysregulation, excessive glucocorticoids, and inflammation with resulting epigenetic changes at both the placental and fetal levels are important areas of continued investigation. PMID:25617041

  4. The Hyaluronic Acid Fillers: Current Understanding of the Tissue Device Interface.

    PubMed

    Greene, Jacqueline J; Sidle, Douglas M

    2015-11-01

    The article is a detailed update regarding cosmetic injectable fillers, specifically focusing on hyaluronic acid fillers. Hyaluronic acid-injectable fillers are used extensively for soft tissue volumizing and contouring. Many different hyaluronic acid-injectable fillers are available on the market and differ in terms of hyaluronic acid concentration, particle size, cross-linking density, requisite needle size, duration, stiffness, hydration, presence of lidocaine, type of cross-linking technology, and cost. Hyaluronic acid is a natural component of many soft tissues, is identical across species minimizing immunogenicity has been linked to wound healing and skin regeneration, and is currently actively being studied for tissue engineering purposes. The biomechanical and biochemical effects of HA on the local microenvironment of the injected site are key to its success as a soft tissue filler. Knowledge of the tissue-device interface will help guide the facial practitioner and lead to optimal outcomes for patients.

  5. Geomorphic and vegetation processes of the Willamette River floodplain, Oregon: current understanding and unanswered science questions

    USGS Publications Warehouse

    Wallick, J. Rose; Jones, Krista L.; O'Connor, Jim E.; Keith, Mackenzie K.; Hulse, David; Gregory, Stanley V.

    2013-01-01

    4. How is the succession of native floodplain vegetation shaped by present-day flow and sediment conditions? Answering these questions will produce baseline data on the current distributions of landforms and habitats (question 1), the extent of the functional floodplain (question 2), and the effects of modern flow and sediment regimes on future floodplain landforms, habitats, and vegetation succession (questions 3 and 4). Addressing questions 1 and 2 is a logical next step because they underlie questions 3 and 4. Addressing these four questions would better characterize the modern Willamette Basin and help in implementing and setting realistic targets for ongoing management strategies, demonstrating their effectiveness at the site and basin scales, and anticipating future trends and conditions.

  6. Understanding the catalyst-free transformation of amorphous carbon into graphene by current-induced annealing

    PubMed Central

    Barreiro, Amelia; Börrnert, Felix; Avdoshenko, Stanislav M.; Rellinghaus, Bernd; Cuniberti, Gianaurelio; Rümmeli, Mark H.; Vandersypen, Lieven M. K.

    2013-01-01

    We shed light on the catalyst-free growth of graphene from amorphous carbon (a–C) by current-induced annealing by witnessing the mechanism both with in-situ transmission electron microscopy and with molecular dynamics simulations. Both in experiment and in simulation, we observe that small a–C clusters on top of a graphene substrate rearrange and crystallize into graphene patches. The process is aided by the high temperatures involved and by the van der Waals interactions with the substrate. Furthermore, in the presence of a–C, graphene can grow from the borders of holes and form a seamless graphene sheet, a novel finding that has not been reported before and that is reproduced by the simulations as well. These findings open up new avenues for bottom-up engineering of graphene-based devices.

  7. Complex function of the knee joint: the current understanding of the knee.

    PubMed

    Hirschmann, Michael T; Müller, Werner

    2015-10-01

    Since the early years of orthopaedics, it is a well-known fact that anatomy follows function. During the evolution of mankind, the knee has been optimally adapted to the forces and loads acting at and through the knee joint. However, anatomy of the knee joint is variable and the only constant is its complex function. In contrast to the time of open surgery, nowadays the majority of reconstructive knee surgery is done arthroscopically. Keyhole surgery is less invasive, but on the backside, the knee surgeon lacks daily visualisation of the complex open anatomy. As open anatomical knowledge is less present in our daily practice, it is even more important to highlight this complex anatomy and function of the knee. It is the purpose of this review to perform a systematic review of knee anatomy, highlight the complex function of the knee joint and present an overview about recent and current knowledge about knee function. Level of evidence Systematic review, Level IV.

  8. Early stages of solar flares - Current status of our understanding and opportunities for future observations

    NASA Technical Reports Server (NTRS)

    Dennis, B. R.

    1986-01-01

    Current models of the energy release and transport mechanisms occurring in solar flares are updated to include the input from data collected with the SMM satellite. The new data cover numerous solar flares observed in X-ray and gamma ray bands over a 6 yr period, combined with data from the Japanese Hinori satellite in 1981-82 and ground-based radio observations. The 300 keV gamma ray data have been instrumental in revealing a 152-158 day period in the frequency of solar flares. Recent analysis has indicated that the periodicity is connected to the rotational spectrum of g-modes in the sun. Other data have shown that hard X-rays are emitted from the footpoints and interactions among coronal magnetic loops, where electron acceleration processes occur that are not well understood. The footpoint emission appear in impulsive events, while the interaction emissions are connected with gradual flares.

  9. Introduction to Indian Ocean biogeochemical processes and ecological variability: Current understanding and emerging perspectives

    NASA Astrophysics Data System (ADS)

    Wiggert, Jerry D.; Hood, Raleigh R.; Naqvi, S. Wajih A.; Brink, Kenneth H.; Smith, Sharon L.

    Despite a history of exploration dating back to the classical era and its leading role as a pathway for trade and cultural exchange for the great civilizations of those times, the Indian Ocean has consistently been subject to less attention in the modern era in terms of oceanographic enquiry. The cornerstone of the Sustained Indian Ocean Biogeochemical and Ecosystem Research (SIBER) initiative has been to promote more frequent and persistent research activities that encompass the entire Indian Ocean basin and to facilitate international cooperation to realize these objectives. This volume's chapters are derived from the plenary talks given by the attendees of the first SIBER conference and are a blend of current knowledge reviews and new results. Thus this collection of papers represents an interdisciplinary contribution to the Indian Ocean literature by the leading members of the Indian Ocean research community.

  10. Disabilities in older African-American women: understanding the current state of the literature.

    PubMed

    Jones, Debbie Ann

    2009-12-01

    The purpose of this review sought to address the following question: What does the current literature report regarding older African-American women with disabilities? A search of PubMed database was done for research on African-American women, ages 45 years and older, who have a disability. Sixty-one articles were reviewed and categorized into groups according to themes. The term disability was only defined in one of the studies. Overall, the studies reviewed revealed racial and ethnic disparities among African-American women with disabilities that included increased hospital days, poor health days, hospitalizations, being functionally totally dependent, and having increased primary and repeat amputations when compared to their White counterparts.

  11. How to understand and interpret current flow in nanopore/electrode devices.

    PubMed

    Albrecht, Tim

    2011-08-23

    Nanopore-based single-molecule sensors have become an important class of analytical devices that have in some cases already reached the market place. Traditionally operated in a two-electrode configuration, devices with three or more electrodes have emerged recently, for example with a view on switching the transport properties of the nanopore or even tunneling-based detection of analytes with the ultimate goal of inexpensive and ultrafast DNA sequencing. How do these additional electrodes affect the current distribution in the cell and hence the sensor performance? This is significantly less clear and thus in focus here. We use impedance modeling of a prototypical three-electrode nanopore sensor and show that, depending on the conditions, standard experimental device characterization is severely affected by the presence of the third electrode. On the other hand, the simulations also provide guidelines on how to avoid such complications, identify "safe" operating conditions, and design criteria for optimized nanopore sensors.

  12. Kiss of the Mutant Mouse: How Genetically Altered Mice Advanced Our Understanding of Kisspeptin's Role in Reproductive Physiology

    PubMed Central

    Elias, Carol F.

    2012-01-01

    The kisspeptin system has emerged as one of the most important circuits within the central network governing reproduction. Although kisspeptin physiology has been examined in many species, much of our understanding of this system has come from mice. Recently, the study of several innovative strains of genetically engineered mouse models has revealed intriguing and unexpected insights into the functions of kisspeptin signaling in the hypothalamus. Here, we review the advancements in our knowledge of the central kisspeptin system through the use of mutant mice. PMID:23011921

  13. Current Practices in Global/International Advanced Pharmacy Practice Experiences: Home/Host Country or Site/Institution Considerations.

    PubMed

    Alsharif, Naser Z; Dakkuri, Adnan; Abrons, Jeanine P; Williams, Dennis; Ombengi, David N; Zheng, HaiAn; Al-Dahir, Sara; Tofade, Toyin; Gim, Suzanna; O'Connell, Mary Beth; Ratka, Anna; Dornblaser, Emily

    2016-04-25

    International outreach by schools and colleges of pharmacy is increasing. In this paper, we provide current practice guidelines to establish and maintain successful global/international advanced pharmacy practice experiences (G/I APPEs) with specific recommendations for home/host country and host site/institution. The paper is based on a literature review (2000-2014) in databases and Internet searches with specific keywords or terms. Educational documents such as syllabi and memoranda of understanding (MoUs) from pharmacy programs were also examined. In addition, a preliminary draft was developed and the findings and recommendations were reviewed in a 90-minute roundtable discussion at the 2014 American Association of Colleges of Pharmacy Annual Meeting. Recommendations for the host country include travel considerations (eg, passport, visa, air travel), safety, housing, transportation, travel alerts and warnings, health issues, and financial considerations. For the home country, considerations for establishment of G/I APPE site (eg, vetting process, MoU, site expectations) are described. The paper is a resource for development of new G/I APPEs and provides guidance for continuous quality improvement of partnerships focusing on G/I pharmacy education.

  14. Current Practices in Global/International Advanced Pharmacy Practice Experiences: Home/Host Country or Site/Institution Considerations

    PubMed Central

    Dakkuri, Adnan; Abrons, Jeanine P.; Williams, Dennis; Ombengi, David N.; Zheng, HaiAn; Al-Dahir, Sara; Tofade, Toyin; Gim, Suzanna; O’Connell, Mary Beth; Ratka, Anna; Dornblaser, Emily

    2016-01-01

    International outreach by schools and colleges of pharmacy is increasing. In this paper, we provide current practice guidelines to establish and maintain successful global/international advanced pharmacy practice experiences (G/I APPEs) with specific recommendations for home/host country and host site/institution. The paper is based on a literature review (2000-2014) in databases and Internet searches with specific keywords or terms. Educational documents such as syllabi and memoranda of understanding (MoUs) from pharmacy programs were also examined. In addition, a preliminary draft was developed and the findings and recommendations were reviewed in a 90-minute roundtable discussion at the 2014 American Association of Colleges of Pharmacy Annual Meeting. Recommendations for the host country include travel considerations (eg, passport, visa, air travel), safety, housing, transportation, travel alerts and warnings, health issues, and financial considerations. For the home country, considerations for establishment of G/I APPE site (eg, vetting process, MoU, site expectations) are described. The paper is a resource for development of new G/I APPEs and provides guidance for continuous quality improvement of partnerships focusing on G/I pharmacy education. PMID:27170809

  15. High Current ESD Test of Advanced Triple Junction Solar Array Coupon

    NASA Technical Reports Server (NTRS)

    Wright, K. H.; Schneider, T. A.; Vaughn, J. A.; Hoang, B.; Wong, F.

    2014-01-01

    A test was conducted on an Advanced Triple Junction (ATJ) coupon that was part of a risk reduction effort in the development of a high-powered solar array design by SSL. The ATJ coupon was a small, 4-cell, two-string configuration that has served as the basic test coupon design used in previous SSL environmental aging campaigns. The coupon has many attributes of the flight design; e.g., substrate structure with graphite face sheets, integrated by-pass diodes, cell interconnects, RTV grout, wire routing, etc. The objective of the present test was to evaluate the performance of the coupon after being subjected to induced electrostatic discharge testing at two string voltages (100 V, 150 V) and four array current (1.65 A, 2.0 A, 2.475 A, and 3.3 A). An ESD test circuit, unique to SSL solar array design, was built that simulates the effect of missing cells and strings in a full solar panel with special primary arc flashover circuitry. A total of 73 primary arcs were obtained that included 7 temporary sustained arcs (TSA) events. The durations of the TSAs ranged from 50 µs to 2.9 ms. All TSAs occurred at a string voltage of 150 V. Post-test Large Area Pulsed Solar Simulator (LAPSS), Dark I-V, and By-Pass Diode tests showed that no degradation occurred due to the TSA events. In addition, the post-test insulation resistance measured was > 50 G-ohms between cells and substrate. These test results indicate a robust design for application to a high-current, high-power mission application.

  16. High Current ESD Test of Advanced Triple Junction Solar Array Coupon

    NASA Technical Reports Server (NTRS)

    Wright, Kenneth H., Jr.; Schneider, Todd A.; Vaughn, Jason A.; Hoang, Bao; Wong, Frankie

    2014-01-01

    Testing was conducted on an Advanced Triple Junction (ATJ) coupon that was part of a risk reduction effort in the development of a high-powered solar array design by Space Systems/Loral, LLC (SSL). The ATJ coupon was a small, 4-cell, two-string configuration that has served as the basic test coupon design used in previous SSL environmental aging campaigns. The coupon has many attributes of the flight design; e.g., substrate structure with graphite face sheets, integrated by-pass diodes, cell interconnects, RTV grout, wire routing, etc. The objective of the present test was to evaluate the performance of the coupon after being subjected to induced electrostatic discharge (ESD) testing at two string voltages (100 V, 150 V) and four array currents (1.65 A, 2.0 A, 2.475 A, and 3.3 A). An ESD test circuit, unique to SSL solar array design, was built that simulates the effect of missing cells and strings in a full solar panel with special primary arc flashover circuitry. A total of 73 primary arcs were obtained that included 7 temporary sustained arcs (TSA) events. The durations of the TSAs ranged from 50 micro-seconds to 2.75 milli-seconds. All TSAs occurred at a string voltage of 150 V. Post-test Large Area Pulsed Solar Simulator (LAPSS), Dark I-V, and By-Pass Diode tests showed that no degradation occurred due to the TSA events. In addition, the post-test insulation resistance measured was > 50 G-ohms between cells and substrate. These test results indicate a robust design for application to a high-current, high-power mission.

  17. High Current ESD Test of Advanced Triple Junction Solar Array Coupon

    NASA Technical Reports Server (NTRS)

    Wright, Kenneth H., Jr.; Schneider, Todd A.; Vaughn, Jason A.; Hoang, Bao; Wong, Frankie

    2015-01-01

    A test was conducted on an Advanced Triple Junction (ATJ) coupon that was part of a risk reduction effort in the development of a high-powered solar array design by SSL. The ATJ coupon was a small, 4-cell, two-string configuration that has served as the basic test coupon design used in previous SSL environmental aging campaigns. The coupon has many attributes of the flight design; e.g., substrate structure with graphite face sheets, integrated by-pass diodes, cell interconnects, RTV grout, wire routing, etc. The objective of the present test was to evaluate the performance of the coupon after being subjected to induced electrostatic discharge testing at two string voltages (100 V, 150 V) and four array current (1.65 A, 2.0 A, 2.475 A, and 3.3 A). An ESD test circuit, unique to SSL solar array design, was built that simulates the effect of missing cells and strings in a full solar panel with special primary arc flashover circuitry. A total of 73 primary arcs were obtained that included 7 temporary sustained arcs (TSA) events. The durations of the TSAs ranged from 50 micros to 2.9 ms. All TSAs occurred at a string voltage of 150 V. Post-test Large Area Pulsed Solar Simulator (LAPSS), Dark I-V, and By-Pass Diode tests showed that no degradation occurred due to the TSA events. In addition, the post-test insulation resistance measured was > 50 G-ohms between cells and substrate. These test results indicate a robust design for application to a high-current, high-power mission application.

  18. Current Understanding of Dysbiosis in Disease in Human and Animal Models.

    PubMed

    DeGruttola, Arianna K; Low, Daren; Mizoguchi, Atsushi; Mizoguchi, Emiko

    2016-05-01

    Inflammatory bowel disease (IBD) is an intestinal inflammatory condition that affects more than 2 million people in the United States. Although the etiology and pathogenesis of IBD are still largely unknown, dysregulated host/enteric microbial interactions are requisite for the development of IBD. So far, many researchers have tried to identify a precise relationship between IBD and an imbalance of the intestinal microbiota, termed "dysbiosis." Despite extensive efforts, it is still largely unknown about the interplay among microbes, their hosts, and their environments, and whether dysbiosis is a causal factor or an effect of IBD. Recently, deep-sequencing analyses of the microbiota in patients with IBD patients have been instrumental in characterizing the strong association between dysbiosis and IBD development, although it is still unable to identify specific-associated species level changes in most cases. Based on many recent reports, dysbiosis of the commensal microbiota is implicated in the pathogenesis of several diseases, including IBD, obesity, and allergic disorders, in both human and animal models. In this review article, the authors have focused on explaining the multiple types of dysbiosis, as well as dysbiosis-related diseases and potential treatments to apply this knowledge to understand a possible cause and potentially find therapeutic strategies for IBD as well as the other dysbiosis-related diseases.

  19. Understanding the Neuro-ophthalmology of Head Trauma: A Review of the Current Literature.

    PubMed

    Samra, Khawla Abu

    2014-01-01

    Head trauma is a major medical, social, economic, national, and public health priority issue in the United States. In severe head trauma, the overwhelming clinical manifestations are so compelling that damage to the visual system is most likely to be ignored. Both the afferent and efferent visual systems are susceptible to injury after head trauma, and physicians should be aware of the visual system and perform a thorough neuro-ophthalmic evaluation in patients presenting with head trauma.Most of the data available on neuro-ophthalmic complications of head trauma including cortical blindness, Horner's syndrome, traumatic internuclear ophthalmoplegia, and ocular motor palsy, comes from case reports highlighting the need for future studies to better understand these complications.This review summarizes some of the most important neuro-ophthalmic complications of head trauma including cortical blindness, Horner's syndrome, traumatic internuclear ophthalmoplegia, and ocular motor palsy. Search of the peer-reviewed literature was conducted using MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Global Health, and MD Consult.

  20. Current Understanding of the Role of Complement in IgA Nephropathy

    PubMed Central

    Maillard, Nicolas; Wyatt, Robert J.; Julian, Bruce A.; Kiryluk, Krzysztof; Gharavi, Ali; Fremeaux-Bacchi, Veronique

    2015-01-01

    Complement activation has a role in the pathogenesis of IgA nephropathy, an autoimmune disease mediated by pathogenic immune complexes consisting of galactose-deficient IgA1 bound by antiglycan antibodies. Of three complement-activation pathways, the alternative and lectin pathways are involved in IgA nephropathy. IgA1 can activate both pathways in vitro, and pathway components are present in the mesangial immunodeposits, including properdin and factor H in the alternative pathway and mannan-binding lectin, mannan–binding lectin–associated serine proteases 1 and 2, and C4d in the lectin pathway. Genome–wide association studies identified deletion of complement factor H–related genes 1 and 3 as protective against the disease. Because the corresponding gene products compete with factor H in the regulation of the alternative pathway, it has been hypothesized that the absence of these genes could lead to more potent inhibition of complement by factor H. Complement activation can take place directly on IgA1–containing immune complexes in circulation and/or after their deposition in the mesangium. Notably, complement factors and their fragments may serve as biomarkers of IgA nephropathy in serum, urine, or renal tissue. A better understanding of the role of complement in IgA nephropathy may provide potential targets and rationale for development of complement-targeting therapy of the disease. PMID:25694468

  1. Current understanding of dysbiosis in disease in human and animal models

    PubMed Central

    DeGruttola, Arianna K.; Low, Daren; Mizoguchi, Atsushi; Mizoguchi, Emiko

    2016-01-01

    Inflammatory bowel disease (IBD) is an intestinal inflammatory condition that affects over two million people in the United States. Although the etiology and pathogenesis of IBD are still largely unknown, dysregulated host/enteric microbial interactions are requisite for the development of IBD. So far, many researchers have tried to identify a precise relationship between IBD and an imbalance of the intestinal microbiota, termed “dysbiosis”. In spite of the extensive efforts, it is still largely unknown about the interplay among microbes, their hosts, and their environments, and whether dysbiosis is a causal factor or an effect of IBD. Recently, deep-sequencing analyses of the microbiota in IBD patients have been instrumental in characterizing the strong association between dysbiosis and IBD development, although it is still unable to identify specific-associated species level changes in most cases. Based on many recent reports, dysbiosis of the commensal microbiota is implicated in the pathogenesis of several diseases, including IBD, obesity, and allergic disorders, in both human and animal models. In this review article, we have focused on explaining the multiple types of dysbiosis, as well as dysbiosis-related diseases and potential treatments in order to apply this knowledge to understand a possible cause and potentially find therapeutic strategies for IBD as well as the other dysbiosis-related diseases. PMID:27070911

  2. Changing currents: a strategy for understanding and predicting the changing ocean circulation.

    PubMed

    Bryden, Harry L; Robinson, Carol; Griffiths, Gwyn

    2012-12-13

    Within the context of UK marine science, we project a strategy for ocean circulation research over the next 20 years. We recommend a focus on three types of research: (i) sustained observations of the varying and evolving ocean circulation, (ii) careful analysis and interpretation of the observed climate changes for comparison with climate model projections, and (iii) the design and execution of focused field experiments to understand ocean processes that are not resolved in coupled climate models so as to be able to embed these processes realistically in the models. Within UK-sustained observations, we emphasize smart, cost-effective design of the observational network to extract maximum information from limited field resources. We encourage the incorporation of new sensors and new energy sources within the operational environment of UK-sustained observational programmes to bridge the gap that normally separates laboratory prototype from operational instrument. For interpreting the climate-change records obtained through a variety of national and international sustained observational programmes, creative and dedicated UK scientists should lead efforts to extract the meaningful signals and patterns of climate change and to interpret them so as to project future changes. For the process studies, individual scientists will need to work together in team environments to combine observational and process modelling results into effective improvements in the coupled climate models that will lead to more accurate climate predictions.

  3. FED-A, an advanced performance FED based on low safety factor and current drive

    SciTech Connect

    Peng, Yueng Kay Martin; Rutherford, P. H.; Hogan, J.T.; Attenberger, S. E.; Holmes, J.A.; Borowski, S. K.; Brown, T. G.; Carreras, B. A.; Ehst, D. A.; Haines, J.R.; Hively, L. M.; Houlberg, Wayne A; Iida, H.; Lee, V. D.; Lynch, S.J.; Reid, R. L.; Rothe, K. E.; Strickler, Dennis J; Stewart, L. D.

    1983-08-01

    This document is one of four describing studies performed in FY 1982 within the context of the Fusion Engineering Device (FED) Program for the Office of Fusion Energy, U.S. Department of Energy. The documents are: 1. FED Baseline Engineering Studies (ORNL/FEDC-82/2), 2. FED-A, An Advanced Performance FED Based on Low Safety Factor and Current Drive (this document), 3. FED-R, A Fusion Device Utilizing Resistive Magnets (ORNL/FEDC-82/1), and 4. Technology Demonstration Facility TDF. These studies extend the FED Baseline concept of FY 1981 and develop innovative and alternative concepts for the FED. The FED-A study project was carried out as part of the Innovative and Alternative Tokamak FED studies, under the direction of P. H. Rutherford, which were part of the national FED program during FY 1982. The studies were performed jointly by senior scientists in the magnetic fusion community and the staff of the Fusion Engineering Design Center (FEDC). Y-K. M. Peng of the FEDC, on assignment from Oak Ridge National Laboratory, served as the design manager.

  4. Current advance methods for the identification of blast resistance genes in rice.

    PubMed

    Tanweer, Fatah A; Rafii, Mohd Y; Sijam, Kamaruzaman; Rahim, Harun A; Ahmed, Fahim; Latif, Mohammad A

    2015-05-01

    Rice blast caused by Magnaporthe oryzae is one of the most devastating diseases of rice around the world and crop losses due to blast are considerably high. Many blast resistant rice varieties have been developed by classical plant breeding and adopted by farmers in various rice-growing countries. However, the variability in the pathogenicity of the blast fungus according to environment made blast disease a major concern for farmers, which remains a threat to the rice industry. With the utilization of molecular techniques, plant breeders have improved rice production systems and minimized yield losses. In this article, we have summarized the current advanced molecular techniques used for controlling blast disease. With the advent of new technologies like marker-assisted selection, molecular mapping, map-based cloning, marker-assisted backcrossing and allele mining, breeders have identified more than 100 Pi loci and 350 QTL in rice genome responsible for blast disease. These Pi genes and QTLs can be introgressed into a blast-susceptible cultivar through marker-assisted backcross breeding. These molecular techniques provide timesaving, environment friendly and labour-cost-saving ways to control blast disease. The knowledge of host-plant interactions in the frame of blast disease will lead to develop resistant varieties in the future.

  5. Advanced model of eddy-current NDE inverse problem with sparse grid algorithm

    NASA Astrophysics Data System (ADS)

    Zhou, Liming; Sabbagh, Harold A.; Sabbagh, Elias H.; Murphy, R. Kim; Bernacchi, William

    2017-02-01

    In model-based inverse problem, some unknown parameters need to be estimated. These parameters are used not only to characterize the physical properties of cracks, but also to describe the position of the probes (such as lift off and angles) in the calibration. After considering the effect of the position of the probes in the inverse problem, the accuracy of the inverse result will be improved. With increasing the number of the parameters in the inverse problems, the burden of calculations will increase exponentially in the traditional full grid method. The sparse grid algorithm, which was introduced by Sergey A. Smolyak, was used in our work. With this algorithm, we obtain a powerful interpolation method that requires significantly fewer support nodes than conventional interpolation on a full grid. In this work, we combined sparse grid toolbox TASMANIAN, which is produced by Oak Ridge National Laboratory, and professional eddy-current NDE software, VIC-3D R◯, to solve a specific inverse problem. An advanced model based on our previous one is used to estimate length and depth of the crack, lift off and two angles of the position of probes. Considering the calibration process, pseudorandom noise is considered in the model and statistical behavior is discussed.

  6. The impact of recent advances in genetics in understanding disease mechanisms underlying the long QT syndromes.

    PubMed

    Harmer, Stephen C; Tinker, Andrew

    2016-07-01

    Long QT syndrome refers to a characteristic abnormality of the electrocardiogram and it is associated with a form of ventricular tachycardia known as torsade-de-pointes and sudden arrhythmic death. It can occur as part of a hereditary syndrome or can be acquired usually because of drug administration. Here we review recent genetic, molecular and cellular discoveries and outline how they have furthered our understanding of this disease. Specifically we focus on compound mutations, genome wide association studies of QT interval, modifier genes and the therapeutic implications of this recent work.

  7. Advances in the understanding of the Fanconi anemia tumor suppressor pathway.

    PubMed

    Pickering, Anna; Zhang, Jun; Panneerselvam, Jayabal; Fei, Peiwen

    2013-12-01

    Extremely high cancer incidence in Fanconi anemia (FA) patients has long suggested that the FA signaling pathway is a tumor suppressor pathway. Indeed, our recent findings, for the first time, indicate that the FA pathway plays a significant role in suppressing the development of non-FA human cancer. Also our studies on FA group D2 protein (FANCD2) have, among the first, documented the crosstalks between the FA and Rad6/Rad18 (HHR6) pathways upon DNA damage. In this review, we will discuss how our studies enhance the understanding of the FA tumor suppressor pathway.

  8. Pediatric Cerebellar Tumors: Emerging Imaging Techniques and Advances in Understanding of Genetic Features.

    PubMed

    Choudhri, Asim F; Siddiqui, Adeel; Klimo, Paul

    2016-08-01

    Cerebellar tumors are the most common group of solid tumors in children. MR imaging provides an important role in characterization of these lesions, surgical planning, and postsurgical surveillance. Preoperative imaging can help predict the histologic subtype of tumors, which can provide guidance for surgical planning. Beyond histology, pediatric brain tumors are undergoing new classification schemes based on genetic features. Intraoperative MR imaging has emerged as an important tool in the surgical management of pediatric brain tumors. Effective understanding of the imaging features of pediatric cerebellar tumors can benefit communication with neurosurgeons and neuro-oncologists and can improve patient management.

  9. Capsaicin: Current Understanding of Its Mechanisms and Therapy of Pain and Other Pre-Clinical and Clinical Uses.

    PubMed

    Fattori, Victor; Hohmann, Miriam S N; Rossaneis, Ana C; Pinho-Ribeiro, Felipe A; Verri, Waldiceu A

    2016-06-28

    In this review, we discuss the importance of capsaicin to the current understanding of neuronal modulation of pain and explore the mechanisms of capsaicin-induced pain. We will focus on the analgesic effects of capsaicin and its clinical applicability in treating pain. Furthermore, we will draw attention to the rationale for other clinical therapeutic uses and implications of capsaicin in diseases such as obesity, diabetes, cardiovascular conditions, cancer, airway diseases, itch, gastric, and urological disorders.

  10. An advanced understanding of the specific effects of xylan and surface lignin contents on enzymatic hydrolysis of lignocellulosic biomass

    SciTech Connect

    Ju, Xiaohui; Engelhard, Mark H.; Zhang, Xiao

    2013-01-17

    A deep understanding of biomass recalcitrance has been hampered by the intricate and heterogeneous nature of pretreated biomass substrates obtained from random deconstruction methods. In this study, we established a unique methodology based on chemical pulping principles to create "reference substrates" with intact cellulose fibers and controlled morphological and chemical properties that enable us to investigate the individual effect of xylan, bulk, and surface lignin content on enzymatic hydrolysis. We also developed and demonstrated an X-ray photoelectron spectroscopy (XPS) technique for quantifying surface lignin content on biomass substrates. The results from this study show that, apart from its hindrance effect, xylan can facilitate cellulose fibril swelling and thus create more accessible surface area, which improves enzyme and substrate interactions. Surface lignin has a significant impact on enzyme adsorption kinetics and hydrolysis rate. Advanced understanding of xylan, bulk, and surface lignin effects provides critical information for an effective biomass conversion process.

  11. Integrated Application of Active Controls (IAAC) technology to an advanced subsonic transport project: Current and advanced act control system definition study

    NASA Technical Reports Server (NTRS)

    1982-01-01

    The Current and Advanced Technology ACT control system definition tasks of the Integrated Application of Active Controls (IAAC) Technology project within the Energy Efficient Transport Program are summarized. The systems mechanize six active control functions: (1) pitch augmented stability; (2) angle of attack limiting; (3) lateral/directional augmented stability; (4) gust load alleviation; (5) maneuver load control; and (6) flutter mode control. The redundant digital control systems meet all function requirements with required reliability and declining weight and cost as advanced technology is introduced.

  12. Fluid Dynamics and MHD of the Solar Convection Zone and Tachocline: Current Understanding and Unsolved Problems

    NASA Astrophysics Data System (ADS)

    Gilman, Peter A.

    My assigned topic is extremely broad, so in this abstract I will state only goals and emphases, not all of which I may be able to discuss in the time allotted. The focus of the talk will be primarily theoretical, but guided by observations. Within the fluid dynamical realm, I will say something about most scales of convection, as well as other classes of fluid processes, particularly global instabilities and waves. I will emphasize the differences in dynamics that should characterize the different domains of differential rotation we now know exist on the Sun: strong radial rotation gradients just below the photosphere; the bulk of the convection zone that has little radial gradient; the tachocline at the bottom; and possible polar vortices. Within the MHD realm, I will focus on the multiple dynamos that may be operating, as well as on processes for getting flux from below the convection zone through it to the solar atmosphere, and the possible role played by global MHD instabilities in the tachocline. A key question is how far below the overshoot layer in the tachocline does the solar cycle magnetic field extend. I will also speculate on the role the equator near the base of the convection zone could play in annihilation of solar cycle flux. In closing, I will try to sketch an integrated picture of the dynamics and MHD of the convection zone and tachocline, identify gaps in our understanding, and hopefully stimulate discussion of which gaps we have the best chance of filling, using the tools of helioseismology and theoretical and numerical calculations.

  13. A Short Review on the Current Understanding of Autism Spectrum Disorders

    PubMed Central

    Park, Hye Ran; Lee, Jae Meen; Moon, Hyo Eun; Lee, Dong Soo; Kim, Bung-Nyun; Kim, Jinhyun; Kim, Dong Gyu

    2016-01-01

    Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders characterized by a deficit in social behaviors and nonverbal interactions such as reduced eye contact, facial expression, and body gestures in the first 3 years of life. It is not a single disorder, and it is broadly considered to be a multi-factorial disorder resulting from genetic and non-genetic risk factors and their interaction. Genetic studies of ASD have identified mutations that interfere with typical neurodevelopment in utero through childhood. These complexes of genes have been involved in synaptogenesis and axon motility. Recent developments in neuroimaging studies have provided many important insights into the pathological changes that occur in the brain of patients with ASD in vivo. Especially, the role of amygdala, a major component of the limbic system and the affective loop of the cortico-striatothalamo-cortical circuit, in cognition and ASD has been proved in numerous neuropathological and neuroimaging studies. Besides the amygdala, the nucleus accumbens is also considered as the key structure which is related with the social reward response in ASD. Although educational and behavioral treatments have been the mainstay of the management of ASD, pharmacological and interventional treatments have also shown some benefit in subjects with ASD. Also, there have been reports about few patients who experienced improvement after deep brain stimulation, one of the interventional treatments. The key architecture of ASD development which could be a target for treatment is still an uncharted territory. Further work is needed to broaden the horizons on the understanding of ASD. PMID:26924928

  14. On the origin of 150-km echoes: Recent observational results and current understanding

    NASA Astrophysics Data System (ADS)

    Patra, Amit

    2012-07-01

    Discovered nearly 45 years ago, the so-called 150-km echoing phenomenon continues to be a puzzle. These are the coherent radar echoes coming from the height region of 140-180 km during daytime and are of special interest to the ionospheric scientists since they are very useful means for estimating the daytime electric fields, a crucial parameter for studying daytime electrodynamics and plasma physics, and can be observed by radar with moderate sensitivity. Although the 150-km echoes are being regularly used for studying low latitude electrodynamics, it is a bit awkward using them in the scientific work without knowing their origin. This paper is meant to present and discuss new results obtained from Gadanki (13.5o N, 79.2o E, mag. lat. 6.5o N), India to elucidate the underlying physical processes, not considered before. Two new findings, one obtained during the passage of a solar eclipse and another linked with the intermediate layer type descending properties of 150-km echoes, clearly indicate the role of electron density gradient in generating the irregularities responsible for the 150-km radar echoes, not envisioned before. Given the fact that Gadanki is located at magnetically low latitude, it is proposed that the descending echoing layers are produced by interchange instability on the gradient of daytime descending ion layer formed by meridional wind shear associated with tidal/gravity waves quite similar to that observed during nighttime. Comparative anatomy of daytime 150-km echoes and nighttime intermediate layer echoes will also be presented and discussed in an effort to have a deeper understanding on the underlying instability processes.

  15. Understanding the emission current limiting step in the carbon nanotube based polymer composite cathodes

    NASA Astrophysics Data System (ADS)

    Carey, David; Connolly, Thomas; Smith, Richard

    2011-03-01

    Carbon nanotube (CNT) based electronic applications often make use of the intrinsically high electrical conductivity of the nanotubes for charge transport. One attractive area for the exploitation of nanotubes is to combine their high electrical conductivity with their high aspect ratio leading to the development CNT based cathodes. In the presence of an electric field the field lines concentrate on the tip of nanotube and the resultant high local electric field (few V/nm) can result in electron tunneling (Fowler -- Nordheim tunneling) from the tip and emission. Embedding a nanotube in a polymer matrix opens up the possibility of a large area and a solution processable way to produce cathodes. We have studied the factors that control the rate limiting step for electron transport in functionalized CNTs in polyvinyl alcohol composites. We demonstrate excellent emission and current transport for nanotube volume fractions down to as low as 1 vol.% and that in the range from 1 vol.% to 7 vol.% the threshold field for emission does not significantly depend on nanotube content. Key to good emission is the ability to disperse the nanotubes efficiently.

  16. Nonampullary duodenal adenoma: Current understanding of its diagnosis, pathogenesis, and clinical management

    PubMed Central

    Lim, Chul-Hyun; Cho, Young-Seok

    2016-01-01

    Nonampullary duodenal adenomas are relatively common in familial adenomatous polyposis (FAP), but nonampullary sporadic duodenal adenomas (SDAs) are rare. Emerging evidence shows that duodenal adenomas, regardless of their anatomic location and whether they are sporadic or FAP-related, share morphologic and molecular features with colorectal adenomas. The available data suggest that duodenal adenomas develop to duodenal adenocarcinomas via similar mechanisms. The optimal approach for management of duodenal adenomas remains to be determined. The techniques for endoscopic resection of duodenal adenoma include snare polypectomy, endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and argon plasma coagulation ablation. EMR may facilitate removal of large duodenal polyps. Although several studies have reported cases of successful ESD for duodenal adenomas, the procedure is technically difficult to perform safely because of the anatomical properties of the duodenum. Although current clinical practice recommends endoscopic resection of all large duodenal adenomas in patients with FAP, endoscopic treatment is usually insufficient to guarantee a polyp-free duodenum. Surgery is indicated for FAP patients with severe polyposis or nonampullary SDAs or FAP-related polyps not amenable to endoscopic resection. Further studies are needed to develop newer endoscopic techniques to guide diagnostic and therapeutic decisions for future management of nonampullary duodenal adenomas. PMID:26811631

  17. Recent Advances in Improvement of Forecast Skill and Understanding Climate Processes Using AIRS Version-5 Products

    NASA Technical Reports Server (NTRS)

    Susskind, Joel; Molnar, Gyula; Iredell, Lena; Rosenberg, Robert

    2012-01-01

    AIRS/AMSU is the state of the art infrared and microwave atmospheric sounding system flying aboard EOS Aqua. These observations, covering the period September 2002 until the present, have been analyzed using the AIRS Science Team Version-5 retrieval algorithm. AIRS is a high spectral resolution infrared grating spectrometer with spect,ral coverage from 650 per centimeter extending to 2660 per centimeter, with low noise and a spectral resolving power of 2400. A brief overview of the AIRS Version-5 retrieval procedure will be presented, including the AIRS channels used in different steps in the retrieval process. Many researchers have used these products to make significant advances in both climate and weather applications. Recent significant results of these experiments will be presented, including results showing that 1) assimilation of AIRS Quality Controlled temperature profiles into a General Circulation Model (GCM) significantly improves the ability to predict storm tracks of intense precipitation events; and 2) anomaly time-series of Outgoing Longwave Radiation (OLR) computed using AIRS sounding products closely match those determined from the CERES instrument, and furthermore explain that the phenomenon that global and especially tropical mean OLR have been decreasing since September 2002 is a result of El Nino/La Nina oscillations during this period.

  18. Advances in Understanding of Swift Heavy-Ion Tracks in Complex Ceramics

    SciTech Connect

    Lang, Maik; Devanathan, Ram; Toulemonde, Marcel; Trautmann, Christina

    2015-02-01

    Tracks produced by swift heavy ions in ceramics are of interest for fundamental science as well as for applications covering different fields such as nanotechnology or fission-track dating of minerals. In the case of pyrochlores with general formula A2B2O7, the track structure and radiation sensitivity shows a clear dependence on the composition. Ion irradiated Gd2Zr2O7, e.g., retains its crystallinity while amorphous tracks are produced in Gd2Ti2O7. Tracks in Ti-containing compositions have a complex morphology consisting of an amorphous core surrounded by a shell of a disordered, defect-fluorite phase. The size of the amorphous core decreases with decreasing energy loss and with increasing Zr content, while the shell thickness seems to be similar over a wide range of energy loss values. The large data set and the complex track structure has made pyrochlore an interesting model system for a general theoretical description of track formation including thermal spike calculations (providing the spatial and temporal evolution of temperature around the ion trajectory) and molecular dynamics (MD) simulations (describing the response of the atomic system).Recent MD advances consider the sudden temperature increase by inserting data from the thermal spike. The combination allows the reproduction of the core-shell track characteristic and sheds light on the early stages of track formation including recrystallization of the molten material produced by the thermal spike.

  19. Recent advances in understanding the genetic architecture of type 2 diabetes

    PubMed Central

    Mohlke, Karen L.; Boehnke, Michael

    2015-01-01

    Genome-wide association (GWAS) and sequencing studies are providing new insights into the genetic basis of type 2 diabetes (T2D) and the inter-individual variation in glycemic traits, including levels of glucose, insulin, proinsulin and hemoglobin A1c (HbA1c). At the end of 2011, established loci (P < 5 × 10−8) totaled 55 for T2D and 32 for glycemic traits. Since then, most new loci have been detected by analyzing common [minor allele frequency (MAF)>0.05] variants in increasingly large sample sizes from populations around the world, and in trans-ancestry studies that successfully combine data from diverse populations. Most recently, advances in sequencing have led to the discovery of four loci for T2D or glycemic traits based on low-frequency (0.005 < MAF ≤ 0.05) variants, and additional low-frequency, potentially functional variants have been identified at GWAS loci. Established published loci now total ∼88 for T2D and 83 for one or more glycemic traits, and many additional loci likely remain to be discovered. Future studies will build on these successes by identifying additional loci and by determining the pathogenic effects of the underlying variants and genes. PMID:26160912

  20. Studying the start of the Maunder Minimum to understand the current situation

    NASA Astrophysics Data System (ADS)

    Neuhäuser, Ralph; Neuhäuser, Dagmar L.

    2016-04-01

    To investigate whether we now enter a Maunder-like grand minimum, we have to compare the current situation with the time around the start of the Maunder minimum. Sunspot observations in the 1610s are of particular importance and relevance, because they are shortly before the start of the Maunder Grand Minimum. While the Maunder Minimum it is usually dated from 1645 to 1715, Vaquero & Trigo (2015) argue that what they call the "Extended Maunder Minimum" would have started in 1618 during or around a Schwabe cycle minimum around that time. We have therefore studied the sunspot record of that time in detail. Hoyt & Schatten (1998) compiled for all known telescopic observers a list of their observations; recent solar activity studies for the past four centuries are based on their compilation. In addition to 12 observers listed by Hoyt & Schatten (1998) for the 1610s, we list six more observers with datable spot observations. Furthermore, while Hoyt & Schatten (1998) argue that Simon Marius would have observed from mid 1617 to the end of 1618 almost every day, but would have never seen a spot, we can show with the original reports by Marius that he observed from Aug 1611 to spring 1619 with a lot of sunspot detections. Similar, while Hoyt & Schatten (1998) argue that Giovanni Riccioli would have observed on almost every day in 1618, but would have never seen a spot, he did not report any own observations at all that year, but quoted Argoli for that there were no spots during the periods with comets in 1618. The data base by Hoyt & Schatten (1998) has several more errors in the 1610s, as we show also for the observations by Harriot, Scheiner, Malapert, Saxonius, and Tarde. We also compare drawings from Jungius with the observations by Harriot, Galilei, and Marius. In contrast to what is specified in Hoyt & Schatten (1998), after Harriot, the two Fabricius (father and son), Scheiner and Cysat, Marius and Schmidnerus are among the earliest datable telescopic sunspot

  1. Current understanding of the mechanism of action of the antiepileptic drug lacosamide.

    PubMed

    Rogawski, Michael A; Tofighy, Azita; White, H Steve; Matagne, Alain; Wolff, Christian

    2015-02-01

    The antiepileptic drug lacosamide [(R)-2-acetamido-N-benzyl-3-methoxypropanamide], a chiral functionalized amino acid, was originally identified by virtue of activity in the mouse and rat maximal electroshock (MES) test. Attention was drawn to lacosamide because of its high oral potency and stereoselectivity. Lacosamide is also active in the 6 Hz seizure model but inactive against clonic seizures in rodents induced by subcutaneous pentylenetetrazol, bicuculline and picrotoxin. It is also ineffective in genetic models of absence epilepsy. At doses greater than those required to confer protection in the MES test, lacosamide inhibits behavioral and electrographic seizures in hippocampal kindled rats. It also effectively terminates seizures in the rat perforant path stimulation status epilepticus model when administered early after the onset of seizures. Lacosamide does not exhibit antiepileptogenic effects in kindling or post-status epilepticus models. The profile of lacosamide in animal seizure and epilepsy models is similar to that of sodium channel blocking antiepileptic drugs, such as phenytoin and carbamazepine. However, unlike these agents, lacosamide does not affect sustained repetitive firing (SRF) on a time scale of hundreds of milliseconds or affect fast inactivation of voltage-gated sodium channels; however, it terminates SRF on a time scale of seconds by an apparent effect on sodium channel slow inactivation. Lacosamide shifts the slow inactivation curve to more hyperpolarized potentials and enhances the maximal fraction of channels that are in the slow inactivated state. Currently, lacosamide is the only known antiepileptic drug in clinical practice that exerts its anticonvulsant activity predominantly by selectively enhancing slow sodium channel inactivation.

  2. Understanding Gully Formation and Seasonal Flows on Recent and Current Mars

    NASA Astrophysics Data System (ADS)

    Gulick, Virginia C.; Glines, Natalie

    2016-10-01

    The discoveries of gullies and seasonal slope flows (RSL) have re-ignited the debate over various channel, valley, and gully formation mechanisms on Mars. The controversy over whether liquid water was involved with gully formation, harkens back to the mid-1970s to early 2000s, where catastrophic flooding, surface runnoff and ground-water sapping processes were strongly debated along with other mechanisms as the primary processes responsible for channel and valley formation on Mars. However, over the past decade, the value of multiple working hypotheses has again become apparent, this time in understanding the formation of Martian gullies and Recurring Slope Lineae. Various mechanisms put forth to explain these landforms include liquid H2O/ice erosion, CO2 ice/frost sublimation, CO2 ice block sliding, water and brine flows, salt deliquescence, and dry granular flows, among others.We carried out detailed morphologic/morphometric studies of gullies in various environmental settings on Mars to evaluate the potential formation processes. Using HiRISE images and DTMs, we mapped and generated detailed longitudinal and cross-sectional profiles of gully systems and estimated volumes for both the gullies and their debris aprons. Several gullies form highly integrated patterns similar to fluvial systems. Additionally, RSL are often found either in the tributaries of these integrated systems or in adjacent regions, implying that RSL may play a role in initiating gully formation or mark the last vestiges of water activity in these locations. We also find that the more highly integrated gullies have volumes significantly larger than their aprons, suggesting that the missing volumes (~40-60% or more) were likely the volatiles involved in gully formation. Additionally, THEMIS and TES surface temperatures of these integrated gully sites, many of which also contain RSL, are at or above freezing seasonally suggesting that the volatile component may be consistent with H2O although CO2

  3. Understanding the mental health of youth living with perinatal HIV infection: lessons learned and current challenges

    PubMed Central

    Mellins, Claude A; Malee, Kathleen M

    2013-01-01

    preclude both conclusions and full understanding of aetiology. Conversely, these limitations present opportunities for future research. Many PHIV+ youth experience adequate mental health despite vulnerabilities. However, the focus of research to date highlights the identification of risks rather than positive attributes, which could inform preventive interventions. Development and evaluation of mental health interventions and preventions are urgently needed to optimize mental health, particularly for PHIV+ youth growing up in low-and-middle income countries. PMID:23782478

  4. Advances in the understanding and clinical management of mastocytosis and clonal mast cell activation syndromes

    PubMed Central

    2016-01-01

    Clonal mast cell activation syndromes and indolent systemic mastocytosis without skin involvement are two emerging entities that sometimes might be clinically difficult to distinguish, and they involve a great challenge for the physician from both a diagnostic and a therapeutic point of view. Furthermore, final diagnosis of both entities requires a bone marrow study; it is recommended that this be done in reference centers. In this article, we address the current consensus and guidelines for the suspicion, diagnosis, classification, treatment, and management of these two entities. PMID:27909577

  5. Advances in understanding quiescent H-mode plasmas in DIII-D

    SciTech Connect

    Burrell, K.H.; West, W.P.; Gohil, P.; Greenfield, C.M.; Groebner, R.J.; Hyatt, A.W.; Kaplan, D.H.; Lao, L.L.; Leonard, A.W.; Osborne, T.H.; Snyder, P.B.; Thomas, D.M.; Strait, E.J.; Doyle, E.J.; Rhodes, T.L.; Wang, G.; Zeng, L.; Austin, M.E.; Casper, T.A.; Jayakumar, R.J.

    2005-05-15

    Recent QH-mode research on DIII-D [J. L. Luxon et al., Plasma Physics and Controlled Nuclear Fusion Research 1996 (International Atomic Energy Agency, Vienna, 1987), Vol. I, p. 159] has used the peeling-ballooning modes model of edge magnetohydrodynamic stability as a working hypothesis to organize the data; several predictions of this theory are consistent with the experimental results. Current ramping results indicate that QH modes operate near the edge current limit set by peeling modes. This operating point explains why QH mode is easier to get at lower plasma currents. Power scans have shown a saturation of edge pressure with increasing power input. This allows QH-mode plasmas to remain stable to edge localized modes (ELMs) to the highest powers used in DIII-D. At present, the mechanism for this saturation is unknown; if the edge harmonic oscillation (EHO) is playing a role here, the physics is not a simple amplitude dependence. The increase in edge stability with plasma triangularity predicted by the peeling-ballooning theory is consistent with the substantial improvement in pedestal pressure achieved by changing the plasma shape from a single null divertor to a high triangularity double null. Detailed ELITE calculations for the high triangularity plasmas have demonstrated that the plasma operating point is marginally stable to peeling-ballooning modes. Comparison of ELMing, coinjected and quiescent, counterinjected discharges with the same shape, current, toroidal field, electron density, and electron temperature indicates that the edge radial electric field or the edge toroidal rotation are also playing a role in edge stability. The EHO produces electron, main ion, and impurity particle transport at the plasma edge which is more rapid than that produced by ELMs under similar conditions. The EHO also decreases the edge rotation while producing little change in the edge electron and ion temperatures. Other edge electromagnetic modes also produce particle

  6. Recent advances in understanding carotenoid-derived signaling molecules in regulating plant growth and development.

    PubMed

    Tian, Li

    2015-01-01

    Carotenoids (C40) are synthesized in plastids and perform numerous important functions in these organelles. In addition, carotenoids can be processed into smaller signaling molecules that regulate various phases of the plant's life cycle. Besides the relatively well-studied phytohormones abscisic acid (ABA) and strigolactones (SLs), additional carotenoid-derived signaling molecules have been discovered and shown to regulate plant growth and development. As a few excellent reviews summarized recent research on ABA and SLs, this mini review will focus on progress made on identification and characterization of the emerging carotenoid-derived signals. Overall, a better understanding of carotenoid-derived signaling molecules has immediate applications in improving plant biomass production which in turn will have far reaching impacts on providing food, feed, and fuel for the growing world population.

  7. Recent advances in understanding neuropathic pain: glia, sex differences, and epigenetics

    PubMed Central

    Machelska, Halina; Celik, Melih Ö.

    2016-01-01

    Neuropathic pain results from diseases or trauma affecting the nervous system. This pain can be devastating and is poorly controlled. The pathophysiology is complex, and it is essential to understand the underlying mechanisms in order to identify the relevant targets for therapeutic intervention. In this article, we focus on the recent research investigating neuro-immune communication and epigenetic processes, which gain particular attention in the context of neuropathic pain. Specifically, we analyze the role of glial cells, including microglia, astrocytes, and oligodendrocytes, in the modulation of the central nervous system inflammation triggered by neuropathy. Considering epigenetics, we address DNA methylation, histone modifications, and the non-coding RNAs in the regulation of ion channels, G-protein-coupled receptors, and transmitters following neuronal damage. The goal was not only to highlight the emerging concepts but also to discuss controversies, methodological complications, and intriguing opinions. PMID:28105313

  8. Advances in the theoretical understanding of photon upconversion in rare-earth activated nanophosphors.

    PubMed

    Liu, Guokui

    2015-03-21

    Photon upconversion in rare earth activated phosphors involves multiple mechanisms of electronic transitions. Stepwise optical excitation, energy transfer, and various nonlinear and collective light-matter interaction processes act together to convert low-energy photons into short-wavelength light emission. Upconversion luminescence from nanomaterials exhibits additional size and surface dependencies. A fundamental understanding of the overall performance of an upconversion system requires basic theories on the spectroscopic properties of solids containing rare earth ions. This review article surveys the recent progress in the theoretical interpretations of the spectroscopic characteristics and luminescence dynamics of photon upconversion in rare earth activated phosphors. The primary aspects of upconversion processes, including energy level splitting, transition probability, line broadening, non-radiative relaxation and energy transfer, are covered with an emphasis on interpreting experimental observations. Theoretical models and methods for analyzing nano-phenomena in upconversion are introduced with detailed discussions on recently reported experimental results.

  9. Recent advances in understanding the enzymatic reactions of [4+2] cycloaddition and spiroketalization.

    PubMed

    Zheng, Qingfei; Tian, Zhenhua; Liu, Wen

    2016-04-01

    Diels-Alder-like [4+2] cycloaddition and ketalization of dihydroxy ketones are cyclization reactions with different mechanisms that produce characteristic cyclohexene and spiroketal units, respectively. Here, we review newly identified, naturally occurring '[4+2] cycloadditionases' and 'spiroketalases' and reveal several similarities between the two types of enzymes. During catalysis, these enzymes control product stereochemistry or/and enhance the transformation rate. They exhibit convergent evolution of [4+2] cycloaddition or spiroketalization activity, which is likely dependent on interactions of variable protein folds with specialized chemical structures. An understanding of these similarities is expected to allow for establishment of the underlying principles for the application and catalyst design of associated enzymatic reactions in organic chemistry and synthetic biology.

  10. Combining natural and man-made DNA tracers to advance understanding of hydrologic flow pathway evolution

    NASA Astrophysics Data System (ADS)

    Dahlke, H. E.; Walter, M. T.; Lyon, S. W.; Rosqvist, G. N.

    2014-12-01

    Identifying and characterizing the sources, pathways and residence times of water and associated constituents is critical to developing improved understanding of watershed-stream connections and hydrological/ecological/biogeochemical models. To date the most robust information is obtained from integrated studies that combine natural tracers (e.g. isotopes, geochemical tracers) with controlled chemical tracer (e.g., bromide, dyes) or colloidal tracer (e.g., carboxilated microspheres, tagged clay particles, microorganisms) applications. In the presented study we explore how understanding of sources and flow pathways of water derived from natural tracer studies can be improved and expanded in space and time by simultaneously introducing man-made, synthetic DNA-based microtracers. The microtracer used were composed of polylactic acid (PLA) microspheres into which short strands of synthetic DNA and paramagnetic iron oxide nanoparticles are incorporated. Tracer experiments using both natural tracers and the DNA-based microtracers were conducted in the sub-arctic, glacierized Tarfala (21.7 km2) catchment in northern Sweden. Isotopic hydrograph separations revealed that even though storm runoff was dominated by pre-event water the event water (i.e. rainfall) contributions to streamflow increased throughout the summer season as glacial snow cover decreased. This suggests that glaciers are a major source of the rainwater fraction in streamflow. Simultaneous injections of ten unique DNA-based microtracers confirmed this hypothesis and revealed that the transit time of water traveling from the glacier surface to the stream decreased fourfold over the summer season leading to instantaneous rainwater contributions during storm events. These results highlight that integrating simultaneous tracer injections (injecting tracers at multiple places at one time) with traditional tracer methods (sampling multiple times at one place) rather than using either approach in isolation can

  11. Imaging mass spectrometry of the visual system: Advancing the molecular understanding of retina degenerations.

    PubMed

    Bowrey, Hannah E; Anderson, David M; Pallitto, Patrick; Gutierrez, Danielle B; Fan, Jie; Crouch, Rosalie K; Schey, Kevin L; Ablonczy, Zsolt

    2016-04-01

    Visual sensation is fundamental for quality of life, and loss of vision to retinal degeneration is a debilitating condition. The eye is the only part of the central nervous system that can be noninvasively observed with optical imaging. In the clinics, various spectroscopic methods provide high spatial resolution images of the fundus and the developing degenerative lesions. However, the currently utilized tools are not specific enough to establish the molecular underpinnings of retinal diseases. In contrast, mass spectrometric imaging (MSI) is a powerful tool to identify molecularly specific disease indicators and classification markers. This technique is particularly well suited to the eye, where molecular information can be correlated with clinical data collected via noninvasive diagnostic imaging modalities. Recent studies during the last few recent years have uncovered a plethora of new spatially defined molecular information on several vision-threatening diseases, including age-related macular degeneration, Stargardt disease, glaucoma, cataract, as well as lipid disorders. Even though MS inside the eye cannot be performed noninvasively, by linking diagnostic and molecular information, these studies are the first step toward the development of smart ophthalmic diagnostic and surgical tools. Here, we provide an overview of current approaches applying MSI technology to ocular pathology.

  12. Can Human Pluripotent Stem Cell-Derived Cardiomyocytes Advance Understanding of Muscular Dystrophies?

    PubMed

    Kalra, Spandan; Montanaro, Federica; Denning, Chris

    2016-08-30

    Muscular dystrophies (MDs) are clinically and molecularly a highly heterogeneous group of single-gene disorders that primarily affect striated muscles. Cardiac disease is present in several MDs where it is an important contributor to morbidity and mortality. Careful monitoring of cardiac issues is necessary but current management of cardiac involvement does not effectively protect from disease progression and cardiac failure. There is a critical need to gain new knowledge on the diverse molecular underpinnings of cardiac disease in MDs in order to guide cardiac treatment development and assist in reaching a clearer consensus on cardiac disease management in the clinic. Animal models are available for the majority of MDs and have been invaluable tools in probing disease mechanisms and in pre-clinical screens. However, there are recognized genetic, physiological, and structural differences between human and animal hearts that impact disease progression, manifestation, and response to pharmacological interventions. Therefore, there is a need to develop parallel human systems to model cardiac disease in MDs. This review discusses the current status of cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSC) to model cardiac disease, with a focus on Duchenne muscular dystrophy (DMD) and myotonic dystrophy (DM1). We seek to provide a balanced view of opportunities and limitations offered by this system in elucidating disease mechanisms pertinent to human cardiac physiology and as a platform for treatment development or refinement.

  13. Can Human Pluripotent Stem Cell-Derived Cardiomyocytes Advance Understanding of Muscular Dystrophies?

    PubMed Central

    Kalra, Spandan; Montanaro, Federica; Denning, Chris

    2016-01-01

    Muscular dystrophies (MDs) are clinically and molecularly a highly heterogeneous group of single-gene disorders that primarily affect striated muscles. Cardiac disease is present in several MDs where it is an important contributor to morbidity and mortality. Careful monitoring of cardiac issues is necessary but current management of cardiac involvement does not effectively protect from disease progression and cardiac failure. There is a critical need to gain new knowledge on the diverse molecular underpinnings of cardiac disease in MDs in order to guide cardiac treatment development and assist in reaching a clearer consensus on cardiac disease management in the clinic. Animal models are available for the majority of MDs and have been invaluable tools in probing disease mechanisms and in pre-clinical screens. However, there are recognized genetic, physiological, and structural differences between human and animal hearts that impact disease progression, manifestation, and response to pharmacological interventions. Therefore, there is a need to develop parallel human systems to model cardiac disease in MDs. This review discusses the current status of cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSC) to model cardiac disease, with a focus on Duchenne muscular dystrophy (DMD) and myotonic dystrophy (DM1). We seek to provide a balanced view of opportunities and limitations offered by this system in elucidating disease mechanisms pertinent to human cardiac physiology and as a platform for treatment development or refinement. PMID:27854224

  14. Recent Advances in the Performance and Understanding of the SNS Ion Source

    NASA Astrophysics Data System (ADS)

    Welton, R. F.; Stockli, M. P.; Murray, S. N.; Keller, R.

    2005-04-01

    The ion source developed for the Spallation Neutron Source (SNS) by Lawrence Berkeley National Laboratory (LBNL), is a radio frequency, multi-cusp source designed to produce ˜ 40 mA of H- with a normalized rms emittance of less than 0.2 pi mm mrad. To date, the source has been utilized in the commissioning of the SNS accelerator and has already demonstrated stable, satisfactory operation at beam currents of ˜30 mA with duty-factors of ˜0.1% for operational periods of several weeks. Once the SNS is fully operational in 2008, a beam current duty-factor of 6% (1 ms pulse length, 60 Hz repetition rate) will be required in order to inject the accelerator. To ascertain the capability of the source to deliver beams at this high duty-factor over sustained time periods, several experimental runs have been conducted, each ˜1 week in length, in which the ion source was continuously operated on a dedicated test stand. The results of these tests are reported as well as a theory of the Cs release and transport processes which were derived from these data. The theory was then employed to develop a more effective source conditioning procedure as well as an improved Cs collar design. Initial results of tests employing a Cs collar with enhanced surface ionization geometry are also discussed.

  15. Understanding Advance Care Planning as a Process of Health Behavior Change

    PubMed Central

    Fried, Terri R.; Bullock, Karen; Iannone, Lynne; O'Leary, John R.

    2009-01-01

    Objectives To explore whether models of health behavior change can help to inform interventions for ACP. Design Qualitative cross-sectional study. Setting Community Participants Sixty-three community dwelling persons age ≥ 65 years and 30 caregivers with experience as surrogate decision-makers. Measurements In focus groups conducted separately with older persons and with caregivers, participants were asked to discuss ways they had planned for future declines in health and why they had or had not engaged in such planning. Transcripts were analyzed using grounded theory. Results Four themes illustrated the potential of applying models of health behavior change to improve ACP. 1) Participants demonstrated variable readiness to engage in ACP and could be in different stages of readiness for different components of ACP, including consideration of treatment goals, completion of advance directives, and communication with families and physicians. 2) Participants identified a wide range of benefits of and barriers to ACP. 3) Participants used a variety of processes of change to progress through stages of readiness, and ACP was only one of a broader set of behaviors that participants engaged in to prepare for declines in their health or for death. 4) Experience with healthcare decision-making for loved ones was a strong influence on perceptions of susceptibility and engagement in ACP. Discussion The variability in participants' readiness, barriers and benefits, perceptions of susceptibility, and use of processes to increase readiness_for participating in each component of ACP suggests the utility of tailored, stage-specific interventions based on individualized assessments to improve ACP. PMID:19682120

  16. Current advances in molecular, biochemical, and computational modeling analysis of microalgal triacylglycerol biosynthesis.

    PubMed

    Lenka, Sangram K; Carbonaro, Nicole; Park, Rudolph; Miller, Stephen M; Thorpe, Ian; Li, Yantao

    2016-01-01

    Triacylglycerols (TAGs) are highly reduced energy storage molecules ideal for biodiesel production. Microalgal TAG biosynthesis has been studied extensively in recent years, both at the molecular level and systems level through experimental studies and computational modeling. However, discussions of the strategies and products of the experimental and modeling approaches are rarely integrated and summarized together in a way that promotes collaboration among modelers and biologists in this field. In this review, we outline advances toward understanding the cellular and molecular factors regulating TAG biosynthesis in unicellular microalgae with an emphasis on recent studies on rate-limiting steps in fatty acid and TAG synthesis, while also highlighting new insights obtained from the integration of multi-omics datasets with mathematical models. Computational methodologies such as kinetic modeling, metabolic flux analysis, and new variants of flux balance analysis are explained in detail. We discuss how these methods have been used to simulate algae growth and lipid metabolism in response to changing culture conditions and how they have been used in conjunction with experimental validations. Since emerging evidence indicates that TAG synthesis in microalgae operates through coordinated crosstalk between multiple pathways in diverse subcellular destinations including the endoplasmic reticulum and plastids, we discuss new experimental studies and models that incorporate these findings for discovering key regulatory checkpoints. Finally, we describe tools for genetic manipulation of microalgae and their potential for future rational algal strain design. This comprehensive review explores the potential synergistic impact of pathway analysis, computational approaches, and molecular genetic manipulation strategies on improving TAG production in microalgae.

  17. Current advances in delivery of biotherapeutics across the blood-brain barrier.

    PubMed

    Rajadhyaksha, Manoj; Boyden, Tracey; Liras, Jennifer; El-Kattan, Ayman; Brodfuehrer, Joanne

    2011-06-01

    Significant efforts through genomic approaches have been dedicated toward the identification of novel protein-protein interactions as promising therapeutic targets for indications such as Alzheimer's disease, Parkinson's disease and neuropsychiatric disorders. Additionally, the number of biotherapeutic agents entering the Pharmaceutical sector continues to increase and according to EvaluatePharma's "World Preview 2014" report, "the compounded annual growth rate of biologics is expected to be 8.5 percent from 2008-2014, eight to 10 times greater than the growth rate of small molecules". However, there are limited examples of success in developing biotherapeutic modalities for central nervous system (CNS) diseases in the drug development pipeline. A primary reason for the lack of application of biotherapeutics to neuroscience targets, is that the blood-brain barrier (BBB) isolates and protects CNS structures creating a unique biochemically and immunologically privileged environment, therefore passage of macromolecules across this barrier has additional challenges. An understanding of the anatomical and physiological properties of this barrier with respect to penetration of biotherapeutics is presented in this review document. In this summary, recent advances in biotherapeutic delivery mechanisms across the BBB including transcranial brain drug delivery, focused ultrasound technology, nasal delivery, absorptive endocytosis, and receptor mediated endocytosis are evaluated using an industrial perspective. With acknowledgement that each approach has advantages and disadvantages, this review discusses the opportunities and challenges that are encountered during application of these methods across a variety of therapeutic areas such as, pain, obesity, neuroscience, and oncology. Utilizing an industrial perspective, including consideration of cost of goods and commercial feasibility for these approaches, this review highlights technology features which would enable industry

  18. ADVANCED SIMULATION CAPABILITY FOR ENVIRONMENTAL MANAGEMENT- CURRENT STATUS AND PHASE II DEMONSTRATION RESULTS

    SciTech Connect

    Seitz, R.

    2013-02-26

    The U.S. Department of Energy (USDOE) Office of Environmental Management (EM), Office of Soil and Groundwater, is supporting development of the Advanced Simulation Capability for Environmental Management (ASCEM). ASCEM is a state-of-the-art scientific tool and approach for understanding and predicting contaminant fate and transport in natural and engineered systems. The modular and open source high-performance computing tool facilitates integrated approaches to modeling and site characterization that enable robust and standardized assessments of performance and risk for EM cleanup and closure activities. The ASCEM project continues to make significant progress in development of computer software capabilities with an emphasis on integration of capabilities in FY12. Capability development is occurring for both the Platform and Integrated Toolsets and High-Performance Computing (HPC) Multiprocess Simulator. The Platform capabilities provide the user interface and tools for end-to-end model development, starting with definition of the conceptual model, management of data for model input, model calibration and uncertainty analysis, and processing of model output, including visualization. The HPC capabilities target increased functionality of process model representations, toolsets for interaction with Platform, and verification and model confidence testing. The Platform and HPC capabilities are being tested and evaluated for EM applications in a set of demonstrations as part of Site Applications Thrust Area activities. The Phase I demonstration focusing on individual capabilities of the initial toolsets was completed in 2010. The Phase II demonstration completed in 2012 focused on showcasing integrated ASCEM capabilities. For Phase II, the Hanford Site deep vadose zone (BC Cribs) served as an application site for an end-to-end demonstration of capabilities, with emphasis on integration and linkages between the Platform and HPC components. Other demonstrations

  19. ADVANCED SIMULATION CAPABILITY FOR ENVIRONMENTAL MANAGEMENT – CURRENT STATUS AND PHASE II DEMONSTRATION RESULTS

    SciTech Connect

    Seitz, Roger; Freshley, Mark D.; Dixon, Paul; Hubbard, Susan S.; Freedman, Vicky L.; Flach, Gregory P.; Faybishenko, Boris; Gorton, Ian; Finsterle, Stefan A.; Moulton, John D.; Steefel, Carl I.; Marble, Justin

    2013-06-27

    The U.S. Department of Energy (USDOE) Office of Environmental Management (EM), Office of Soil and Groundwater, is supporting development of the Advanced Simulation Capability for Environmental Management (ASCEM). ASCEM is a state-of-the-art scientific tool and approach for understanding and predicting contaminant fate and transport in natural and engineered systems. The modular and open source high-performance computing tool facilitates integrated approaches to modeling and site characterization that enable robust and standardized assessments of performance and risk for EM cleanup and closure activities. The ASCEM project continues to make significant progress in development of computer software capabilities with an emphasis on integration of capabilities in FY12. Capability development is occurring for both the Platform and Integrated Toolsets and High-Performance Computing (HPC) Multiprocess Simulator. The Platform capabilities provide the user interface and tools for end-to-end model development, starting with definition of the conceptual model, management of data for model input, model calibration and uncertainty analysis, and processing of model output, including visualization. The HPC capabilities target increased functionality of process model representations, toolsets for interaction with Platform, and verification and model confidence testing. The Platform and HPC capabilities are being tested and evaluated for EM applications in a set of demonstrations as part of Site Applications Thrust Area activities. The Phase I demonstration focusing on individual capabilities of the initial toolsets was completed in 2010. The Phase II demonstration completed in 2012 focused on showcasing integrated ASCEM capabilities. For Phase II, the Hanford Site deep vadose zone (BC Cribs) served as an application site for an end-to-end demonstration of capabilities, with emphasis on integration and linkages between the Platform and HPC components. Other demonstrations

  20. Advancing the application of systems thinking in health: understanding the dynamics of neonatal mortality in Uganda

    PubMed Central

    2014-01-01

    Background Of the three million newborns that die each year, Uganda ranks fifth highest in neonatal mortality rates, with 43,000 neonatal deaths each year. Despite child survival and safe motherhood programmes towards reducing child mortality, insufficient attention has been given to this critical first month of life. There is urgent need to innovatively employ alternative solutions that take into account the intricate complexities of neonatal health and the health systems. In this paper, we set out to empirically contribute to understanding the causes of the stagnating neonatal mortality by applying a systems thinking approach to explore the dynamics arising from the neonatal health complexity and non-linearity and its interplay with health systems factors, using Uganda as a case study. Methods Literature reviews and interviews were conducted in two divisions of Kampala district with high neonatal mortality rates with mothers at antenatal clinics and at home, village health workers, community leaders, healthcare decision and policy makers, and frontline health workers from both public and private health facilities. Data analysis and brainstorming sessions were used to develop causal loop diagrams (CLDs) depicting the causes of neonatal mortality, which were validated by local and international stakeholders. Results We developed two CLDs for demand and supply side issues, depicting the range of factors associated with neonatal mortality such as maternal health, level of awareness of maternal and newborn health, and availability and quality of health services, among others. Further, the reinforcing and balancing feedback loops that resulted from this complexity were also examined. The potential high leverage points include special gender considerations to ensure that girls receive essential education, thereby increasing maternal literacy rates, improved socioeconomic status enabling mothers to keep healthy and utilise health services, improved supervision, and