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Sample records for advance current understanding

  1. Microstructural understanding and critical current optimization of advanced high field superconductors

    SciTech Connect

    Bonney, L.A.; Willis, T.C.; Larbalestier, D.C.

    1993-01-01

    It is of great importance to improve critical current density, J[sub c] in A15 superconductors for high field magnet applications. Most current work to improve J[sub c] in A15 wires concentrates on increasing the overall J[sub c] by increasing the fraction of superconducting phase in the wire, by improving the uniformity of the superconductor cross section along the length of the wire and by adjusting the strainstate of the A15 layer. The goal of the A15 work in this group was to investigate the intrinsic J[sub c] of the A15 layer itself. To do this, a better understanding of factors controlling the intrinsic J[sub c]of the Nb[sub 3]Sn was pursued.

  2. 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

  3. 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

  4. Status of High Latitude Precipitation Estimates: The Role of GPM in Advancing our Current Understanding

    NASA Astrophysics Data System (ADS)

    Behrangi, A.; Richardson, M.; Christensen, M.; Huffman, G. J.; Adler, R. F.; Stephens, G. L.; Lambrigtsen, B.

    2015-12-01

    This presentation reviews the current status of precipitation estimation from observation and reanalysis at high latitudes and discusses new insights gained by GPM. An intercomparison of high-latitude precipitation characteristics from observation-based and reanalysis products is performed. Precipitation products from GPM and the cloud profiling radar on the CloudSat satellite provide an independent assessment to other products which have already been widely used, these being the observationally-based GPCP, GPCC and CMAP and the reanalyses ERA-Interim, MERRA and NCEP-DOE. Seasonal and annual total precipitation in both hemispheres poleward of 55° latitude is considered in all products, and GPM and CloudSat products are used to assess frequency of precipitation occurrence by phase, defined as rain, snow or mixed phase. Estimates of snowfall over Antarctica and Greenland are compared from various products. A number of disagreements on regional or seasonal scales are identified which will be reported and discussed. These estimates from observations and reanalyses provide useful insights for diagnostic assessment of precipitation products in high latitudes, quantifying the current uncertainties among observations and reanalyses, and establishing a benchmark for assessment of climate models.

  5. Microstructural understanding and critical current optimization of advanced high field superconductors. Progress report, February 1, 1991--March 31, 1993

    SciTech Connect

    Bonney, L.A.; Willis, T.C.; Larbalestier, D.C.

    1993-04-01

    It is of great importance to improve critical current density, J{sub c} in A15 superconductors for high field magnet applications. Most current work to improve J{sub c} in A15 wires concentrates on increasing the overall J{sub c} by increasing the fraction of superconducting phase in the wire, by improving the uniformity of the superconductor cross section along the length of the wire and by adjusting the strainstate of the A15 layer. The goal of the A15 work in this group was to investigate the intrinsic J{sub c} of the A15 layer itself. To do this, a better understanding of factors controlling the intrinsic J{sub c}of the Nb{sub 3}Sn was pursued.

  6. 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

  7. 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

  8. Recent advances in understanding dengue.

    PubMed

    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

  9. 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.

  10. 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

  11. Recent advances in understanding vitiligo.

    PubMed

    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

  12. 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

  13. Recent advances in understanding vitiligo.

    PubMed

    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

  14. 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

  15. Recent advances in understanding psoriasis

    PubMed Central

    Eberle, Franziska C.; Brück, Jürgen; Holstein, Julia; Hirahara, Kiyoshi; Ghoreschi, Kamran

    2016-01-01

    T helper (Th) cells producing interleukin (IL)-17, IL-22, and tumor necrosis factor (TNF) form the key T cell population driving psoriasis pathogenesis. They orchestrate the inflammation in the skin that results in the proliferation of keratinocytes and endothelial cells. Besides Th17 cells, other immune cells that are capable of producing IL-17-associated cytokines participate in psoriatic inflammation. Recent advances in psoriasis research improved our understanding of the cellular and molecular players that are involved in Th17 pathology and inflammatory pathways in the skin. The inflammation-driving actions of TNF in psoriasis are already well known and antibodies against TNF are successful in the treatment of Th17-mediated psoriatic skin inflammation. A further key cytokine with potent IL-17-/IL-22-promoting properties is IL-23. Therapeutics directly neutralizing IL-23 or IL-17 itself are now extending the therapeutic spectrum of antipsoriatic agents and further developments are on the way. The enormous progress in psoriasis research allows us to control this Th17-mediated inflammatory skin disease in many patients. PMID:27158469

  16. Radiodermatitis: A Review of Our Current Understanding.

    PubMed

    Singh, Manni; Alavi, Afsaneh; Wong, Rebecca; Akita, Sadanori

    2016-06-01

    Radiodermatitis (radiation dermatitis, radiation-induced skin reactions, or radiation injury) is a significant side effect of ionizing radiation delivered to the skin during cancer treatment as well as a result of nuclear attacks and disasters, such as that which occurred in Fukushima in 2011. More specifically, 95 % of cancer patients receiving radiation therapy will develop some form of radiodermatitis, including erythema, dry desquamation, and moist desquamation. These radiation skin reactions result in a myriad of complications, including delays in treatment, diminished aesthetic appeal, and reduced quality of life. Recent technological advancements and novel treatment regimens have only been successful in partly ameliorating these adverse side effects. This article examines the current knowledge surrounding the pathogenesis, clinical manifestations, differential diagnoses, prevention, and management of radiodermatitis. Future research should examine therapies that incorporate the current understanding of the pathophysiology of radiodermatitis while measuring effectiveness using objective and universal outcome measures.

  17. Radiodermatitis: A Review of Our Current Understanding.

    PubMed

    Singh, Manni; Alavi, Afsaneh; Wong, Rebecca; Akita, Sadanori

    2016-06-01

    Radiodermatitis (radiation dermatitis, radiation-induced skin reactions, or radiation injury) is a significant side effect of ionizing radiation delivered to the skin during cancer treatment as well as a result of nuclear attacks and disasters, such as that which occurred in Fukushima in 2011. More specifically, 95 % of cancer patients receiving radiation therapy will develop some form of radiodermatitis, including erythema, dry desquamation, and moist desquamation. These radiation skin reactions result in a myriad of complications, including delays in treatment, diminished aesthetic appeal, and reduced quality of life. Recent technological advancements and novel treatment regimens have only been successful in partly ameliorating these adverse side effects. This article examines the current knowledge surrounding the pathogenesis, clinical manifestations, differential diagnoses, prevention, and management of radiodermatitis. Future research should examine therapies that incorporate the current understanding of the pathophysiology of radiodermatitis while measuring effectiveness using objective and universal outcome measures. PMID:27021652

  18. 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.

  19. Advances in understanding erythropoiesis: evolving perspectives.

    PubMed

    Nandakumar, Satish K; Ulirsch, Jacob C; Sankaran, Vijay G

    2016-04-01

    Red blood cells (RBCs) are generated from haematopoietic stem and progenitor cells (HSPCs) through the step-wise process of differentiation known as erythropoiesis. In this review, we discuss our current understanding of erythropoiesis and highlight recent advances in this field. During embryonic development, erythropoiesis occurs in three distinct waves comprising first, the yolk sac-derived primitive RBCs, followed sequentially by the erythro-myeloid progenitor (EMP) and HSPC-derived definitive RBCs. Recent work has highlighted the complexity and variability that may exist in the hierarchical arrangement of progenitors responsible for erythropoiesis. Using recently defined cell surface markers, it is now possible to enrich for erythroid progenitors and precursors to a much greater extent than has been possible before. While a great deal of knowledge has been gained on erythropoiesis from model organisms, our understanding of this process is currently being refined through human genetic studies. Genes mutated in erythroid disorders can now be identified more rapidly by the use of next-generation sequencing techniques. Genome-wide association studies on erythroid traits in healthy populations have also revealed new modulators of erythropoiesis. All of these recent developments have significant promise not only for increasing our understanding of erythropoiesis, but also for improving our ability to intervene when RBC production is perturbed in disease. PMID:26846448

  20. 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

  1. Recent advances in understanding apicomplexan parasites.

    PubMed

    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

  2. Advances in understanding illness anxiety.

    PubMed

    Harding, Kelli J; Skritskaya, Natalia; Doherty, Emily; Fallon, Brian A

    2008-08-01

    Illness anxiety, also known in its more severe form as hypochondriasis, is a debilitating and chronic condition in which normal bodily symptoms are misinterpreted as signs of serious medical illness. Patients suffer with the fear that they are ill despite reassurance to the contrary and often overuse medical services in the process. This article critically evaluates the recent literature on illness anxiety and related, medically unexplained symptoms, highlighting new and interesting findings in the areas of prevalence, classification/diagnosis, management, and evidence-based treatment and new frontiers in understanding illness anxiety, such as brain imaging, neuroimmunology, and cyberchondria. PMID:18627669

  3. Advances in understanding pituitary tumors

    PubMed Central

    Renner, Ulrich; Karl Stalla, Günter

    2014-01-01

    Pituitary tumors are common in the general population. Since neuroimaging techniques have improved, pituitary tumors are more often diagnosed incidentally. About 16.7% of the general population show changes in the pituitary gland. Predominantly, pituitary tumors are benign pituitary adenomas. Pituitary carcinomas or aggressive pituitary tumors are extremely rare. They might develop from benign adenomas. New genetic and epigenetic abnormalities help us to understand pituitary tumorigenesis and might lead to therapeutical targeting drugs in the future. Macroadenomas (>1 cm) can lead to visual field disturbances, compression of cranial nerves, hypopituitarism, and infiltration of the cavernous sinuses. The functional status of the pituitary tumor is important. About half to one third of all pituitary tumors are non-functioning pituitary adenomas. The other pituitary tumors show a specific pattern of hormone secretion. About 25% to 41% of all pituitary tumors are prolactinomas, acromegaly with production of growth hormone represents 10% to 15% of adenomas, Cushing's disease with production of adrenocorticotropic hormone accounts for 10%, and other hormonal characteristics are less common. Transsphenoidal resection and total adenomectomy are desirable. Radiosurgery has enriched the surgical treatment options. Surgical treatment is the intervention of choice except for prolactinomas, where pharmaceutical treatment is recommended. Pharmaceutical treatment consists of dopamine agonists such as cabergoline and somatostatin analogues that include octreotide and pasireotide; retinoic acid is of theoretical interest while peroxisome proliferator-activated receptor-gamma-ligands are not clinically useful. In acromegaly, pegvisomant is a further treatment option. Temozolomide should be considered in aggressive pituitary tumors. In general, pharmaceutical options developed recently have extended the repertoire of treatment possibilities of pituitary tumors. PMID:24592317

  4. Advances in understanding damage by salt crystallization.

    PubMed

    Espinosa-Marzal, Rosa M; Scherer, George W

    2010-06-15

    The single most important cause of the deterioration of monuments in the Mediterranean basin, and elsewhere around the world, is the crystallization of salt within the pores of the stone. Considerable advances have been made in recent years in elucidating the fundamental mechanisms responsible for salt damage. As a result, new methods of treatment are being proposed that offer the possibility of attacking the cause of the problem, rather than simply treating the symptoms. In this Account, we review the thermodynamics and kinetics of crystallization, then examine how a range of technological innovations have been applied experimentally to further the current understanding of in-pore crystallization. We close with a discussion of how computer modeling now provides particularly valuable insight, including quantitative estimates of both the interaction forces between the mineral and the crystal and the stresses induced in the material. Analyzing the kinetics and thermodynamics of crystal growth within the pores of a stone requires sensitive tools used in combination. For example, calorimetry quantifies the amount of salt that precipitates in the pores of a stone during cooling, and dilatometric measurements on a companion sample reveal the stress exerted by the salt. Synchrotron X-rays can penetrate the stone and identify the metastable phases that often appear in the first stages of crystallization. Atomic force microscopy and environmental scanning electron microscopy permit study of the nanometric liquid film that typically lies between salt and stone; this film controls the magnitude of the pressure exerted and the kinetics of relaxation of the stress. These experimental advances provide validation for increasingly advanced simulations, using continuum models of reactive transport on a macroscopic scale and molecular dynamics on the atomic scale. Because of the fundamental understanding of the damage mechanisms that is beginning to emerge, it is possible to devise

  5. 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

  6. 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

  7. 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

  8. Recent advances in understanding hepatitis C.

    PubMed

    Douam, Florian; Ding, Qiang; Ploss, Alexander

    2016-01-01

    The past decade has seen tremendous progress in understanding hepatitis C virus (HCV) biology and its related disease, hepatitis C. Major advances in characterizing viral replication have led to the development of direct-acting anti-viral therapies that have considerably improved patient treatment outcome and can even cure chronic infection. However, the high cost of these treatments, their low barrier to viral resistance, and their inability to prevent HCV-induced liver cancer, along with the absence of an effective HCV vaccine, all underscore the need for continued efforts to understand the biology of this virus. Moreover, beyond informing therapies, enhanced knowledge of HCV biology is itself extremely valuable for understanding the biology of related viruses, such as dengue virus, which is becoming a growing global health concern. Major advances have been realized over the last few years in HCV biology and pathogenesis, such as the discovery of the envelope glycoprotein E2 core structure, the generation of the first mouse model with inheritable susceptibility to HCV, and the characterization of virus-host interactions that regulate viral replication or innate immunity. Here, we review the recent findings that have significantly advanced our understanding of HCV and highlight the major challenges that remain. PMID:26918166

  9. Recent advances in understanding and managing asthma.

    PubMed

    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

  10. 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

  11. 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.

  12. 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

  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 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

  15. Current advances in orthodontic pain.

    PubMed

    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

  16. 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

  17. 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

  18. Recent advances in understanding and managing cholestasis

    PubMed Central

    Wagner, Martin; Trauner, Michael

    2016-01-01

    Cholestatic liver diseases are hereditary or acquired disorders with impaired hepatic excretion and enterohepatic circulation of bile acids and other cholephiles. The distinct pathological mechanisms, particularly for the acquired forms of cholestasis, are not fully revealed, but advances in the understanding of the molecular mechanisms and identification of key regulatory mechanisms of the enterohepatic circulation of bile acids have unraveled common and central mechanisms, which can be pharmacologically targeted. This overview focuses on the central roles of farnesoid X receptor, fibroblast growth factor 19, and apical sodium-dependent bile acid transporter for the enterohepatic circulation of bile acids and their potential as new drug targets for the treatment of cholestatic liver disease. PMID:27134744

  19. Advances in the understanding and management of heart transplantation

    PubMed Central

    Singh, Dhssraj

    2015-01-01

    Cardiac transplantation represents one of the great triumphs in modern medicine and remains the cornerstone in the treatment of advanced heart failure. In this review, we contextualize pivotal developments in our understanding and management of cardiac transplant immunology, histopathology, rejection surveillance, drug development and surgery. We also discuss current limitations in their application and the impact of the left ventricular assist devices in bridging this gap. PMID:26097725

  20. 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

  1. 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.

  2. 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. PMID:27610224

  3. Advances in Understanding and Managing Chronic Urticaria.

    PubMed

    Moolani, Yasmin; Lynde, Charles; Sussman, Gordon

    2016-01-01

    There have been recent advances in the classification and management of chronic urticaria. The new term chronic spontaneous urticaria (CSU) has replaced chronic idiopathic urticaria and chronic autoimmune urticaria. In addition, chronic inducible urticaria (CINDU) has replaced physical urticaria and includes other forms of inducible urticaria, such as cholinergic and aquagenic urticaria. Furthermore, novel research has resulted in a new understanding with guidelines being revised in the past year by both the American Academy of Allergy, Asthma, and Immunology (AAAAI) and the European Academy of Allergy and Clinical Immunology (EAACI)/Global Allergy and Asthma European Network (GA (2)LEN)/European Dermatology Forum (EDF)/World Allergy Organization (WAO). There are some differences in the recommendations, which will be discussed, but the core updates are common to both groups. The basic treatment for chronic urticaria involves second-generation non-sedating non-impairing H 1 antihistamines as first-line treatment. This is followed by up to a 4-fold increase in the licensed dose of these H 1 antihistamines. The major therapeutic advance in recent years has been in third-line treatment with omalizumab, a humanized monoclonal anti-immunoglobulin E (anti-IgE) antibody that prevents binding of IgE to the high-affinity IgE receptor. Several multicenter randomized controlled trials have shown safety and efficacy of omalizumab for CSU. There are also some small studies showing efficacy of omalizumab in CINDU. While there were previously many treatment options which were lacking in strong evidence, we are moving into an era where the treatment algorithm for chronic urticaria is simplified and contains more evidence-based, effective, and less toxic treatment options.

  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. Current Understandings of Spontaneous Isolated Superior Mesenteric Artery Dissection.

    PubMed

    Kim, Young-Wook

    2016-06-01

    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

  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. 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.

  8. Advances in the understanding of transplant glomerulopathy.

    PubMed

    Husain, Sufia; Sis, Banu

    2013-08-01

    Transplant glomerulopathy is a sign of chronic kidney allograft damage. It has poor survival and no effective therapies. This entity develops as a maladaptive repair/remodeling response to sustained endothelial injury and is characterized by duplication/multilamination of capillary basement membranes. This review provides up-to-date information for transplant glomerulopathy, including new insights into underlying causes and mechanisms, and highlights unmet needs in diagnostics. Transplant glomerulopathy is widely accepted as the principal manifestation of chronic antibody-mediated rejection, mostly with HLA antigen class II antibodies. However, recent data suggest that at least in some patients, there also is an association with hepatitis C virus infection, autoimmunity, and late thrombotic microangiopathy. Furthermore, intragraft molecular studies reveal nonresolving inflammation after sustained endothelial injury as a key mechanism and therapeutic target. Unfortunately, current international criteria rely heavily on light microscopy and miss patients at early stages, when they likely are treatable. Therefore, better tools, such as electron microscopy or molecular probes, are needed to detect patients when kidney injury is in an early active phase. Better understanding of causes and effector mechanisms coupled with early diagnosis can lead to the development of new therapeutics for transplant glomerulopathy and improved kidney outcomes.

  9. Iron bath smelting - current status and understanding

    SciTech Connect

    Fruehan, R.J.

    1990-01-01

    Currently there is a worldwide effort to develop an iron and steelmaking process which uses coal directly rather than coke for reduction and energy. The most promising of the new processes is Bath Smelting in which coal, iron ore and oxygen or air are reacted in an iron bath. Research and development of the process is underway in Europe, Australia, Japan and the USA; while other countries are planning work for the near future. A brief description of the processes and the current state of their development is briefly discussed. The current state of knowledge on the critical basic phenomena which control bath smelting are reviewed. The major production limiting processes, reduction of iron oxide, heat transfer and slag foaming are discussed. A simple reduction model is presented which predicts how the production rate will vary with operating parameters and estimates the rate itself. From the foam index for smelting slags, and the gas generation for the specific operating conditions, the foam height in the process can be estimated. Coke in the slag can significantly reduce slag foaming. Future developments are briefly discussed. 15 refs., 16 figs., 1 tab.

  10. Current understanding of SEP acceleration and transport

    NASA Astrophysics Data System (ADS)

    Cohen, C. M. S.

    2016-03-01

    Through new missions and unusual solar conditions, solar cycle 24 has afforded the opportunity for expanding our understanding of solar energetic particle (SEP) acceleration and transport. With complementary SEP observations from multiple spacecraft separated significantly in longitude, it has been possible to examine the longitudinal distribution of energetic particles in individual events, rather than relying on statistical event studies. Unprecedented 360° views of the Sun, in multiple wavelengths and coronagraphs, has made it possible to identify solar source regions regardless of where they are located and to more accurately determine the properties of related coronal mass ejections. The unusually quiet conditions during the onset of cycle 24 allowed smaller SEP events to be examined and their source regions to be unambiguously identified. This paper reviews some of the unexpected results from multi-spacecraft SEP observations made over this solar cycle and discusses their implications for particle acceleration near the Sun and transport through the inner heliosphere.

  11. Treatment Perspectives Based on Our Current Understanding of Concussion.

    PubMed

    Gay, Michael

    2016-09-01

    Sports-related concussion also referred to in the literature as mild traumatic brain injury remains a popular area of study for physicians, neurologists, neuropsychologists, neuroimaging, athletic trainers, and researchers across the other areas of brain sciences. Treatment for concussion is an emerging area of focus with investigators seeking to improve outcomes and protect patients from the deleterious short-term and long-term consequences which have been extensively studied and identified. Broadly, current treatment strategies for athletes recovering from concussion have remained largely unchanged since early 2000s. Knowledge of the complex pathophysiology surrounding injury should improve or advance our ability to identify processes which may serve as targets for therapeutic intervention. Clinicians working with athletes recovering from sports-related concussion should have an advanced understanding of the injury cascade and also be aware of the current efforts within the research to treat concussion. In addition, how clinicians use the word "treatment" should be carefully defined and promoted so the patient is aware of the level of intervention and what stage of recovery or healing is being affected by a specific intervention. The purpose of this review is to bring together efforts across disciplines of brain science into 1 platform where clinicians can assimilate this information before making best practices decisions regarding the treatment of patients and athletes under their care.

  12. Treatment Perspectives Based on Our Current Understanding of Concussion.

    PubMed

    Gay, Michael

    2016-09-01

    Sports-related concussion also referred to in the literature as mild traumatic brain injury remains a popular area of study for physicians, neurologists, neuropsychologists, neuroimaging, athletic trainers, and researchers across the other areas of brain sciences. Treatment for concussion is an emerging area of focus with investigators seeking to improve outcomes and protect patients from the deleterious short-term and long-term consequences which have been extensively studied and identified. Broadly, current treatment strategies for athletes recovering from concussion have remained largely unchanged since early 2000s. Knowledge of the complex pathophysiology surrounding injury should improve or advance our ability to identify processes which may serve as targets for therapeutic intervention. Clinicians working with athletes recovering from sports-related concussion should have an advanced understanding of the injury cascade and also be aware of the current efforts within the research to treat concussion. In addition, how clinicians use the word "treatment" should be carefully defined and promoted so the patient is aware of the level of intervention and what stage of recovery or healing is being affected by a specific intervention. The purpose of this review is to bring together efforts across disciplines of brain science into 1 platform where clinicians can assimilate this information before making best practices decisions regarding the treatment of patients and athletes under their care. PMID:27482780

  13. 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. PMID:22341151

  14. 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

  15. Colistin: understanding and applying recent pharmacokinetic advances.

    PubMed

    Ortwine, Jessica K; Kaye, Keith S; Li, Jian; Pogue, Jason M

    2015-01-01

    Colistin, the most widely used polymyxin antibiotic, was originally introduced in the late 1950s before the establishment of the present-day drug approval process. Originally shelved due to toxicity concerns, colistin, in the form of its inactive prodrug colistin methanesulfonate, has undergone a renaissance in the past 15 years. Unfortunately, this is not because of an improved adverse-effect profile but because colistin is among the only remaining antibiotics with activity against multidrug-resistant gram-negative bacilli. Pharmacokinetic and pharmacodynamic data are limited to guide the appropriate use of colistin; however, important advances have occurred over the past 5 years. Since its reintroduction, published reports regarding colistin have produced discordant results in terms of both efficacy and safety. Because the efficacy and toxicity of colistin are dose dependent, the impact of discordant dosing recommendations cannot be understated. This review highlights the issues leading to differing and often conflicting dosing recommendations, reviews the recent pharmacokinetic advances, and provides recommendations for the optimal use of colistin.

  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. Advanced techniques in current signature analysis

    SciTech Connect

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

    1992-03-01

    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 an 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 (>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. 3 refs.

  18. 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

  19. Recent advances in understanding ichthyosis pathogenesis.

    PubMed

    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 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.

  1. 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.

  2. 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

  3. 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

  4. Advances in the understanding of conduction disturbances.

    PubMed

    Kulbertus, H E

    1978-09-01

    The interest towards intraventricular conduction defects started some 10 yr after the introduction of the string galvanometer by Einthoven. As early as 1910, it was known that conduction blockade could occur along either branch of the intraventricular conducting pathway. It took some 20 yr to identify properly the electrocardiographic manifestations of right and left bundle branch blocks. A further 30 yr were needed to obtain a sound correlation between these functional disorders and the presence of anatomical lesions. The more recent introduction of the concept of left hemiblocks further improved our understanding of intraventricular conduction defects. The latter concept is based on the hypothesis of the anatomical and functional bifascicularity of the left bundle branch, a hypothesis which cannot be accepted without some reservations. Later developments indicated that left hemiblocks associated with right bundle branch block represent manifestations of bilateral conduction disturbances (incomplete bilateral bundle branch block). Such an association may constitute a forerunner of complete atrioventricular block, or an indicator of the possibility of sudden death. Whether these complications occur frequently or unfrequently in the setting of incomplete bilateral bundle branch block remains an unsettled question. PMID:699953

  5. 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.

  6. Advanced Eddy current NDE steam generator tubing.

    SciTech Connect

    Bakhtiari, S.

    1999-03-29

    As part of a multifaceted project on steam generator integrity funded by the U.S. Nuclear Regulatory Commission, Argonne National Laboratory is carrying out research on the reliability of nondestructive evaluation (NDE). A particular area of interest is the impact of advanced eddy current (EC) NDE technology. This paper presents an overview of work that supports this effort in the areas of numerical electromagnetic (EM) modeling, data analysis, signal processing, and visualization of EC inspection results. Finite-element modeling has been utilized to study conventional and emerging EC probe designs. This research is aimed at determining probe responses to flaw morphologies of current interest. Application of signal processing and automated data analysis algorithms has also been addressed. Efforts have focused on assessment of frequency and spatial domain filters and implementation of more effective data analysis and display methods. Data analysis studies have dealt with implementation of linear and nonlinear multivariate models to relate EC inspection parameters to steam generator tubing defect size and structural integrity. Various signal enhancement and visualization schemes are also being evaluated and will serve as integral parts of computer-aided data analysis algorithms. Results from this research will ultimately be substantiated through testing on laboratory-grown and in-service-degraded tubes.

  7. 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…

  8. Looking up: Recent advances in understanding and treating peritoneal carcinomatosis.

    PubMed

    Lambert, Laura A

    2015-01-01

    Until recently, a diagnosis of peritoneal carcinomatosis was uniformly accompanied by a grim prognosis that was typically measured in weeks to months. Consequently, the management of carcinomatosis revolves largely around palliation of symptoms such as bowel obstruction, nausea, pain, fatigue, and cachexia. A prior lack of effective treatment options created the nihilistic view that currently exists and persists despite improvements in the efficacy of systemic therapy and the evolution of multimodality approaches including surgery and intraperitoneal chemotherapy. This article reviews the evolution and current state of treatment options for patients with peritoneal carcinomatosis. In addition, it highlights recent advances in understanding the molecular biology of carcinomatosis and the focus of current and future clinical trials. Finally, this article provides practical management options for the palliation of common complications of carcinomatosis. It is hoped that the reader will recognize that carcinomatosis is no longer an imminent death sentence and that through continued research and therapeutic innovation, clinicians can make an even greater impact on this form of metastatic cancer.

  9. 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…

  10. Current Understanding and Future Directions for Vocal Fold Mechanobiology

    PubMed Central

    Li, Nicole Y.K.; Heris, Hossein K.; Mongeau, Luc

    2013-01-01

    The vocal folds, which are located in the larynx, are the main organ of voice production for human communication. The vocal folds are under continuous biomechanical stress similar to other mechanically active organs, such as the heart, lungs, tendons and muscles. During speech and singing, the vocal folds oscillate at frequencies ranging from 20 Hz to 3 kHz with amplitudes of a few millimeters. The biomechanical stress associated with accumulated phonation is believed to alter vocal fold cell activity and tissue structure in many ways. Excessive phonatory stress can damage tissue structure and induce a cell-mediated inflammatory response, resulting in a pathological vocal fold lesion. On the other hand, phonatory stress is one major factor in the maturation of the vocal folds into a specialized tri-layer structure. One specific form of vocal fold oscillation, which involves low impact and large amplitude excursion, is prescribed therapeutically for patients with mild vocal fold injuries. Although biomechanical forces affect vocal fold physiology and pathology, there is little understanding of how mechanical forces regulate these processes at the cellular and molecular level. Research into vocal fold mechanobiology has burgeoned over the past several years. Vocal fold bioreactors are being developed in several laboratories to provide a biomimic environment that allows the systematic manipulation of physical and biological factors on the cells of interest in vitro. Computer models have been used to simulate the integrated response of cells and proteins as a function of phonation stress. The purpose of this paper is to review current research on the mechanobiology of the vocal folds as it relates to growth, pathogenesis and treatment as well as to propose specific research directions that will advance our understanding of this subject. PMID:24812638

  11. 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

  12. Advances in genetics: widening our understanding of prostate cancer

    PubMed Central

    Pine, Angela C.; Fioretti, Flavia F.; Brooke, Greg N.; Bevan, Charlotte L.

    2016-01-01

    Prostate cancer is a leading cause of cancer-related death in Western men. Our understanding of the genetic alterations associated with disease predisposition, development, progression, and therapy response is rapidly improving, at least in part, owing to the development of next-generation sequencing technologies. Large advances have been made in our understanding of the genetics of prostate cancer through the application of whole-exome sequencing, and this review summarises recent advances in this field and discusses how exome sequencing could be used clinically to promote personalised medicine for prostate cancer patients. PMID:27408704

  13. 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

  14. 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.

  15. 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.

  16. Behavioral cardiology: current advances and future directions.

    PubMed

    Rozanski, Alan

    2014-07-01

    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.

  17. 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

  18. 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

  19. Recent advances in understanding of chronic kidney disease

    PubMed Central

    Yamaguchi, Junna; Tanaka, Tetsuhiro; Nangaku, Masaomi

    2015-01-01

    Chronic kidney disease (CKD) is defined as any condition that causes reduced kidney function over a period of time. Fibrosis, tubular atrophy and interstitial inflammation are the hallmark of pathological features in CKD. Regardless of initial insult, CKD has some common pathways leading CKD to end-stage kidney disease, including hypoxia in the tubulointerstitium and proteinuria. Recent advances in genome editing technologies and stem cell research give great insights to understand the pathogenesis of CKD, including identifications of the origins of renal myofibroblasts and tubular epithelial cells upon injury. Environmental factors such as hypoxia, oxidative stress, and epigenetic factors in relation to CKD are also discussed. PMID:26937272

  20. Advances in understanding mechanisms underpinning lithium-air batteries

    NASA Astrophysics Data System (ADS)

    Aurbach, Doron; McCloskey, Bryan D.; Nazar, Linda F.; Bruce, Peter G.

    2016-09-01

    The rechargeable lithium-air battery has the highest theoretical specific energy of any rechargeable battery and could transform energy storage if a practical device could be realized. At the fundamental level, little was known about the reactions and processes that take place in the battery, representing a significant barrier to progress. Here, we review recent advances in understanding the chemistry and electrochemistry that govern the operation of the lithium-air battery, especially the reactions at the cathode. The mechanisms of O2 reduction to Li2O2 on discharge and the reverse process on charge are discussed in detail, as are their consequences for the rate and capacity of the battery. The various parasitic reactions involving the cathode and electrolyte during discharge and charge are also considered. We also provide views on understanding the stability of the cathode and electrolyte and examine design principles for better lithium-air batteries.

  1. 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.

  2. Advances in understanding mechanisms underpinning lithium–air batteries

    NASA Astrophysics Data System (ADS)

    Aurbach, Doron; McCloskey, Bryan D.; Nazar, Linda F.; Bruce, Peter G.

    2016-09-01

    The rechargeable lithium–air battery has the highest theoretical specific energy of any rechargeable battery and could transform energy storage if a practical device could be realized. At the fundamental level, little was known about the reactions and processes that take place in the battery, representing a significant barrier to progress. Here, we review recent advances in understanding the chemistry and electrochemistry that govern the operation of the lithium–air battery, especially the reactions at the cathode. The mechanisms of O2 reduction to Li2O2 on discharge and the reverse process on charge are discussed in detail, as are their consequences for the rate and capacity of the battery. The various parasitic reactions involving the cathode and electrolyte during discharge and charge are also considered. We also provide views on understanding the stability of the cathode and electrolyte and examine design principles for better lithium–air batteries.

  3. 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. PMID:26963026

  4. 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.

  5. Recent advances in managing and understanding diabetic nephropathy

    PubMed Central

    Tang, Sydney C.W.; Chan, Gary C.W.; Lai, Kar Neng

    2016-01-01

    Diabetic nephropathy is the commonest cause of end-stage renal disease in most developed economies. Current standard of care for diabetic nephropathy embraces stringent blood pressure control via blockade of the renin-angiotensin-aldosterone system and glycemia control. Recent understanding of the pathophysiology of diabetic nephropathy has led to the development of novel therapeutic options. This review article focuses on available data from landmark studies on the main therapeutic approaches and highlights some novel management strategies. PMID:27303648

  6. 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.

  7. 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. PMID:23962797

  8. The genetics of juvenile idiopathic arthritis: current understanding and future prospects.

    PubMed

    Cobb, Joanna E; Hinks, Anne; Thomson, Wendy

    2014-04-01

    Understanding the genetic risk of JIA, a relatively rare chronic disease, is a challenging task, but recent research in this field has shown great advances. This review summarizes the current understanding of the genetic architecture of JIA susceptibility and proposes where this work is heading in the coming years. Insights into how we might progress this relatively understudied field will be provided, highlighting how the field will move towards the ultimate goals of predicting long-term disease outcomes at onset, predicting drug response, and move towards more targeted treatment options for children with JIA. PMID:24049100

  9. 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).

  10. 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). PMID:26667914

  11. 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

  12. 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.

  13. Current advances in synchrotron radiation instrumentation for MX experiments.

    PubMed

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

    2016-07-15

    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. Furthermore 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. A 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. The most critical optical components are discussed, as are aspects of endstation design, sample delivery, visualisation and positioning, the sample environment, beam shaping, detectors and data acquisition and processing. PMID:27046341

  14. 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

  15. The Vaginal Microbiome: Current Understanding and Future Directions.

    PubMed

    Martin, David H; Marrazzo, Jeanne M

    2016-08-15

    This article summarizes the highlights of the expert technical consultation on bacterial vaginosis (BV), sponsored by the National Institute of Allergy and Infectious Disease and held in Washington, DC, on 8-9 April 2015. Many issues touched on in this article are discussed in much greater detail in the 6 preceding articles in this supplement to The Journal of Infectious Diseases There was a consensus among the meeting attendees concerning the most important research issues in the field: the pathogenesis of the syndrome, way to optimize treatment, and the relative roles of sexual transmission and endogenous infection in BV epidemiology. This article concludes with a listing of BV and genitourinary tract research priorities that were discussed and agreed on by attendees. The most important of these included better characterization of vaginal microbiome community state subtypes, application of advanced "-omic" technologies to improve understanding of BV pathogenesis, further investigation of the relationships between the male and female genitourinary tract microbiomes, and the development of new drugs for BV treatment. PMID:27449871

  16. 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.

  17. Sweetened beverages and health: current state of scientific understandings.

    PubMed

    Rippe, James M; Saltzman, Edward

    2013-01-01

    This article summarizes the presentations from the "Sweetened Beverages and Health: Current State of Scientific Understandings" symposium held at the ASN Annual Meeting in Boston, MA on April 23, 2013. The metabolic and health effects of sugar-sweetened beverages were discussed from a variety of points of view by 5 different presenters. Dr. David Allison drew a distinction between conjecture and proof related to sweetened beverages and obesity. Dr. Richard Mattes discussed differences between solid and liquid calories. Dr. Miguel Alonso-Alonso reviewed potential contributions of functional neuroimaging, particularly as they relate to whether sugar is potentially "addictive." Dr. Kimber Stanhope discussed work related to experiments comparing fructose to glucose. Dr. James Rippe presented evidence from randomized controlled trials from his research organization showing no differences among high-fructose corn syrup, sucrose, glucose, or fructose at normal human consumption amounts. PMID:24038246

  18. Current understanding of interactions between nanoparticles and the immune system.

    PubMed

    Dobrovolskaia, Marina A; Shurin, Michael; Shvedova, Anna A

    2016-05-15

    The delivery of drugs, antigens, and imaging agents benefits from using nanotechnology-based carriers. The successful translation of nanoformulations to the clinic involves thorough assessment of their safety profiles, which, among other end-points, includes evaluation of immunotoxicity. The past decade of research focusing on nanoparticle interaction with the immune system has been fruitful in terms of understanding the basics of nanoparticle immunocompatibility, developing a bioanalytical infrastructure to screen for nanoparticle-mediated immune reactions, beginning to uncover the mechanisms of nanoparticle immunotoxicity, and utilizing current knowledge about the structure-activity relationship between nanoparticles' physicochemical properties and their effects on the immune system to guide safe drug delivery. In the present review, we focus on the most prominent pieces of the nanoparticle-immune system puzzle and discuss the achievements, disappointments, and lessons learned over the past 15years of research on the immunotoxicity of engineered nanomaterials.

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

    PubMed Central

    Williams, Wendy M.

    2011-01-01

    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. PMID:21300892

  20. Notochord morphogenesis in mice: Current understanding & open questions.

    PubMed

    Balmer, Sophie; Nowotschin, Sonja; Hadjantonakis, Anna-Katerina

    2016-05-01

    The notochord is a structure common to all chordates, and the feature that the phylum Chordata has been named after. It is a rod-like mesodermal structure that runs the anterior-posterior length of the embryo, adjacent to the ventral neural tube. The notochord plays a critical role in embryonic tissue patterning, for example the dorsal-ventral patterning of the neural tube. The cells that will come to form the notochord are specified at gastrulation. Axial mesodermal cells arising at the anterior primitive streak migrate anteriorly as the precursors of the notochord and populate the notochordal plate. Yet, even though a lot of interest has centered on investigating the functional and structural roles of the notochord, we still have a very rudimentary understanding of notochord morphogenesis. The events driving the formation of the notochord are rapid, taking place over the period of approximately a day in mice. In this commentary, we provide an overview of our current understanding of mouse notochord morphogenesis, from the initial specification of axial mesendodermal cells at the primitive streak, the emergence of these cells at the midline on the surface of the embryo, to their submergence and organization of the stereotypically positioned notochord. We will also discuss some key open questions. Developmental Dynamics 245:547-557, 2016. © 2016 Wiley Periodicals, Inc. PMID:26845388

  1. Fluvial Morphodynamics: advancing understanding using Multibeam Echo Sounders (MBES)

    NASA Astrophysics Data System (ADS)

    Parsons, D. R.; Best, J. L.

    2012-12-01

    Accurately and reliably determining riverbed morphology is key to understanding linkages between flow fields, sediment transport and bed roughness in a range of aquatic environments, including large fluvial channels. Modern shallow-water multibeam echo sounder (MBES) systems are now allowing us to acquire bathymetric data at unprecedented resolutions that are millimetric in precision and centimetric in accuracy. Such systems, and the morphological resolution they can supply, are capable of revealing the complex three-dimensional patterns in riverbed morphology that are facilitating a holistic examination of system morphodynamics, at the field scale, that was unimaginable just a few years ago. This paper presents a range of MBES acquired examples to demonstrate how the methodological developments in this technology are leading to advances in our substantive understanding of large river systems. This includes examples that show linkages across scales, and in particular the morphodynamics of superimposed bedforms and bars revealed by such high-resolution data, which have broad implications for a range of applications, including flood prediction, engineering design and reconstructing ancient sedimentary environments.

  2. Social understanding: How does it fare with advancing years?

    PubMed

    Sullivan, Susan; Ruffman, Ted

    2004-02-01

    Until recently, theory of mind abilities have received little attention beyond the childhood years. However, pioneering work carried out by Happé, Winner, and Brownell (1998) has opened the doors on a new and exciting area of research that examines theory of mind abilities in later years. Happé et al. reported that theory of mind performance was superior in the elderly. Yet, in direct contrast to these findings, Maylor, Moulson, Muncer, and Taylor (2002) report a decline in theory of mind abilities with advancing years. We used Happé et al.'s task and, like Maylor et al., found a decline in theory of mind abilities in the elderly. Yet this deficit was related to a decline in fluid abilities. We then examined whether deficits in social understanding in the elderly could also be independent of fluid abilities. We used two new tasks; identifying emotions from still photos and identifying emotions and cognitions from video clips. Again we found a decline in social understanding in the elderly, and in this case, the decline was independent of changes in fluid abilities. PMID:15005864

  3. 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

  4. Recent Advances in Understanding Particle Acceleration Processes in Solar Flares

    NASA Astrophysics Data System (ADS)

    Zharkova, V. V.; Arzner, K.; Benz, A. O.; Browning, P.; Dauphin, C.; Emslie, A. G.; Fletcher, L.; Kontar, E. P.; Mann, G.; Onofri, M.; Petrosian, V.; Turkmani, R.; Vilmer, N.; Vlahos, L.

    2011-09-01

    We review basic theoretical concepts in particle acceleration, with particular emphasis on processes likely to occur in regions of magnetic reconnection. Several new developments are discussed, including detailed studies of reconnection in three-dimensional magnetic field configurations (e.g., current sheets, collapsing traps, separatrix regions) and stochastic acceleration in a turbulent environment. Fluid, test-particle, and particle-in-cell approaches are used and results compared. While these studies show considerable promise in accounting for the various observational manifestations of solar flares, they are limited by a number of factors, mostly relating to available computational power. Not the least of these issues is the need to explicitly incorporate the electrodynamic feedback of the accelerated particles themselves on the environment in which they are accelerated. A brief prognosis for future advancement is offered.

  5. 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

  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. PMID:26353794

  7. Recent scientific advances in leiomyoma (uterine fibroids) research facilitates better understanding and management.

    PubMed

    Taylor, Darlene K; Holthouser, Kristine; Segars, James H; Leppert, Phyllis C

    2015-01-01

    Uterine leiomyomas (fibroids) are the most prevalent medical problem of the female reproductive tract, but there are few non-surgical treatment options. Although many advances in the understanding of the molecular components of these tumors have occurred over the past five years, an effective pharmaceutical approach remains elusive. Further, there is currently no clinical method to distinguish a benign uterine leiomyoma from a malignant leiomyosarcoma prior to treatment, a pressing need given concerns about the use of the power morcellator for minimally invasive surgery. This paper reviews current studies regarding the molecular biology of uterine fibroids, discusses non-surgical approaches and suggests new cutting-edge therapeutic and diagnostic approaches.

  8. Understanding stroke recovery and rehabilitation: current and emerging approaches.

    PubMed

    Dombovy, Mary L

    2004-01-01

    Although stroke is the third leading cause of death in the United States, it is the significant disability among survivors that has the greatest impact on healthcare and society. It is currently accepted that comprehensive rehabilitation programs improve outcome following stroke. We are now trying to discern which specific therapeutic approaches work and which do not. Years of animal research have resulted in a better understanding of what occurs in the brain following stroke and how the brain may reorganize in response to treatment. Repetitive use of the involved extremities appears key to optimal behavioral recovery and optimal brain reorganization. The advent of technology such as functional magnetic resonance imaging and transcortical magnetic stimulation has allowed the study of brain reorganization following stroke and rehabilitation in humans. Certain drugs also appear to influence neuroplasticity after stroke. Timing of therapy and drug delivery appears crucial; the optimal "critical period" has not yet been clearly identified. New approaches are slow to reach widespread adoption. Neural transplantation combined with repetitive training approaches produces behavioral recovery in animals and offers hope for the future.

  9. 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

  10. Recent advances in understanding and diagnosing hepatitis B virus infection.

    PubMed

    Fourati, Slim; Pawlotsky, Jean-Michel

    2016-01-01

    Hepatitis B virus (HBV) infects approximately 240 million individuals worldwide. Recent advances in the virology, immunopathogenesis, and diagnosis of HBV infection are summarized in this review article. The identification of a hepatocyte-specific cellular receptor for HBV, the sodium taurocholate co-transporting polypeptide (NTCP), made it possible to develop reliable cell culture systems and better understand the early steps of the viral lifecycle. Viral and host factors involved in covalently closed circular DNA synthesis, stability, and transcriptional regulation have also been identified and provide potential targets for new drugs. Based on recent evidence showing trained immunity in immune-tolerant patients, the immune tolerance and immune clearance phases have been renamed the non-inflammatory and inflammatory phases, respectively. New diagnostic and monitoring tools are now available, including rapid diagnostic tests for hepatitis B surface antigen (HBsAg) detection, HBsAg quantification assays, anti-HBc antibody quantification assays, an HBV core-related antigen (HBcrAg) quantification test, new HBV DNA detection and quantification assays, and an HBV RNA quantification test. Their clinical utility is under study. Finally, new antiviral and immune modulation approaches are in the preclinical or early clinical developmental stages, with the goal to achieve functional cure or ideally (if possible) eradication of HBV infection.

  11. Recent advances in understanding and diagnosing hepatitis B virus infection

    PubMed Central

    Fourati, Slim; Pawlotsky, Jean-Michel

    2016-01-01

    Hepatitis B virus (HBV) infects approximately 240 million individuals worldwide. Recent advances in the virology, immunopathogenesis, and diagnosis of HBV infection are summarized in this review article. The identification of a hepatocyte-specific cellular receptor for HBV, the sodium taurocholate co-transporting polypeptide (NTCP), made it possible to develop reliable cell culture systems and better understand the early steps of the viral lifecycle. Viral and host factors involved in covalently closed circular DNA synthesis, stability, and transcriptional regulation have also been identified and provide potential targets for new drugs. Based on recent evidence showing trained immunity in immune-tolerant patients, the immune tolerance and immune clearance phases have been renamed the non-inflammatory and inflammatory phases, respectively. New diagnostic and monitoring tools are now available, including rapid diagnostic tests for hepatitis B surface antigen (HBsAg) detection, HBsAg quantification assays, anti-HBc antibody quantification assays, an HBV core-related antigen (HBcrAg) quantification test, new HBV DNA detection and quantification assays, and an HBV RNA quantification test. Their clinical utility is under study. Finally, new antiviral and immune modulation approaches are in the preclinical or early clinical developmental stages, with the goal to achieve functional cure or ideally (if possible) eradication of HBV infection. PMID:27635243

  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 and diagnosing hepatitis B virus infection

    PubMed Central

    Fourati, Slim; Pawlotsky, Jean-Michel

    2016-01-01

    Hepatitis B virus (HBV) infects approximately 240 million individuals worldwide. Recent advances in the virology, immunopathogenesis, and diagnosis of HBV infection are summarized in this review article. The identification of a hepatocyte-specific cellular receptor for HBV, the sodium taurocholate co-transporting polypeptide (NTCP), made it possible to develop reliable cell culture systems and better understand the early steps of the viral lifecycle. Viral and host factors involved in covalently closed circular DNA synthesis, stability, and transcriptional regulation have also been identified and provide potential targets for new drugs. Based on recent evidence showing trained immunity in immune-tolerant patients, the immune tolerance and immune clearance phases have been renamed the non-inflammatory and inflammatory phases, respectively. New diagnostic and monitoring tools are now available, including rapid diagnostic tests for hepatitis B surface antigen (HBsAg) detection, HBsAg quantification assays, anti-HBc antibody quantification assays, an HBV core-related antigen (HBcrAg) quantification test, new HBV DNA detection and quantification assays, and an HBV RNA quantification test. Their clinical utility is under study. Finally, new antiviral and immune modulation approaches are in the preclinical or early clinical developmental stages, with the goal to achieve functional cure or ideally (if possible) eradication of HBV infection.

  14. Advances in the understanding of trauma-induced coagulopathy.

    PubMed

    Chang, Ronald; Cardenas, Jessica C; Wade, Charles E; Holcomb, John B

    2016-08-25

    Ten percent of deaths worldwide are due to trauma, and it is the third most common cause of death in the United States. Despite a profound upregulation in procoagulant mechanisms, one-quarter of trauma patients present with laboratory-based evidence of trauma-induced coagulopathy (TIC), which is associated with poorer outcomes including increased mortality. The most common causes of death after trauma are hemorrhage and traumatic brain injury (TBI). The management of TIC has significant implications in both because many hemorrhagic deaths could be preventable, and TIC is associated with progression of intracranial injury after TBI. This review covers the most recent evidence and advances in our understanding of TIC, including the role of platelet dysfunction, endothelial activation, and fibrinolysis. Trauma induces a plethora of biochemical and physiologic changes, and despite numerous studies reporting differences in coagulation parameters between trauma patients and uninjured controls, it is unclear whether some of these differences may be "normal" after trauma. Comparisons between trauma patients with differing outcomes and use of animal studies have shed some light on this issue, but much of the data continue to be correlative with causative links lacking. In particular, there are little data linking the laboratory-based abnormalities with true clinically evident coagulopathic bleeding. For these reasons, TIC continues to be a significant diagnostic and therapeutic challenge. PMID:27381903

  15. Recent advances in understanding and diagnosing hepatitis B virus infection.

    PubMed

    Fourati, Slim; Pawlotsky, Jean-Michel

    2016-01-01

    Hepatitis B virus (HBV) infects approximately 240 million individuals worldwide. Recent advances in the virology, immunopathogenesis, and diagnosis of HBV infection are summarized in this review article. The identification of a hepatocyte-specific cellular receptor for HBV, the sodium taurocholate co-transporting polypeptide (NTCP), made it possible to develop reliable cell culture systems and better understand the early steps of the viral lifecycle. Viral and host factors involved in covalently closed circular DNA synthesis, stability, and transcriptional regulation have also been identified and provide potential targets for new drugs. Based on recent evidence showing trained immunity in immune-tolerant patients, the immune tolerance and immune clearance phases have been renamed the non-inflammatory and inflammatory phases, respectively. New diagnostic and monitoring tools are now available, including rapid diagnostic tests for hepatitis B surface antigen (HBsAg) detection, HBsAg quantification assays, anti-HBc antibody quantification assays, an HBV core-related antigen (HBcrAg) quantification test, new HBV DNA detection and quantification assays, and an HBV RNA quantification test. Their clinical utility is under study. Finally, new antiviral and immune modulation approaches are in the preclinical or early clinical developmental stages, with the goal to achieve functional cure or ideally (if possible) eradication of HBV infection. PMID:27635243

  16. 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.

  17. 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.

  18. Recent Advances in Understanding and Managing Autism Spectrum Disorders.

    PubMed

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

    2015-12-01

    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.

  19. 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.

  20. Current advances in targeted therapies for metastatic gastric cancer: improving patient care.

    PubMed

    Aguiar, Pedro Nazareth; Muniz, Thiago Pimentel; Miranda, Raelson Rodrigues; Tadokoro, Hakaru; Forones, Nora Manoukian; Monteiro, Ines-de-Paula; Castelo-Branco, Pedro; Janjigian, Yelena Y; Mello, Ramon Andrade de

    2016-03-01

    In this article, we review the literature on the current advances in targeted therapies for metastatic gastric cancer aimed at improving patient care. We conclude that the key to guiding targeted therapy is individual biomarkers, which are not completely elucidated. HER2 overexpression is the only predictive biomarker currently in use. Furthermore, it is necessary to understand that gastric tumors are heterogeneous; therefore, is impossible to evaluate a novel biological compound without evaluating personal biomarkers. The selection of patients who are able to receive each treatment is paramount for improving advanced gastric cancer survival and reducing unnecessary costs.

  1. 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

  2. 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.

  3. 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

  4. Biomarkers in inflammatory bowel disease: current practices and recent advances.

    PubMed

    Iskandar, Heba N; Ciorba, Matthew A

    2012-04-01

    Crohn's disease and ulcerative colitis represent the two main forms of the idiopathic chronic inflammatory bowel diseases (IBD). Currently available blood and stool based biomarkers provide reproducible, quantitative tools that can complement clinical assessment to aid clinicians in IBD diagnosis and management. C-reactive protein and fecal based leukocyte markers can help the clinician distinguish IBD from noninflammatory diarrhea and assess disease activity. The ability to differentiate between forms of IBD and predict risk for disease complications is specific to serologic tests including antibodies against Saccharomyces cerevisiae and perinuclear antineutrophil cytoplasmic proteins. Advances in genomic, proteomic, and metabolomic array based technologies are facilitating the development of new biomarkers for IBD. The discovery of novel biomarkers, which can correlate with mucosal healing or predict long-term disease course has the potential to significantly improve patient care. This article reviews the uses and limitations of currently available biomarkers and highlights recent advances in IBD biomarker discovery. PMID:22424434

  5. 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.

  6. 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.

  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. 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

  9. 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.

  10. 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. PMID:26709218

  11. 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,…

  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. Students' Understanding of Advanced Properties of Java Exceptions

    ERIC Educational Resources Information Center

    Rashkovits, Rami; Lavy, Ilana

    2012-01-01

    This study examines how Information Systems Engineering School students on the verge of their graduation understand the mechanism of exception handling. The main contributions of this paper are as follows: we construct a questionnaire aimed at examining students' level of understanding concerning exceptions; we classify and analyse the students'…

  14. Current status and advances in flash fire modeling

    SciTech Connect

    Rew, P.J.; Deaves, D.M.; Madison, T.

    1995-12-31

    When a dispersing cloud of flammable vapor is ignited, it can burn in a number of different ways. A flash fire or cloud fire occurs if ignition takes place within the flammable region of a gas cloud, generally at a point remote from the source. A review of the modeling of flash fires (cloud fires) is presented. The present understanding of flash fires is discussed through reference to past incidents and current models. Full scale flash fire trials are reviewed, providing a database of relevant experimental data. Outline proposals are given for improving the current prediction methodologies for the direct (burn fatalities) and indirect (escalation) effects of flash fires.

  15. Current understandings about cognition and the neurobiological correlates in schizophrenia

    PubMed Central

    Kar, Sujita Kumar; Jain, Meha

    2016-01-01

    Schizophrenia is a severe mental disorder. Cognitive deficits are one of the core features of schizophrenia. Multiple domains of cognition (executive function, attention/vigilance, working memory, verbal fluency, visuospatial skills, processing speed, and social cognition) are affected in patients with schizophrenia. Deficits in cognition led to impairment in the real world functioning. Identifying the cognitive deficits and early intervention is required for better functional outcome. This review focuses on conceptual understanding of cognition with its neurobiological correlates in schizophrenia and its different clinical implications. PMID:27365960

  16. 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.

  17. 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. PMID:27119542

  18. 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.

  19. Current advances and future perspectives in extrusion-based bioprinting.

    PubMed

    Ozbolat, Ibrahim T; Hospodiuk, Monika

    2016-01-01

    Extrusion-based bioprinting (EBB) is a rapidly growing technology that has made substantial progress during the last decade. It has great versatility in printing various biologics, including cells, tissues, tissue constructs, organ modules and microfluidic devices, in applications from basic research and pharmaceutics to clinics. Despite the great benefits and flexibility in printing a wide range of bioinks, including tissue spheroids, tissue strands, cell pellets, decellularized matrix components, micro-carriers and cell-laden hydrogels, the technology currently faces several limitations and challenges. These include impediments to organ fabrication, the limited resolution of printed features, the need for advanced bioprinting solutions to transition the technology bench to bedside, the necessity of new bioink development for rapid, safe and sustainable delivery of cells in a biomimetically organized microenvironment, and regulatory concerns to transform the technology into a product. This paper, presenting a first-time comprehensive review of EBB, discusses the current advancements in EBB technology and highlights future directions to transform the technology to generate viable end products for tissue engineering and regenerative medicine. PMID:26561931

  20. 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.

  1. Recent scientific advances in leiomyoma (uterine fibroids) research facilitates better understanding and management.

    PubMed

    Taylor, Darlene K; Holthouser, Kristine; Segars, James H; Leppert, Phyllis C

    2015-01-01

    Uterine leiomyomas (fibroids) are the most prevalent medical problem of the female reproductive tract, but there are few non-surgical treatment options. Although many advances in the understanding of the molecular components of these tumors have occurred over the past five years, an effective pharmaceutical approach remains elusive. Further, there is currently no clinical method to distinguish a benign uterine leiomyoma from a malignant leiomyosarcoma prior to treatment, a pressing need given concerns about the use of the power morcellator for minimally invasive surgery. This paper reviews current studies regarding the molecular biology of uterine fibroids, discusses non-surgical approaches and suggests new cutting-edge therapeutic and diagnostic approaches. PMID:26236472

  2. Recent scientific advances in leiomyoma (uterine fibroids) research facilitates better understanding and management

    PubMed Central

    Taylor, Darlene K.; Holthouser, Kristine; Segars, James H.; Leppert, Phyllis C.

    2015-01-01

    Uterine leiomyomas (fibroids) are the most prevalent medical problem of the female reproductive tract, but there are few non-surgical treatment options. Although many advances in the understanding of the molecular components of these tumors have occurred over the past five years, an effective pharmaceutical approach remains elusive. Further, there is currently no clinical method to distinguish a benign uterine leiomyoma from a malignant leiomyosarcoma prior to treatment, a pressing need given concerns about the use of the power morcellator for minimally invasive surgery. This paper reviews current studies regarding the molecular biology of uterine fibroids, discusses non-surgical approaches and suggests new cutting-edge therapeutic and diagnostic approaches. PMID:26236472

  3. 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

  4. Current understanding of the relationship between periodontal and systemic diseases

    PubMed Central

    Mawardi, Hani H.; Elbadawi, Lena S.; Sonis, Stephen T.

    2015-01-01

    Periodontal disease (PD) is among the most common infectious diseases affecting humans. While the burden of periodontal disease on oral health has been extensively investigated, a possible specific relationship between the disease and systemic health is a relatively new area of interest. More recently it has been suggested that PD has an etiological role in the development of atherosclerotic cardiovascular disease, diabetes mellitus, and preterm low-birth weight, among others. In this review, we critically evaluate the current knowledge on the relation between PD and systemic diseases overall, and specifically with cardiovascular diseases. The best available evidence today suggests that the infection and inflammatory reaction associated with PD may contribute toward systemic disease. It is critical that dentists and physicians are well informed of the potential general health impact of periodontal disease so that they are in a position to knowledgeably counsel patients. PMID:25719577

  5. Understanding Neuropathic Corneal Pain--Gaps and Current Therapeutic Approaches.

    PubMed

    Goyal, Sunali; Hamrah, Pedram

    2016-01-01

    The richly innervated corneal tissue is one of the most powerful pain generators in the body. Corneal neuropathic pain results from dysfunctional nerves causing perceptions such as burning, stinging, eye-ache, and pain. Various inflammatory diseases, neurological diseases, and surgical interventions can be the underlying cause of corneal neuropathic pain. Recent efforts have been made by the scientific community to elucidate the pathophysiology and neurobiology of pain resulting from initially protective physiological reflexes, to a more persistent chronic state. The goal of this clinical review is to briefly summarize the pathophysiology of neuropathic corneal pain, describe how to systematically approach the diagnosis of these patients, and finally summarizing our experience with current therapeutic approaches for the treatment of corneal neuropathic pain.

  6. The current structural and functional understanding of APOBEC deaminases.

    PubMed

    Bransteitter, Ronda; Prochnow, Courtney; Chen, Xiaojiang S

    2009-10-01

    The apolipoprotein B mRNA-editing enzyme catalytic polypeptide (APOBEC) family of cytidine deaminases has emerged as an intensively studied field as a result of their important biological functions. These enzymes are involved in lipid metabolism, antibody diversification, and the inhibition of retrotransposons, retroviruses, and some DNA viruses. The APOBEC proteins function in these roles by deaminating single-stranded (ss) DNA or RNA. There are two high-resolution crystal structures available for the APOBEC family, Apo2 and the C-terminal catalytic domain (CD2) of Apo3G or Apo3G-CD2 [Holden et al. (Nature 456:121-124, 2008); Prochnow et al. (Nature 445:447-451, 2007)]. Additionally, the structure of Apo3G-CD2 has also been determined using NMR [Chen et al. (Nature 452:116-119, 2008); Furukawa et al. (EMBO J 28:440-451, 2009); Harjes et al. (J Mol Biol, 2009)]. A detailed structural analysis of the APOBEC proteins and a comparison to other zinc-coordinating deaminases can facilitate our understanding of how APOBEC proteins bind nucleic acids, recognize substrates, and form oligomers. Here, we review the recent development of structural and functional studies that apply to Apo3G as well as the APOBEC deaminase family. PMID:19547914

  7. 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

  8. 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

  9. Current understanding on the neurophysiology of behavioral thermoregulation.

    PubMed

    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.

  10. Current challenges with understanding greigite (Fe3S4) magnetism

    NASA Astrophysics Data System (ADS)

    Chang, L.; Roberts, A. P.; Winklhofer, M.; Vasiliev, I.; Dekkers, M. J.; Krijgsman, W.

    2014-12-01

    Greigite (Fe3S4) is a widespread authigenic magnetic mineral in anoxic sediments, and is also commonly biosynthesized by magnetotactic bacteria in aqueous environments. Despite the importance of greigite in paleomagnetic and environmental magnetic studies, knowledge of its magnetic properties is at a much lower level than for more common rock-forming magnetic minerals. Much recent progress has been made to develop a more complete understanding of the magnetic properties of greigite and the range of grain sizes in which greigite occurs in nature. We present results of new determinations of a range of fundamental magnetic properties of greigite, including the saturation magnetization, the magnetocrystalline anisotropy, and calculated rock magnetic properties. In addition, we provide evidence for the preservation of greigite magnetofossils in ancient sediments, which has important implications for assessing the reliability of paleomagnetic records carried by greigite. Finally, we present an integrated study from a Messinian former Black Sea sedimentary sequence to unravel environmental controls on diagenetic greigite formation, and demonstrates the usefulness of greigite for studying long-term climate variability in anoxic environments.

  11. Current understanding on the neurophysiology of behavioral thermoregulation.

    PubMed

    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

  12. Current therapies and technological advances in aqueous aerosol drug delivery.

    PubMed

    Watts, Alan B; McConville, Jason T; Williams, Robert O

    2008-09-01

    Recent advances in aerosolization technology have led to renewed interest in pulmonary delivery of a variety of drugs. Pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs) have experienced success in recent years; however, many limitations are presented by formulation difficulties, inefficient delivery, and complex device designs. Simplification of the formulation process as well as adaptability of new devices has led many in the pharmaceutical industry to reconsider aerosolization in an aqueous carrier. In the acute care setting, breath-enhanced air-jet nebulizers are controlling and minimizing the amount of wasted medication, while producing a high percentage of respirable droplets. Vibrating mesh nebulizers offer advantages in higher respirable fractions (RFs) and slower velocity aerosols when compared with air-jet nebulizers. Vibrating mesh nebulizers incorporating formulation and patient adaptive components provide improvements to continuous nebulization technology by generating aerosol only when it is most likely to reach the deep lung. Novel innovations in generation of liquid aerosols are now being adapted for propellant-free pulmonary drug delivery to achieve unprecedented control over dose delivered and are leading the way for the adaptation of systemic drugs for delivery via the pulmonary route. Devices designed for the metered dose delivery of insulin, morphine, sildenafil, triptans, and various peptides are all currently under investigation for pulmonary delivery to treat nonrespiratory diseases. Although these devices are currently still in clinical testing (with the exception of the Respimat), metered dose liquid inhalers (MDLIs) have already shown superior outcomes to current pulmonary and systemic delivery methods.

  13. 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)

  14. 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.

  15. 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

  16. 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.

  17. Advances in Understanding Multiple Stellar Generations in Globular Clusters

    NASA Astrophysics Data System (ADS)

    Piotto, Giampaolo

    2011-10-01

    This is a proposal to use WFC3 for striking new advances in the populations of globular clusters {GC}. Now that recent work {much of it by our own group} has shattered the 50-year-old belief that each GC represents a single event of star-birth, with a single chemical composition, we propose to exploit the superb UV throughput of WFC3 to split main sequences with an unprecedented fineness, and follow them in all evolutionary sequences, up to the horizontal branch {HB}, in a quest to finally solve the long-sought "second parameterâ??. From our vantage point in the midst of these developments, we feel that the present-day situation merits a concentration of efforts on HST UV resources, that, in a few years, will not be available any more. We are therefore proposing to observe two classical second-parameter GC couples {NGC 288/NGC 362 and M3/M13}, and three clusters with extreme HB extensions {NGC2808,M80,M15} in F275W/F336W/F438W bands. The main-sequence study will cast particular light on the question of helium enrichment, whereas the clear separation of the more advanced evolutionary sequences {SGB, RGB, HB} will allow us to identify the evolutionary paths of each individual sub-population. In this way, we shall gather critical information capable of shedding fresh light on the sequence of events that have been responsible for the subsequent formation of the various sub-populations.

  18. 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

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

    PubMed

    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.

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

    PubMed

    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

  1. 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

  2. Advances in the Understanding of the Pathogenesis of Inflammatory Acne.

    PubMed

    Kircik, Leon H

    2016-01-01

    Acne vulgaris (AV) is the most common skin disorder. It was traditionally thought that AV lesions developed after abnormal desquamation of the keratinocytes that line the sebaceous follicle, leading to hyperkeratinization and microcomedone formation. However, in recent years there has been a paradigm shift with regard to understanding the pathogenesis of AV, and it is now viewed as a primary inflammatory skin disorder. Research has implicated the presence of subclinical inflammation in the normal skin of acne patients, even before microcomedone formation. This article will review the novel concepts that play a role in the new pathogenesis of acne vulgaris.

  3. Recent advances in understanding transfer ions across aqueous interfaces

    SciTech Connect

    Wick, Collin D.; Dang, Liem X.

    2008-06-06

    Understanding the composition of aqueous interfaces, and the mechanism for ion transport across them is of fundamental importance for biological, environmental, and industrial processes. Molecular dynamics simulations, using the potential of mean force technique serves as a technique to map out the free energy profile across interfaces. In some cases, where the free energy of ion transfer is known experimentally between two phases, the potential of mean force technique can allow validation of the simulation results against experiment for this property. In addition, the inclusion of polarizability in the interaction potential can be of paramount importance for understanding interfacial properties and the ion transfer mechanism in interfacial environments. This review discusses some of the recent studies of ion transport across aqueous interfaces, and gives insights on the ion transport mechanism and why certain interfacial behavior is observed. This work was supported by the Office of Basic Energy Sciences of the Department of Energy, in part by the Chemical Sciences program and in part by the Engineering and Geosciences Division. The Pacific Northwest National Laboratory is operated by Battelle for the U.S. Department of Energy.

  4. 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.

  5. 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

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

    PubMed

    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

  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. PMID:26258129

  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. 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.

  10. 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

  11. Recent advances in the understanding and management of rosacea

    PubMed Central

    2014-01-01

    Rosacea is a chronic relapsing inflammatory facial dermatosis. There are several known triggers but the pathogenesis remains unknown. Recent achievements in understanding this disease point to the importance of skin-environmental interactions. This includes physical and chemical factors, but also microbial factors. The impairment of the skin barrier function and the activation of the innate immune defences are major and connected pathways contributing to an ongoing inflammatory response in the affected skin. This becomes modulated by endogenous factors like neurovascular, drugs, and psychological factors. These factors offer new therapeutic targets for rosacea treatment. There is a broader range of anti-inflammatory compounds available with a favourable safety record. Only recently have persistent erythema and flushing been addressed by new drug formulations. PMID:25184040

  12. Diabetic retinopathy: recent advances towards understanding neurodegeneration and vision loss.

    PubMed

    Barber, Alistair J

    2015-06-01

    Diabetic retinopathy (DR) is one of the most common retinal diseases world-wide. It has a complex pathology that involves the vasculature of the inner retina and breakdown of the blood-retinal barrier. Extensive research has determined that DR is not only a vascular disease but also has a neurodegenerative component and that essentially all types of cells in the retina are affected, leading to chronic loss of visual function. A great deal of work using animal models of DR has established the loss of neurons and pathology of other cell types, including supporting glial cells. There has also been an increased emphasis on measuring retinal function in the models, as well as further validation and extension of the animal studies by clinical and translational research. This article will attempt to summarize the more recent developments in research towards understanding the complexities of retinal neurodegeneration and functional vision loss in DR.

  13. Advances in the understanding of cervical spine deformity.

    PubMed

    Sharan, Alok D; Krystal, Jonathan D; Singla, Amit; Nassr, Ahmad; Kang, James D; Riew, K Daniel

    2015-01-01

    Cervical spine deformities pose substantial challenges for spine surgeons. The anatomy and biomechanics of the cervical spine play an important role in the decision-making process regarding treatment. The etiology of cervical deformities can be congenital, developmental, iatrogenic, degenerative, or inflammatory. Dropped head syndrome has been recently described but is poorly understood. Patients have variable presentations ranging from neck pain to an inability to maintain head position and neural compromise. Radiographic angles are important to monitor the deformity and plan the surgical correction. Treatment is focused on relieving pain, preventing and improving neurologic compromise, and improving overall spinal alignment and balance. The surgical approach and the level of fusion should be individualized on a case-by-case basis. The surgeon can greatly improve a patient's quality of life by understanding the nature of the patient's deformity and fully considering all treatment options. PMID:25745925

  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. PMID:25453329

  15. 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.

  16. Advances in understanding and treatment of Tourette syndrome.

    PubMed

    McNaught, Kevin St P; Mink, Jonathan W

    2011-12-01

    Tourette syndrome is a hereditary, childhood-onset neurodevelopmental disorder that was first clearly described in France in 1885. This disorder is characterized by sudden, rapid, recurrent, nonrhythmic movements (motor tics) or sounds (vocal or phonic tics), often preceded by premonitory sensations or urges. Some individuals also have psychiatric comorbidities, notably attention-deficit hyperactivity disorder or obsessive-compulsive disorder. Tourette syndrome occurs worldwide, in all races and ethnicities, in both sexes and in children as well as in adults. Estimates of its prevalence in children vary, with rates of up to 1% being reported, but rates of 0.3-0.8% are thought to accurately reflect the occurrence of the disorder. Research has led to progress in many aspects of Tourette syndrome, although many questions and unmet needs remain. For example, except for rare cases, the genetic basis remains elusive. The anatomical and neuronal changes in the brain that underlie Tourette syndrome are also unclear, although the evidence increasingly implicates alterations in basal ganglia function. Treatment is often unnecessary for individuals with mild tics, but for those with moderate to severe forms of the syndrome, some drugs are available, albeit frequently ineffective. Behavioral and surgical therapies, in particular deep brain stimulation, are currently undergoing development and show promising results. This Review examines the history of Tourette syndrome and describes its clinical presentation. The article also provides an overview of the epidemiology and pathophysiology of this disorder. Current treatment strategies and potential future therapies are also discussed. PMID:22064610

  17. Recent advances in understanding myelofibrosis and essential thrombocythemia.

    PubMed

    Vainchenker, William; Constantinescu, Stefan N; Plo, Isabelle

    2016-01-01

    The classic BCR-ABL-negative myeloproliferative neoplasms (MPNs), a form of chronic malignant hemopathies, have been classified into polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). ET and PMF are two similar disorders in their pathogenesis, which is marked by a key role of the megakaryocyte (MK) lineage. Whereas ET is characterized by MK proliferation, PMF is also associated with aberrant MK differentiation (myelodysplasia), leading to the release of cytokines in the marrow environment, which causes the development of myelofibrosis. Thus, PMF is associated with both myeloproliferation and different levels of myelodysplastic features. MPNs are mostly driven by mutated genes called MPN drivers, which abnormally activate the cytokine receptor/JAK2 pathway and their downstream effectors. The recent discovery of CALR mutations has closed a gap in our knowledge and has shown that this mutated endoplasmic reticulum chaperone activates the thrombopoietin receptor MPL and JAK2. These genetic studies have shown that there are two main types of MPNs: JAK2V617F-MPNs, including ET, PV, and PMF, and the MPL-/CALR-MPNs, which include only ET and PMF. These MPN driver mutations are associated with additional mutations in genes involved in epigenetics, splicing, and signaling, which can precede or follow the acquisition of MPN driver mutations. They are involved in clonal expansion or phenotypic changes or both, leading to myelofibrosis or leukemic transformation or both. Only a few patients with ET exhibit mutations in non-MPN drivers, whereas the great majority of patients with PMF harbor one or several mutations in these genes. However, the entire pathogenesis of ET and PMF may also depend on other factors, such as the patient's constitutional genetics, the bone marrow microenvironment, the inflammatory response, and age. Recent advances allowed a better stratification of these diseases and new therapeutic approaches with the development

  18. 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.

  19. Recent advances in understanding transcription termination by RNA polymerase II

    PubMed Central

    Loya, Travis J.; Reines, Daniel

    2016-01-01

    Transcription termination is a fundamental process in which RNA polymerase ceases RNA chain extension and dissociates from the chromatin template, thereby defining the end of the transcription unit. Our understanding of the biological role and functional importance of termination by RNA polymerase II and the range of processes in which it is involved has grown significantly in recent years. A large set of nucleic acid-binding proteins and enzymes have been identified as part of the termination machinery. A greater appreciation for the coupling of termination to RNA processing and metabolism has been recognized. In addition to serving as an essential step at the end of the transcription cycle, termination is involved in the regulation of a broad range of cellular processes. More recently, a role for termination in pervasive transcription, non-coding RNA regulation, genetic stability, chromatin remodeling, the immune response, and disease has come to the fore. Interesting mechanistic questions remain, but the last several years have resulted in significant insights into termination and an increasing recognition of its biological importance. PMID:27408690

  20. The slit ventricle syndrome: advances based on technology and understanding.

    PubMed

    Rekate, Harold L

    2004-01-01

    Despite many articles on slit ventricle syndrome (SVS) over the last 25 years, accepted terminology regarding the definition of this condition is lacking. Any shunted individual with a severe headache disorder in the context of ventricles that are normal or smaller than normal can be said to suffer from SVS, even though there are at least five forms of the condition. Logical management of SVS requires an understanding of the specific pathogenesis of the problem in individual patients, whether based on monitoring of intracranial pressure (ICP) or observation at the time of shunt failure or symptoms. Overdrainage syndromes, whether intermittent proximal obstruction or low pressure states, are best managed with valve upgrades and the addition of devices that retard siphoning. Increased ICP without ventriculomegaly at the time of shunt failure is best managed by shunting devices that access the cortical subarachnoid space such as lumboperitoneal shunts or shunts involving the cisterna magna. Cranial expansion operations and subtemporal decompression should be limited to patients with craniofacial syndromes.

  1. Recent Advances in Our Understanding of Star Formation

    NASA Astrophysics Data System (ADS)

    Elmegreen, Bruce

    2013-06-01

    Our understanding of star formation in the cores of molecular clouds has steadily improved over the last decade as new telescopes covering a wide range of wavelengths have become available and as computer simulations have grown in size and complexity to include the most important physical processes during core collapse. Star formation generally appears to be linked to compressive turbulent flows in an environment with strong self-gravity, and to the resulting segmentation and collapse of stream-fed filaments and cores into multiple stellar systems. At the same time, new surveys on galactic scales covering ultraviolet to millimeter wavelengths, and new galaxy-scale simulations, have given an increasingly coherent picture in which the areal-average star formation rate depends mostly on the surface density of molecules, with many of the small-scale details either averaged out or unimportant. How these two frameworks join together is still a mystery that drives considerable research on such topics as the origin of the initial stellar mass function, analytical approximations to star formation rates that are useful at sub-grid levels in cosmological simulations, cluster formation and the fraction of young stars born in bound clusters, and stellar feedback that powers gas heating and motions in the interstellar medium and galactic halo. This review will highlight recent results and future directions in the broad field of star formation research.

  2. 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.

  3. 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.

  4. 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

  5. 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). PMID:18826921

  6. 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).

  7. 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).

  8. Cryptosporidium species in humans and animals: current understanding and research needs.

    PubMed

    Ryan, Una; Fayer, Ronald; Xiao, Lihua

    2014-11-01

    Cryptosporidium is increasingly recognized as one of the major causes of moderate to severe diarrhoea in developing countries. With treatment options limited, control relies on knowledge of the biology and transmission of the members of the genus responsible for disease. Currently, 26 species are recognized as valid on the basis of morphological, biological and molecular data. Of the nearly 20 Cryptosporidium species and genotypes that have been reported in humans, Cryptosporidium hominis and Cryptosporidium parvum are responsible for the majority of infections. Livestock, particularly cattle, are one of the most important reservoirs of zoonotic infections. Domesticated and wild animals can each be infected with several Cryptosporidium species or genotypes that have only a narrow host range and therefore have no major public health significance. Recent advances in next-generation sequencing techniques will significantly improve our understanding of the taxonomy and transmission of Cryptosporidium species, and the investigation of outbreaks and monitoring of emerging and virulent subtypes. Important research gaps remain including a lack of subtyping tools for many Cryptosporidium species of public and veterinary health importance, and poor understanding of the genetic determinants of host specificity of Cryptosporidium species and impact of climate change on the transmission of Cryptosporidium. PMID:25111501

  9. 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

  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. Current Pharmacological Advances in the Treatment of Cardiac Arrest

    PubMed Central

    Papastylianou, Andry; Mentzelopoulos, S.

    2012-01-01

    Cardiac arrest is defined as the sudden cessation of spontaneous ventilation and circulation. Within 15 seconds of cardiac arrest, the patient loses consciousness, electroencephalogram becomes flat after 30 seconds, pupils dilate fully after 60 seconds, and cerebral damage takes place within 90–300 seconds. It is essential to act immediately as irreversible damage can occur in a short time. Cardiopulmonary resuscitation (CPR) is an attempt to restore spontaneous circulation through a broad range of interventions which are early defibrillation, high-quality and uninterrupted chest compressions, advanced airway interventions, and pharmacological interventions. Drugs should be considered only after initial shocks have been delivered (when indicated) and chest compressions and ventilation have been started. During cardiopulmonary resuscitation, no specific drug therapy has been shown to improve survival to hospital discharge after cardiac arrest, and only few drugs have a proven benefit for short-term survival. This paper reviews current pharmacological treatment of cardiac arrest. There are three groups of drugs relevant to the management of cardiac arrest: vasopressors, antiarrhythmics, and other drugs such as sodium bicarbonate, calcium, magnesium, atropine, fibrinolytic drugs, and corticosteroids. PMID:22145080

  12. 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.

  13. Breast cancer stem cells: current advances and clinical implications.

    PubMed

    Luo, Ming; Clouthier, Shawn G; Deol, Yadwinder; Liu, Suling; Nagrath, Sunitha; Azizi, Ebrahim; Wicha, Max S

    2015-01-01

    There is substantial evidence that many cancers, including breast cancer, are driven by a population of cells that display stem cell properties. These cells, termed cancer stem cells (CSCs) or tumor initiating cells, not only drive tumor initiation and growth but also mediate tumor metastasis and therapeutic resistance. In this chapter, we summarize current advances in CSC research with a major focus on breast CSCs (BCSCs). We review the prevailing methods to isolate and characterize BCSCs and recent evidence documenting their cellular origins and phenotypic plasticity that enables them to transition between mesenchymal and epithelial-like states. We describe in vitro and clinical evidence that these cells mediate metastasis and treatment resistance in breast cancer, the development of novel strategies to isolate circulating tumor cells (CTCs) that contain CSCs and the use of patient-derived xenograft (PDX) models in preclinical breast cancer research. Lastly, we highlight several signaling pathways that regulate BCSC self-renewal and describe clinical implications of targeting these cells for breast cancer treatment. The development of strategies to effectively target BCSCs has the potential to significantly improve the outcomes for patients with breast cancer.

  14. Laboratory markers in ulcerative colitis: Current insights and future advances.

    PubMed

    Cioffi, Michele; Rosa, Antonella De; Serao, Rosalba; Picone, Ilaria; Vietri, Maria Teresa

    2015-02-15

    important in the future. The progress of molecular biology tools (microarrays, proteomics and nanotechnology) have revolutionised the field of the biomarker discovery. The advances in bioinformatics coupled with cross-disciplinary collaborations have greatly enhanced our ability to retrieve, characterize and analyse large amounts of data generated by the technological advances. The techniques available for biomarkers development are genomics (single nucleotide polymorphism genotyping, pharmacogenetics and gene expression analyses) and proteomics. In the future, the addition of new serological markers will add significant benefit. Correlating serologic markers with genotypes and clinical phenotypes should enhance our understanding of pathophysiology of UC. PMID:25685607

  15. Laboratory markers in ulcerative colitis: Current insights and future advances.

    PubMed

    Cioffi, Michele; Rosa, Antonella De; Serao, Rosalba; Picone, Ilaria; Vietri, Maria Teresa

    2015-02-15

    important in the future. The progress of molecular biology tools (microarrays, proteomics and nanotechnology) have revolutionised the field of the biomarker discovery. The advances in bioinformatics coupled with cross-disciplinary collaborations have greatly enhanced our ability to retrieve, characterize and analyse large amounts of data generated by the technological advances. The techniques available for biomarkers development are genomics (single nucleotide polymorphism genotyping, pharmacogenetics and gene expression analyses) and proteomics. In the future, the addition of new serological markers will add significant benefit. Correlating serologic markers with genotypes and clinical phenotypes should enhance our understanding of pathophysiology of UC.

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. Current Advances in the Metabolomics Study on Lotus Seeds.

    PubMed

    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.

  2. Understanding Brain Injury and Neurodevelopmental Disabilities in the Preterm Infant: The Evolving Role of Advanced MRI

    PubMed Central

    Mathur, Amit M.; Neil, Jeffrey J.; Inder, Terrie E.

    2010-01-01

    The high incidence of neurodevelopmental disability in premature infants requires continued efforts at understanding the underlying microstructural changes in the brain that cause this perturbation in normal development. Magnetic resonance imaging (MRI) methods offer great potential to fulfill this need. Serial MR imaging and the application of newer analysis techniques such as, diffusion tensor imaging (DTI), volumetric MR analysis, cortical surface analysis, functional connectivity (fcMRI) and diffusion tractography, provide important insights into the trajectory of brain development in the premature infant and the impact of injury on this developmental trajectory. While some of these imaging techniques are currently available in the research setting only, other measures such as DTI and brain metric measures can be used clinically. MR imaging also has enormous potential to be used as a surrogate, short-term outcome measure in clinical studies evaluating new therapeutic interventions of neuroprotection of the developing brain. In this article we review the current status of these advanced MR imaging techniques. PMID:20109973

  3. 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

  4. [Current understanding and future prospects for intravascular large B-cell lymphoma].

    PubMed

    Shimada, Kazuyuki

    2015-08-01

    Intravascular large B-cell lymphoma (IVLBCL) is a rare distinct disease entity of the extranodal large B-cell lymphoma type, characterized by the selective growth of tumor cells in the lumina of small vessels of various organs. Lack of remarkable lymphadenopathy and non-specific clinical abnormalities including fever of unknown origin and lactate dehydrogenase elevation generally make timely and accurate diagnosis difficult. Recent diagnostic advances in the detection of this disease using FDG-PET/CT and random skin biopsies are expected to increase the diagnostic yield. Regarding the therapeutic aspects of this disease, improvement of clinical outcomes by the application of anti-CD20 monoclonal antibody, rituximab, and a high risk of CNS recurrence have been indicated. Thus, a prospective phase II trial of immunochemotherapy combined with CNS prophylaxis is now ongoing. Previously, the difficulty of obtaining sufficient tumor samples hampered biological investigations but the novel technique developing xenograft models is opening the door to uncovering the underlying mechanisms by focusing on the fundamental biological question: "Why do tumor cells become lodged in the lumina of vessels?" This review describes the current understanding of research on IVLBCL and discusses the future prospects for this disease entity. PMID:26345563

  5. Technological advances in perioperative monitoring: Current concepts and clinical perspectives.

    PubMed

    Chilkoti, Geetanjali; Wadhwa, Rachna; Saxena, Ashok Kumar

    2015-01-01

    Minimal mandatory monitoring in the perioperative period recommended by Association of Anesthetists of Great Britain and Ireland and American Society of Anesthesiologists are universally acknowledged and has become an integral part of the anesthesia practice. The technologies in perioperative monitoring have advanced, and the availability and clinical applications have multiplied exponentially. Newer monitoring techniques include depth of anesthesia monitoring, goal-directed fluid therapy, transesophageal echocardiography, advanced neurological monitoring, improved alarm system and technological advancement in objective pain assessment. Various factors that need to be considered with the use of improved monitoring techniques are their validation data, patient outcome, safety profile, cost-effectiveness, awareness of the possible adverse events, knowledge of technical principle and ability of the convenient routine handling. In this review, we will discuss the new monitoring techniques in anesthesia, their advantages, deficiencies, limitations, their comparison to the conventional methods and their effect on patient outcome, if any.

  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. 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.

  8. 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. PMID:26318845

  9. [Recent advances in the understanding and treatment of diffuse large B-cell lymphoma].

    PubMed

    Gergely, Lajos; Illés, Árpád

    2016-07-01

    Diffuse large B-cell lymphoma is the most common type of non-Hodgkin's lymphoma. Using the conventional cyclophosphamide adriablastin vincristin prednisolon polychemotherapy about 50% of the patients were cured. The addition of rituximab to the regimen increased the cure rate to 60%. This is a major improvement, however, further advance is still needed to increase the cure rate. The extensive genetic testing performed recently revealed several important pathognomic mutations as potential targets in this disease. Routine diagnosis of patients now includes the use of (18)Fluor-deoxy-glucose positron emission computer tomography, according to the recent Lugano classification system. With all these data we can better predict the prognosis of patients, and we can select candidates for novel targeted therapies as well. Answering these questions, and utilizing novel therapies possibly will further increase the cure rate in the near future. This paper summarizes current diagnostic and therapeutic approaches and describes recent understanding in the mutations and pathognomic changes resulting in the disease. The authors also summarize the data available on experimental therapies possibly entering clinical pratice in the forthcoming years. Orv. Hetil., 2016, 157(31), 1232-1241. PMID:27476519

  10. Recent Advances in Understanding the Role of Nutrition in Human Genome Evolution12

    PubMed Central

    Ye, Kaixiong; Gu, Zhenglong

    2011-01-01

    Dietary transitions in human history have been suggested to play important roles in the evolution of mankind. Genetic variations caused by adaptation to diet during human evolution could have important health consequences in current society. The advance of sequencing technologies and the rapid accumulation of genome information provide an unprecedented opportunity to comprehensively characterize genetic variations in human populations and unravel the genetic basis of human evolution. Series of selection detection methods, based on various theoretical models and exploiting different aspects of selection signatures, have been developed. Their applications at the species and population levels have respectively led to the identification of human specific selection events that distinguish human from nonhuman primates and local adaptation events that contribute to human diversity. Scrutiny of candidate genes has revealed paradigms of adaptations to specific nutritional components and genome-wide selection scans have verified the prevalence of diet-related selection events and provided many more candidates awaiting further investigation. Understanding the role of diet in human evolution is fundamental for the development of evidence-based, genome-informed nutritional practices in the era of personal genomics. PMID:22332091

  11. 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.

  12. 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

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

    PubMed

    Berg, Regina; Straub, Bernd F

    2013-01-01

    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

  14. 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.

  15. 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...

  16. 48 CFR 1552.215-74 - Advanced understanding-uncompensated time.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 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...

  17. 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...

  18. Current advances in proteomic analysis of (fatty) liver.

    PubMed

    Molette, C; Théron, L; Marty-Gasset, N; Fernandez, X; Rémignon, H

    2012-07-19

    In this review, an overview on proteomic studies conducted in livers of farm animals is conducted with a special focus on liver steatosis in waterfowl. Several studies had interest in understanding liver metabolism in dairy cows under various conditions (e.g. fasting) or the evolution of liver proteome during embryonic phases or growing periods in chicken. Those studies provide interesting results leading to a better understanding of the liver metabolism. Liver steatosis development in waterfowl represents a special case and a focus on proteomic studies conducted in these birds will be done. Indeed, recent studies aimed at resolving protein evolution during overfeeding in duck. Proteomic analysis combining two complementary approaches (2-dimensional electrophoresis gels and shot gun strategy) in order to better understand the mechanisms underlying the variability of cooking yield of fatty liver will be presented.

  19. 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

  20. Early Gastric Cancer: Current Advances of Endoscopic Diagnosis and Treatment.

    PubMed

    Zhu, Linlin; Qin, Jinyu; Wang, Jin; Guo, Tianjiao; Wang, Zijing; Yang, Jinlin

    2016-01-01

    Endoscopy is a major method for early gastric cancer screening because of its high detection rate, but its diagnostic accuracy depends heavily on the availability of endoscopic instruments. Many novel endoscopic techniques have been shown to increase the diagnostic yield of early gastric cancer. With the improved detection rate of EGC, the endoscopic treatment has become widespread due to advances in the instruments available and endoscopist's experience. The aim of this review is to summarize frequently-used endoscopic diagnosis and treatment in early gastric cancer (EGC). PMID:26884753

  1. 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. PMID:24187807

  2. 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

  3. 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

  4. 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

  5. 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

  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. Psychopharmacology of ADHD in pediatrics: current advances and issues

    PubMed Central

    Greydanus, Donald E; Nazeer, Ahsan; Patel, Dilip R

    2009-01-01

    Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral developmental disorder found in 3% to 8% of children and adolescents. An important part of ADHD management is psychopharmacology, which includes stimulants, norepinephrine reuptake inhibitors, alpha-2 agonists, and antidepressants. Medications with the best evidence-based support for ADHD management are the stimulants methylphenidate and amphetamine. A number of newer, long-acting stimulants are now available and a number of new medications are considered that are under current research. PMID:19557112

  8. Electrode-electrolyte interface in Li-ion batteries: current understanding and new insights.

    PubMed

    Gauthier, Magali; Carney, Thomas J; Grimaud, Alexis; Giordano, Livia; Pour, Nir; Chang, Hao-Hsun; Fenning, David P; Lux, Simon F; Paschos, Odysseas; Bauer, Christoph; Maglia, Filippo; Lupart, Saskia; Lamp, Peter; Shao-Horn, Yang

    2015-11-19

    Understanding reactions at the electrode/electrolyte interface (EEI) is essential to developing strategies to enhance cycle life and safety of lithium batteries. Despite research in the past four decades, there is still limited understanding by what means different components are formed at the EEI and how they influence EEI layer properties. We review findings used to establish the well-known mosaic structure model for the EEI (often referred to as solid electrolyte interphase or SEI) on negative electrodes including lithium, graphite, tin, and silicon. Much less understanding exists for EEI layers for positive electrodes. High-capacity Li-rich layered oxides yLi2-xMnO3·(1-y)Li1-xMO2, which can generate highly reactive species toward the electrolyte via oxygen anion redox, highlight the critical need to understand reactions with the electrolyte and EEI layers for advanced positive electrodes. Recent advances in in situ characterization of well-defined electrode surfaces can provide mechanistic insights and strategies to tailor EEI layer composition and properties. PMID:26510477

  9. Current Advances in Developing Inhibitors of Bacterial Multidrug Efflux Pumps.

    PubMed

    Mahmood, Hannah Y; Jamshidi, Shirin; Sutton, J Mark; Rahman, Khondaker M

    2016-01-01

    Antimicrobial resistance represents a significant challenge to future healthcare provision. An acronym ESKAPEE has been derived from the names of the organisms recognised as the major threats although there are a number of other organisms, notably Neisseria gonorrhoeae, that have become equally challenging to treat in the clinic. These pathogens are characterised by the ability to rapidly develop and/or acquire resistance mechanisms in response to exposure to different antimicrobial agents. A key part of the armoury of these pathogens is a series of efflux pumps, which effectively exclude or reduce the intracellular concentration of a large number of antibiotics, making the pathogens significantly more resistant. These efflux pumps are the topic of considerable interest, both from the perspective of basic understanding of efflux pump function, and its role in drug resistance but also as targets for the development of novel adjunct therapies. The necessity to overcome antimicrobial resistance has encouraged investigations into the characterisation of resistance-modifying efflux pump inhibitors to block the mechanisms of drug extrusion, thereby restoring antibacterial susceptibility and returning existing antibiotics into the clinic. A greater understanding of drug recognition and transport by multidrug efflux pumps is needed to develop clinically useful inhibitors, given the breadth of molecules that can be effluxed by these systems. This review discusses different bacterial EPIs originating from both natural source and chemical synthesis and examines the challenges to designing successful EPIs that can be useful against multidrug resistant bacteria. PMID:26947776

  10. Chemotherapy in advanced bladder cancer: current status and future

    PubMed Central

    2011-01-01

    Bladder cancer occurs in the majority of cases in males. It represents the seventh most common cancer and the ninth most common cause of cancer deaths for men. Transitional cell carcinoma is the most predominant histological type. Bladder cancer is highly chemosensitive. In metastatic setting, chemotherapy based on cisplatin should be considered as standard treatment of choice for patients with good performance status (0-1) and good renal function-glomerular filtration rate (GFR) > 60 mL/min. The standard treatment is based on cisplatin chemotherapy regimens type MVAC, HD-MVAC, gemcitabine plus cisplatin (GC) or dose dense GC. In unfit patients, carboplatin based regimes; gemcitabine plus carboplatin or methotrexate plus carboplatin plus vinblastine (MCAVI) are reasonable options. The role of targeted therapies when used alone, or in combination with chemotherapy, or in maintenance, was evaluated; targeting angiogenesis seem to be very promising. The purpose of this literature review is to highlight the role of chemotherapy in the management of advanced transitional cell carcinoma of the bladder. PMID:21906310

  11. 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.

  12. 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

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

    PubMed

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

    2014-04-01

    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 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.

  14. Advances in kinase targeting: current clinical use and clinical trials.

    PubMed

    Rask-Andersen, Mathias; Zhang, Jin; Fabbro, Doriano; Schiöth, Helgi B

    2014-11-01

    Phosphotransferases, also known as kinases, are the most intensively studied protein drug target category in current pharmacological research, as evidenced by the vast number of kinase-targeting agents enrolled in active clinical trials. This development has emerged following the great success of small-molecule, orally available protein kinase inhibitors for the treatment of cancer, starting with the introduction of imatinib (Gleevec®) in 2003. The pharmacological utility of kinase-targeting has expanded to include treatment of inflammatory diseases, and rapid development is ongoing for kinase-targeted therapies in a broad array of indications in ophthalmology, analgesia, central nervous system (CNS) disorders, and the complications of diabetes, osteoporosis, and otology. In this review we highlight specifically the kinase drug targets and kinase-targeting agents being explored in current clinical trials. This analysis is based on a recent estimate of all established and clinical trial drug mechanisms of action, utilizing private and public databases to create an extensive dataset detailing aspects of more than 3000 approved and experimental drugs. PMID:25312588

  15. The NEDICES Study: Recent Advances in the Understanding of the Epidemiology of Essential Tremor

    PubMed Central

    Romero, Juan Pablo; Benito-León, Julián; Bermejo-Pareja, Félix

    2012-01-01

    Background Essential tremor (ET) is the most common tremor disorder. ET has classically been viewed as a benign monosymptomatic condition. Yet over the past 10 years, a growing body of evidence indicates that this is a progressive condition that is clinically heterogeneous, and may be associated with a variety of different features. Large epidemiological studies such as the Neurological Disorders of Central Spain (NEDICES), a longitudinal, population-based survey, have contributed significantly to the changing view of the disease. Our aim is to review some of the main results of NEDICES within the larger framework of the epidemiology of ET. Methods Data for this review were gathered from all our articles published up to October 2011 regarding NEDICES study and “Essential Tremor”. Results We have published 18 articles up to October 2011. The prevalence, incidence, and mortality of ET were analyzed in this cohort. In addition, ET was found to be associated with increased frailty and low morale, as well as with a series of non-motor manifestations, including cognitive deficits, mild cognitive impairment, dementia, depressive symptoms, and hearing impairment. Finally, the link between ET and Parkinson's disease (PD) was formally quantified in the NEDICES study, which demonstrated that the risk of developing incident PD was 4.3 times higher in prevalent ET cases than in age-matched controls without ET. Conclusions This review highlights the contributions of NEDICES towards the advancement of current knowledge of the epidemiology and clinical features of ET, and emphasizes the importance of population-based studies towards the understanding of complex, ageing-related diseases. PMID:23439396

  16. 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

  17. Advances in mechanistic understanding of release rate control mechanisms of extended-release hydrophilic matrix tablets.

    PubMed

    Timmins, Peter; Desai, Divyakant; Chen, Wei; Wray, Patrick; Brown, Jonathan; Hanley, Sarah

    2016-08-01

    Approaches to characterizing and developing understanding around the mechanisms that control the release of drugs from hydrophilic matrix tablets are reviewed. While historical context is provided and direct physical characterization methods are described, recent advances including the role of percolation thresholds, the application on magnetic resonance and other spectroscopic imaging techniques are considered. The influence of polymer and dosage form characteristics are reviewed. The utility of mathematical modeling is described. Finally, how all the information derived from applying the developed mechanistic understanding from all of these tools can be brought together to develop a robust and reliable hydrophilic matrix extended-release tablet formulation is proposed. PMID:27444495

  18. Effect of Current Electricity Simulation Supported Learning on the Conceptual Understanding of Elementary and Secondary Teachers

    ERIC Educational Resources Information Center

    Kumar, David Devraj; Thomas, P. V.; Morris, John D.; Tobias, Karen M.; Baker, Mary; Jermanovich, Trudy

    2011-01-01

    This study examined the impact of computer simulation and supported science learning on a teacher's understanding and conceptual knowledge of current electricity. Pre/Post tests were used to measure the teachers' concept attainment. Overall, there was a significant and large knowledge difference effect from Pre to Post test. Two interesting…

  19. Advanced therapy medicinal products: current and future perspectives

    PubMed Central

    Hanna, Eve; Rémuzat, Cécile; Auquier, Pascal; Toumi, Mondher

    2016-01-01

    Background Advanced therapy medicinal products (ATMPs) are innovative therapies that encompass gene therapy, somatic cell therapy, and tissue-engineered products. These therapies are expected to bring important health benefits, but also to substantially impact the pharmaceuticals budget. Objective The aim of this study was to characterise the ATMPs in development and discuss future implications in terms of market access. Methods Clinical trials were searched in the following databases: EudraCT (EU Drug Regulating Authorities Clinical Trials), ClinicalTrials.gov, and ICTRP (International Clinical Trials Registry Platform of the World Health Organization). Trials were classified by category of ATMP as defined by European regulation EC No. 1394/2007, as well as by development phase and disease area. Results The database search identified 939 clinical trials investigating ATMPs (85% ongoing, 15% completed). The majority of trials were in the early stages (Phase I, I/II: 64.3%, Phase II, II/III: 27.9%, Phase 3: 6.9%). Per category of ATMP, we identified 53.6% of trials for somatic cell therapies, 22.8% for tissue-engineered products, 22.4% for gene therapies, and 1.2% for combined products (incorporating a medical device). Disease areas included cancer (24.8%), cardiovascular diseases (19.4%), musculoskeletal (10.5%), immune system and inflammation (11.5%), neurology (9.1%), and others. Of the trials, 47.2% enrolled fewer than 25 patients. Due to the complexity and specificity of ATMPs, new clinical trial methodologies are being considered (e.g., small sample size, non-randomised trials, single-arm trials, surrogate endpoints, integrated protocols, and adaptive designs). Evidence generation post-launch will become unavoidable to address payers’ expectations. Conclusion ATMPs represent a fast-growing field of interest. Although most of the products are in an early development phase, the combined trial phase and the potential to cure severe chronic conditions suggest

  20. Current treatment of medulloblastoma: recent advances and future challenges.

    PubMed

    Rood, Brian R; Macdonald, Tobey J; Packer, Roger J

    2004-10-01

    Medulloblastoma (MB) is the most common malignant brain tumor of childhood, yet it makes up only 1% of adult brain tumors. MB is uniquely sensitive to chemotherapy and radiation, but successful surgical resection continues to be an important component of therapeutic success. Progress in the treatment of MB has occurred in multiple areas from improved neurosurgical techniques, refined dosing and delivery of radiation, and optimized chemotherapy. Tumors are currently risk-stratified as average risk or high risk depending on clinical factors such as age, extent of resection, and presence of metastases. Molecular biology is beginning to improve upon clinical prognostication and may soon provide the means to accurately predict response to therapy. Treatment for average-risk MB has achieved a level of success that allows efforts to be focused on the limitation of adverse treatment effects. Therapy for high-risk and relapsed MB has been positively affected by the advent of high-dose chemotherapy with stem cell rescue. In addition, molecular targets are being elucidated and new therapeutic agents are being tested for safety and efficacy. Treatment for this disease has evolved a great deal over the preceding decades, but a great deal of work remains to be done to effect reliable cures while reducing long-term sequelae of therapy.

  1. Sexual dysfunction in the older woman: an overview of the current understanding and management.

    PubMed

    Walsh, Kathleen E; Berman, Jennifer R

    2004-01-01

    of women with sexual complaints should include a detailed psychological, social and medical history and thorough physical examination including a hormonal profile. Current treatment options are dependent on the diagnosis and include physical therapy, psychological counselling, hormonal supplements, medication changes and sexual devices. There has also been a burgeoning interest in investigational medications for female sexual dysfunction, from centrally acting (e.g. serotonin agonists) to peripheral, localised treatment (e.g. vasodilating creams). The area of female sexuality and sexual dysfunction has been undergoing important critical changes within the last 10 years. Researchers and clinicians are continuing to recognise the need to try and understand both the psychological and physiological aspects of the female sexual experience and how they influence one another. PMID:15287824

  2. 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

  3. Recent advances in addictive disorders. Prevention. Current research and trends.

    PubMed

    Kumpfer, K L; Hopkins, R

    1993-03-01

    The AOD prevention programs of the 1990s should be resiliency-focused and include interventions of sufficient dosage and strength. Although some child behavioral technology exists to tackle successfully changes in resiliency, additional prevention strategies need to be developed and studied. In some way, the prevention field is hampered by the lack of sufficient research in the child and adolescent psychiatry and psychology fields, that includes transactional research in parenting and child rearing for high-risk youth. We simply do not know enough to determine how parents and other adults can best foster resilience in children. Questions that arise include how much to protect children from environmental stressors and how much to push them to confront new life stressors in the form of challenges to develop new skills or talents. There are no simple answers to these questions, but a number of useful guidelines could help parents and teachers to increase resilience in youth. Some of the guidelines currently being stressed include developing in youth an increased sense of responsibility for their own success, helping them to identify their talents, motivating them to dedicate their lives to helping society rather than feeling their only purpose in life is to be consumers, providing realistic appraisals and feedback for youth rather than graciously building up their self-esteem, stressing multicultural competence in an ever-shrinking world, encouraging and valuing education and skills training, increasing cooperative solutions to problems rather than competitive or aggressive solutions, and increasing a sense of responsibility for others and caring for others. Clearly, these are important objectives for creating the type of citizens that can make American strong in the twentieth century. PMID:8456037

  4. Malignant gliomas: current perspectives in diagnosis, treatment, and early response assessment using advanced quantitative imaging methods.

    PubMed

    Ahmed, Rafay; Oborski, Matthew J; Hwang, Misun; Lieberman, Frank S; Mountz, James M

    2014-01-01

    Malignant gliomas consist of glioblastomas, anaplastic astrocytomas, anaplastic oligodendrogliomas and anaplastic oligoastrocytomas, and some less common tumors such as anaplastic ependymomas and anaplastic gangliogliomas. Malignant gliomas have high morbidity and mortality. Even with optimal treatment, median survival is only 12-15 months for glioblastomas and 2-5 years for anaplastic gliomas. However, recent advances in imaging and quantitative analysis of image data have led to earlier diagnosis of tumors and tumor response to therapy, providing oncologists with a greater time window for therapy management. In addition, improved understanding of tumor biology, genetics, and resistance mechanisms has enhanced surgical techniques, chemotherapy methods, and radiotherapy administration. After proper diagnosis and institution of appropriate therapy, there is now a vital need for quantitative methods that can sensitively detect malignant glioma response to therapy at early follow-up times, when changes in management of nonresponders can have its greatest effect. Currently, response is largely evaluated by measuring magnetic resonance contrast and size change, but this approach does not take into account the key biologic steps that precede tumor size reduction. Molecular imaging is ideally suited to measuring early response by quantifying cellular metabolism, proliferation, and apoptosis, activities altered early in treatment. We expect that successful integration of quantitative imaging biomarker assessment into the early phase of clinical trials could provide a novel approach for testing new therapies, and importantly, for facilitating patient management, sparing patients from weeks or months of toxicity and ineffective treatment. This review will present an overview of epidemiology, molecular pathogenesis and current advances in diagnoses, and management of malignant gliomas.

  5. 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.

  6. UNDERSTANDING AND PREVENTING ACL INJURIES: CURRENT BIOMECHANICAL AND EPIDEMIOLOGIC CONSIDERATIONS - UPDATE 2010

    PubMed Central

    Ford, Kevin R.; Hoogenboom, Barbara J.; Myer, Gregory D.

    2010-01-01

    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. PMID:21655382

  7. 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…

  8. Current Understanding of the Formation and Adaptation of Metabolic Systems Based on Network Theory

    PubMed Central

    Takemoto, Kazuhiro

    2012-01-01

    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. PMID:24957641

  9. Improving Understanding of the Agulhas Current and Its Global Climate Impacts

    NASA Astrophysics Data System (ADS)

    Beal, Lisa; Biastoch, Arne

    2010-05-01

    Working Group on the Climatic Importance of the Greater Agulhas System; Portland, Oregon, 20-21 February 2010; The first meeting of the new Scientific Committee on Oceanic Research (SCOR) Working Group 136 was held to discuss recent developments in understanding the greater Agulhas Current system and future research directions. The overarching goal of the working group is to improve understanding and awareness of the regional and global climate impacts of the Agulhas Current, a major western boundary current that flows along the east coast of Africa, and its interocean leakage. In addition to studying modern circulation, the working group is motivated by recent paleodata that suggest that through the currents' southern influence on the Atlantic meridional overturning circulation (AMOC), changes in the leakage of warm and salty Agulhas waters into the Atlantic may have triggered the end of ice ages. In terms of global climate, this arguably puts the importance of the greater Agulhas system on a par with Heinrich (land-ice release) events and high-latitude deepwater formation.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

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

    PubMed

    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

  16. 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.

  17. 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.

  18. Understanding the Behavior of Advanced High-Strength Steels Using Atom Probe Tomography

    NASA Astrophysics Data System (ADS)

    Pereloma, Elena; Beladi, Hossein; Zhang, Laichang; Timokhina, Ilana

    2012-11-01

    The key evidence for understanding the mechanical behavior of advanced high strength steels was provided by atom probe tomography (APT). Chemical overstabilization of retained austenite (RA) leading to the limited transformation-induced plasticity (TRIP) effect was deemed to be the main factor responsible for the low ductility of nanostructured bainitic steel. Appearance of the yield point on the stress-strain curve of prestrained and bake-hardened transformation-induced plasticity steel is due to the unlocking from weak carbon atmospheres of newly formed during prestraining dislocations.

  19. 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

  20. Applying mass spectrometry based proteomic technology to advance the understanding of multiple myeloma

    PubMed Central

    2010-01-01

    Multiple myeloma (MM) is the second most common hematological malignancy in adults. It is characterized by clonal proliferation of terminally differentiated B lymphocytes and over-production of monoclonal immunoglobulins. Recurrent genomic aberrations have been identified to contribute to the aggressiveness of this cancer. Despite a wealth of knowledge describing the molecular biology of MM as well as significant advances in therapeutics, this disease remains fatal. The identification of biomarkers, especially through the use of mass spectrometry, however, holds great promise to increasing our understanding of this disease. In particular, novel biomarkers will help in the diagnosis, prognosis and therapeutic stratification of MM. To date, results from mass spectrometry studies of MM have provided valuable information with regards to MM diagnosis and response to therapy. In addition, mass spectrometry was employed to study relevant signaling pathways activated in MM. This review will focus on how mass spectrometry has been applied to increase our understanding of MM. PMID:20374647

  1. 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

  2. Current understanding of metformin effect on the control of hyperglycemia in diabetes.

    PubMed

    An, Hongying; He, Ling

    2016-03-01

    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 more than 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 regard to the role of AMPK in metformin's action and the mechanism of AMPK activation. In this review, we 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

  3. 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.

  4. 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

  5. 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

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

    PubMed Central

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

    2015-01-01

    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. PMID:25954092

  7. 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.

  8. 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.

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

    DOE PAGES

    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 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

  10. 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.

  11. 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.

  12. Recent advances in the understanding of endometriosis: the role of inflammatory mediators in disease pathogenesis and treatment

    PubMed Central

    Nothnick, Warren; Alali, Zahraa

    2016-01-01

    In this review, we focus on recent advancements in our understanding of the roles of inflammatory mediators in endometriosis pathophysiology and the potential for improved therapies based upon targeting these pathways. We review the association between endometriosis and inflammation and the initial promise of anti-tumor necrosis factor therapies based upon experimental evidence, and how and why these studies have not translated to the clinic. We then discuss emerging data on the role of inter-relationship among macrophage migration inhibitory factor, prostaglandin E 2, and estrogen receptor-beta, and the potential utility of targeting these factors in endometriosis treatment. In doing so, we highlight the strengths and discuss the current research on identification of novel, anti-inflammatory-based therapy and the necessity to expand experimental endpoints to include clinically relevant measures when assessing the efficacy of potential new therapies for endometriosis. PMID:26949527

  13. Role of extrahepatic UDP-glucuronosyltransferase 1A1: Advances in understanding breast milk-induced neonatal hyperbilirubinemia.

    PubMed

    Fujiwara, Ryoichi; Maruo, Yoshihiro; Chen, Shujuan; Tukey, Robert H

    2015-11-15

    Newborns commonly develop physiological hyperbilirubinemia (also known as jaundice). With increased bilirubin levels being observed in breast-fed infants, breast-feeding has been recognized as a contributing factor for the development of neonatal hyperbilirubinemia. Bilirubin undergoes selective metabolism by UDP-glucuronosyltransferase (UGT) 1A1 and becomes a water soluble glucuronide. Although several factors such as gestational age, dehydration and weight loss, and increased enterohepatic circulation have been associated with breast milk-induced jaundice (BMJ), deficiency in UGT1A1 expression is a known cause of BMJ. It is currently believed that unconjugated bilirubin is metabolized mainly in the liver. However, recent findings support the concept that extrahepatic tissues, such as small intestine and skin, contribute to bilirubin glucuronidation during the neonatal period. We will review the recent advances made towards understanding biological and molecular events impacting BMJ, especially regarding the role of extrahepatic UGT1A1 expression. PMID:26342858

  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. Combining transcranial direct current stimulation and neuroimaging: novel insights in understanding neuroplasticity

    PubMed Central

    Sandrini, Marco

    2012-01-01

    In recent years, noninvasive brain stimulation techniques like transcranial direct current stimulation (tDCS) have gained immense popularity owing to their effects on modulating cortical activity and consequently motor and cognitive performance. However, the neurophysiology underlying such neuroplastic changes is less understood. This article critically evaluates the contemporary approach of combined tDCS and neuroimaging as a means to provide novel insights in understanding the neurophysiological and neuroplastic processes modulated by this brain stimulation technique. We end by briefly suggesting further lines of inquiry. PMID:21832036

  16. 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.

  17. 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%.

  18. Current Understanding on EGFR and Wnt/β-Catenin Signaling in Glioma and Their Possible Crosstalk

    PubMed Central

    Paul, Indranil; Bhattacharya, Seemana; Chatterjee, Anirban

    2013-01-01

    Glioblastoma multiformes (GBMs) are extensively heterogeneous at both cellular and molecular levels. Current therapeutic strategies include targeting of key signaling molecules using pharmacological inhibitors in combination with genotoxic agents such as temozolomide. In spite of all efforts, the prognosis of glioma patients remains dismal. Therefore, a proper understanding of individual molecular pathways responsible for the progression of GBM is necessary. The epidermal growth factor receptor (EGFR) pathway is probably the most significant signaling pathway clinically implicated in glioma. Not surprisingly, anti-EGFR therapies mostly prevail for therapeutic purposes. The Wnt/β-catenin pathway is well implicated in multiple tumors; however, its role in glioma has only recently started to emerge. We give a concise account of the current understanding of the role of both these pathways in glioma. Last, taking evidences from a limited literature, we outline a number of points where these pathways intersect each other and put forward the possibility of combinatorially targeting them for treatment of glioma. PMID:24386505

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

    PubMed

    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

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

    PubMed

    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.

  1. 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

  2. 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. PMID:26187035

  3. 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.

  4. 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

  5. Advances in understanding the mechanisms of erythropoiesis in homeostasis and disease.

    PubMed

    Liang, Raymond; Ghaffari, Saghi

    2016-09-01

    Anaemia or decreased blood haemoglobin is the most common blood disorder often characterized by reduced red blood cell (RBC) numbers. RBCs are produced from differentiation and commitment of haematopoietic stem cells to the erythroid lineage by a process called erythropoiesis. Coordination of erythropoietin receptor signalling with several erythroid transcription factors including GATA1 is essential for this process. A number of additional players that are critical for RBC production have been identified in recent years. Major technological advances, such as the development of RNA interference, genetically modified animals, including zebrafish, and imaging flow cytometry have led to these discoveries; the emergence of -omics approaches in combination with the optimization of ex vivo erythroid cultures have also produced a more comprehensive understanding of erythropoiesis. Here we summarize studies describing novel regulators of erythropoiesis that modulate erythroid cell production in the context of human erythroid disorders involving hypoxia, iron regulation, immune-related molecules, and the transcription factor FOXO3. PMID:27442953

  6. [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.

  7. 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.

  8. 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.

  9. Involving Volunteers in Your Advancement Programs. The Best of "CASE Currents."

    ERIC Educational Resources Information Center

    Smith, Virginia Carter, Ed.; Alberger, Patricia LaSalle, Ed.

    A compilation of the best articles from "CASE Currents" on involving volunteers in institutional advancement programs is presented. Overall topics include: management of volunteers, working with trustees (volunteers at the top), benefits of participation for volunteers, and involving volunteers in fund raising, public relations, student…

  10. Grammar Coding in the "Oxford Advanced Learner's Dictionary of Current English."

    ERIC Educational Resources Information Center

    Wekker, Herman

    1992-01-01

    Focuses on the revised system of grammar coding for verbs in the fourth edition of the "Oxford Advanced Learner's Dictionary of Current English" (OALD4), comparing it with two other similar dictionaries. It is shown that the OALD4 is found to be more favorable on many criteria than the other comparable dictionaries. (16 references) (VWL)

  11. Recent advances in understanding the biology, epidemiology and control of chlamydial infections in koalas.

    PubMed

    Polkinghorne, Adam; Hanger, Jon; Timms, Peter

    2013-08-30

    The koala (Phascolarctos cinereus) is recognised as a threatened wildlife species in various parts of Australia. A major contributing factor to the decline and long-term viability of affected populations is disease caused by the obligate intracellular bacteria, Chlamydia. Two chlamydial species infect the koala, Chlamydia pecorum and Chlamydia pneumoniae, and have been reported in nearly all mainland koala populations. Chlamydial infections of koalas are associated with ocular infections leading to blindness and genital tract infections linked to infertility, among other serious clinical manifestations. Diagnosis can be based on clinical presentation alone, however, it is complicated by the observation that many koala chlamydial infections occur with no overt signs of clinical disease. Instead, accurate diagnosis requires detailed clinical assessment and confirmatory testing by a range of PCR-based assays. Antibiotic treatment for koala chlamydial infection is possible, however, results on its success are mixed. A more practical solution for the protection of diseased populations is the application of a koala Chlamydia vaccine, with recent trials indicating promising results. Interestingly, molecular epidemiology studies of koala C. pecorum infections and recent comparative genomic analyses of koala C. pneumoniae have revealed potential differences in their origin that will have wider ramifications for our understanding of human chlamydial infections and host adaptation of the chlamydiae. This review summarises changes to the taxonomy of koala chlamydial infections and recent advances in our understanding of the epidemiology, diagnosis, treatment, control and evolution of Chlamydia infections in this iconic wildlife species.

  12. 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.

  13. Serrated polyps of the large intestine: current understanding of diagnosis, pathogenesis, and clinical management.

    PubMed

    Rosty, Christophe; Hewett, David G; Brown, Ian S; Leggett, Barbara A; Whitehall, Vicki L J

    2013-03-01

    Approximately 30% of colorectal carcinomas develop via the serrated neoplasia pathway characterized by widespread DNA methylation and frequent BRAF mutation. Serrated polyps represent a heterogeneous group of polyps which are the precursor lesions to serrated pathway colorectal carcinomas. The histological classification of serrated polyps has evolved over the last two decades to distinguish three separate entities: hyperplastic polyp, sessile serrated adenoma (SSA), and traditional serrated adenoma (TSA). The malignant potential of SSAs and TSAs has been clearly demonstrated. SSAs are more challenging to detect by colonoscopy and are likely to account for some interval carcinomas of the proximal colon. Serrated polyposis syndrome is now widely recognized as conferring a high risk of colorectal carcinoma although its cause remains elusive. The current understanding of the actual malignant potential of each serrated polyp subtype is still limited due to the lack of large-scale prospective studies. Patient management guidelines have been recently updated although high-level evidence to support them is still required.

  14. 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.

  15. 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

  16. 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.

  17. Current Challenge in Consumer Health Informatics: Bridging the Gap between Access to Information and Information Understanding

    PubMed Central

    Alpay, Laurence; Verhoef, John; Xie, Bo; Te'eni, Dov; Zwetsloot-Schonk, J.H.M.

    2009-01-01

    The number of health-related websites has proliferated over the past few years. Health information consumers confront a myriad of health related resources on the internet that have varying levels of quality and are not always easy to comprehend. There is thus a need to help health information consumers to bridge the gap between access to information and information understanding—i.e. to help consumers understand health related web-based resources so that they can act upon it. At the same time health information consumers are becoming not only more involved in their own health care but also more information technology minded. One way to address this issue is to provide consumers with tailored information that is contextualized and personalized e.g. directly relevant and easily comprehensible to the person's own health situation. This paper presents a current trend in Consumer Health Informatics which focuses on theory-based design and development of contextualized and personalized tools to allow the evolving consumer with varying backgrounds and interests to use online health information efficiently. The proposed approach uses a theoretical framework of communication in order to support the consumer's capacity to understand health-related web-based resources. PMID:20419038

  18. Foot-ankle simulators: A tool to advance biomechanical understanding of a complex anatomical structure.

    PubMed

    Natsakis, Tassos; Burg, Josefien; Dereymaeker, Greta; Jonkers, Ilse; Vander Sloten, Jos

    2016-05-01

    In vitro gait simulations have been available to researchers for more than two decades and have become an invaluable tool for understanding fundamental foot-ankle biomechanics. This has been realised through several incremental technological and methodological developments, such as the actuation of muscle tendons, the increase in controlled degrees of freedom and the use of advanced control schemes. Furthermore, in vitro experimentation enabled performing highly repeatable and controllable simulations of gait during simultaneous measurement of several biomechanical signals (e.g. bone kinematics, intra-articular pressure distribution, bone strain). Such signals cannot always be captured in detail using in vivo techniques, and the importance of in vitro experimentation is therefore highlighted. The information provided by in vitro gait simulations enabled researchers to answer numerous clinical questions related to pathology, injury and surgery. In this article, first an overview of the developments in design and methodology of the various foot-ankle simulators is presented. Furthermore, an overview of the conducted studies is outlined and an example of a study aiming at understanding the differences in kinematics of the hindfoot, ankle and subtalar joints after total ankle arthroplasty is presented. Finally, the limitations and future perspectives of in vitro experimentation and in particular of foot-ankle gait simulators are discussed. It is expected that the biofidelic nature of the controllers will be improved in order to make them more subject-specific and to link foot motion to the simulated behaviour of the entire missing body, providing additional information for understanding the complex anatomical structure of the foot. PMID:27160562

  19. 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.

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

    PubMed

    Bouain, Nadia; Doumas, Patrick; Rouached, Hatem

    2016-08-01

    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

  1. Two-phase unsaturated flow at Yucca Mountain, Nevada - A Report on Current Understanding

    SciTech Connect

    Pruess, K.

    1998-08-01

    The U.S. civilian nuclear waste program is unique in its focus on disposal of high-level wastes in the unsaturated zone (UZ), above the water table. The potential repository site currently under investigation is located in a semi-arid region of the southwestern U.S. at Yucca Mountain, Nevada. The geology of the site consists of layered sequences of faulted, fractured, and bedded tuffs. The groundwater table is approximately 600 m beneath the land surface, while the proposed repository horizon is at a nominal depth of approximately 375 m. In this kind of environment, two-phase flow is not just a localized perturbation to natural conditions, as in the saturated zone, but is the predominant mode of water and gas flow. The purpose of this report is to review the current understanding of gas and water flow, and mass transport, in the unique hydrogeologic environment of Yucca Mountain. Characteristics of the Yucca Mountain site are examined, and concepts and mathematical modeling approaches are described for variably saturated flow in thick unsaturated zones of fractured rock. The paper includes a brief summary of the disposal concept and repository design, as developed by a team of engineering contractors to the U.S. Department of Energy (DOE), with strong participation from the DOE National Laboratories.

  2. 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

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

    PubMed

    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

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

    PubMed

    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.

  5. 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.

  6. 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. PMID:27013225

  7. 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.

  8. Advanced semiconductor diagnosis by multidimensional electron-beam-induced current technique.

    PubMed

    Chen, J; Yuan, X; Sekiguchi, T

    2008-01-01

    We present advanced semiconductor diagnosis by using electron-beam-induced current (EBIC) technique. By varying the parameters such as temperature, accelerating voltage (V(acc)), bias voltage, and stressing time, it is possible to extend EBIC application from conventional defect characterization to advanced device diagnosis. As an electron beam can excite a certain volume even beneath the surface passive layer, EBIC can be effectively employed to diagnose complicated devices with hybrid structure. Three topics were selected to demonstrate EBIC applications. First, the recombination activities of grain boundaries and their interaction with Fe impurity in photovoltaic multicrystalline Si (mc-Si) are clarified by temperature-dependent EBIC. Second, the detection of dislocations between strained-Si and SiGe virtual substrate are shown to overcome the limitation of depletion region. Third, the observation of leakage sites in high-k gate dielectric is demonstrated for the characterization of advanced hybrid device structures.

  9. 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

  10. 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.

  11. 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.

  12. Salivary biomarkers for detection of oral squamous cell carcinoma – current state and recent advances

    PubMed Central

    Yakob, Maha; Fuentes, Laurel; Wang, Marilene B.; Abemayor, Elliot; Wong, David T.W.

    2014-01-01

    Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm of the oral cavity. Detection of OSCC is currently based on thorough clinical oral examination combined with biopsy for histological analysis. Most cases of OSCC are not detected until the cancer has developed into advanced stages; thus, a reliable early stage diagnostic marker is needed. This literature review presents an overview of the status of current advances in salivary diagnostics for OSCC. Though many protein and mRNA salivary biomarkers have been identified that can detect OSCC with high sensitivity and specificity, the most discernable findings occur with the use of multiple markers. Studies that incorporate proteomic, transcriptomic, and potentially additional “omics”, including methylomics, need to be initiated to bring technology to clinical applications and allow the best use of saliva in diagnosing OSCC. PMID:24883261

  13. 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.

  14. 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.

  15. Left Ventricular Dyssynchrony by Three-Dimensional Echocardiography: Current Understanding and Potential Future Clinical Applications.

    PubMed

    Cai, Qiangjun; Ahmad, Masood

    2015-08-01

    Left ventricular mechanical dyssynchrony is an important prognostic factor for patients with symptomatic systolic heart failure and has emerged as a therapeutic target for cardiac resynchronization therapy (CRT). However, approximately one-third of patients fail to improve after CRT based on current guideline recommendations and electrocardiographic criteria. Two-dimensional echocardiography and tissue Doppler-based techniques have shown variable results in assessment of left ventricular (LV) dyssynchrony and have limited value in clinical practice. Three-dimensional echocardiography (3DE) is an appealing novel imaging modality that has been recently used in quantitative evaluation of global and regional LV function. There is accumulating evidence that 3DE measurement of LV systolic dyssynchrony index may potentially play a role in predicting the short- and long-term response to CRT and further improve patient selection for CRT. New developments in 3DE speckle tracking technique and strain analysis may further improve the accuracy of LV mechanical dyssynchrony assessment in this population. In addition, recent studies suggest that mechanical dyssynchrony is present in patients with LV hypertrophy and diastolic heart failure. Three-dimensional echocardiographic assessment of dyssynchrony may aid in diagnosis and in predicting long-term outcome in these patients. We will summarize current understanding of 3DE techniques and parameters in assessment of LV mechanical dyssynchrony in the population of patients with systolic heart failure, LV hypertrophy, and diastolic heart failure. A number of the novel 3DE techniques described in this review are early in their stage of development, and they will continue to evolve and need further testing in large multicenter studies.

  16. 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

  17. Oculopharyngeal muscular dystrophy: recent advances in the understanding of the molecular pathogenic mechanisms and treatment strategies.

    PubMed

    Abu-Baker, Aida; Rouleau, Guy A

    2007-02-01

    Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset disorder characterized by progressive eyelid drooping, swallowing difficulties and proximal limb weakness. OPMD is caused by a small expansion of a short polyalanine tract in the poly (A) binding protein nuclear 1 protein (PABPN1). The mechanism by which the polyalanine expansion mutation in PABPN1 causes disease is unclear. PABPN1 is a nuclear multi-functional protein which is involved in pre-mRNA polyadenylation, transcription regulation, and mRNA nucleocytoplasmic transport. The distinct pathological hallmark of OPMD is the presence of filamentous intranuclear inclusions (INIs) in patient's skeletal muscle cells. The exact relationship between mutant PABPN1 intranuclear aggregates and pathology is not clear. OPMD is a unique disease sharing common pathogenic features with other polyalanine disorders, as well as with polyglutamine and dystrophic disorders. This chapter aims to review the rapidly growing body of knowledge concerning OPMD. First, we outline the background of OPMD. Second, we compare OPMD with other trinucleotide repeat disorders. Third, we discuss the recent advances in the understanding of the molecular mechanisms underlying OPMD pathogenesis. Finally, we review recent therapeutic strategies for OPMD.

  18. Advances in the understanding of plaque composition and treatment options: year in review.

    PubMed

    Tomey, Matthew I; Narula, Jagat; Kovacic, Jason C

    2014-04-29

    Atherosclerosis research has classically followed 2 intertwining lines of investigation concerning atherosclerosis as a local process (the "high-risk plaque") and as a systemic disease (the "high-risk patient"). Over time, the weight of attention has swung, like a pendulum, between these 2 related foci. With optimal medical therapy and attention to risk factors firmly established as fundamental aspects of management, in the past year, we have nevertheless perceived a shift in the pendulum toward renewed focus on the local plaque. We contend that this shift results from a convergence of major advances in understanding the biology of plaque progression, novel sophisticated invasive and noninvasive imaging modalities for the in vivo characterization of plaque composition and inflammation, and emerging data and technologies that have renewed interest in locally targeted interventions. Here, we review the dynamic and exciting progress that has occurred over the last 12 months in this arena, while acknowledging future work that remains to be done to refine and validate new imaging modalities and therapies.

  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. Recent advances in the understanding of the Aspergillus fumigatus cell wall.

    PubMed

    Lee, Mark J; Sheppard, Donald C

    2016-03-01

    Over the past several decades, research on the synthesis and organization of the cell wall polysaccharides of Aspergillus fumigatus has expanded our knowledge of this important fungal structure. Besides protecting the fungus from environmental stresses and maintaining structural integrity of the organism, the cell wall is also the primary site for interaction with host tissues during infection. Cell wall polysaccharides are important ligands for the recognition of fungi by the innate immune system and they can mediate potent immunomodulatory effects. The synthesis of cell wall polysaccharides is a complicated process that requires coordinated regulation of many biosynthetic and metabolic pathways. Continuous synthesis and remodeling of the polysaccharides of the cell wall is essential for the survival of the fungus during development, reproduction, colonization and invasion. As these polysaccharides are absent from the human host, these biosynthetic pathways are attractive targets for antifungal development. In this review, we present recent advances in our understanding of Aspergillus fumigatus cell wall polysaccharides, including the emerging role of cell wall polysaccharides in the host-pathogen interaction.

  1. Advances in the formation, use and understanding of multi-cellular spheroids

    PubMed Central

    Achilli, Toni-Marie; Meyer, Julia; Morgan, Jeffrey R

    2015-01-01

    Introduction Developing in vitro models for studying cell biology and cell physiology is of great importance to the fields of biotechnology, cancer research, drug discovery, toxicity testing, as well as the emerging fields of tissue engineering and regenerative medicine. Traditional two dimensional (2D) methods of mammalian cell culture have several limitations and it is increasingly recognized that cells grown in a three dimensional (3D) environment more closely represent normal cellular function due to the increased cell-to-cell interactions, and by mimicking the in vivo architecture of natural organs and tissues. Areas Covered In this review, we discuss the methods to form 3D multi-cellular spheroids, the advantages and limitations of these methods, and assays used to characterize the function of spheroids. The use of spheroids has led to many advances in basic cell sciences, including understanding cancer cell interactions, creating models for drug discovery and cancer metastasis, and they are being investigated as basic units for engineering tissue constructs. As so, this review will focus on contributions made to each of these fields using spheroid models. Expert Opinion Multi-cellular spheroids are rich in biological content and mimic better the in vivo environment than 2D cell culture. New technologies to form and analyze spheroids are rapidly increasing their adoption and expanding their applications. PMID:22784238

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

    DOE PAGES

    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 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

  3. 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.

  4. Recent advances in modeling discontinuities in anisotropic and heterogeneous materials in eddy current NDE

    SciTech Connect

    Aldrin, John C.; Sabbagh, Harold A.; Murphy, R. Kim; Sabbagh, Elias H.

    2011-06-23

    Recent advances are presented to model discontinuities in random anisotropies that arise in certain materials, such as titanium alloys. A numerical model is developed to provide a full anisotropic representation of each crystalline in a gridded region of the material. Several simulated and experimental demonstrations are presented highlighting the effect of grain noise on eddy current measurements. Agreement between VIC-3D(c) model calculations and experimental data in titanium alloy specimens with known flaws is demonstrated.

  5. Recent advances in understanding inflammation and remodeling in the airways in chronic obstructive pulmonary disease.

    PubMed

    Sohal, Sukhwinder Singh; Ward, Chris; Danial, Wan; Wood-Baker, Richard; Walters, Eugene Haydn

    2013-06-01

    The authors have reviewed the current literature on airway inflammation and remodeling in smoking-related chronic obstructive pulmonary disease (COPD). Detailed data on airway remodeling in COPD are especially sparse and how these changes lead to decline in lung function is not well understood. Small airway fibrosis and obliteration are likely to be the main contributors to physiological airway dysfunction and occur earlier than any subsequent development of emphysema. One potential mechanism contributing to small airway fibrosis/obliteration and change in extracellular matrix is epithelial-mesenchymal transition. When associated with angiogenesis (so-called epithelial-mesenchymal transition type 3) it may well also be the link with the development of cancer, which is closely associated with COPD, predominantly in large airways. The authors have focused on our recent publications in these areas. Further investigations teasing out these mechanisms will help improve our understanding of key airway disease processes in COPD, which may have major therapeutic implications.

  6. Advances in methodology and current prospects for primary drug therapies for Alzheimer's disease.

    PubMed

    Knopman, D S

    2000-01-01

    There has been gratifying progress in the development of drugs for Alzheimer's disease (AD). Even though the current generation of medications, the cholinesterase inhibitors (CEIs), has produced only modest benefits, our concept of an "effective" therapy has matured considerably over this time. A less visible but equally important advance has been a quantum leap in expertise in clinical trial methodology. This chapter reviews the methodological underpinnings of clinical trials in AD: patient selection issues, key design issues, and an overview of currently available agents and the prospects for drugs of the future.

  7. 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

  8. 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.

  9. Current Understanding and Remaining Challenges in Modeling Long-Term Degradation of Borosilicate Nuclear Waste Glasses

    SciTech Connect

    Vienna, John D.; Ryan, Joseph V.; Gin, Stephane; Inagaki, Yaohiro

    2013-12-01

    Chemical durability is not a single material property that can be uniquely measured. Instead it is the response to a host of coupled material and environmental processes whose rates are estimated by a combination of theory, experiment, and modeling. High-level nuclear waste (HLW) glass is perhaps the most studied of any material yet there remain significant technical gaps regarding their chemical durability. The phenomena affecting the long-term performance of HLW glasses in their disposal environment include surface reactions, transport properties to and from the reacting glass surface, and ion exchange between the solid glass and the surrounding solution and alteration products. The rates of these processes are strongly influenced and are coupled through the solution chemistry, which is in turn influenced by the reacting glass and also by reaction with the near-field materials and precipitation of alteration products. Therefore, those processes must be understood sufficiently well to estimate or bound the performance of HLW glass in its disposal environment over geologic time-scales. This article summarizes the current state of understanding of surface reactions, transport properties, and ion exchange along with the near-field materials and alteration products influences on solution chemistry and glass reaction rates. Also summarized are the remaining technical gaps along with recommended approaches to fill those technical gaps.

  10. 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.

  11. 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.

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

    PubMed

    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 from elucidating 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

  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. 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

  15. 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.

  16. 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. PMID:25295051

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. Neoclassical Transport Including Impurities and the Bootstrap Current in Advanced Helical Systems

    SciTech Connect

    Nishimura, Shin; Sugama, Hideo

    2004-07-15

    A recently developed method to calculate the neoclassical viscosity, diffusion, and current coefficients in general nonsymmetric toroidal plasmas by using the direct solution of the linearized drift kinetic equation with the pitch-angle-scattering collision operator is applied to impurity transport problems and bootstrap current calculations in stellarators. In this new method based on the basic idea of the so-called moment approach, the collisional momentum conservation is taken into account, and thus, it is applicable to the heat and particle diffusivity in advanced stellarators with quasi symmetry, and also to plasma flows currents, and viscosities in general nonsymmetric multispecies plasmas. In this paper, the impurity flow and the bootstrap current observed in the neoclassical internal transport barrier operation in the Compact Helical System are compared with theoretical calculations. Another topic is the benchmark test of existing analytical expressions for the bootstrap currents by comparing with numerically obtained current coefficients. The geometric factor, which is required for the current calculation based on the moment method, given by our new method is compared with these formulas.

  2. Issues and Advances in Understanding Landslide-Generated Tsunamis: Toward a Unified Model

    NASA Astrophysics Data System (ADS)

    Geist, E. L.; Locat, J.; Lee, H. J.; Lynett, P. J.; Parsons, T.; Kayen, R. E.; Hart, P. E.

    2008-12-01

    The physics of tsunamis generated from submarine landslides is highly complex, involving a cross- disciplinary exchange in geophysics. In the 10 years following the devastating Papua New Guinea tsunami, there have been significant advances in understanding landslide-generated tsunamis. However, persistent issues still remain related to submarine landslide dynamics that may be addressed with collection of new marine geologic and geophysical observations. We review critical elements of landslide tsunamis in the hope of developing a unified model that encompasses all stages of the process from triggering to tsunami runup. Because the majority of non-volcanogenic landslides that generate tsunamis are triggered seismically, advances in understanding inertial displacements and changes in strength and rheologic properties in response to strong-ground motion need to be included in a unified model. For example, interaction between compliant marine sediments and multi-direction ground motion results in greater permanent plastic displacements than predicted by traditional rigid-block analysis. When considering the coupling of the overlying water layer in the generation of tsunamis, the post-failure dynamics of landslides is important since the overall rate of seafloor deformation for landslides is less than or comparable to the phase speed of tsunami waves. As such, the rheologic and mechanical behavior of the slide material needs to be well understood. For clayey and silty debris flows, a non-linear (Herschel-Bulkley) and bilinear rheology have recently been developed to explain observed runout distances and deposit thicknesses. An additional complexity to this rheology is the inclusion of hydrate-laden sediment that commonly occurs along continental slopes. Although it has been proposed in the past that gas hydrate dissociation may provide potential failure planes for slide movement, it is unclear how zones of rigid hydrate-bearing sediment surrounded by a more viscoplastic

  3. 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

  4. Theoretical study of the source-drain current and gate leakage current to understand the graphene field-effect transistors.

    PubMed

    Yu, Cui; Liu, Hongmei; Ni, Wenbin; Gao, Nengyue; Zhao, Jianwei; Zhang, Haoli

    2011-02-28

    We designed acene molecules attached to two semi-infinite metallic electrodes to explore the source-drain current of graphene and the gate leakage current of the gate dielectric material in the field-effect transistors (FETs) device using the first-principles density functional theory combined with the non-equilibrium Green's function formalism. In the acene-based molecular junctions, we modify the connection position of the thiol group at one side, forming different electron transport routes. The electron transport routes besides the shortest one are defined as the cross channels. The simulation results indicate that electron transport through the cross channels is as efficient as that through the shortest one, since the conductance is weakly dependent on the distance. Thus, it is possible to connect the graphene with multiple leads, leading the graphene as a channel utilized in the graphene-based FETs in the mesoscopic system. When the conjugation of the cross channel is blocked, the junction conductance decreases dramatically. The differential conductance of the BA-1 is nearly 7 (54.57 μS) times as large as that of the BA-4 (7.35 μS) at zero bias. Therefore, the blocked graphene can be employed as the gate dielectric material in the top-gated graphene FET device, since the leakage current is small. The graphene-based field-effect transistors fabricated with a single layer of graphene as the channel and the blocked graphene as the gate dielectric material represent one way to overcome the problem of miniaturization which faces the new generation of transistors.

  5. 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.

  6. 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.

  7. 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.

  8. Current Updates on Therapeutic Advances in the Management of Cardiovascular Diseases.

    PubMed

    Jabir, Nasimudeen R; Siddiqui, Ali Nasir; Firoz, Chelapram Kandy; Ashraf, Ghulam Md; Zaidi, Syed Kashif; Khan, Mohd Shahnawaz; Shakil, Shazi; Alama, Mohammed Nabil; Kamal, Mohammad Amjad; Tabrez, Shams

    2016-01-01

    Despite the significant advances in the medical research and treatment methods, the rate of mortality associated with cardiovascular disease (CVD) is continuously rising and it remains the leading cause of death worldwide. There are several treatment methods for CVD and associated complications that have been considered till now. The current treatment methods cannot produce rapid cure, but could prevent or reduce the progression of this devastating disease. In the current article, we have summarized the use of various pharmacological agents viz. HMG-CoA reductase inhibitors (statins), antihypertensive, thrombolytic and anticoagulation agents that are currently being used for the management of CVD which targets different biochemical or molecular events. Based on our article, more research in this field is advocated which will provide the rapid and effective treatment methods in order to avoid fatal complications associated with CVD. PMID:26601967

  9. 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

  10. 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...

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

    PubMed Central

    2014-01-01

    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. PMID:25037625

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

    PubMed

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

    2014-01-01

    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.

  13. 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

  14. 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…

  15. Rational design and optimization of downstream processes of virus particles for biopharmaceutical applications: current advances.

    PubMed

    Vicente, Tiago; Mota, José P B; Peixoto, Cristina; Alves, Paula M; Carrondo, Manuel J T

    2011-01-01

    The advent of advanced therapies in the pharmaceutical industry has moved the spotlight into virus-like particles and viral vectors produced in cell culture holding great promise in a myriad of clinical targets, including cancer prophylaxis and treatment. Even though a couple of cases have reached the clinic, these products have yet to overcome a number of biological and technological challenges before broad utilization. Concerning the manufacturing processes, there is significant research focusing on the optimization of current cell culture systems and, more recently, on developing scalable downstream processes to generate material for pre-clinical and clinical trials. We review the current options for downstream processing of these complex biopharmaceuticals and underline current advances on knowledge-based toolboxes proposed for rational optimization of their processing. Rational tools developed to increase the yet scarce knowledge on the purification processes of complex biologicals are discussed as alternative to empirical, "black-boxed" based strategies classically used for process development. Innovative methodologies based on surface plasmon resonance, dynamic light scattering, scale-down high-throughput screening and mathematical modeling for supporting ion-exchange chromatography show great potential for a more efficient and cost-effective process design, optimization and equipment prototyping.

  16. 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.

  17. 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.

  18. 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.

  19. Detection and Sizing of Fatigue Cracks in Steel Welds with Advanced Eddy Current Techniques

    NASA Astrophysics Data System (ADS)

    Todorov, E. I.; Mohr, W. C.; Lozev, M. G.

    2008-02-01

    Butt-welded specimens were fatigued to produce cracks in the weld heat-affected zone. Advanced eddy current (AEC) techniques were used to detect and size the cracks through a coating. AEC results were compared with magnetic particle and phased-array ultrasonic techniques. Validation through destructive crack measurements was also conducted. Factors such as geometry, surface treatment, and crack tightness interfered with depth sizing. AEC inspection techniques have the potential of providing more accurate and complete sizing flaw data for manufacturing and in-service inspections.

  20. Targeted therapy for advanced gastric cancer: A review of current status and future prospects

    PubMed Central

    Kanat, Ozkan; O’Neil, Bert; Shahda, Safi

    2015-01-01

    In the West in particular, the vast majority of gastric cancer (GC) patients present with advanced-stage disease. Although combination chemotherapy is still the most important component of treatment for these patients, it confers a modest survival advantage. Recently, increased knowledge of the key molecular signaling pathways involved in gastric carcinogenesis has led to the discovery of specific molecular-targeted therapeutic agents. Some of these agents such as trastuzumab and ramucirumab have changed the treatment paradigm for this disease. In this paper, we will summarize the current clinical status of targeted drug therapy in the management of GC. PMID:26690491

  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. Advances in Wound Healing: A Review of Current Wound Healing Products

    PubMed Central

    Murphy, Patrick S.; Evans, Gregory R. D.

    2012-01-01

    Successful wound care involves optimizing patient local and systemic conditions in conjunction with an ideal wound healing environment. Many different products have been developed to influence this wound environment to provide a pathogen-free, protected, and moist area for healing to occur. Newer products are currently being used to replace or augment various substrates in the wound healing cascade. This review of the current state of the art in wound-healing products looks at the latest applications of silver in microbial prophylaxis and treatment, including issues involving resistance and side effects, the latest uses of negative pressure wound devices, advanced dressings and skin substitutes, biologic wound products including growth factor applications, and hyperbaric oxygen as an adjunct in wound healing. With the abundance of available products, the goal is to find the most appropriate modality or combination of modalities to optimize healing. PMID:22567251

  3. 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

  4. 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

    This report summarizes the current understanding of floodplain processes and landforms for the Willamette River and its major tributaries. The area of focus encompasses the main stem Willamette River above Newberg and the portions of the Coast Fork Willamette, Middle Fork Willamette, McKenzie, and North, South and main stem Santiam Rivers downstream of U.S. Army Corps of Engineers dams. These reaches constitute a large portion of the alluvial, salmon-bearing rivers in the Willamette Basin. The geomorphic, or historical, floodplain of these rivers has two zones - the active channel where coarse sediment is mobilized and transported during annual flooding and overbank areas where fine sediment is deposited during higher magnitude floods. Historically, characteristics of the rivers and geomorphic floodplain (including longitudinal patterns in channel complexity and the abundance of side channels, islands and gravel bars) were controlled by the interactions between floods and the transport of coarse sediment and large wood. Local channel responses to these interactions were then shaped by geologic features like bedrock outcrops and variations in channel slope. Over the last 150 years, floods and the transport of coarse sediment and large wood have been substantially reduced in the basin. With dam regulation, nearly all peak flows are now confined to the main channels. Large floods (greater than 10-year recurrence interval prior to basinwide flow regulation) have been largely eliminated. Also, the magnitude and frequency of small floods (events that formerly recurred every 2–10 years) have decreased substantially. The large dams trap an estimated 50–60 percent of bed-material sediment—the building block of active channel habitats—that historically entered the Willamette River. They also trap more than 80 percent of the estimated bed material in the lower South Santiam River and Middle and Coast Forks of the Willamette River. Downstream, revetments further

  5. 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.

  6. Corneal stem cells and tissue engineering: Current advances and future perspectives.

    PubMed

    de Araujo, Aline Lütz; Gomes, José Álvaro Pereira

    2015-06-26

    Major advances are currently being made in regenerative medicine for cornea. Stem cell-based therapies represent a novel strategy that may substitute conventional corneal transplantation, albeit there are many challenges ahead given the singularities of each cellular layer of the cornea. This review recapitulates the current data on corneal epithelial stem cells, corneal stromal stem cells and corneal endothelial cell progenitors. Corneal limbal autografts containing epithelial stem cells have been transplanted in humans for more than 20 years with great successful rates, and researchers now focus on ex vivo cultures and other cell lineages to transplant to the ocular surface. A small population of cells in the corneal endothelium was recently reported to have self-renewal capacity, although they do not proliferate in vivo. Two main obstacles have hindered endothelial cell transplantation to date: culture protocols and cell delivery methods to the posterior cornea in vivo. Human corneal stromal stem cells have been identified shortly after the recognition of precursors of endothelial cells. Stromal stem cells may have the potential to provide a direct cell-based therapeutic approach when injected to corneal scars. Furthermore, they exhibit the ability to deposit organized connective tissue in vitro and may be useful in corneal stroma engineering in the future. Recent advances and future perspectives in the field are discussed.

  7. 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.

  8. 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

  9. 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…

  10. 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.

  11. Macroscopic phenomena and microscopic processes: Student understanding of transients in direct current electric circuits

    NASA Astrophysics Data System (ADS)

    Thacker, Beth Ann; Ganiel, Uri; Boys, Donald

    1999-07-01

    Studies of student understanding of simple electric dc circuits have shown that many of them find it very difficult to apply qualitative reasoning to explain the observed phenomena. It has been suggested that these difficulties may be due to their failure to construct models of microscopic processes that lead to these phenomena. Indeed, in the traditional courses, such models have generally not been emphasized. In the present study, we compared the performance of different groups of university students in answering a questionnaire designed to probe their understanding of the relationship between macroscopic phenomena of transients in a dc circuit and the microscopic processes that can explain these phenomena. One group studied from a traditional text, the second group used a recently developed text that emphasizes models of microscopic processes. We also conducted detailed interviews with some of the students. From an analysis of the performance of these two groups, and also from a comparison with a previous study on Israeli high school students, we found that most of the students whose instructional experiences included an emphasis on the development of models of microscopic processes developed a better understanding of the transient phenomena studied. They applied qualitative considerations in their analyses and were able to develop coherent models to describe their observations. Overall, they demonstrated a superior understanding of the physical phenomena.

  12. 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…

  13. 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…

  14. 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…

  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. An update on recent advances in the understanding of non-neoplastic diseases of the salivary glands.

    PubMed

    Scully, C

    1992-08-01

    The recent advances in the understanding of the non-neoplastic disorders of salivary glands are summarised in this paper. The common infections are discussed and newer aspects of juvenile recurrent parotitis outlined. The benign lympho-epithelial lesion is reviewed in relation to Sjogren's syndrome and the salivary gland pathology seen in relation to infection with human immunodeficiency virus. A range of unusual conditions that may affect the minor salivary glands in particular, and can cause diagnosis dilemmas, is summarised.

  17. Plasma Shape and Current Density Profile Control in Advanced Tokamak Operating Scenarios

    NASA Astrophysics Data System (ADS)

    Shi, Wenyu

    The need for new sources of energy is expected to become a critical problem within the next few decades. Nuclear fusion has sufficient energy density to potentially supply the world population with its increasing energy demands. The tokamak is a magnetic confinement device used to achieve controlled fusion reactions. Experimental fusion technology has now reached a level where tokamaks are able to produce about as much energy as is expended in heating the fusion fuel. The next step towards the realization of a nuclear fusion tokamak power plant is ITER, which will be capable of exploring advanced tokamak (AT) modes, characterized by a high fusion gain and plasma stability. The extreme requirements of the advanced modes motivates researchers to improve the modeling of the plasma response as well as the design of feedback controllers. This dissertation focuses on several magnetic and kinetic control problems, including the plasma current, position and shape control, and data-driven and first-principles-driven modeling and control of plasma current density profile and the normalized plasma pressure ratio betaN. The plasma is confined within the vacuum vessel by an external electromagnetic field, produced primarily by toroidal and poloidal field coils. The outermost closed plasma surface or plasma boundary is referred to as the shape of the plasma. A central characteristic of AT plasma regimes is an extreme elongated shape. The equilibrium among the electromagnetic forces acting on an elongated plasma is unstable. Moreover, the tokamak performance is improved if the plasma is located in close proximity to the torus wall, which guarantees an efficient use of available volume. As a consequence, feedback control of the plasma position and shape is necessary. In this dissertation, an Hinfinity-based, multi-input-multi-output (MIMO) controller for the National Spherical Torus Experiment (NSTX) is developed, which is used to control the plasma position, shape, and X

  18. Understanding energy loss in parallelly connected microbial fuel cells: Non-Faradaic current.

    PubMed

    An, Junyeong; Sim, Junyoung; Feng, Yujie; Lee, Hyung-Sool

    2016-03-01

    In this work, the mechanisms of energy loss in parallel connection of microbial fuel cells (MFCs) is explored using two MFC units producing different open circuit voltage (OCV) and current. In open circuit mode, non-Faradaic current flows in low OCV unit, implying energy loss caused by different OCVs in parallelly stacked MFCs. In a stacked MFC in parallel under close circuit mode, it is confirmed that energy loss occurs until the working voltage in high OCV unit becomes identical to the other unit having low OCV. This result indicates that different voltage between individual MFC units can cause energy loss due to both non-Faradic and Faradaic current that flow from high voltage unit to low voltage unit even in parallelly stacked MFCs.

  19. Understanding energy loss in parallelly connected microbial fuel cells: Non-Faradaic current.

    PubMed

    An, Junyeong; Sim, Junyoung; Feng, Yujie; Lee, Hyung-Sool

    2016-03-01

    In this work, the mechanisms of energy loss in parallel connection of microbial fuel cells (MFCs) is explored using two MFC units producing different open circuit voltage (OCV) and current. In open circuit mode, non-Faradaic current flows in low OCV unit, implying energy loss caused by different OCVs in parallelly stacked MFCs. In a stacked MFC in parallel under close circuit mode, it is confirmed that energy loss occurs until the working voltage in high OCV unit becomes identical to the other unit having low OCV. This result indicates that different voltage between individual MFC units can cause energy loss due to both non-Faradic and Faradaic current that flow from high voltage unit to low voltage unit even in parallelly stacked MFCs. PMID:26744801

  20. 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.…

  1. Advancing One's Understanding of School Counseling through Publication: The "What" and "How" of Writing an Article

    ERIC Educational Resources Information Center

    Klein, James F.

    2008-01-01

    Writing for publication is a great privilege and one that should be approached deliberately as well as innovatively. As experts in our respective fields, writing for publication is an opportunity to share original thoughts, take positions, and/or report findings as well as simultaneously advance foundational knowledge in our areas. The power and…

  2. 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…

  3. 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…

  4. How Syntactic Reasoners Can Develop Understanding, Evaluate Conjectures, and Generate Counterexamples in Advanced Mathematics

    ERIC Educational Resources Information Center

    Weber, Keith

    2009-01-01

    This paper presents a case study of a highly successful student whose exploration of an advanced mathematical concept relies predominantly on syntactic reasoning, such as developing formal representations of mathematical ideas and making logical deductions. This student is observed as he learns a new mathematical concept and then completes…

  5. 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.…

  6. 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…

  7. Biology of Saccular Cerebral Aneurysms: A Review of Current Understanding and Future Directions

    PubMed Central

    Fennell, Vernard S.; Kalani, M. Yashar S.; Atwal, Gursant; Martirosyan, Nikolay L.; Spetzler, Robert F.

    2016-01-01

    Understanding the biology of intracranial aneurysms is a clinical quandary. How these aneurysms form, progress, and rupture is poorly understood. Evidence indicates that well-established risk factors play a critical role, along with immunologic factors, in their development and clinical outcomes. Much of the expanding knowledge of the inception, progression, and rupture of intracranial aneurysms implicates inflammation as a critical mediator of aneurysm pathogenesis. Thus, therapeutic targets exploiting this arm of aneurysm pathogenesis have been implemented, often with promising outcomes. PMID:27504449

  8. Current understanding of the physics of type III solar radio bursts

    NASA Technical Reports Server (NTRS)

    Papadopoulos, K.

    1980-01-01

    One of the most exciting plasma physics investigations of recent years has been connected with the understanding of a new strong turbulent plasma state excited by propagating electron beams. This new state is initiated on the linear level by parametric instabilities (OTS, modulational, etc.) and results in a very dynamic state composed of collective clusters of modes called solitons, cavitons, spikons, etc. Introduction of these concepts into the classic beam-plasma interaction problem has rendered quasi-linear and weak turbulence theories inapplicable over most of the interesting parameter range, and helped explain many paradoxes connected with the propagation of beams in the laboratory and space. Following a brief review of these nonlinear notions, the means by which their application to type III solar radiobursts has revolutionized understanding of their propagation, radioemission and scaling properties and has guided the in situ observations towards a more complete understanding are demonstrated. A particular burst (May 16, 1971) is analyzed in detail and compared with numerical predictions.

  9. The Effects of Analogy on Students' Understanding of Direct Current Circuits and Attitudes towards Physics Lessons

    ERIC Educational Resources Information Center

    Ugur, Gokhan; Dilber, Refik; Senpolat, Yasemin; Duzgun, Bahattin

    2012-01-01

    This study investigated the effects of analogy on the elimination of students' misconceptions about direct current circuits, students' achievement and the attitudes towards physics lessons. The sample of this study consisted of 51 11th grade students from two different classes. While one of the classes was the experimental group where analogy was…

  10. 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…

  11. 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…

  12. [Current understanding of signaling transduction pathway and biological functions of Karrikins].

    PubMed

    Luo, Xiaofeng; Qi, Ying; Meng, Yongjie; Shuai, Haiwei; Chen, Feng; Yang, Wenyu; Shu, Kai

    2016-01-01

    Karrikins are a class of signaling molecules discovered in wildfire smoke, which can significantly promote seed germination in some species (such as Arabidopsis and Avena fatua). The structures of Karrikins were first elucidated in 2004. At present, six different types of Karrikins have been documented, and their biological activities vary significantly. So far, studies for Karrikins have become a hot spot in the plant molecular biology field. Recent advances demonstrate that Karrikins regulate plant photomorphogenesis and leaf differentiation effectively, in addition to the effect on seed germination. Furthermore, Karrikins share highly similar molecular structures and signaling transduction pathways with strigolactone. In this review, we summarize the history of discovery, signaling transduction pathways, physiological functions and ecological significance of Karrikins, and further discuss the future research directions. PMID:26787523

  13. Impacts of Particulate Air Pollution on Asthma: Current Understanding and Future Perspectives.

    PubMed

    Takizawa, Hajime

    2015-01-01

    The impacts of air pollution on human health and disease have been attracting attention, especially in industrialized countries and areas with heavy traffic burdens. Fine particulate matters (PMs) are considered as an important air pollutant, since it was reported that there was a significant relationship between PM2.5 levels and mortality by cohort studies in 1990s. Epidemiological and toxicological studies have strongly suggested a causative relationship between fine particulate air pollution and increased incidence as well as exacerbations of asthma, and other respiratory disorders. Recent advances in research have elucidated that PMs primarily and secondarily induce oxidative stresses which result both in pro- and antiinflammatory activities. It has been demonstrated that gene polymorphisms of antioxidant enzymes might change responses to particulate air pollution exposures. To prevent health hazardous effects of particles, it is crucial to screen susceptible subpopulations and establish chemoprevention strategies in the world. Novel techniques and modalities are patented for future progress on better control of air pollution.

  14. 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

  15. 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.

  16. Current practices and reform proposals for the regulation of advanced medicinal products in Canada.

    PubMed

    Viswanathan, Sowmya; Bubela, Tania

    2015-01-01

    We describe the Canadian regulatory framework for evaluating advanced medicinal products based on current policies, guidance documents and regulations and analyze proposed reforms. Our analysis is based on a documentary review supplemented by discussions with Health Canada officials. We present an overview of the Canadian regulatory framework for cell and gene therapy, medical devices and manufacturing facilities. We use the approval of Prochymal™ to highlight Canada's conditional marketing approval system. Finally, we discuss proposed changes to the regulatory framework in response to identified gaps, stakeholder consultations and international harmonization initiatives. Based on our analyses, we suggest that Canadian regulators have taken a reasonable approach in applying their regulatory framework without compromising on product safety. PMID:26237706

  17. Current Animal Models of Postoperative Spine Infection and Potential Future Advances

    PubMed Central

    Stavrakis, A. I.; Loftin, A. H.; Lord, E. L.; Hu, Y.; Manegold, J. E.; Dworsky, E. M.; Scaduto, A. A.; Bernthal, N. M.

    2015-01-01

    Implant related infection following spine surgery is a devastating complication for patients and can potentially lead to significant neurological compromise, disability, morbidity, and even mortality. This paper provides an overview of the existing animal models of postoperative spine infection and highlights the strengths and weaknesses of each model. In addition, there is discussion regarding potential modifications to these animal models to better evaluate preventative and treatment strategies for this challenging complication. Current models are effective in simulating surgical procedures but fail to evaluate infection longitudinally using multiple techniques. Potential future modifications to these models include using advanced imaging technologies to evaluate infection, use of bioluminescent bacterial species, and testing of novel treatment strategies against multiple bacterial strains. There is potential to establish a postoperative spine infection model using smaller animals, such as mice, as these would be a more cost-effective screening tool for potential therapeutic interventions. PMID:26131448

  18. Non-small cell lung cancer: current treatment and future advances.

    PubMed

    Zappa, Cecilia; Mousa, Shaker A

    2016-06-01

    Lung cancer has a poor prognosis; over half of people diagnosed with lung cancer die within one year of diagnosis and the 5-year survival is less than 18%. Non-small cell lung cancer (NSCLC) accounts for the majority of all lung cancer cases. Risk factors for developing NSCLC have been identified, with cigarette smoking being a major factor along with other environmental and genetic risk factors. Depending on the staging of lung cancer, patients are eligible for certain treatments ranging from surgery to radiation to chemotherapy as well as targeted therapy. With the advancement of genetics and biomarkers testing, specific mutations have been identified to better target treatment for individual patients. This review discusses current treatments including surgery, chemotherapy, radiotherapy, and immunotherapy as well as how biomarker testing has helped improve survival in patients with NSCLC. PMID:27413711

  19. Non-small cell lung cancer: current treatment and future advances

    PubMed Central

    Zappa, Cecilia

    2016-01-01

    Lung cancer has a poor prognosis; over half of people diagnosed with lung cancer die within one year of diagnosis and the 5-year survival is less than 18%. Non-small cell lung cancer (NSCLC) accounts for the majority of all lung cancer cases. Risk factors for developing NSCLC have been identified, with cigarette smoking being a major factor along with other environmental and genetic risk factors. Depending on the staging of lung cancer, patients are eligible for certain treatments ranging from surgery to radiation to chemotherapy as well as targeted therapy. With the advancement of genetics and biomarkers testing, specific mutations have been identified to better target treatment for individual patients. This review discusses current treatments including surgery, chemotherapy, radiotherapy, and immunotherapy as well as how biomarker testing has helped improve survival in patients with NSCLC. PMID:27413711

  20. Current practices and reform proposals for the regulation of advanced medicinal products in Canada.

    PubMed

    Viswanathan, Sowmya; Bubela, Tania

    2015-01-01

    We describe the Canadian regulatory framework for evaluating advanced medicinal products based on current policies, guidance documents and regulations and analyze proposed reforms. Our analysis is based on a documentary review supplemented by discussions with Health Canada officials. We present an overview of the Canadian regulatory framework for cell and gene therapy, medical devices and manufacturing facilities. We use the approval of Prochymal™ to highlight Canada's conditional marketing approval system. Finally, we discuss proposed changes to the regulatory framework in response to identified gaps, stakeholder consultations and international harmonization initiatives. Based on our analyses, we suggest that Canadian regulators have taken a reasonable approach in applying their regulatory framework without compromising on product safety.

  1. 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

  2. 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).

  3. 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. PMID:23799244

  4. 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

  5. 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.

  6. Understanding the transition between memory and threshold switching due to the compliance current

    NASA Astrophysics Data System (ADS)

    Chang, Seo Hyoung; Lee, Jae Sung

    2016-06-01

    The switching-type transition induced by external parameters, e.g., the thermal conductance and the temperature, has been intensively investigated by using the thermal random circuit breaker (RCB) network model. Recently, some researchers argued that the thermal RCB network model was not able to predict the switching-type transition induced by a new parameter, i.e., the compliance current. However, we demonstrate that the compliance current-induced transition can be explained by using the thermal RCB network model. This work clearly demonstrates that the basic mechanism of unipolar resistance switching is closely related to the formation and the rupture of conducting filaments due to the bias voltage and thermal effects.

  7. Current Understanding on Aflatoxin Biosynthesis and Future Perspective in Reducing Aflatoxin Contamination

    PubMed Central

    Yu, Jiujiang

    2012-01-01

    Traditional molecular techniques have been used in research in discovering the genes and enzymes that are involved in aflatoxin formation and genetic regulation. We cloned most, if not all, of the aflatoxin pathway genes. A consensus gene cluster for aflatoxin biosynthesis was discovered in 2005. The factors that affect aflatoxin formation have been studied. In this report, the author summarized the current status of research progress and future possibilities that may be used for solving aflatoxin contamination. PMID:23202305

  8. Endocrine-like Signaling in Cnidarians: Current Understanding and Implications for Ecophysiology.

    PubMed

    Tarrant, Ann M

    2005-01-01

    The vertebrate endocrine system is well-characterized, with many reports of disruption by environmental chemicals. In contrast, cnidarians are less compartmentalized, physiological regulation is poorly understood, and the potential for disruption is unknown. Endocrine-like activity has not been systematically studied in cnidarians, but several classical vertebrate hormones (e.g., steroids, iodinated organic compounds, neuropeptides, and indoleamines) have been identified in cnidarian tissues. Investigators have made progress in identifying putative bioregulatory molecules in cnidarians, and testing the effects of these individual compounds. Less progress has been made in elucidating signaling pathways. For example, putative gonadotropin-releasing hormone and sex steroids have been identified in cnidarian tissues, but it is unknown whether these compounds are components of a larger signal cascade comparable to the vertebrate hypothalamic-pituitary-gonadal axis. Further, while sex steroids and iodinated organic compounds may help to regulate cnidarian physiology, the mechanisms of action are unknown. Homologs to the vertebrate steroid and thyroid receptors have not been identified in cnidarians, so more research is needed to understand the mechanisms of endocrine-like signaling in cnidarians. Elucidation of cnidarian regulatory pathways will provide insight into evolution of hormonal signaling. These studies will also improve understanding of how cnidarians respond to environmental cues and will provide a basis to investigate disruption of physiological processes by physical and chemical stressors.

  9. 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. PMID:27331654

  10. 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.

  11. 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. PMID:18269510

  12. 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

  13. Regenerative medicine and hair loss: how hair follicle culture has advanced our understanding of treatment options for androgenetic alopecia.

    PubMed

    Higgins, Claire A; Christiano, Angela M

    2014-01-01

    Many of the current drug therapies for androgenetic alopecia were discovered serendipitously, with hair growth observed as an off-target effect when drugs were used to treat a different disorder. Subsequently, several studies using cultured cells have enabled identification of hair growth modulators with similar properties to the currently available drugs, which may also provide clinical benefit. In situations where the current therapeutics do not work, follicular unit transplantation is an alternative surgical option. More recently, the concept of follicular cell implantation, or hair follicle neogenesis, has been attempted, exploiting the inherent properties of cultured hair follicle cells to induce de novo hair growth in balding scalp. In this review, we discuss both the advances in cell culture techniques that have led to a wider range of potential therapeutics to promote hair growth, in addition to detailing current knowledge on follicular cell implantation, and the challenges in making this approach a reality.

  14. 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.

  15. Endocrine and Bone Complications in β-Thalassemia Intermedia: Current Understanding and Treatment

    PubMed Central

    Noureldine, MohammadHassan A.; Abbas, Hussein A.

    2015-01-01

    Thalassemia intermedia (TI), also known as nontransfusion dependent thalassemia (NTDT), is a type of thalassemia where affected patients do not require lifelong regular transfusions for survival but may require occasional or even frequent transfusions in certain clinical settings and for defined periods of time. NTDT encompasses three distinct clinical forms: β-thalassemia intermedia (β-TI), Hb E/β-thalassemia, and α-thalassemia intermedia (Hb H disease). Over the past decade, our understanding of the molecular features, pathophysiology, and complications of NTDT particularly β-TI has increased tremendously but data on optimal treatment of disease and its various complications are still lacking. In this paper, we shall review a group of commonly encountered complications in β-TI, mainly endocrine and bone complications. PMID:25834825

  16. 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

  17. 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.

  18. Current Advance and Future Prospects of Tissue Engineering Approach to Dentin/Pulp Regenerative Therapy.

    PubMed

    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

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. Genetic basis of pulmonary arterial hypertension: current understanding and future directions.

    PubMed

    Newman, John H; Trembath, Richard C; Morse, Jane A; Grunig, Ekkehard; Loyd, James E; Adnot, Serge; Coccolo, Fabio; Ventura, Carlo; Phillips, John A; Knowles, James A; Janssen, Bart; Eickelberg, Oliver; Eddahibi, Saadia; Herve, Phillipe; Nichols, William C; Elliott, Gregory

    2004-06-16

    Mutations in two receptors of the transforming growth factor-beta family have recently been shown to be present in the majority of cases of inherited (familial) pulmonary arterial hypertension (PAH). Study of the biology of these receptors, bone morphogenetic protein receptor type-2 (BMPR2), and activin-like kinase type-1 (ALK-1) will certainly reveal pathogenic mechanisms of disease. Exonic mutations in BMPR2 are found in about 50% of patients with familial PAH, and ALK1 mutations are found in a minority of patients with hereditary hemorrhagic telangiectasia and co-existent PAH. Because familial PAH is highly linked to chromosome 2q33, it is likely that the remaining 50% of family cases without exonic mutations have either intronic BMPR2 abnormalities or alterations in the promoter or regulatory genes. Also, only about 10% of patients with "sporadic" idiopathic PAH have identifiable BMPR2 mutations. Mutations in BMPR2 confer a 15% to 20% chance of developing PAH in a carrier's lifetime. Thus, there must be gene-gene or gene-environment interactions that either enhance or prevent the development of the vascular disease in persons carrying a mutation, and there must be other patterns of susceptibility based on genetic makeup. To elucidate the genetic basis of PAH further, investigations are needed, including genome scanning for major and minor genes, analysis of genetic profiles of patients for candidate genes likely to modify risk for disease (e.g., serotonin transporter alleles, nitric oxide-synthases), proteomics, transgenic mice, and altered signal transduction. Advances in genetic testing, presymptomatic screening, and biomarkers should permit early detection of disease in those at risk of PAH and allow trials of preventive therapy in carriers.

  4. 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…

  5. Bridging Identities and Disciplines: Advances and Challenges in Understanding Multiple Identities

    ERIC Educational Resources Information Center

    Phinney, Jean S.

    2008-01-01

    The chapters in this volume address the need for a better understanding of the development of intersecting identities over age and context. The chapters provide valuable insights into the development of identities, particularly group identities. They highlight common processes across identities, such as the role of contrast and comparison and the…

  6. Geology, geochemistry, and geophysics of the Moon: Status of current understanding

    NASA Astrophysics Data System (ADS)

    Jaumann, R.; Hiesinger, H.; Anand, M.; Crawford, I. A.; Wagner, R.; Sohl, F.; Jolliff, B. L.; Scholten, F.; Knapmeyer, M.; Hoffmann, H.; Hussmann, H.; Grott, M.; Hempel, S.; Köhler, U.; Krohn, K.; Schmitz, N.; Carpenter, J.; Wieczorek, M.; Spohn, T.; Robinson, M. S.; Oberst, J.

    2012-12-01

    The Moon is key to understanding both Earth and our Solar System in terms of planetary processes and has been a witness of the Solar System history for more than 4.5 Ga. Building on earlier telescopic observations, our knowledge about the Moon was transformed by the wealth of information provided by Apollo and other space missions. These demonstrated the value of the Moon for understanding the fundamental processes that drive planetary formation and evolution. The Moon was understood as an inert body with its geology mainly restricted to impact and volcanism with associated tectonics, and a relative simple composition. Unlike Earth, an absence of plate tectonics has preserved a well-defined accretion and geological evolution record. However recent missions to the Moon show that this traditional view of the lunar surface is certainly an over simplification. For example, although it has long been suspected that ice might be preserved in cold traps at the lunar poles, recent results also indicate the formation and retention of OH- and H2O outside of polar regions. These volatiles are likely to be formed as a result of hydration processes operating at the lunar surface including the production of H2O and OH by solar wind protons interacting with oxygen-rich rock surfaces produced during micrometeorite impact on lunar soil particles. Moreover, on the basis of Lunar Prospector gamma-ray data, the lunar crust and underlying mantle has been found to be divided into distinct terranes that possess unique geochemical, geophysical, and geological characteristics. The concentration of heat producing elements on the nearside hemisphere of the Moon in the Procellarum KREEP Terrane has apparently led to the nearside being more volcanically active than the farside. Recent dating of basalts has shown that lunar volcanism was active for almost 3 Ga, starting at about 3.9-4.0 Ga and ceasing at ˜1.2 Ga. A recent re-processing of the seismic data supports the presence of a partially

  7. 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

  8. 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.

  9. Understanding Glycomechanics using Mathematical Modeling: A review of current approaches to simulate cellular glycosylation reaction networks

    PubMed Central

    Puri, Apurv; Neelamegham, Sriram

    2011-01-01

    Following the footsteps of genomics and proteomics, recent years have witnessed the growth of large-scale experimental methods in the field of glycomics. In parallel, there has also been growing interest in developing Systems Biology based methods to study the glycome. The combined goals of these endeavors is to identify glycosylation dependent mechanisms regulating human physiology, check-points that can control the progression of pathophysiology, and modifications to reaction pathways that can result in more uniform biopharmaceutical processes. In these efforts, mathematical models of N- and O-linked glycosylation have emerged as paradigms for the field. While these are relatively few in number, nevertheless, the existing models provide a basic framework that can be used to develop more sophisticated analysis strategies for glycosylation in the future. The current review surveys these computational models with focus on the underlying mathematics and assumptions, and with respect to their ability to generate experimentally testable hypotheses. PMID:22090146

  10. 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.

  11. 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.

  12. The gut microbiota and metabolic disease: current understanding and future perspectives.

    PubMed

    Arora, T; Bäckhed, F

    2016-10-01

    The human gut microbiota has been studied for more than a century. However, of nonculture-based techniques exploiting next-generation sequencing for analysing the microbiota, development has renewed research within the field during the past decade. The observation that the gut microbiota, as an environmental factor, contributes to adiposity has further increased interest in the field. The human microbiota is affected by the diet, and macronutrients serve as substrates for many microbially produced metabolites, such as short-chain fatty acids and bile acids, that may modulate host metabolism. Obesity predisposes towards type 2 diabetes and cardiovascular disease. Recently, it has been established that levels of butyrate-producing bacteria are reduced in patients with type 2 diabetes, whereas levels of Lactobacillus sp. are increased. Recent data suggest that the reduced levels of butyrate-producing bacteria might be causally linked to type 2 diabetes. Bariatric surgery, which promotes long-term weight loss and diabetes remission, alters the gut microbiota in both mice and humans. Furthermore, by transferring the microbiota from postbariatric surgery patients to mice, it has been demonstrated that an altered microbiota may contribute to the improved metabolic phenotype following this intervention. Thus, greater understanding of alterations of the gut microbiota, in combination with dietary patterns, may provide insights into how the gut microbiota contributes to disease progression and whether it can be exploited as a novel diagnostic, prognostic and therapeutic target. PMID:27071815

  13. 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

  14. Two-phase unsaturated flow at Yucca Mountain, Nevada: A report on current understanding

    NASA Astrophysics Data System (ADS)

    Pruess, Karsten

    Thick unsaturated zones in semi-arid regions have some unique attributes that are favorable for long-term isolation of hazardous wastes. The disposal concept at Yucca Mountain takes advantage of low ambient water fluxes. Evaluation of site suitability must be based on an understanding of two-phase (liquid-gas) fluid flow and heat transfer processes in a heterogeneous, fractured rock mass. A large body of relevant knowledge has been accumulated in various fields, including petroleum and geothermal reservoir engineering, chemical engineering, civil engineering, and soil science. Complications at Yucca Mountain arise from the partly episodic and localized nature of water seepage in fracture networks. This limits the applicability of spatial and temporal averaging, and poses great challenges for numerical modeling. Significant flow and heat transfer effects may occur in the gas phase. Observations of natural and man-made chemical tracers as well as controlled field experiments have provided much useful information on mass transport at Yucca Mountain, including the occurrence of fast preferential flow. It is now clear that fracture-matrix interactions are considerably weaker than would be expected from a concept of water flowing in fractures as areally extensive sheets. The Yucca Mountain system is expected to be quite robust in coping with larger seepage rates, as may occur under future more pluvial climatic conditions.

  15. 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. PMID:23129709

  16. The gut microbiota and metabolic disease: current understanding and future perspectives.

    PubMed

    Arora, T; Bäckhed, F

    2016-10-01

    The human gut microbiota has been studied for more than a century. However, of nonculture-based techniques exploiting next-generation sequencing for analysing the microbiota, development has renewed research within the field during the past decade. The observation that the gut microbiota, as an environmental factor, contributes to adiposity has further increased interest in the field. The human microbiota is affected by the diet, and macronutrients serve as substrates for many microbially produced metabolites, such as short-chain fatty acids and bile acids, that may modulate host metabolism. Obesity predisposes towards type 2 diabetes and cardiovascular disease. Recently, it has been established that levels of butyrate-producing bacteria are reduced in patients with type 2 diabetes, whereas levels of Lactobacillus sp. are increased. Recent data suggest that the reduced levels of butyrate-producing bacteria might be causally linked to type 2 diabetes. Bariatric surgery, which promotes long-term weight loss and diabetes remission, alters the gut microbiota in both mice and humans. Furthermore, by transferring the microbiota from postbariatric surgery patients to mice, it has been demonstrated that an altered microbiota may contribute to the improved metabolic phenotype following this intervention. Thus, greater understanding of alterations of the gut microbiota, in combination with dietary patterns, may provide insights into how the gut microbiota contributes to disease progression and whether it can be exploited as a novel diagnostic, prognostic and therapeutic target.

  17. 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

  18. Current Understanding of the Role of Complement in IgA Nephropathy.

    PubMed

    Maillard, Nicolas; Wyatt, Robert J; Julian, Bruce A; Kiryluk, Krzysztof; Gharavi, Ali; Fremeaux-Bacchi, Veronique; Novak, Jan

    2015-07-01

    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.

  19. 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.

  20. 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…

  1. 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

  2. A Short Review on the Current Understanding of Autism Spectrum Disorders.

    PubMed

    Park, Hye Ran; Lee, Jae Meen; Moon, Hyo Eun; Lee, Dong Soo; Kim, Bung-Nyun; Kim, Jinhyun; Kim, Dong Gyu; Paek, Sun Ha

    2016-02-01

    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

  3. 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.

  4. The potential of hydrodynamic damage to animal cells of industrial relevance: current understanding.

    PubMed

    Hu, Weiwei; Berdugo, Claudia; Chalmers, Jeffrey J

    2011-10-01

    Suspension animal cell culture is now routinely scaled up to bioreactors on the order of 10,000 L, and greater, to meet commercial demand. However, the concern of the 'shear sensitivity' of animal cells still remains, not only within the bioreactor, but also in the downstream processing. As the productivities continue to increase, titer of ~10 g/L are now reported with cell densities greater than 2 × 10(7) cells/mL. Such high, and potentially higher cell densities will inevitably translate to increased demand in mass transfer and mixing. In addition, achieving productivity gains in both the upstream stage and downstream processes can subject the cells to aggressive environments such as those involving hydrodynamic stresses. The perception of 'shear sensitivity' has historically put an arbitrary upper limit on agitation and aeration in bioreactor operation; however, as cell densities and productivities continue to increase, mass transfer requirements can exceed those imposed by these arbitrary low limits. Therefore, a better understanding of how animal cells, used to produce therapeutic products, respond to hydrodynamic forces in both qualitative and quantitative ways will allow an experimentally based, higher, "upper limit" to be created to guide the design and operation of future commercial, large scale bioreactors. With respect to downstream hydrodynamic conditions, situations have already been achieved in which practical limits with respect to hydrodynamic forces have been experienced. This review mainly focuses on publications from both the academy and industry regarding the effect of hydrodynamic forces on industrially relevant animal cells, and not on the actual scale-up of bioreactors. A summary of implications and remaining challenges will also be presented. PMID:21785843

  5. 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

    2016-01-01

    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. PMID:27367653

  6. 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

    2016-01-01

    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.

  7. Acute kidney injury following cardiac surgery: current understanding and future directions.

    PubMed

    O'Neal, Jason B; Shaw, Andrew D; Billings, Frederic T

    2016-07-04

    Acute kidney injury (AKI) complicates recovery from cardiac surgery in up to 30 % of patients, injures and impairs the function of the brain, lungs, and gut, and places patients at a 5-fold increased risk of death during hospitalization. Renal ischemia, reperfusion, inflammation, hemolysis, oxidative stress, cholesterol emboli, and toxins contribute to the development and progression of AKI. Preventive strategies are limited, but current evidence supports maintenance of renal perfusion and intravascular volume while avoiding venous congestion, administration of balanced salt as opposed to high-chloride intravenous fluids, and the avoidance or limitation of cardiopulmonary bypass exposure. AKI that requires renal replacement therapy occurs in 2-5 % of patients following cardiac surgery and is associated with 50 % mortality. For those who recover from renal replacement therapy or even mild AKI, progression to chronic kidney disease in the ensuing months and years is more likely than for those who do not develop AKI. Cardiac surgery continues to be a popular clinical model to evaluate novel therapeutics, off-label use of existing medications, and nonpharmacologic treatments for AKI, since cardiac surgery is fairly common, typically elective, provides a relatively standardized insult, and patients remain hospitalized and monitored following surgery. More efficient and time-sensitive methods to diagnose AKI are imperative to reduce this negative outcome. The discovery and validation of renal damage biomarkers should in time supplant creatinine-based criteria for the clinical diagnosis of AKI.

  8. 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. PMID:25962963

  9. Acute kidney injury following cardiac surgery: current understanding and future directions.

    PubMed

    O'Neal, Jason B; Shaw, Andrew D; Billings, Frederic T

    2016-01-01

    Acute kidney injury (AKI) complicates recovery from cardiac surgery in up to 30 % of patients, injures and impairs the function of the brain, lungs, and gut, and places patients at a 5-fold increased risk of death during hospitalization. Renal ischemia, reperfusion, inflammation, hemolysis, oxidative stress, cholesterol emboli, and toxins contribute to the development and progression of AKI. Preventive strategies are limited, but current evidence supports maintenance of renal perfusion and intravascular volume while avoiding venous congestion, administration of balanced salt as opposed to high-chloride intravenous fluids, and the avoidance or limitation of cardiopulmonary bypass exposure. AKI that requires renal replacement therapy occurs in 2-5 % of patients following cardiac surgery and is associated with 50 % mortality. For those who recover from renal replacement therapy or even mild AKI, progression to chronic kidney disease in the ensuing months and years is more likely than for those who do not develop AKI. Cardiac surgery continues to be a popular clinical model to evaluate novel therapeutics, off-label use of existing medications, and nonpharmacologic treatments for AKI, since cardiac surgery is fairly common, typically elective, provides a relatively standardized insult, and patients remain hospitalized and monitored following surgery. More efficient and time-sensitive methods to diagnose AKI are imperative to reduce this negative outcome. The discovery and validation of renal damage biomarkers should in time supplant creatinine-based criteria for the clinical diagnosis of AKI. PMID:27373799

  10. 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...

  11. Off-axis neutral beam current drive for advanced scenario development in DIII-D

    SciTech Connect

    Murakami, Masanori; Park, Jin Myung; Petty, C C.; Luce, T.C.; Heidbrink, W. W.; Osborne, T.H.; Prater, R.; Wade, M R; Unterberg, E. A.

    2009-01-01

    Modification of the two existing DIII-D neutral beamlines is planned to allow vertical steering to provide off-axis neutral beam current drive (NBCD) peaked as far off-axis as half the plasma minor radius. New calculations for a downward-steered beam indicate strong current drive with good localization off-axis so long as the toroidal magnetic field, B-T, and the plasma current, I-p, point in the same direction. This is due to good alignment of neutral beam injection (NBI) with the local pitch of the magnetic field lines. This model has been tested experimentally on DIII-D by injecting equatorially mounted NBs into reduced size plasmas that are vertically displaced with respect to the vessel midplane. The existence of off-axis NBCD is evident in the changes seen in sawtooth behaviour in the internal inductance. By shifting the plasma upwards or downwards, or by changing the sign of the toroidal field, off-axis NBCD profiles measured with motional Stark effect data and internal loop voltage show a difference in amplitude (40-45%) consistent with differences predicted by the changed NBI alignment with respect to the helicity of the magnetic field lines. The effects of NBI direction relative to field line helicity can be large even in ITER: off-axis NBCD can be increased by more than 30% if the B-T direction is reversed. Modification of the DIII-D NB system will strongly support scenario development for ITER and future tokamaks as well as provide flexible scientific tools for understanding transport, energetic particles and heating and current drive.

  12. Recent advancements in understanding endogenous heart regeneration-insights from adult zebrafish and neonatal mice.

    PubMed

    Rubin, Nicole; Harrison, Michael R; Krainock, Michael; Kim, Richard; Lien, Ching-Ling

    2016-10-01

    Enhancing the endogenous regenerative capacity of the mammalian heart is a promising strategy that can lead to potential treatment of injured cardiac tissues. Studies on heart regeneration in zebrafish and neonatal mice have shown that cardiomyocyte proliferation is essential for replenishing myocardium. We will review recent advancements that have demonstrated the importance of Neuregulin 1/ErbB2 and innervation in regulating cardiomyocyte proliferation using both adult zebrafish and neonatal mouse heart regeneration models. Emerging findings suggest that different populations of macrophages and inflammation might contribute to regenerative versus fibrotic responses. Finally, we will discuss variation in the severity of the cardiac injury and size of the wound, which may explain the range of outcomes observed in different injury models.

  13. Advances in the management and understanding of autoimmune lymphoproliferative syndrome (ALPS)

    PubMed Central

    Teachey, David T.; Seif, Alix E.; Grupp, Stephan A.

    2010-01-01

    Summary 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. PMID:19930184

  14. Challenges and Opportunities for Advancing Ionosphere-Thermosphere Understanding through Remote Sensing from Space (Invited)

    NASA Astrophysics Data System (ADS)

    Meier, R. R.

    2013-12-01

    The ionosphere and thermosphere (IT) system was among the first fields explored at the beginning of the space age. Much progress in understanding the system has been made over the ensuing decades, so much so that the vernacular has evolved from 'IT Exploration' to 'Space Weather'. This evolution is largely a consequence of the recognition that space weather can seriously compromise a host of technological systems in space and on the ground. Societal demands for forecasting space weather place extraordinary requirements on both observational capabilities and detailed understanding. Important challenges remain to be addressed in order to approach a level of capability similar to that of tropospheric weather. These include understanding of the IT response to forcing from solar radiation and solar wind, to forcing from lower altitude processes, understanding of the internal processes that constitute the responses, and identification of the causes of long-term climate change. A systematic approach for meeting many of the challenges has been laid out in the Solar and Space Physics 2012 Decadal Survey. Several space missions have been recommended for implementation in the latter part of the decade. However, near term opportunities to lay the foundation for these missions come with the selection by NASA of ICON and GOLD. Their operational periods are expected to overlap with each other as well as with complementary missions from other agencies, such as SSULI, SSUSI, and COSMIC. Remote sensing instrumentation on these missions fulfills a uniquely important role. From low earth orbit, limb imagers deliver altitude profiles of composition, temperature and winds on local and regional scales. Earth disk imagers from a high altitude perspective not only provide context for local observations, but also column measurements of the O/N2 ratio and temperature. The O/N2 ratio has proven to be an exceptionally useful diagnostic of IT dynamics, especially when paired with independent

  15. 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

  16. Current advances in tissue repair and regeneration: the future is bright.

    PubMed

    Ninov, Nikolay; Yun, Maximina H

    2015-04-01

    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

  17. Current status and recent advances of liver transplantation from donation after cardiac death

    PubMed Central

    Perera, M Thamara PR; Bramhall, Simon R

    2011-01-01

    The last decade saw increased organ donation activity from donors after cardiac death (DCD). This contributed to a significant proportion of transplant activity. Despite certain drawbacks, liver transplantation from DCD donors continues to supplement the donor pool on the backdrop of a severe organ shortage. Understanding the pathophysiology has provided the basis for modulation of DCD organs that has been proven to be effective outside liver transplantation but remains experimental in liver transplantation models. Research continues on how best to further increase the utility of DCD grafts. Most of the work has been carried out exploring the use of organ preservation using machine assisted perfusion. Both ex-situ and in-situ organ perfusion systems are tested in the liver transplantation setting with promising results. Additional techniques involved pharmacological manipulation of the donor, graft and the recipient. Ethical barriers and end-of-life care pathways are obstacles to widespread clinical application of some of the recent advances to practice. It is likely that some of the DCD offers are in fact probably “prematurely” offered without ideal donor management or even prior to brain death being established. The absolute benefits of DCD exist only if this form of donation supplements the existing deceased donor pool; hence, it is worthwhile revisiting organ donation process enabling us to identify counter remedial measures. PMID:22180833

  18. 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

  19. 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

  20. Air pollution toxicology--a brief review of the role of the science in shaping the current understanding of air pollution health risks.

    PubMed

    Stanek, Lindsay Wichers; Brown, James S; Stanek, John; Gift, Jeff; Costa, Daniel L

    2011-03-01

    Human and animal toxicology has had a profound impact on our historical and current understanding of air pollution health effects. Early animal toxicological studies of air pollution had distinctively military or workplace themes. With the discovery that ambient air pollution episodes led to excess illness and death, there became an emergence of toxicological studies that focused on industrial air pollution encountered by the general public. Not only did the pollutants investigated evolve from ambient mixtures to individual pollutants but also the endpoints and outcomes evaluated became more sophisticated, resulting in our present state of the science. Currently, a large toxicological database exists for the effects of particulate matter and ozone, and we provide a focused review of some of the major contributions to the biological understanding for these two "criteria" air pollutants. A limited discussion of the toxicological advancements in the scientific knowledge of two hazardous air pollutants, formaldehyde and phosgene, is also included. Moving forward, the future challenge of air pollution toxicology lies in the health assessment of complex mixtures and their interactions, given the projected impacts of climate change and altered emissions on ambient conditions. In the coming years, the toxicologist will need to be flexible and forward thinking in order to dissect the complexity of the biological system itself, as well as that of air pollution in all its varied forms.

  1. Progress toward advanced understanding of metabotropic glutamate receptors: structure, signaling and therapeutic indications

    PubMed Central

    Yin, Shen; Niswender, Colleen M.

    2014-01-01

    The metabotropic glutamate (mGlu) receptors are a group of Class C Seven Transmembrane Spanning/G Protein Coupled Receptors (7TMRs/GPCRs). These receptors are activated by glutamate, one of the standard amino acids and the major excitatory neurotransmitter. By activating G protein-dependent and non G protein-dependent signaling pathways, mGlus modulate glutamatergic transmission in both the periphery and throughout the central nervous system. Since the discovery of the first mGlu receptor, especially the last decade, a great deal of progress has been made in understanding the signaling, structure, pharmacological manipulation and therapeutic indications of the 8 mGlu members. PMID:24793301

  2. 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.

  3. Recent advances in understanding the molecular basis of group B Streptococcus virulence

    PubMed Central

    Maisey, Heather C.; Doran, Kelly S.; Nizet, Victor

    2009-01-01

    Group B Streptococcus commonly colonises healthy adults without symptoms, yet under certain circumstances displays the ability to invade host tissues, evade immune detection and cause serious invasive disease. Consequently, Group B Streptococcus remains a leading cause of neonatal pneumonia, sepsis and meningitis. Here we review recent information on the bacterial factors and mechanisms that direct host–pathogen interactions involved in the pathogenesis of Group B Streptococcus infection. New research on host signalling and inflammatory responses to Group B Streptococcus infection is summarised. An understanding of the complex interplay between Group B Streptococcus and host provides valuable insight into pathogen evolution and highlights molecular targets for therapeutic intervention. PMID:18803886

  4. 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. PMID:27423803

  5. Innate and adaptive immunity in the development of depression: An update on current knowledge and technological advances.

    PubMed

    Haapakoski, Rita; Ebmeier, Klaus P; Alenius, Harri; Kivimäki, Mika

    2016-04-01

    The inflammation theory of depression, proposed over 20years ago, was influenced by early studies on T cell responses and since then has been a stimulus for numerous research projects aimed at understanding the relationship between immune function and depression. Observational studies have shown that indicators of immunity, especially C reactive protein and proinflammatory cytokines, such as interleukin 6, are associated with an increased risk of depressive disorders, although the evidence from randomized trials remains limited and only few studies have assessed the interplay between innate and adaptive immunity in depression. In this paper, we review current knowledge on the interactions between central and peripheral innate and adaptive immune molecules and the potential role of immune-related activation of microglia, inflammasomes and indoleamine-2,3-dioxygenase in the development of depressive symptoms. We highlight how combining basic immune methods with more advanced 'omics' technologies would help us to make progress in unravelling the complex associations between altered immune function and depressive disorders, in the identification of depression-specific biomarkers and in developing immunotherapeutic treatment strategies that take individual variability into account.

  6. Innate and adaptive immunity in the development of depression: An update on current knowledge and technological advances

    PubMed Central

    Haapakoski, Rita; Ebmeier, Klaus P.; Alenius, Harri; Kivimäki, Mika

    2016-01-01

    The inflammation theory of depression, proposed over 20 years ago, was influenced by early studies on T cell responses and since then has been a stimulus for numerous research projects aimed at understanding the relationship between immune function and depression. Observational studies have shown that indicators of immunity, especially C reactive protein and proinflammatory cytokines, such as interleukin 6, are associated with an increased risk of depressive disorders, although the evidence from randomized trials remains limited and only few studies have assessed the interplay between innate and adaptive immunity in depression. In this paper, we review current knowledge on the interactions between central and peripheral innate and adaptive immune molecules and the potential role of immune-related activation of microglia, inflammasomes and indoleamine-2,3-dioxygenase in the development of depressive symptoms. We highlight how combining basic immune methods with more advanced ‘omics’ technologies would help us to make progress in unravelling the complex associations between altered immune function and depressive disorders, in the identification of depression-specific biomarkers and in developing immunotherapeutic treatment strategies that take individual variability into account. PMID:26631274

  7. 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

  8. 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. PMID:27170809

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. BK Virus in Kidney Transplant: Current Concepts, Recent Advances, and Future Directions.

    PubMed

    Sharma, Rajeev; Tzetzo, Stephanie; Patel, Sunil; Zachariah, Mareena; Sharma, Sonakshi; Melendy, Thomas

    2016-08-01

    BK virus nephropathy is a challenging clinical problem in kidney transplant recipients with wide range of surveillance and management practices, based on individual experience. BK virus reactivation in kidney transplant recipients can result in BK virus nephropathy and graft loss. The most effective strategy for early diagnosis and treatment of BK virus nephropathy is regular monitoring for BK virus, currently achieved by quantification of viral DNA in blood by quantitative polymerase chain reaction. Immunosuppression reduction remains the mainstay of treatment; however, viral clearance is often followed by acute rejection, likely secondary to a delay between immune reconstitution and viral clearance. Impaired cell-mediated immune response to BK virus has been shown to correlate with progression to BK virus nephropathy, while reconstitution of this response correlates with resolution of nephropathy. There is recent research to support monitoring BK virus-specific cell-mediated immune response as a predictor of disease progression and resolution. In this article, we review the current concepts and recent developments in understanding BK virus-associated disease in the context of kidney transplant and outline areas for future research.

  15. Dengue: recent advances in biology and current status of translational research.

    PubMed

    Swaminathan, Sathyamangalam; Khanna, Navin

    2009-03-01

    Dengue is a very rapidly growing public health problem being currently faced by approximately 40% of the global population living in more than a hundred tropical and sub-tropical countries. It is a viral disease, caused by four types of dengue viruses, transmitted by mosquitoes, to an estimated 50 million people each year. Vector control methods to contain transmission have not been successful and there is currently no useful diagnostic test, drug or vaccine to combat dengue disease. However, as a result of the heightened awareness of its magnitude and its potential to spread beyond the tropical world, dengue has begun to emerge out of the list of neglected diseases in recent years. New interest in this disease has drawn scientists from multiple disciplines into the dengue arena. This has resulted in novel insights into several aspects of dengue virus biology and identified potential drug targets. Several tetravalent vaccines are being developed. Newer animal models that mirror some of the salient features of dengue disease are becoming available to investigate the mechanism of pathogenesis and to aid in drug and vaccine discovery efforts. The realization that therapeutic and prophylactic intervention can be cost-effective has resulted in vigorous industry-driven translational initiatives to develop drugs and vaccines. Dengue research is at a critical juncture and the implementation of existing knowledge supplemented by a better understanding of pathogenesis promises to make a tangible impact in the combat against dengue in the coming years. PMID:19275624

  16. Spermatogonial stem cells: Current biotechnological advances in reproduction and regenerative medicine.

    PubMed

    Aponte, Pedro Manuel

    2015-05-26

    Spermatogonial stem cells (SSCs) are the germ stem cells of the seminiferous epithelium in the testis. Through the process of spermatogenesis, they produce sperm while concomitantly keeping their cellular pool constant through self-renewal. SSC biology offers important applications for animal reproduction and overcoming human disease through regenerative therapies. To this end, several techniques involving SSCs have been developed and will be covered in this article. SSCs convey genetic information to the next generation, a property that can be exploited for gene targeting. Additionally, SSCs can be induced to become embryonic stem cell-like pluripotent cells in vitro. Updates on SSC transplantation techniques with related applications, such as fertility restoration and preservation of endangered species, are also covered on this article. SSC suspensions can be transplanted to the testis of an animal and this has given the basis for SSC functional assays. This procedure has proven technically demanding in large animals and men. In parallel, testis tissue xenografting, another transplantation technique, was developed and resulted in sperm production in testis explants grafted into ectopical locations in foreign species. Since SSC culture holds a pivotal role in SSC biotechnologies, current advances are overviewed. Finally, spermatogenesis in vitro, already demonstrated in mice, offers great promises to cope with reproductive issues in the farm animal industry and human clinical applications. PMID:26029339

  17. 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.

  18. Spermatogonial stem cells: Current biotechnological advances in reproduction and regenerative medicine

    PubMed Central

    Aponte, Pedro Manuel

    2015-01-01

    Spermatogonial stem cells (SSCs) are the germ stem cells of the seminiferous epithelium in the testis. Through the process of spermatogenesis, they produce sperm while concomitantly keeping their cellular pool constant through self-renewal. SSC biology offers important applications for animal reproduction and overcoming human disease through regenerative therapies. To this end, several techniques involving SSCs have been developed and will be covered in this article. SSCs convey genetic information to the next generation, a property that can be exploited for gene targeting. Additionally, SSCs can be induced to become embryonic stem cell-like pluripotent cells in vitro. Updates on SSC transplantation techniques with related applications, such as fertility restoration and preservation of endangered species, are also covered on this article. SSC suspensions can be transplanted to the testis of an animal and this has given the basis for SSC functional assays. This procedure has proven technically demanding in large animals and men. In parallel, testis tissue xenografting, another transplantation technique, was developed and resulted in sperm production in testis explants grafted into ectopical locations in foreign species. Since SSC culture holds a pivotal role in SSC biotechnologies, current advances are overviewed. Finally, spermatogenesis in vitro, already demonstrated in mice, offers great promises to cope with reproductive issues in the farm animal industry and human clinical applications. PMID:26029339

  19. 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.

  20. Spermatogonial stem cells: Current biotechnological advances in reproduction and regenerative medicine.

    PubMed

    Aponte, Pedro Manuel

    2015-05-26

    Spermatogonial stem cells (SSCs) are the germ stem cells of the seminiferous epithelium in the testis. Through the process of spermatogenesis, they produce sperm while concomitantly keeping their cellular pool constant through self-renewal. SSC biology offers important applications for animal reproduction and overcoming human disease through regenerative therapies. To this end, several techniques involving SSCs have been developed and will be covered in this article. SSCs convey genetic information to the next generation, a property that can be exploited for gene targeting. Additionally, SSCs can be induced to become embryonic stem cell-like pluripotent cells in vitro. Updates on SSC transplantation techniques with related applications, such as fertility restoration and preservation of endangered species, are also covered on this article. SSC suspensions can be transplanted to the testis of an animal and this has given the basis for SSC functional assays. This procedure has proven technically demanding in large animals and men. In parallel, testis tissue xenografting, another transplantation technique, was developed and resulted in sperm production in testis explants grafted into ectopical locations in foreign species. Since SSC culture holds a pivotal role in SSC biotechnologies, current advances are overviewed. Finally, spermatogenesis in vitro, already demonstrated in mice, offers great promises to cope with reproductive issues in the farm animal industry and human clinical applications.

  1. Advances in enantioselective analysis of chiral brominated flame retardants. Current status, limitations and future perspectives.

    PubMed

    Badea, Silviu-Laurentiu; Niculescu, Violeta Carolina; Ionete, Roxana-Elena; Eljarrat, Ethel

    2016-10-01

    Enantioselective analysis is a powerful tool for the discrimination of biotic and abiotic transformation processes of chiral environmental contaminants because their environmental biodegradation is mostly stereospecific. However, it is challenging when applied to new contaminants since enantioselective analysis methods are currently available only for a limited number of compounds. The enantioselective analysis of chiral novel brominated flame retardants (NBFRs) either using gas chromatography (GC) or liquid chromatography (LC) with various chiral stationary phases (CSP) coupled with various mass spectrometric techniques was extensively discussed. The elution order of hexabromocyclododecane (HBCD) enantiomers in chiral LC was reviewed using the experimental LC data combined also with predictions from a multi-mode Hamiltonian dynamics simulation model based on interaction energies of HBCD enantiomers with β-permethylated cyclodextrin. The further development of analytical methodologies for new chiral BFRs using advanced hyphenated analytical techniques, but also the next generation mass spectrometer analyzers (i.e. GC-Qrbitrap MS-MS, LC-Qrbitrap MS-MS), will contribute to a better characterization of the transformation pathways of chiral BFRs.

  2. Advances in enantioselective analysis of chiral brominated flame retardants. Current status, limitations and future perspectives.

    PubMed

    Badea, Silviu-Laurentiu; Niculescu, Violeta Carolina; Ionete, Roxana-Elena; Eljarrat, Ethel

    2016-10-01

    Enantioselective analysis is a powerful tool for the discrimination of biotic and abiotic transformation processes of chiral environmental contaminants because their environmental biodegradation is mostly stereospecific. However, it is challenging when applied to new contaminants since enantioselective analysis methods are currently available only for a limited number of compounds. The enantioselective analysis of chiral novel brominated flame retardants (NBFRs) either using gas chromatography (GC) or liquid chromatography (LC) with various chiral stationary phases (CSP) coupled with various mass spectrometric techniques was extensively discussed. The elution order of hexabromocyclododecane (HBCD) enantiomers in chiral LC was reviewed using the experimental LC data combined also with predictions from a multi-mode Hamiltonian dynamics simulation model based on interaction energies of HBCD enantiomers with β-permethylated cyclodextrin. The further development of analytical methodologies for new chiral BFRs using advanced hyphenated analytical techniques, but also the next generation mass spectrometer analyzers (i.e. GC-Qrbitrap MS-MS, LC-Qrbitrap MS-MS), will contribute to a better characterization of the transformation pathways of chiral BFRs. PMID:27265736

  3. [How far has our understanding of mechanisms of general anesthesia advanced?: preface and comments].

    PubMed

    Yamada, Yoshitsugu

    2011-05-01

    Although the great advance has been made in clinical anesthesia practice, the fundamental mechanisms of anesthetic action still remain to be an unsolved mystery. The early lipid membrane theory based on Meyer and Overton's law was taken over by the proteo-centric view of mechanism. Studies at the molecular and cellular level have shown that anesthetics act on a wide rage of functional proteins, including ligand-gated ion channels (GABA, glycine, NMDA receptors), two pore domain K channels and other ion channels. The effects on the individual channels, however, differ among various types of anesthetics. Elucidating how anesthetics work on the neuronal pathways is important to find the link between the molecular studies and in vivo action of anesthetics. Anesthesia disrupts the linkages between cortical and thalamic neurons and those among the cortical neurons, as well as depression and activation of the arousal and sleep nuclei, respectively. Functional brain imaging has revealed the global effects of general anesthetics on the human brain. Taken together, the disruption of thalamocortical connectivity and the integrative properties of the cerebral cortex might be an essential common feature of anesthetic action. PMID:21626856

  4. 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.

  5. 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.

  6. 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.

  7. Recent advances in understanding carotenoid-derived signaling molecules in regulating plant growth and development

    PubMed Central

    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. PMID:26442092

  8. 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

  9. 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.

  10. Current understanding of genetics and genetic testing and information needs and preferences of adults with inherited retinal disease.

    PubMed

    McKibbin, Martin; Ahmed, Mushtaq; Allsop, Matthew J; Downey, Louise; Gale, Richard; Grant, Hilary Louise; Potrata, Barbara; Willis, Thomas A; Hewison, Jenny

    2014-09-01

    Advances in sequencing technology and the movement of genetic testing into all areas of medicine will increase opportunities for molecular confirmation of a clinical diagnosis. For health-care professionals without formal genetics training, there is a need to know what patients understand about genetics and genetic testing and their information needs and preferences for the disclosure of genetic testing results. These topics were explored during face-to-face interviews with 50 adults with inherited retinal disease, selected in order to provide a diversity of opinions. Participants had variable understanding of genetics and genetic testing, including basic concepts such as inheritance patterns and the risk to dependents, and many did not understand the term 'genetic counselling'. Most were keen for extra information on the risk to others, the process for genetic testing and how to share the information with other family members. Participants were divided as to whether genetic testing should be offered at the time of the initial diagnosis or later. Many would prefer the results to be given by face-to-face consultation, supplemented by further information in a format accessible to those with visual impairment. Health-care professionals and either leaflets or websites of trusted agencies were the preferred sources of information. Permission should be sought for disclosure of genetic information to other family members. The information needs of many patients with inherited retinal disease appear to be unmet. An understanding of their information needs and preferences is required to help health-care professionals provide optimal services that meet patient expectations. PMID:24398793

  11. ADVANCING THE UNDERSTANDING OF BEHAVIORS ASSOCIATED WITH BACILLE CALMETTE GUÉRIN INFECTION USING MULTIVARIATE ANALYSIS

    PubMed Central

    Rodriguez-Zas, Sandra L.; Nixon, Scott E.; Lawson, Marcus A.; Mccusker, Robert H.; Southey, Bruce R.; O’Connor, Jason C.; Dantzer, Robert; Kelley, Keith W.

    2014-01-01

    Behavioral indicators in the murine Bacille Calmette Guérin (BCG) model of inflammation have been studied individually; however, the variability of the behaviors across BCG levels and the mouse-to-mouse variation within BCG-treatment group are only partially understood. The objectives of this study were: 1) to gain a comprehensive understanding of sickness and depression-like behaviors in a BCG model of inflammation using multivariate approaches, and 2) to explore behavioral differences between BCG-treatment groups and among mice within group. Adult mice were challenged with either 0mg (saline), 5mg or 10mg of BCG (BCG-treatment groups: BCG0, BCG5, or BCG10, respectively) at Day 0 of the experiment. Sickness indicators included body weight changes between Day 0 and Day 2 and between Day 2 and Day 5, and horizontal locomotor activity and vertical activity (rearing) measured at Day 6. Depression-like indicators included duration of immobility in the forced swim test and in the tail suspension test at Day 6 and sucrose consumption in the sucrose preference test at Day 7. The simultaneous consideration of complementary sickness and depression-like indicators enabled a more precise characterization of behavioral changes associated with BCG-treatment and of mouse-to-mouse variation, relative to the analysis of indicators individually. Univariate and multivariate analyses confirmed differences between BCG-treatment groups in weight change early on the trial. Significant differences between BCG-treatment groups in depression-like behaviors were still measurable after Day 5. The potential for multivariate models to account for the correlation between behavioral indicators and to augment the analytical precision relative to univariate models was demonstrated both for sickness and for depression-like indicators. Unsupervised learning approaches revealed the complementary information provided by the sickness and depression-like indicators considered. Supervised learning

  12. 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

  13. 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.

  14. 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. PMID:27321475

  15. 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

  16. The Ease of Language Understanding (ELU) model: theoretical, empirical, and clinical advances

    PubMed Central

    Rönnberg, Jerker; Lunner, Thomas; Zekveld, Adriana; Sörqvist, Patrik; Danielsson, Henrik; Lyxell, Björn; Dahlström, Örjan; Signoret, Carine; Stenfelt, Stefan; Pichora-Fuller, M. Kathleen; Rudner, Mary

    2013-01-01

    Working memory is important for online language processing during conversation. We use it to maintain relevant information, to inhibit or ignore irrelevant information, and to attend to conversation selectively. Working memory helps us to keep track of and actively participate in conversation, including taking turns and following the gist. This paper examines the Ease of Language Understanding model (i.e., the ELU model, Rönnberg, 2003; Rönnberg et al., 2008) in light of new behavioral and neural findings concerning the role of working memory capacity (WMC) in uni-modal and bimodal language processing. The new ELU model is a meaning prediction system that depends on phonological and semantic interactions in rapid implicit and slower explicit processing mechanisms that both depend on WMC albeit in different ways. It is based on findings that address the relationship between WMC and (a) early attention processes in listening to speech, (b) signal processing in hearing aids and its effects on short-term memory, (c) inhibition of speech maskers and its effect on episodic long-term memory, (d) the effects of hearing impairment on episodic and semantic long-term memory, and finally, (e) listening effort. New predictions and clinical implications are outlined. Comparisons with other WMC and speech perception models are made. PMID:23874273

  17. Children are not just little adults: recent advances in understanding of diffuse intrinsic pontine glioma biology.

    PubMed

    Schroeder, Kristin M; Hoeman, Christine M; Becher, Oren J

    2014-01-01

    Diffuse intrinsic pontine glioma (DIPG) is a high-grade glioma that originates in the pons and is seen exclusively in children. Despite numerous efforts to improve treatment, DIPG remains incurable with 90% of children dying within 2 y of diagnosis, making it one of the leading causes of death in children with brain tumors. With the advent of new genomic tools, the genetic landscape of DIPG is slowly being unraveled. The most common genetic alterations include a K27M mutation in H3.3 or H3.1, which are found in up to 78% of DIPGs, whereas p53 mutations are found in up to 77%. Other recently discovered alterations include amplification of components of the receptor tyrosine kinase/Ras/phosphatidylinositol 3-kinase signaling pathway, particularly platelet-derived growth factor receptor A. Recapitulating such alterations, genetically engineered DIPG preclinical models have been developed, and DIPG xenograft models have also been established. Both models have strengths and weaknesses but can help with the prioritization of novel agents for clinical trials for children with DIPG. As we move forward, it is important that we continue to study the complex and unique biology of DIPG and develop improved preclinical models to increase our understanding of DIPG pathogenesis, allowing translation into successful therapies in the not too distant future. PMID:24192697

  18. How Prognostic and Predictive Biomarkers Are Transforming Our Understanding and Management of Advanced Gastric Cancer

    PubMed Central

    Mulder, Karen; Spratlin, Jennifer

    2014-01-01

    Background. Gastric cancer (GC) is the second leading cause of cancer death worldwide. GC is a heterogeneous disease in terms of histology, anatomy, and epidemiology. There is also wide variability in how GC is treated in both the resectable and unresectable settings. Identification of prognostic and predictive biomarkers is critical to help direct and tailor therapy for this deadly disease. Methods. A literature search was done using Medline and MeSH terms for GC and predictive biomarkers and prognostic biomarkers. The search was limited to human subjects and the English language. There was no limit on dates. Published data and unpublished abstracts with clinical relevance were included. Results. Many potential prognostic and predictive biomarkers have been assessed for GC, some of which are becoming practice changing. This review is focused on clinically relevant biomarkers, including EGFR, HER2, various markers of angiogenesis, proto-oncogene MET, and the mammalian target of rapamycin. Conclusion. GC is a deadly and heterogeneous disease for which biomarkers are beginning to change our understanding of prognosis and management. The recognition of predictive biomarkers, such as HER2 and vascular endothelial growth factor, has been an exciting development in the management of GC, validating the use of targeted drugs trastuzumab and ramucirumab. MET is another potential predictive marker that may be targeted in GC with drugs such as rilotumumab, foretinib, and crizotinib. Further identification and validation of prognostic and predictive biomarkers has the potential transform how this deadly disease is managed. PMID:25142842

  19. Understanding Pulsed Plasma Jets with Advanced Simulations, Ground and Space Experiments

    NASA Astrophysics Data System (ADS)

    Gatsonis, Nikolaos

    2004-11-01

    Pulsed plasma jets are found in diverse areas, such as thruster plume/spacecraft interactions, artificial release experiments, space plasma physics, and plasma materials processing. We review recent experimental and computational work and elucidate on physical characteristics and processes relevant to electric propulsion plumes. We present first results of experimental investigations of pulsed plasma thruster (PPT) plumes that led to the development of a new method of operation for triple and quadruple Langmuir probes. This novel current-mode method involves biasing all probe electrodes and requires the measurement of probe currents providing the electron temperature, the electron density and the ratio of ion speed to most probable thermal speed. We review the current-mode probe theory for a single species, two-temperature, collisionless plasma along with formal sensitivity analysis of the new diagnostic. The NASA Glenn Research Center laboratory Teflon® PPT used in the experiments was operating at discharge energies of 5, 20 and 40 Joules, with a pulse duration of 10-15 microseconds, ablating 20-50 micrograms/pulse. We present current-mode triple and quadruple probe measurements obtained at various locations in the plume of the plasma source. Extensive comparisons between double probe and current-mode probe measurements validate the new method. We present next computational modeling of plumes from a NASA Glenn Research Center laboratory micro Pulsed Plasma Thruster. The axisymmetric, hybrid (fluid/particle) methodology that introduced several new modeling and algorithmic approaches. Neutrals are modeled with the Direct Simulation Monte Carlo (DSMC) method and ions with a Hybrid-Particle-in-Cell (hybrid-PIC) collisional method. Electrons are modeled as a massless fluid with a momentum equation. The Non-Time-Counter methodology is used for neutral-neutral, elastic ion-neutral, and charge exchange collisions. Ion-electron collisions are modeled with the use of a

  20. Some advances towards a better understanding of wave propagation in civil engineering multiwires trands

    NASA Astrophysics Data System (ADS)

    Laguerre, L.; Treyssede, F.

    Steel members of civil engineering structures undergo degradations mainly due to corrosion and mechanical fatigue. In this context, non-destructive inspection techniques using mechanical guided waves have potential to monitor these structures. Even if wave propagation is not yet fully understood in these structures, useful results can be derived for inspection methodology by using wave modeling in cylindrical waveguide, embedded or not. However, further improvement can be expected from the development of wave propagation simulation tools for real-life structures. Indeed, several difficulties arise in the understanding of guided ultrasonic waves in such structures, partly due to the helical geometry and the inter-wire coupling effects. Moreover, these structures are pre-stressed and can be free or embedded in solid material. This paper shows some recent research results at LCPC. A first part deals with experimental results on the guided wave propagation in a commonly used steel member, the seven wire strand (i.e one straight single cylindrical wire surrounded by six helical wires). The second part aims at numerically investigating the propagation of elastic waves in free helical waveguides. A numerical method is chosen based on a semi-analytical finite element technique that relies on a specific non-orthogonal curvilinear coordinate system. This system is shown to be translationally invariant along the helix centerline so that a spatial Fourier transform can be explicitly performed along the axis to reduce the problem to two dimensions. The method can thus readily be used for the analysis of helical structures by considering the special case of no curvature. Results for single straight and helical wires are first computed. A dispersion analysis for a seven wire strand with simplified contact conditions is then performed.