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Sample records for advance current understanding

  1. 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.

  2. 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

  3. Advancing current approaches to disease management evaluation: capitalizing on heterogeneity to understand what works and for whom

    PubMed Central

    2013-01-01

    Background Evaluating large-scale disease management interventions implemented in actual health care settings is a complex undertaking for which universally accepted methods do not exist. Fundamental issues, such as a lack of control patients and limited generalizability, hamper the use of the ‘gold-standard’ randomized controlled trial, while methodological shortcomings restrict the value of observational designs. Advancing methods for disease management evaluation in practice is pivotal to learn more about the impact of population-wide approaches. Methods must account for the presence of heterogeneity in effects, which necessitates a more granular assessment of outcomes. Methods This paper introduces multilevel regression methods as valuable techniques to evaluate ‘real-world’ disease management approaches in a manner that produces meaningful findings for everyday practice. In a worked example, these methods are applied to retrospectively gathered routine health care data covering a cohort of 105,056 diabetes patients who receive disease management for type 2 diabetes mellitus in the Netherlands. Multivariable, multilevel regression models are fitted to identify trends in clinical outcomes and correct for differences in characteristics of patients (age, disease duration, health status, diabetes complications, smoking status) and the intervention (measurement frequency and range, length of follow-up). Results After a median one year follow-up, the Dutch disease management approach was associated with small average improvements in systolic blood pressure and low-density lipoprotein, while a slight deterioration occurred in glycated hemoglobin. Differential findings suggest that patients with poorly controlled diabetes tend to benefit most from disease management in terms of improved clinical measures. Additionally, a greater measurement frequency was associated with better outcomes, while longer length of follow-up was accompanied by less positive results

  4. 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

  5. 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

  6. Recent advances in understanding schizophrenia.

    PubMed

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

    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

  7. 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

  8. Advances in understanding cartilage remodeling

    PubMed Central

    Li, Yefu; Xu, Lin

    2015-01-01

    Cartilage remodeling is currently among the most popular topics in osteoarthritis research. Remodeling includes removal of the existing cartilage and replacement by neo-cartilage. As a loss of balance between removal and replacement of articular cartilage develops (particularly, the rate of removal surpasses the rate of replacement), joints will begin to degrade. In the last few years, significant progress in molecular understanding of the cartilage remodeling process has been made. In this brief review, we focus on the discussion of some current “controversial” observations in articular cartilage degeneration: (1) the biological effect of transforming growth factor-beta 1 on developing and mature articular cartilages, (2) the question of whether aggrecanase 1 (ADAMTS4) and aggrecanase 2 (ADAMTS5) are key enzymes in articular cartilage destruction, and (3) chondrocytes versus chondron in the development of osteoarthritis. It is hoped that continued discussion and investigation will follow to better clarify these topics. Clarification will be critical for those in search of novel therapeutic targets for the treatment of osteoarthritis. PMID:26380073

  9. 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

  10. Current understanding of auditory neuropathy.

    PubMed

    Boo, Nem-Yun

    2008-12-01

    Auditory neuropathy is defined by the presence of normal evoked otoacoustic emissions (OAE) and absent or abnormal auditory brainstem responses (ABR). The sites of lesion could be at the cochlear inner hair cells, spiral ganglion cells of the cochlea, synapse between the inner hair cells and auditory nerve, or the auditory nerve itself. Genetic, infectious or neonatal/perinatal insults are the 3 most commonly identified underlying causes. Children usually present with delay in speech and language development while adult patients present with hearing loss and disproportionately poor speech discrimination for the degree of hearing loss. Although cochlear implant is the treatment of choice, current evidence show that it benefits only those patients with endocochlear lesions, but not those with cochlear nerve deficiency or central nervous system disorders. As auditory neuropathy is a disorder with potential long-term impact on a child's development, early hearing screen using both OAE and ABR should be carried out on all newborns and infants to allow early detection and intervention. PMID:19904452

  11. 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

  12. 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

  13. 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

  14. Advances in Understanding the Biosynthesis of Fumonisins

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  15. 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

  16. 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

  17. Recent advances in understanding hepatitis C

    PubMed Central

    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

  18. 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

  19. 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

  20. 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

  1. Advances in understanding and treating premature ejaculation.

    PubMed

    Saitz, Theodore R; Serefoglu, Ege Can

    2015-11-01

    Over the past several years, many advances have been made in our understanding of the epidemiology, pathophysiology, and management of premature ejaculation. Newly developed definitions of premature ejaculation are now available, and our perception of the classification, prevalence, aetiological factors, and treatment options for premature ejaculation have evolved. Despite ongoing research, there remains much to be learned about all aspects of this common sexual disorder, in particular effective clinical diagnosis and treatment options. PMID:26502991

  2. Current understanding of the aeronomy of Mars

    NASA Astrophysics Data System (ADS)

    Nagy, Andrew F.; Grebowsky, Joseph M.

    2015-12-01

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

  3. Recent advances in understanding and managing rhabdomyosarcoma

    PubMed Central

    Hiniker, Susan M.

    2015-01-01

    Rhabdomyosarcoma is the most common childhood soft tissue sarcoma and the fourth most common pediatric solid tumor. For most patients, treatment consists of a multimodality approach, including chemotherapy, surgery, and/or radiotherapy. To guide treatment, patients with rhabdomyosarcoma are risk stratified based on a number of factors. These factors include clinical group, which depends largely on the extent of resection and nodal involvement, and stage, which takes into account tumor size, invasion, nodal involvement, and disease site. Histology of the tumor and age at diagnosis are also factored into risk stratification. Recent advances in understanding the biology of the disease have allowed for the further sub-classification of rhabdomyosarcoma. In addition, elucidation of additional clinical features associated with poor prognosis has allowed for better understanding of risk and provides more clarity regarding those patients who require more intensive therapy. Many areas of active investigation are ongoing, including the following: further delineation of the biological underpinnings of the various disease subtypes with the possibility of molecularly targeted therapy; a better understanding of clinical risk factors, including the evaluation and management of potentially involved lymph nodes; determination of the appropriate role of post-treatment imaging and assessment of response to therapy; and incorporation of advanced radiotherapeutic techniques, including conformal intensity-modulated photon and proton therapy. PMID:26097732

  4. 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

  5. Lymphangioleiomyomatosis: Current understanding and potential treatments.

    PubMed

    Moir, Lyn M

    2016-02-01

    Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease affecting predominantly young women. Clinical symptoms of this progressive disease include dyspnoea, cough, recurrent pneumothorax, hemoptysis and chylothorax. LAM is generally aggressive in nature and ultimately results in respiratory failure. Important hallmark features of this metastatic disease include the formation of lesions of abnormal smooth muscle cells, cystic destruction of the lung tissue and lymphangiogenesis affecting the lungs, abdomen and lymphatics. Research over the last 10-15 years has significantly enhanced our understanding of the molecular and cellular processes associated with LAM. These processes include mutational inactivation of the tuberous sclerosis complex genes, TSC1 and TSC2, activation of the mammalian target of rapamycin (mTOR) pathway, enhanced cell proliferation and migration, lymphangiogenesis, metastatic spread through the blood and lymphatic circulations, sex steroid sensitivity and dysregulated autophagy. Despite this increased knowledge there is currently no cure for LAM and treatment options remain limited. Whilst the mTOR inhibitor rapamycin has shown some benefit in patients with LAM, with stabilisation of lung function and improved quality of life, cessation of treatment results in recurrence of the disease progression. This highlights the urgent need to identify novel targets and new treatment regimens. The focus of this review is to summarise our current understanding of the cellular and molecular processes associated with LAM and highlight emerging treatments. PMID:26713679

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. Advances in Understanding and Managing Chronic Urticaria

    PubMed Central

    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 2LEN)/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. PMID:26949520

  13. 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. PMID:26949520

  14. Current understanding and neurobiology of epileptic encephalopathies.

    PubMed

    Auvin, Stéphane; Cilio, Maria Roberta; Vezzani, Annamaria

    2016-08-01

    Epileptic encephalopathies are a group of diseases in which epileptic activity itself contributes to severe cognitive and behavioral impairments above and beyond what might be expected from the underlying pathology alone. These impairments can worsen over time. This concept has been continually redefined since its introduction. A few syndromes are considered epileptic encephalopathies: early myoclonic encephalopathy and Ohtahara syndrome in the neonatal period, epilepsy of infancy with migrating focal seizures, West syndrome or infantile spasms, Dravet syndrome during infancy, Lennox-Gastaut syndrome, epileptic encephalopathy with continuous spikes-and-waves during sleep, and Landau-Kleffner syndrome during childhood. The inappropriate use of this term to refer to all severe epilepsy syndromes with intractable seizures and severe cognitive dysfunction has led to confusion regarding the concept of epileptic encephalopathy. Here, we review our current understanding of those epilepsy syndromes considered to be epileptic encephalopathies. Genetic studies have provided a better knowledge of neonatal and infantile epilepsy syndromes, while neuroimaging studies have shed light on the underlying causes of childhood-onset epileptic encephalopathies such as Lennox-Gastaut syndrome. Apart from infantile spasm models, we lack animal models to explain the neurobiological mechanisms at work in these conditions. Experimental studies suggest that neuroinflammation may be a common neurobiological pathway that contributes to seizure refractoriness and cognitive involvement in the developing brain. PMID:26992889

  15. Bias: a review of current understanding.

    PubMed

    Adebiyi, A O

    2010-09-01

    The results of many research findings have come under scrutiny in recent years due to the introduction of systematic errors at one stage or the other of the research. Over the years, literature has been rife about the issue of bias with many authors describing unique types of bias. More often, researchers have often been left in the dark about the basic concept of this important phenomenon. Using a method of cross referencing, exploded tree search, consultation of textbooks of epidemiology and conference proceedings, this article examines the basic concept of bias and the current understanding of bias as present in various literature. A simple classification of biases into conceptualization, selection and information biases is proposed. A distinction is made of confounding as describing an association that is true but potentially misleading and bias which on the other hand creates an association that is not true. The article further goes on to describe the different types of biases applicable to different study designs before concluding on the need for researchers to pay attention to the issue of bias so as to make their studies useful to readers. PMID:21416795

  16. Current understanding of coronary artery calcification

    PubMed Central

    Liu, Wei; Zhang, Yue; Yu, Cheuk-Man; Ji, Qing-Wei; Cai, Meng; Zhao, Ying-Xin; Zhou, Yu-Jie

    2015-01-01

    Coronary artery calcification (CAC) is highly prevalent in patients with coronary heart disease (CHD) and is associated with major adverse cardiovascular events. There are two recognized type of CAC—intimal and medial calcification, and each of them have specific risk factors. Several theories about the mechanism of vascular calcification have been put forward, and we currently believe that vascular calcification is an active, regulated process. CAC can usually be found in patients with severe CHD, and this asymptomatic phenomenon make early diagnosis of CAC important. Coronary computed tomographic angiography is the main noninvasive tool to detect calcified lesions. Measurement of coronary artery calcification by scoring is a reasonable metric for cardiovascular risk assessment in asymptomatic adults at intermediate risk. To date, effective medical treatment of CAC has not been identified. Several strategies of percutaneous coronary intervention have been applied to CHD patients with CAC, but with unsatisfactory results. Prognosis of CAC is still a major problem of CHD patients. Thus, more details about the mechanisms of CAC need to be elucidated in order to improve the understanding and treatment of CAC. PMID:26788045

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. Adverse cutaneous drug eruptions: current understanding.

    PubMed

    Hoetzenecker, W; Nägeli, M; Mehra, E T; Jensen, A N; Saulite, I; Schmid-Grendelmeier, P; Guenova, E; Cozzio, A; French, L E

    2016-01-01

    Adverse cutaneous drug reactions are recognized as being major health problems worldwide causing considerable costs for health care systems. Most adverse cutaneous drug reactions follow a benign course; however, up to 2% of all adverse cutaneous drug eruptions are severe and life-threatening. These include acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Physicians should be aware of specific red flags to rapidly identify these severe cutaneous drug eruptions and initiate appropriate treatment. Besides significant progress in clinical classification and treatment, recent studies have greatly enhanced our understanding in the pathophysiology of adverse cutaneous drug reactions. Genetic susceptibilities to certain drugs have been identified in SJS/TEN patients, viral reactivation in DRESS has been elucidated, and the discovery of tissue resident memory T cells helps to better understand the recurrent site-specific inflammation in patients with fixed drug eruption. PMID:26553194

  2. CURRENT EPIDEMIOLOGICAL UNDERSTANDING OF CITRUS HUANGLONGBING

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Huanglongbing (HLB) is the most destructive citrus pathosystem worldwide. Previously known primarily from Asia and Africa it was introduced into the Western hemisphere in 2004. All infected commercial citrus industries continue to decline due to inadequate current control methods. HLB increase an...

  3. Current understanding of mdig/MINA in human cancers

    PubMed Central

    Thakur, Chitra; Chen, Fei

    2015-01-01

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

  4. 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.

  5. Recent advances in understanding and treating ARDS

    PubMed Central

    Baron, Rebecca M.; Levy, Bruce D.

    2016-01-01

    Acute respiratory distress syndrome represents a complex syndrome with considerable morbidity and mortality, for which there exist no targeted treatment strategies. However, recent advances in clinical care have improved outcomes, and we will review a number of these approaches here, as well as explore the mechanisms underlying the benefit of intervention that might point us in the direction toward future treatment and preventive strategies for this devastating syndrome. PMID:27158460

  6. 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

  7. 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

  8. Advances in understanding and managing bullous pemphigoid

    PubMed Central

    Zhao, Cathy Y.; Murrell, Dedee F.

    2015-01-01

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

  9. Advances in understanding and managing atopic dermatitis

    PubMed Central

    Barton, Michael; Sidbury, Robert

    2015-01-01

    Atopic dermatitis is a chronic, pruritic skin disease characterized by an improperly functioning skin barrier and immune dysregulation. We review proposed atopic dermatitis pathomechanisms, emphasizing how these impact current perspectives on natural history, role of allergic sensitization, and future therapeutic targets. PMID:26918129

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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…

  17. 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.

  18. 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…

  19. 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

  20. Advances in the understanding and operations of superconducting colliders

    SciTech Connect

    Annala, G.; Bauer, P.; Bottura, L.; Martens, M.A.; Sammut, N.; Velev, G.; Shiltsev, V.; /Fermilab

    2005-05-01

    Chromaticity drift during injection is a well-known phenomenon in superconducting colliders, such as the Tevatron, HERA and RHIC. Imperfect compensation of the drift effects can contribute to beam loss and emittance growth. It is caused by the drift of the sextupole component in the dipole magnets due to current redistribution in its superconducting coils. Recently extensive studies of chromaticity drift were conducted at the Tevatron, aiming at the improvement of the luminosity performance in the ongoing run II. These studies included not only beam experiments, but also extensive off-line magnetic measurements on spare Tevatron dipoles. Less known, until recently, is that chromaticity drift is often accompanied by tune and coupling drift. This was recently discovered in the Tevatron. We believe that these effects are the product of systematic beam offset in conjunction with the sextupole drifts (and their compensation in the chromaticity correctors). These discoveries are most relevant to the upcoming LHC, where the drift effects will have even more dramatic consequences given the high beam current. It is therefore not a surprise that CERN has been the source of major advances in the understanding of dynamic effects during the LHC superconducting magnet development. The following will briefly review the CERN results as well as those of the recent Fermilab studies. A new result, which will be presented here also, is related to fast drifts occurring in the first few seconds of the injection plateau. Again, these fast drifts were observed first in the Tevatron and efforts are underway to explain them. Finally this paper will attempt to derive the implications of these drift effects on LHC commissioning and operation.

  1. 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.

  2. 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

  3. Fish Vaccines: Current State and Future Advances

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  4. 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.

  5. Recent Molecular Advances in Our Understanding of Glioma

    PubMed Central

    Pisapia, David

    2015-01-01

    Our molecular understanding of glioma has undergone a sea change over the last decade. In this review, we discuss two recent articles that employed whole genome sequencing to subclassify gliomas vis-à-vis known molecular alterations. We further discuss the relevance of these findings vis-à-vis current treatment paradigms. PMID:26244119

  6. The current understanding on the diamond machining of silicon carbide

    NASA Astrophysics Data System (ADS)

    Goel, Saurav

    2014-06-01

    The Glenn Research Centre of NASA, USA (www.grc.nasa.gov/WWW/SiC/, silicon carbide electronics) is in pursuit of realizing bulk manufacturing of silicon carbide (SiC), specifically by mechanical means. Single point diamond turning (SPDT) technology which employs diamond (the hardest naturally-occurring material realized to date) as a cutting tool to cut a workpiece is a highly productive manufacturing process. However, machining SiC using SPDT is a complex process and, while several experimental and analytical studies presented to date aid in the understanding of several critical processes of machining SiC, the current knowledge on the ductile behaviour of SiC is still sparse. This is due to a number of simultaneously occurring physical phenomena that may take place on multiple length and time scales. For example, nucleation of dislocation can take place at small inclusions that are of a few atoms in size and once nucleated, the interaction of these nucleations can manifest stresses on the micrometre length scales. The understanding of how these stresses manifest during fracture in the brittle range, or dislocations/phase transformations in the ductile range, is crucial to understanding the brittle-ductile transition in SiC. Furthermore, there is a need to incorporate an appropriate simulation-based approach in the manufacturing research on SiC, owing primarily to the number of uncertainties in the current experimental research that includes wear of the cutting tool, poor controllability of the nano-regime machining scale (effective thickness of cut), and coolant effects (interfacial phenomena between the tool, workpiece/chip and coolant), etc. In this review, these two problems are combined together to posit an improved understanding on the current theoretical knowledge on the SPDT of SiC obtained from molecular dynamics simulation.

  7. Microscopic understanding of spin current probed by shot noise

    NASA Astrophysics Data System (ADS)

    Arakawa, Tomonori

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

  8. 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

  9. Recent Advances in Understanding and Engineering Polyketide Synthesis

    PubMed Central

    Zhang, Wenjun; Liu, Joyce

    2016-01-01

    Polyketides are a diverse group of natural products that form the basis of many important drugs. The engineering of the polyketide synthase (PKS) enzymes responsible for the formation of these compounds has long been considered to have great potential for producing new bioactive molecules. Recent advances in this field have contributed to the understanding of this powerful and complex enzymatic machinery, particularly with regard to domain activity and engineering, unique building block formation and incorporation, and programming rules and limitations. New developments in tools for in vitro biochemical analysis, full-length megasynthase structural studies, and in vivo heterologous expression will continue to improve our fundamental understanding of polyketide synthesis as well as our ability to engineer the production of polyketides. PMID:26962443

  10. 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

  11. 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.

  12. 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

  13. Advancing our understanding of the human microbiome using QIIME

    PubMed Central

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

    2014-01-01

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

  14. 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

  15. 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

  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. 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

  18. 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

  19. 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. PMID:26739622

  20. 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

  1. Advances in understanding the urine-concentrating mechanism.

    PubMed

    Sands, Jeff M; Layton, Harold E

    2014-01-01

    The renal medulla produces concentrated urine through the generation of an osmotic gradient that progressively increases from the cortico-medullary boundary to the inner medullary tip. In the outer medulla, the osmolality gradient arises principally from vigorous active transport of NaCl, without accompanying water, from the thick ascending limbs of short- and long-looped nephrons. In the inner medulla, the source of the osmotic gradient has not been identified. Recently, there have been important advances in our understanding of key components of the urine-concentrating mechanism, including (a) better understanding of the regulation of water, urea, and sodium transport proteins; (b) better resolution of the anatomical relationships in the medulla; and (c) improvements in mathematical modeling of the urine-concentrating mechanism. Continued experimental investigation of signaling pathways regulating transepithelial transport, both in normal animals and in knockout mice, and incorporation of the resulting information into mathematical simulations may help to more fully elucidate the mechanism for concentrating urine in the inner medulla. PMID:24245944

  2. Advances in mechanistic understanding and treatment approaches to Tourette syndrome.

    PubMed

    Shprecher, David R; Kious, Brent M; Himle, Michael H

    2015-11-01

    Tourette syndrome (TS) is a childhood onset neurodevelopmental disorder characterized by semi-involuntary, repetitive movements and sounds (motor and phonic tics). Transient tics in childhood are common, and their persistence in TS may be due to failure of maturation of frontal-subcortical circuits mediated by genetic predisposition and environmental factors. Tic improvement by young adult years is common, but its mechanism and predictive factors are unclear. Though tics can often be managed with nonmedical therapies, pharmacotherapy is often used for refractory, severe, or injurious tics but is complicated by side effects and incomplete benefit. This review summarizes the current understanding of TS pathophysiology, current and future treatment options, and recommendations for future research. PMID:26645901

  3. 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

  4. 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.

  5. 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

  6. 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

  7. 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

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

    PubMed

    Bhattacharya, Surajit; Mishra, R K

    2015-01-01

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

  9. 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

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

    PubMed

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

    2016-07-01

    An understanding of the underlying pathophysiology of tethered cord syndrome (TCS) and modern management strategies have only developed within the past few decades. Current understanding of this entity first began with the understanding and management of spina bifida; this later led to the gradual recognition of spina bifida occulta and the symptoms associated with tethering of the filum terminale. In the 17th century, Dutch anatomists provided the first descriptions and initiated surgical management efforts for spina bifida. In the 19th century, the term "spina bifida occulta" was coined and various presentations of spinal dysraphism were appreciated. The association of urinary, cutaneous, and skeletal abnormalities with spinal dysraphism was recognized in the 20th century. Early in the 20th century, some physicians began to suspect that traction on the conus medullaris caused myelodysplasia-related symptoms and that prophylactic surgical management could prevent the occurrence of clinical manifestations. It was not, however, until later in the 20th century that the term "tethered spinal cord" and the modern management of TCS were introduced. This gradual advancement in understanding at a time before the development of modern imaging modalities illustrates how, over the centuries, anatomists, pathologists, neurologists, and surgeons used clinical examination, a high level of suspicion, and interest in the subtle and overt clinical appearances of spinal dysraphism and TCS to advance understanding of pathophysiology, clinical appearance, and treatment of this entity. With the availability of modern imaging, spinal dysraphism can now be diagnosed and treated as early as the intrauterine stage. PMID:26967990

  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.

  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. Equine rotaviruses--current understanding and continuing challenges.

    PubMed

    Bailey, Kirsten E; Gilkerson, James R; Browning, Glenn F

    2013-11-29

    Equine rotaviruses were first detected in foals over 30 years ago and remain a major cause of infectious diarrhoea in foals. During this time, there has been substantial progress in the development of sensitive methods to detect rotaviruses in foals, enabling surveillance of the genotypes present in various horse populations. However, there has been limited epidemiological investigation into the significance of these circulating genotypes, their correlation with disease and the use of vaccination in these animal populations. Our knowledge of the pathogenesis of rotavirus infection in foals is based on a limited number of studies on a small number of foals and, therefore, most of our understanding in this area has been extrapolated from studies in other species. Questions such as the concentrations of rotavirus particles shed in the faeces of infected foals, both with and without diarrhoea, and factors determining the presence or absence of clinical disease remain to be investigated, as does the relative and absolute efficacy of currently available vaccines. The answer to these questions may help direct research into the development of more effective control measures. PMID:23932076

  14. 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

  15. Advances in our understanding of mechanisms of venous thrombus resolution.

    PubMed

    Altmann, Johanna; Sharma, Smriti; Lang, Irene M

    2016-01-01

    Traditionally, venous thrombosis has been seen as the consequence of a regulated cascade of proteolytic steps leading to the polymerization of fibrinogen and fibrin crosslinking that is facilitated by platelets. A new view of thrombosis is providing a more integrated concept, with components of the vascular wall contributing to the vascular remodeling of thrombosis. Angiogenesis and inflammation are two key mechanisms that safeguard venous thrombus resolution and restitution of vascular patency after thrombosis. Disturbance of these processes leads to thrombus persistence and has potentially severe consequences for affected patients. Examples for clinical conditions associated with recurrent or persisting venous thrombosis are post-thrombotic syndrome or chronic thromboembolic pulmonary hypertension. Recently, studies using animal models of venous thrombosis have contributed to a better understanding of thrombus non-resolution that will eventually lead to modification of current treatment concepts. For example, recent data suggest that innate immunity is involved in the modification of thrombosis. PMID:26629617

  16. Hot spots and dark current in advanced plasma wakefield accelerators

    NASA Astrophysics Data System (ADS)

    Manahan, G. G.; Deng, A.; Karger, O.; Xi, Y.; Knetsch, A.; Litos, M.; Wittig, G.; Heinemann, T.; Smith, J.; Sheng, Z. M.; Jaroszynski, D. A.; Andonian, G.; Bruhwiler, D. L.; Rosenzweig, J. B.; Hidding, B.

    2016-01-01

    Dark current can spoil witness bunch beam quality and acceleration efficiency in particle beam-driven plasma wakefield accelerators. In advanced schemes, hot spots generated by the drive beam or the wakefield can release electrons from higher ionization threshold levels in the plasma media. These electrons may be trapped inside the plasma wake and will then accumulate dark current, which is generally detrimental for a clear and unspoiled plasma acceleration process. Strategies for generating clean and robust, dark current free plasma wake cavities are devised and analyzed, and crucial aspects for experimental realization of such optimized scenarios are discussed.

  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. PMID:26520954

  18. 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.

  19. 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

  20. 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.

  1. 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; de Mello, Ramon Andrade

    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. PMID:26838766

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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

  8. Recent advances in the understanding of homogeneous dielectric barrier discharges

    NASA Astrophysics Data System (ADS)

    Massines, F.; Gherardi, N.; Naudé, N.; Ségur, P.

    2009-08-01

    This paper is a state of the art of the understanding on the physics of homogeneous dielectric barrier discharges at atmospheric pressure. It is based on the analysis of present and previous work about the behavior of these discharges and the conditions to get them. Mechanisms controlling the homogeneity during gas breakdown and discharge development are successively discussed. The breakdown has to be a Townsend one, the ionization has to be slow enough to avoid a large avalanche development. During the breakdown, the discharge homogeneity is related to the ratio of the secondary emission at the cathode (γ coefficient) on the ionization in the gas bulk (α coefficient). Higher is this ratio, higher is the pressure × gas gap product (Pd) value for which a Townsend breakdown is obtained. Among the phenomena enhancing the secondary emission there is the negative charge of the dielectric on the cathode surface, the trapping of ions in the gas and the existence of excited state having a long lifetime compared to the time between two consecutive discharges. The first phenomenon is always present when the electrodes are covered by a solid dielectric, the second one is related to the formation of a positive column and the third one is specific of the gas. During the discharge development, the homogeneity is mainly controlled by the voltage or the current imposed by the electrical circuit/electrode configuration and by the gas ability to be slowly ionized. Larger is the contribution of a multiple step ionization process like Penning ionization, higher will be the working domain of the discharge. A decrease of the gas voltage during the discharge development is a solution to enhance the contribution of this process. After 20 years of research a lot of mechanisms have been understood however there is still open questions like the nature of the Inhibited homogeneous DBD, surface energy transfers, role of attachment and detachment...

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

    PubMed

    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

  10. 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

  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. 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'…

  13. Telocytes in the reproductive organs: Current understanding and future challenges.

    PubMed

    Cretoiu, Dragos; Cretoiu, Sanda Maria

    2016-07-01

    Over the past decades, we were witnessing spectacular molecular medicine advances. However, many of the reproductive medicine problems, such as fertility issues and premature birth still represent major challenges for obstetrics and gynecology worldwide. A new cell population - the telocytes (TCs) - were described in the interstitial space of many organs, and their possible implications in many important physiological and pathological processes should not be overlooked. In this article, we present a historical perspective outlining the landmarks in the discovery, evolution and achievements in the field of TCs over the last ten years. We focused on the potential roles of TCs in morphogenesis and maintenance of the normal three-dimensional architecture of tissues, in controlling of the stem cell microenvironment, as having anti-inflammatory and cancer-suppressing properties, participating in the immune surveillance, all mediated by direct homo- and heterocellular junctions or indirectly by extracellular vesicle release. Here, we overview the advances on TCs research in the reproductive organs (uterus and fallopian tube), accessory reproductive organs of female (mammary glands) and the temporary endocrine organ-placenta. PMID:27021165

  14. Current advances in radiotherapy of head and neck malignancies.

    PubMed

    Roopashri, G; Baig, Muqeet

    2013-12-01

    Necessity is the mother of all inventions. This is also true in case of cancer therapy. With increasing incidence of head and neck malignancies, remarkable developments have been made towards cancer development and treatment which continues to be a major challenge. Approximately fifty percent of all cancer patients receive radiotherapy which contributes towards forty percent of curative treatment for cancer. New developments in radiation oncology have helped to improve outlook for patients and find more effective treatment. With the advent of new technologies, radiotherapy seems to be promising in patients with head and neck malignancies these advancements include Altered fractionation, Three-dimensional conformal radiotherapy, Intensity-modulated radiotherapy, Image Guided Radiotherapy, Stereotactic radiation, Charged-particle radiotherapy, and Intraoperative radiotherapy. How to cite this article: Roopashri G, Baig M. Current advances in radiotherapy of head and neck malignancies. J Int Oral Health 2013; 5(6):119-23 . PMID:24453456

  15. Current stage of understanding and description of hadronic elastic diffraction

    SciTech Connect

    Godizov, A. A.

    2013-04-15

    Current situation with phenomenological description of high-energy nucleon-nucleon diffractive elastic scattering is reviewed. Comparison of various model predictions with the recent D0 and TOTEM data on the nucleon-nucleon differential cross-sections is presented.

  16. Current stage of understanding and description of hadronic elastic diffraction

    NASA Astrophysics Data System (ADS)

    Godizov, A. A.

    2013-04-01

    Current situation with phenomenological description of high-energy nucleon-nucleon diffractive elastic scattering is reviewed. Comparison of various model predictions with the recent D0 and TOTEM data on the nucleon-nucleon differential cross-sections is presented.

  17. 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.

  18. 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

  19. Myocardial Viability and Revascularization: Current Understanding and Future Directions.

    PubMed

    Patel, Pavan; Ivanov, Alexander; Ramasubbu, Kumudha

    2016-06-01

    The initial observation of functional recovery in dysfunctional myocardium following revascularization led to the introduction of the concept of hibernating myocardium. Since then, the pathophysiologic basis of hibernating myocardium has been well described. Multiple imaging modalities have been utilized to prospectively detect viable myocardium and thus predict its functional recovery following revascularization. It has been hypothesized that viability imaging will be instrumental in the selection of patients with ischemic cardiomyopathy likely to benefit from revascularization. Multiple observational studies built a large body of evidence supporting this concept. However, data from prospective studies failed to substantiate utility of viability testing. This review aims to summarize the current literature and describe the role of viability imaging in current clinical practice as well as future directions. PMID:27115143

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

    PubMed

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

    2016-02-01

    Inflammation is a complex biologic response that is essential for eliminating microbial pathogens and repairing tissue after injury. AKI associates with intrarenal and systemic inflammation; thus, improved understanding of the cellular and molecular mechanisms underlying the inflammatory response has high potential for identifying effective therapies to prevent or ameliorate AKI. In the past decade, much knowledge has been generated about the fundamental mechanisms of inflammation. Experimental work in small animal models has revealed many details of the inflammatory response that occurs within the kidney after typical causes of AKI, including insights into the molecular signals released by dying cells, the role of pattern recognition receptors, the diverse subtypes of resident and recruited immune cells, and the phased transition from destructive to reparative inflammation. Although this expansion of the basic knowledge base has increased the number of mechanistically relevant targets of intervention, progress in developing therapies that improve AKI outcomes by modulation of inflammation remains slow. In this article, we summarize the most important recent developments in understanding the inflammatory mechanisms of AKI, highlight key limitations of the commonly used animal models and clinical trial designs that may prevent successful clinical application, and suggest priority approaches for research toward clinical translation in this area. PMID:26561643

  1. Hollow current profile scenarios for advanced tokamak reactor operations

    SciTech Connect

    Gourdain, P.-A.; Leboeuf, J.-N.

    2009-11-15

    Advanced tokamak scenarios are a possible approach to boosting reactor performances. Such schemes usually trigger current holes, a particular magnetohydrodynamics equilibrium where no current or pressure gradients exist in the core of the plasma. While such equilibria have large bootstrap fractions, flat pressure profiles in the plasma core may not be optimal for a reactor. However, moderate modifications of the equilibrium current profile can lead to diamagnetism where most of the pressure gradient is now balanced by poloidal currents and the toroidal magnetic field. In this paper, we consider the properties of diamagnetic current holes, also called ''dual equilibria,'' and demonstrate that fusion throughput can be significantly increased in such scenarios. Their stability is investigated using the DCON code. Plasmas with a beta peak of 30% and an average beta of 6% are found stable to both fixed and free-boundary modes with toroidal mode numbers n=1-4, as well as Mercier and high-n ballooning modes. This is not surprising as these scenarios have a normal beta close to 3.

  2. 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

  3. 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

  4. Coronary Vasospastic Angina: Current Understanding and the Role of Inflammation

    PubMed Central

    Hung, Ming-Jui; Cherng, Wen-Jin

    2013-01-01

    Coronary vasospastic angina (CVsA) plays an important role in myocardial ischemia including stable angina, acute coronary syndromes, and sudden cardiac death. Inflammation status from either endothelium or adventitia can cause endothelial dysfunction. Thereafter, the endothelial dysfunction further induces vascular smooth muscle hypercontraction through the enhanced rho-kinase with the resultant clinical event. With better understanding of the interactions between inflammation, endothelium, and smooth muscle cells, we and other investigators have provided new insights into the basic pathophysiology of CVsA. Apart from calcium channel blockers, nitrates, and the rho-kinase inhibitor fasudil, anti-inflammatory treatment is helpful in some patients with refractory CVsA. Additional studies are needed to clarify the mechanisms of recurrent CVsA. PMID:27122679

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

    PubMed Central

    Atsawarungruangkit, Amporn; Pongprasobchai, Supot

    2015-01-01

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

  6. Current perspectives in the treatment of advanced prostate cancer.

    PubMed

    Valdespino, Victor; Tsagozis, Panagiotis; Pisa, Pavel

    2007-01-01

    Prostate cancer (PC) continues to be an important world health problem for men. Patients with locally confined PC are treated with either radiotherapy or surgery. However, treatment of more advanced stages of the disease is problematic. Initially, androgen deprivation offers a period of clinical stability, which is however invariably followed by progression to non-responsiveness to hormonal manipulation. Current management of patients with androgen-independent prostate cancer (AIPC) displays modest response rates and achieves only short-term benefit. Recently, knowledge in the complex pathophysiology of advanced PC has led to the identification of mechanisms and target molecules permitting the introduction of new therapies. Consequently, many investigational treatments are ongoing for AIPC in Phase-II and Phase-III trials aiming at the combination of chemotherapeutic regimens along with immunotherapy targeting PC-associated antigens. Other attractive options are gene therapy, as well as the targeting of survival signaling, differentiation, and apoptosis of the malignant PC cells. Further treatment modalities are directed against the tumor microenvironment, bone metastasis, or both. Collectively, the aforementioned efforts introduce a new era in the management of advanced PC. Novel pharmaceutical compounds and innovative approaches, integrated into the concept of individualized therapy will hopefully, during the next decade, improve the outcome and survival for hundreds of thousands of men worldwide. PMID:17873302

  7. 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

  8. 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

  9. 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. PMID:26959131

  10. 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

  11. 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.

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

    PubMed

    Jain, Shashank; Patel, Niketkumar; Lin, Senshang

    2015-06-01

    Identification of lead compounds with higher molecular weight and lower aqueous solubility has become increasingly prevalent with the advent of high throughput screening. Poor aqueous solubility of these lipophilic compounds can drastically affect the dissolution rate and subsequently the drug absorbed in the systemic circulation, imposing a significant burden of time and money during drug development process. Various pre-formulation and formulation strategies have been applied in the past that can improve the aqueous solubility of lipophilic compounds by manipulating either the crystal lattice properties or the activity coefficient of a solute in solution or both, if possible. However, despite various strategies available in the armor of formulation scientist, solubility issue still remains an overriding problem in the drug development process. It is perhaps due to the insufficient conceptual understanding of solubility and dissolution phenomenon that hinders the judgment in selecting suitable strategy for improving aqueous solubility and/or dissolution rate. This article, therefore, focuses on (i) revisiting the theoretical and mathematical concepts associated with solubility and dissolution, (ii) their application in making rationale decision for selecting suitable pre-formulation and formulation strategies and (iii) the relevant research performed in this field in past decade. PMID:25342479

  13. 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

  14. 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

  15. Understanding movement data and movement processes: current and emerging directions.

    PubMed

    Schick, Robert S; Loarie, Scott R; Colchero, Fernando; Best, Benjamin D; Boustany, Andre; Conde, Dalia A; Halpin, Patrick N; Joppa, Lucas N; McClellan, Catherine M; Clark, James S

    2008-12-01

    Animal movement has been the focus on much theoretical and empirical work in ecology over the last 25 years. By studying the causes and consequences of individual movement, ecologists have gained greater insight into the behavior of individuals and the spatial dynamics of populations at increasingly higher levels of organization. In particular, ecologists have focused on the interaction between individuals and their environment in an effort to understand future impacts from habitat loss and climate change. Tools to examine this interaction have included: fractal analysis, first passage time, Lévy flights, multi-behavioral analysis, hidden markov models, and state-space models. Concurrent with the development of movement models has been an increase in the sophistication and availability of hierarchical bayesian models. In this review we bring these two threads together by using hierarchical structures as a framework for reviewing individual models. We synthesize emerging themes in movement ecology, and propose a new hierarchical model for animal movement that builds on these emerging themes. This model moves away from traditional random walks, and instead focuses inference on how moving animals with complex behavior interact with their landscape and make choices about its suitability. PMID:19046362

  16. Recent advances in understanding the pathogenesis of Lawsonia intracellularis infections.

    PubMed

    Vannucci, F A; Gebhart, C J

    2014-03-01

    Proliferative enteropathy is an infectious disease caused by an obligate intracellular bacterium, Lawsonia intracellularis, and characterized by thickening of the intestinal epithelium due to enterocyte proliferation. The disease is endemic in swine herds and has been occasionally reported in various other species. Furthermore, outbreaks among foals began to be reported on breeding farms worldwide within the past 5 years. Cell proliferation is directly associated with bacterial infection and replication in the intestinal epithelium. As a result, mild to severe diarrhea is the major clinical sign described in infected animals. The dynamics of L. intracellularis infection in vitro and in vivo have been well characterized, but little is known about the genetic basis for the pathogenesis or ecology of this organism. The present review focuses on the recent advances regarding the pathogenesis and host-pathogen interaction of L. intracellularis infections. PMID:24476941

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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)

  2. Imaging for understanding speech communication: Advances and challenges

    NASA Astrophysics Data System (ADS)

    Narayanan, Shrikanth

    2005-04-01

    Research in speech communication has relied on a variety of instrumentation methods to illuminate details of speech production and perception. One longstanding challenge has been the ability to examine real-time changes in the shaping of the vocal tract; a goal that has been furthered by imaging techniques such as ultrasound, movement tracking, and magnetic resonance imaging. The spatial and temporal resolution afforded by these techniques, however, has limited the scope of the investigations that could be carried out. In this talk, we focus on some recent advances in magnetic resonance imaging that allow us to perform near real-time investigations on the dynamics of vocal tract shaping during speech. Examples include Demolin et al. (2000) (4-5 images/second, ultra-fast turbo spin echo) and Mady et al. (2001,2002) (8 images/second, T1 fast gradient echo). A recent study by Narayanan et al. (2004) that used a spiral readout scheme to accelerate image acquisition has allowed for image reconstruction rates of 24 images/second. While these developments offer exciting prospects, a number of challenges lie ahead, including: (1) improving image acquisition protocols, hardware for enhancing signal-to-noise ratio, and optimizing spatial sampling; (2) acquiring quality synchronized audio; and (3) analyzing and modeling image data including cross-modality registration. [Work supported by NIH and NSF.

  3. Recent Advances in Understanding Integrative Control of Potassium Homeostasis

    PubMed Central

    Youn, Jang H.; McDonough, Alicia A.

    2016-01-01

    The potassium homeostatic system is very tightly regulated. Recent studies have shed light on the sensing and molecular mechanisms responsible for this tight control. In addition to classic feedback regulation mediated by a rise in extracellular fluid (ECF) [K+], there is evidence for a feedforward mechanism: Dietary K+ intake is sensed in the gut, and an unidentified gut factor is activated to stimulate renal K+ excretion. This pathway may explain renal and extrarenal responses to altered K+ intake that occur independently of changes in ECF [K+]. Mechanisms for conserving ECF K+ during fasting or K+ deprivation have been described: Kidney NADPH oxidase activation initiates a cascade that provokes the retraction of K+ channels from the cell membrane, and muscle becomes resistant to insulin stimulation of cellular K+ uptake. How these mechanisms are triggered by K+ deprivation remains unclear. Cellular AMP kinase–dependent protein kinase activity provokes the acute transfer of K+ from the ECF to the ICF, which may be important in exercise or ischemia. These recent advances may shed light on the beneficial effects of a high-K+ diet for the cardiovascular system. PMID:18759636

  4. Advances in Understanding Bronchiolitis Obliterans After Lung Transplantation.

    PubMed

    Verleden, Stijn E; Sacreas, Annelore; Vos, Robin; Vanaudenaerde, Bart M; Verleden, Geert M

    2016-07-01

    Bronchiolitis obliterans syndrome (BOS) remains a major complication after lung transplantation, causing significant morbidity and mortality in a majority of recipients. BOS is believed to be the clinical correlate of chronic allograft dysfunction, and is defined as an obstructive pulmonary function defect in the absence of other identifiable causes, mostly not amenable to treatment. Recently, it has become clear that BOS is not the only form of chronic allograft dysfunction and that other clinical phenotypes exist; however, we focus exclusively on BOS. Radiologic findings typically demonstrate air trapping, mosaic attenuation, and hyperinflation. Pathologic examination reveals obliterative bronchiolitis lesions and a pure obliteration of the small airways (< 2 mm), with a relatively normal surrounding parenchyma. In this review, we highlight recent advances in diagnosis, pathologic examination, and risk factors, such as microbes, viruses, and antibodies. Although the pathophysiological mechanisms remain largely unknown, we review the role of the airway epithelium and inflammation and the various experimental animal models. We also clarify the clinical and therapeutic implications of these findings. Although significant progress has been made, the exact pathophysiological mechanisms and adequate therapy for posttransplantation BOS remain unknown, highlighting the need for further research to improve long-term posttransplantation BOS-free and overall survival. PMID:27212132

  5. 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

  6. Advances in understanding and treating dystrophic epidermolysis bullosa

    PubMed Central

    Vanden Oever, Michael J

    2014-01-01

    Epidermolysis bullosa is a group of inherited disorders that can be both systemic and life-threatening. Standard treatments for the most severe forms of this disorder, typically limited to palliative care, are ineffective in reducing the morbidity and mortality due to complications of the disease. Emerging therapies—such as the use of allogeneic cellular therapy, gene therapy, and protein therapy—have all shown promise, but it is likely that several approaches will need to be combined to realize a cure. For recessive dystrophic epidermolysis bullosa, each particular therapeutic approach has added to our understanding of type VII collagen (C7) function and the basic biology surrounding the disease. The efficacy of these therapies and the mechanisms by which they function also give us insight into developing future strategies for treating this and other extracellular matrix disorders. PMID:24860657

  7. Recent Advances in Understanding and Managing Tourette Syndrome.

    PubMed

    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

  8. 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

  9. Advances in the Understanding of Cobalamin Assimilation and Metabolism

    PubMed Central

    Quadros, Edward V.

    2009-01-01

    Summary The haematological and neurological consequences of cobalamin deficiency define the essential role of this vitamin in key metabolic reactions. The identification of cubilin-amnionless as the receptors for intestinal absorption of intrinsic factor-bound cobalamin and the plasma membrane receptor for cellular uptake of transcobalamin bound cobalamin have provided a clearer understanding of the absorption and cellular uptake of this vitamin. As the genes involved in the intracellular processing of cobalamins and genetic defects of these pathways are identified, the metabolic disposition of cobalamins and the proteins involved are being recognized. The synthesis of methylcobalamin and 5’deoxyadenosylcobalamin, their utilization in conjunction with methionine synthase and methylmalonylCoA mutase, respectively, and the metabolic consequences of defects in these pathways could provide insights into the clinical presentation of cobalamin deficiency. PMID:19832808

  10. Understanding type 1 diabetes through genetics: advances and prospects.

    PubMed

    Polychronakos, Constantin; Li, Quan

    2011-11-01

    Starting with early crucial discoveries of the role of the major histocompatibility complex, genetic studies have long had a role in understanding the biology of type 1 diabetes (T1D), which is one of the most heritable common diseases. Recent genome-wide association studies (GWASs) have given us a clearer picture of the allelic architecture of genetic susceptibility to T1D. Fine mapping and functional studies are gradually revealing the complex mechanisms whereby immune self-tolerance is lost, involving multiple aspects of adaptive immunity. The triggering of these events by dysregulation of the innate immune system has also been implicated by genetic evidence. Finally, genetic prediction of T1D risk is showing promise of use for preventive strategies. PMID:22005987

  11. 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

  12. 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.

  13. Recent advances in understanding myelofibrosis and essential thrombocythemia

    PubMed Central

    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

  14. Advances in the Understanding and Treatment of Head Injury

    PubMed Central

    Evans, Joseph P.

    1966-01-01

    The author describes his personal involvement in head injury prevention and management over the past 40 years. He reviews the evolution of knowledge concerning the role of increased intracranial pressure, and considers the importance of cerebral vasoparalysis in the production of signs and symptoms following head injury, and the development of methods of recording intracranial pressure continuously, over hours and days. The development of an experimental compression model has led to a fuller understanding of edema of the brain and has provided a means of studying, by light and electron microscopy, the histological changes that result from edema. More recently, analyses of biochemical changes and disturbed membrane function have opened up a new avenue of potential treatment. Moreover, it is now clear that cerebral vascular dilatation and abrupt pressure increase can be produced in the monkey, in over 50% of cases, by lesions in the dorsomedial nucleus of the hypothalamus. Similar lesions may occur in the human and this suggests other therapeutic approaches. There is, then, a genuine hope of a breakthrough in the management of head injuries. ImagesFig. 1Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9Fig. 10Fig. 11Fig. 12Fig. 16Fig. 21 PMID:5928533

  15. 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

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. 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

  1. 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

  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. Beyond vascular inflammation--recent advances in understanding atherosclerosis.

    PubMed

    Wolf, Dennis; Zirlik, Andreas; Ley, Klaus

    2015-10-01

    Atherosclerosis is the most life-threatening pathology worldwide. Its major clinical complications, stroke, myocardial infarction, and heart failure, are on the rise in many regions of the world--despite considerable progress in understanding cause, progression, and consequences of atherosclerosis. Originally perceived as a lipid-storage disease of the arterial wall (Die cellularpathologie in ihrer begründung auf physiologische und pathologische gewebelehre. August Hirschwald Verlag Berlin, [1871]), atherosclerosis was recognized as a chronic inflammatory disease in 1986 (New Engl J Med 314:488-500, 1986). The presence of lymphocytes in atherosclerotic lesions suggested autoimmune processes in the vessel wall (Clin Exp Immunol 64:261-268, 1986). Since the advent of suitable mouse models of atherosclerosis (Science 258:468-471, 1992; Cell 71:343-353, 1992; J Clin Invest 92:883-893, 1993) and the development of flow cytometry to define the cellular infiltrate in atherosclerotic lesions (J Exp Med 203:1273-1282, 2006), the origin, lineage, phenotype, and function of distinct inflammatory cells that trigger or inhibit the inflammatory response in the atherosclerotic plaque have been studied. Multiphoton microscopy recently enabled direct visualization of antigen-specific interactions between T cells and antigen-presenting cells in the vessel wall (J Clin Invest 122:3114-3126, 2012). Vascular immunology is now emerging as a new field, providing evidence for protective as well as damaging autoimmune responses (Int Immunol 25:615-622, 2013). Manipulating inflammation and autoimmunity both hold promise for new therapeutic strategies in cardiovascular disease. Ongoing work (J Clin Invest 123:27-36, 2013; Front Immunol 2013; Semin Immunol 31:95-101, 2009) suggests that it may be possible to develop antigen-specific immunomodulatory prevention and therapy-a vaccine against atherosclerosis. PMID:26100516

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

    PubMed Central

    2013-01-01

    von Willebrand disease (VWD) is the most common autosomally inherited bleeding disorder. The disease represents a range of quantitative and qualitative pathologies of the adhesive glycoprotein von Willebrand factor (VWF). The pathogenic mechanisms responsible for the type 2 qualitative variants of VWF are now well characterized, with most mutations representing missense substitutions influencing VWF multimer structure and interactions with platelet GPIbα and collagen and with factor VIII. The molecular pathology of type 3 VWD has been similarly well characterized, with an array of different mutation types producing either a null phenotype or the production of VWF that is not secreted. In contrast, the pathogenetic mechanisms responsible for type 1 VWD remain only partially resolved. In the hemostasis laboratory, the measurement of VWF:Ag and VWF:RCo are key components in the diagnostic algorithm for VWD, although the introduction of direct GPIbα-binding assays may become the functional assay of choice. Molecular genetic testing can provide additional benefit, but its utility is currently limited to type 2 and 3 VWD. The treatment of bleeding in VWD involves the use of desmopressin and plasma-derived VWF concentrates and a variety of adjunctive agents. Finally, a new recombinant VWF concentrate has just completed clinical trial evaluation and has demonstrated excellent hemostatic efficacy and safety. PMID:24065240

  6. 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).

  7. 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

  8. Nanocarriers for respiratory diseases treatment: recent advances and current challenges.

    PubMed

    Trapani, Adriana; Gioia, Sante Di; Castellani, Stefano; Carbone, Annalucia; Cavallaro, Gennara; Trapani, Giuseppe; Conese, Massimo

    2014-01-01

    Pulmonary delivery of locally-acting drugs encapsulated in nanocarriers provides several advantages for the treatment of respiratory diseases such as asthma, chronic obstructive pulmonary diseases, cystic fibrosis, tuberculosis and lung cancer. These advantages include, among others, sustained drug delivery to the lungs, reduced therapeutic dose and improved patient compliance. The aim of this review is to give an updated overview on recent advances recorded in the last few years in this field as well as on the major challenges still existing and that remain to be overcome before any clinical application. After an outline on the cellular and extracellular barriers affecting drug delivery to the airways both in physiological and pathological conditions, the significant developments recorded using inhaled polymeric- and lipid-based nanocarriers for drug and gene delivery to the lung are presented. In this discussion, the major challenges existing in the field are evidenced including the understanding of the factors governing the mucus penetration capability of these nanocarriers and the identification of new technologies for delivering drugs to specific regions or cell types of the lungs. In this regard, the recognition of receptor expressed only at lung level may facilitate drug targeting to this organ and it should improve the therapeutic efficacy of nanocarrier-based treatments for respiratory diseases. PMID:24678708

  9. 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

  10. 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

  11. 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.

  12. Advanced altitude simulation facility P8 - current status

    NASA Astrophysics Data System (ADS)

    Pauly, C.; Suslov, D.; Haidn, O. J.

    2011-10-01

    The paper reports the current status of a DLR Lampoldshausen project towards the design, erection, and operation of an advanced altitude simulation facility at the European R&T Facility P8. The system will allow for testing subscale thrust chamber assemblies (TCAs) including surrounding supersonic flow around the nozzle. This facility will allow for investigation into the specific features of altitude simulation facilities but also on the interaction of nozzle and its exhaust plume and the surrounding coflow for subsonic, transitional, and low supersonic coflow conditions. The design bases entirely on the broad experience on design and operation of various altitude simulation facilities such as the satellite engine bench P1.0, the cryogenic and storable upper-stage engine facilities P4.1 and P4.2, sophisticated engineering design tools and continuous numerical effort. Knowledge about nozzle and thrust chamber design and operation bases on broad investigations carried out at the cold-flow facility P6.2 and the hot-fire M3 and P8 test benches.

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

    PubMed Central

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

    2015-01-01

    very 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

  14. 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

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

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

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

  17. A Case Study on Advanced Technology: Understanding the Impact of Advanced Technology on Student Performance

    ERIC Educational Resources Information Center

    Morris, Jill Sellars

    2010-01-01

    While research has focused on the effect of technology on student performance, it is not yet known how advanced technology, such as Promethean boards influence student achievement. The purpose of this mixed-method study was to examine how Promethean boards impact academic performance of elementary school students in third and fifth grade…

  18. Current Advances in Detection and Treatment of Babesiosis

    PubMed Central

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

    2012-01-01

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

  19. 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

  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. PMID:27379154

  2. Radical Prostatectomy for Locally Advanced Prostate Cancer: Current Status.

    PubMed

    Faria, Eliney F; Chapin, Brian F; Muller, Roberto L; Machado, Roberto D; Reis, Rodolfo B; Matin, Surena F

    2015-07-01

    In the past, prostate cancer (PC) could only be detected clinically, and delayed diagnosis of locally advanced or metastatic disease at presentation was common. Prostate-specific antigen testing and magnetic resonance imaging led to PC detection in a much earlier stage. However, controversy about the best treatment for locally advanced PC remains. Recent refinements in surgery and radiation therapy have improved outcomes, but no comparative study has yet conclusively determined superiority of one option over the other. In this review, we present the most recent evidence about the role of radical prostatectomy for locally advanced PC treatment from a surgeon's perspective. PMID:26048432

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

    PubMed

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

    2016-04-01

    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. 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…

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

    PubMed Central

    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. PMID:25788767

  6. 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

  7. 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

  8. [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

  9. 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

  10. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  12. The Effect of Explicit Embedded Reflective Instruction on Nature of Science Understandings in Advanced Science Students

    ERIC Educational Resources Information Center

    Koksal, Mustafa Serdar; Cakiroglu, Jale; Geban, Omer

    2013-01-01

    The purpose of this study is to investigate the effectiveness of explicit-embedded-reflective (EER) instruction in nature of science (NOS) understandings of ninth-grade advanced science students. This study was conducted with 71 students, who were divided into three groups, by using non-equivalent quasi-experimental design. In the treatment…

  13. 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.

  14. 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

  15. 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.

  16. 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

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

    SciTech Connect

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

    2006-03-01

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

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

    SciTech Connect

    A.V.G. Chizmeshya

    2003-12-19

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

  19. 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

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

    PubMed Central

    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. 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

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

    PubMed Central

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

    2015-01-01

    Cancer is a leading cause of death worldwide; due to the lack of ideal cancer biomarkers for early detection or diagnosis, most patients present with late-stage disease at the time of diagnosis, thus limiting the potential for successful treatment. Traditional cancer treatments, including surgery, chemotherapy and radiation therapy, have demonstrated very limited efficacy for patients with late-stage disease. Therefore, innovative and effective cancer treatments are urgently needed for cancer patients with late-stage and refractory disease. Cancer immunotherapy, particularly adoptive cell transfer, has shown great promise in the treatment of patients with late-stage disease, including those who are refractory to standard therapies. In this review, we will highlight recent advances and discuss future directions in adoptive cell transfer based cancer immunotherapy. PMID:25524383

  3. 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

  4. Immunotherapy for advanced melanoma: Current knowledge and future directions.

    PubMed

    Nakamura, Kenta; Okuyama, Ryuhei

    2016-08-01

    Melanoma is one of the most aggressive cancers and is responsible for a large proportion of skin cancer-related deaths. The recent development of novel immunotherapeutic approaches has led to great advances in melanoma therapy. Because melanoma cells often express tumor-specific neo-antigens, significant therapeutic effects are mediated via immunotherapy-induced activation of cytotoxic T lymphocytes (CTLs); however, the effects depend on the immune status of the patient. At present, various immunotherapies have been approved and new clinical trials are progressing. These immunotherapies act in several ways, including CTL brake release, induction of CTL activation, transfer of CTLs, and modification of the tumor microenvironment to facilitate CTL activation. In the near future, patient-tailored immunotherapies and combination therapies are expected. In addition, it is important to monitor the status of the patient's immune response when selecting the most effective immunotherapy strategy. PMID:27302423

  5. Illness understanding in patients with advanced lung cancer: curse or blessing?

    PubMed

    Janssens, Annelies; Kohl, Sisca; Michielsen, Toke; Van Langendonck, Shana; Hiddinga, Birgitta I; van Meerbeeck, Jan P

    2016-04-01

    Early palliative care (EPC) should be introduced from the start of the treatment of patients with advanced lung cancer. Unfortunately, this is often not integrated in daily oncologic care. This letter wants to emphasize the importance of offering a holistic approach, meaning EPC to optimize quality of life (QoL). Illness understanding is important because patients with better understanding of their disease choose more often for symptom control and less for an aggressive treatment at the end of life. This illness understanding should be achieved during communication with the treating oncologist. Based on the limited available literature about illness understanding, it seems that an EPC program is necessary when breaking bad news, in order to maintain or improve QoL in patients. PMID:27121741

  6. 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

  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. 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

  9. 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

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

    ERIC Educational Resources Information Center

    Carroll, Erich C.

    2013-01-01

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

  11. 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

  12. 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.

  13. Advancing the understanding, monitoring and prediction of North American drought in support of NIDIS

    NASA Astrophysics Data System (ADS)

    Mariotti, Annarita; Pulwarty, Roger

    2014-05-01

    The NOAA's Drought Task Force was established in October 2011 with the goal of achieving significant new advances in the ability to understand, monitor and predict drought over North America. The Task Force is an initiative of NOAA's Climate Program Office Modeling, Analysis, Predictions, and Projections (MAPP) program in support of the National Integrated Drought Information System NIDIS. It brings together over thirty-five leading drought scientists research laboratories and/or operational centers from NOAA, other U.S. agencies laboratories and academia. Their concerted research effort builds on individual MAPP research projects and related drought-research sector developments. The projects span the wide spectrum of drought research needed to make fundamental advances, from those aimed at the basic understanding of drought mechanisms to those evaluating new drought monitoring and prediction tools for operational and service purposes. In this presentation we will show how a coordinated, sustained multidisciplinary effort to assess understanding of both past droughts and emergent events contributes to the effectiveness of early warning systems. This contribution will present an overview of Drought Task Force activities to date, including highlights of research activities and how the group has been working in partnership with NIDIS to advance the science underpinning the development, assessment and provision of drought information.

  14. 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

  15. Advanced electromagnetic design of cavities for high current accelerators

    SciTech Connect

    Krawczyk, F.L.

    1995-05-01

    For high-current accelerators such as those proposed for transmutation technologies or spallation sources, preconstruction numerical modeling has a high importance. Non axisymmetric cavities require a full 3-D modeling. A complex analysis of structures beyond tuning and the calculation of Q and shunt impedance is required and also the interaction with the mechanical properties of the structures has to be taken into account. This paper reports on recent work done at LANL for proposed beam funnels, a new normal-conducting medium-energy structure (CCDTL) and superconducting cavities for medium energy. The electromagnetic calculations have been done with MAFIA, Rel 3.2, the thermal and stress analysis results reported come from the ABAQUS engineering code.

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

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

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

  17. 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

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

    PubMed Central

    Teague, Andrea; Lim, Kian-Huat

    2015-01-01

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

  19. 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

  20. Injectable Poly-L-Lactic Acid: Understanding Its Use in the Current Era.

    PubMed

    Lorenc, Z Paul; Greene, Thomas; Gottschalk, Ronald W

    2016-06-01

    A survey of Sculptra® Aesthetic injectors was conducted to understand how the product is being currently reconstituted and injected. Questions were asked of injectors to understand their reasons for choice and volume of diluent(s), additions, and time for the reconstitution process. These results are discussed in the context of the past history of the product over the last decade, with a focus on adverse events such as papules and nodules.

    J Drugs Dermatol. 2016;15(6):759-762. PMID:27272085

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

    PubMed Central

    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. PMID:24711712

  2. NOAA Drought Task Force: A Coordinated Research Initiative to Advance Drought Understanding, Monitoring and Prediction

    NASA Astrophysics Data System (ADS)

    Mariotti, A.; Barrie, D.

    2014-12-01

    The NOAA's Drought Task Force was first established in October 2011 and renewed in October 2014 with the goal of achieving significant new advances in the ability to understand, monitor and predict drought over North America. The Task Force is an initiative of NOAA's Climate Program Office Modeling, Analysis, Predictions, and Projections (MAPP) program in support of the National Integrated Drought Information System NIDIS. The Drought Task Force also represents an important research contribution to efforts to develop an international Global Drought Information System (GDIS). The Drought Task Force brings together leading drought scientists research laboratories and/or operational centers from NOAA, other U.S. agencies laboratories and academia. Their concerted research effort builds on individual MAPP research projects and related drought-research sector developments. The projects span the wide spectrum of drought research needed to make fundamental advances, from those aimed at the basic understanding of drought mechanisms to those evaluating new drought monitoring and prediction tools for operational and service purposes. This contribution will present an overview of Drought Task Force activities and plans to date, including highlights of research activities and how the group has been working in partnership with NIDIS and synergy with GDIS to advance the science underpinning the development, assessment and provision of drought information.

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

    NASA Technical Reports Server (NTRS)

    Opila, Elizabeth J.

    2004-01-01

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

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

    PubMed

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

    2010-12-01

    This invited clinical commentary summarizes the current state of knowledge in the area of prevention of anterior cruciate ligament (ACL) injuries. ACL injuries occur with a four to six fold greater incidence in female compared to male athletes playing the same high risk sports. The combination of increased risk of ACL injury and a 10-fold increase in sports participation since the enactment of Title IX in 1972 has led to an almost epidemic rise in ACL injuries in female athletes. Examination of the mechanisms responsible for this sex disparity in ACL rupture accelerated in the last two decades. A summary of these findings and a synthesis and framework for understanding the results of the intense investigation of this research are detailed herein. This clinical commentary focuses on the current understanding, identification and interventional targeting of the primary neuromuscular and biomechanical risk factors associated with the ACL injury mechanism in high-risk individuals. PMID:21655382

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

    PubMed Central

    ROY CHOWDHURY, Uttio; FAUTSCH, Michael P.

    2015-01-01

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

  6. 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

  7. Advances in the understanding of host response associated with tumor PDT

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen

    2007-02-01

    Photodynamic therapy (PDT) is clinically established modality used for treatment of solid cancers and other conditions, which destroys lesions by localized generation of cytotoxic oxygen species mediated by administered drugs (photosensitizers) that are activated at targeted sites by exposure to light. Since over 20 years ago it has become increasingly clear that important contribution to the antitumor effect of PDT is secured by host reaction induced by this therapy and manifested as inflammatory and immune response. Presented is an overview of advances in the understanding of this host response associated with tumor PDT by tracing its evolution from initial breakthroughs and discoveries in the early 1980s, followed by advances preceding recent developments, and concluding with recently acquired knowledge and directions for clinical exploitation. Tribute is given to researchers making important contributions to this field during the last three decades including Drs. Gianfranco Canti, Julia Levy, and Barbara Henderson.

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

    PubMed

    Tunick, Michael H; Gummalla, Sanjay

    2014-06-25

    A symposium titled "Advances in the Understanding of Dairy and Cheese Flavors" was held in September 2013 at the American Chemical Society's 246th National Meeting in Indianapolis, IN, USA. The symposium, which was sponsored by the Division of Agricultural and Food Chemistry, was to discuss the state of the art in the detection and quantitation of flavor in dairy products. The authors of two of the presentations have been selected to expand on their talks by submitting full papers about their research. PMID:24911867

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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.

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

    PubMed Central

    Weiss, Brendan M; Kuehl, W Michael

    2010-01-01

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

  17. 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

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

    PubMed

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

    2016-02-10

    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

  19. 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.

  20. 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

  1. 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

  2. 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

  3. 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

  4. First results on fast wave current drive in advanced tokamak discharges in DIII-D

    SciTech Connect

    Prater, R.; Cary, W.P.; Baity, F.W.

    1995-07-01

    Initial experiments have been performed on the DIII-D tokamak on coupling, direct electron heating, and current drive by fast waves in advanced tokamak discharges. These experiments showed efficient central heating and current drive in agreement with theory in magnitude and profile. Extrapolating these results to temperature characteristic of a power plant (25 keV) gives current drive efficiency of about 0.3 MA/m{sup 2}.

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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.

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

    DOE PAGESBeta

    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

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

    PubMed Central

    Olsson, Ida

    2010-01-01

    Significant progress has been made in understanding the functional organisation of the cell nucleus. Still many questions remain to be answered about the relationship between the spatial organisation of the nucleus and the regulation of the genome function. There are many conflicting data in the field making it very difficult to merge published results on mammalian cells into one model on subnuclear chromatin organisation. The fission yeast, Schizosaccharomyces pombe, over the last decades has emerged as a valuable model organism in understanding basic biological mechanisms, especially the cell cycle and chromosome biology. In this review we describe and compare the nuclear organisation in mammalian and fission yeast cells. We believe that fission yeast is a good tool to resolve at least some of the contradictions and unanswered questions concerning functional nuclear architecture, since S. pombe has chromosomes structurally similar to that of human. S. pombe also has the advantage over higher eukaryotes in that the genome can easily be manipulated via homologous recombination making it possible to integrate the tools needed for visualisation of chromosomes using live-cell microscopy. Classical genetic experiments can be used to elucidate what factors are involved in a certain mechanism. The knowledge we have gained during the last few years indicates similarities between the genome organisation in fission yeast and mammalian cells. We therefore propose the use of fission yeast for further advancement of our understanding of functional nuclear organisation. PMID:21113595

  13. 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

  14. 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

  15. Comparison of intergrated coal gasification combined cycle power plants with current and advanced gas turbines

    SciTech Connect

    Banda, B.M.; Evans, T.F.; McCone, A.I.; Westisik, J.H.

    1984-08-01

    Two recent conceptual design studies examined ''grass roots'' integrated gasification-combined cycle (IGCC) plants for the Albany Station site of Niagara Mohawk Power Corporation. One of these studies was based on the Texaco Gasifier and the other was developed around the British Gas Co.-Lurgi slagging gasifier. Both gasifiers were operated in the ''oxygen-blown'' mode, producing medium Btu fuel gas. The studies also evaluated plant performance with both current and advanced gas turbines. Coalto-busbar efficiencies of approximately 35 percent were calculated for Texaco IGCC plants using current technology gas turbines. Efficiencies of approximately 39 percent were obtained for the same plant when using advanced technology gas turbines.

  16. 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

  17. 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.

  18. 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

  19. 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

  20. Advances and limits of using population genetics to understand local adaptation.

    PubMed

    Tiffin, Peter; Ross-Ibarra, Jeffrey

    2014-12-01

    Local adaptation shapes species diversity, can be a stepping stone to ecological speciation, and can facilitate species range expansion. Population genetic analyses, which complement organismal approaches in advancing our understanding of local adaptation, have become widespread in recent years. We focus here on using population genetics to address some key questions in local adaptation: what traits are involved? What environmental variables are the most important? Does local adaptation target the same genes in related species? Do loci responsible for local adaptation exhibit trade-offs across environments? After discussing these questions we highlight important limitations to population genetic analyses including challenges with obtaining high-quality data, deciding which loci are targets of selection, and limits to identifying the genetic basis of local adaptation. PMID:25454508

  1. Advanced MRI techniques to improve our understanding of experience-induced neuroplasticity.

    PubMed

    Tardif, Christine Lucas; Gauthier, Claudine Joëlle; Steele, Christopher John; Bazin, Pierre-Louis; Schäfer, Andreas; Schaefer, Alexander; Turner, Robert; Villringer, Arno

    2016-05-01

    Over the last two decades, numerous human MRI studies of neuroplasticity have shown compelling evidence for extensive and rapid experience-induced brain plasticity in vivo. To date, most of these studies have consisted of simply detecting a difference in structural or functional images with little concern for their lack of biological specificity. Recent reviews and public debates have stressed the need for advanced imaging techniques to gain a better understanding of the nature of these differences - characterizing their extent in time and space, their underlying biological and network dynamics. The purpose of this article is to give an overview of advanced imaging techniques for an audience of cognitive neuroscientists that can assist them in the design and interpretation of future MRI studies of neuroplasticity. The review encompasses MRI methods that probe the morphology, microstructure, function, and connectivity of the brain with improved specificity. We underline the possible physiological underpinnings of these techniques and their recent applications within the framework of learning- and experience-induced plasticity in healthy adults. Finally, we discuss the advantages of a multi-modal approach to gain a more nuanced and comprehensive description of the process of learning. PMID:26318050

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

    SciTech Connect

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

    2012-05-30

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

  3. Recent advances in the understanding and management of IgA nephropathy

    PubMed Central

    Lai, Kar Neng; Leung, Joseph C.K.; Tang, Sydney C.W.

    2016-01-01

    Since its first description in 1968, IgA nephropathy has remained the most common form of primary glomerulonephritis leading to chronic kidney disease in developed countries. The clinical progression varies, and consequent end-stage renal disease occurs in 30% to 40% of patients 20 to 30 years after the first clinical presentation. Current data implicate overproduction of aberrantly glycosylated IgA1 as being pivotal in the induction of renal injury. Effective and specific treatment is still lacking, and new therapeutic approaches will be developed after better understanding the disease pathogenesis.

  4. Current understanding of synergistic interplay of chitosan nanoparticles and anticancer drugs: merits and challenges.

    PubMed

    Kandra, Prameela; Kalangi, Hemalatha Padma Jyoti

    2015-03-01

    Recent advances have been made in cancer chemotherapy through the development of conjugates for anticancer drugs. Many drugs have problems of poor stability, water insolubility, low selectivity, high toxicity, and side effects. Most of the chitosan nanoparticles showed to be good drug carriers because of their biocompatibility, biodegradability, and it can be readily modified. The anticancer drug with chitosan nanoparticles displays efficient anticancer effects with a decrease in the adverse effects of the original drug due to the predominant distribution into the tumor site and a gradual release of free drug from the conjugate which enhances drug solubility, stability, and efficiency. In this review, we discuss wider applications of numerous modified chitosan nanoparticles against different tumors and also focusing on the administration of anticancer drugs through various routes. We propose the interaction between nanosized drug carrier and tumor tissue to understand the synergistic interplay. Finally, we elaborate merits of drug delivery system at the tumor site, with emphasizing future challenges in cancer chemotherapy. PMID:25698508

  5. 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)

  6. 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…

  7. Io. [history of studies and current level of understanding of this satellite

    NASA Technical Reports Server (NTRS)

    Nash, Douglas B.; Yoder, Charles F.; Carr, Michael H.; Gradie, Jonathan; Hunten, Donald M.

    1986-01-01

    The present work reviews the history of Io studies and describes the current level of understanding of Io's physics, chemistry, geology, orbital dynamics, and geophysics. Consideration is given to the satellite's internal, superficial, atmospheric, plasma, and magnetospheric properties and how they interrelate. A pictorial map of Io's surface based on Voyager 1 and 2 images is presented. It is found that Io's surface color and spectra are dominated by sulfur compounds which may include various sulfur allotropes. Volcanic processes yielding three kinds of surface features (vent regions, plains, and mountains) dominate Io's surface geology. The Io plasma torus corotates with Jupiter's magnetic field in the plane of Jupiter's centrifugal equator centered at Io's orbital radius.

  8. A mother cell-to-forespore channel: current understanding and future challenges.

    PubMed

    Crawshaw, Adam D; Serrano, Mónica; Stanley, Will A; Henriques, Adriano O; Salgado, Paula S

    2014-09-01

    Formation of endospores allows some bacteria to survive extreme nutrient limitation. The resulting dormant cell, the spore, persists in the environment and is highly resistant to physical and chemical stresses. During spore formation, cells divide asymmetrically and the mother cell engulfs the developing spore, encasing it within a double membrane and isolating it from the medium. Communication between mother cell and isolated forespore involves a specialised connection system that allows nurturing of the forespore and continued macromolecular synthesis, required to finalise spore maturation. Here, we review current understanding of this feeding channel formed by a forespore protein, SpoIIQ, and a mother cell protein, SpoIIIAH, in the model organism Bacillus subtilis and the important human pathogen Clostridium difficile. We also analyse the presence of this channel across endospore-forming bacteria and highlight the main questions still remaining. PMID:25105965

  9. 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

  10. Enhancing our understanding of current therapies for Hepatitis C virus (HCV)

    PubMed Central

    Gogela, Neliswa A.; Lin, Ming V.; Wisocky, Jessica L.; Chung, Raymond T.

    2015-01-01

    Great progress has been made in understanding the HCV genome and its molecular virology. This understanding has culminated in the development of direct acting antiviral (DAA) agents targeting HCV viral proteins. Telaprevir (TVR) and boceprevir (BOC) were the first DAAs introduced for treatment of genotype1 HCV in 2011; when used in combination with pegylated interferon (pegIFN) and ribavirin (RBV), these protease inhibitors improved efficacy in patients with chronic HCV infection compared to the traditional dual therapy. However, this combination was associated with adverse events that often led to early termination of therapy. In late 2013, the FDA approved a second wave of DAAs, sofosbuvir (SOF) and simeprevir (SMV). The use of SOF with SMV opened the door for IFN-free combination regimens. This combination was highly efficacious and well tolerated in patients with HCV genotype 1. Sofosbuvir and ledipasvir (LDV) fixed dose oral combination (FDC) therapy were recently approved, elevating SVR rates to over 95%. We are anticipating the approval of additional IFN-free regimens with comparable efficacy and tolerability but with the addition of pangenotypic coverage, fewer drug-drug interactions and a high barrier to resistance. This review will summarize current management for chronic HCV infection. PMID:25761432

  11. Enhancing our understanding of current therapies for hepatitis C virus (HCV).

    PubMed

    Gogela, Neliswa A; Lin, Ming V; Wisocky, Jessica L; Chung, Raymond T

    2015-03-01

    Great progress has been made in understanding the HCV genome and its molecular virology. This understanding has culminated in the development of direct-acting antiviral (DAA) agents targeting HCV viral proteins. Telaprevir (TVR) and boceprevir (BOC) were the first DAAs introduced for treatment of genotype 1 HCV in 2011; when used in combination with pegylated interferon (pegIFN) and ribavirin (RBV), these protease inhibitors improved efficacy in patients with chronic HCV infection compared to the traditional dual therapy. However, this combination was associated with adverse events that often led to early termination of therapy. In late 2013, the FDA approved a second wave of DAAs, sofosbuvir (SOF) and simeprevir (SMV). The use of SOF with SMV opened the door for IFN-free combination regimens. This combination was highly efficacious and well tolerated in patients with HCV genotype 1. Sofosbuvir and ledipasvir (LDV) fixed-dose oral combination (FDC) therapy, and paritaprevir/ritonavir, ombitasvir and dasabuvir ± RBV were recently approved, elevating sustained virologic response (SVR) rates to over 95 %. We are anticipating the approval of additional IFN-free regimens with comparable efficacy and tolerability but with the addition of pangenotypic coverage, fewer drug-drug interactions, and a high barrier to resistance. This review will summarize current management for chronic HCV infection. PMID:25761432

  12. 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

  13. NIDDK international conference report on diabetes and depression: current understanding and future directions.

    PubMed

    Holt, Richard I G; de Groot, Mary; Lucki, Irwin; Hunter, Christine M; Sartorius, Norman; Golden, Sherita H

    2014-08-01

    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

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. A systematic review of HIV/AIDS-related stigma and discrimination in India: current understanding and future needs.

    PubMed

    Bharat, Shalini

    2011-01-01

    HIV/AIDS-related stigma is recognised as a major barrier to HIV prevention efforts and an impediment to mitigating its impact on individuals and communities. This paper reviews the existing research literature on AIDS stigma in India with the objective of documenting the current status of research, highlighting major findings and identifying key gaps remaining. Thirty publications were identified through a careful search of which a majority focused on stigma assessment and very few on stigma measurement, conceptual aspects of stigma or stigma reduction interventions. A few standardised stigma measures are available but more are required to assess causes of stigma among general population and compounded and internalised stigma among positive people. Research exploring linkages between stigma and HIV services uptake or the effect of HIV care and treatment programs on stigma levels are largely missing and need to be prioritised. In addition, more research is needed to advance conceptual understanding of stigma within the cultural context of the country including research on the neglected groups such as, transgender people. Context-specific (health care, community) interventions are needed to address various forms of stigma - enacted, perceived, internalised and layered - including structural approaches besides inter-personal and information-based approaches. A major gap relates to meager research on developing and evaluating stigma reduction interventions and needs priority focus. Overall, the review recommends developing a national agenda on AIDS stigma research and interventions to help realise the government's goal of stigma reduction. PMID:23237728

  2. Understanding the cancer cell phenotype beyond the limitations of current omics analyses.

    PubMed

    Moreno-Sánchez, Rafael; Saavedra, Emma; Gallardo-Pérez, Juan Carlos; Rumjanek, Franklin D; Rodríguez-Enríquez, Sara

    2016-01-01

    Efforts to understand the mechanistic principles driving cancer metabolism and proliferation have been lately governed by genomic, transcriptomic and proteomic studies. This paper analyzes the caveats of these approaches. As molecular biology's central dogma proposes a unidirectional flux of information from genes to mRNA to proteins, it has frequently been assumed that monitoring the changes in the gene sequences and in mRNA and protein contents is sufficient to explain complex cellular processes. Such a stance commonly disregards that post-translational modifications can alter the protein function/activity and also that regulatory mechanisms enter into action, to coordinate the protein activities of pathways/cellular processes, in order to keep the cellular homeostasis. Hence, the actual protein activities (as enzymes/transporters/receptors) and their regulatory mechanisms ultimately dictate the final outcomes of a pathway/cellular process. In this regard, it is here documented that the mRNA levels of many metabolic enzymes and transcriptional factors have no correlation with the respective protein contents and activities. The validity of current clinical mRNA-based tests and proposed metabolite biomarkers for cancer detection/prognosis is also discussed. Therefore, it is proposed that, to achieve a thorough understanding of the modifications undergone by proliferating cancer cells, it is mandatory to experimentally analyze the cellular processes at the functional level. This could be achieved (a) locally, by examining the actual protein activities in the cell and their kinetic properties (or at least kinetically characterize the most controlling steps of the pathway/cellular process); (b) systemically, by analyzing the main fluxes of the pathway/cellular process, and how they are modulated by metabolites, all which should contribute to comprehending the regulatory mechanisms that have been altered in cancer cells. By adopting a more holistic approach it may

  3. 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.

  4. Advanced Tokamak Regimes in Alcator C-Mod with Lower Hybrid Current Drive

    NASA Astrophysics Data System (ADS)

    Parker, R.; Bonoli, P.; Gwinn, D.; Hutchinson, I.; Porkolab, M.; Ramos, J.; Bernabei, S.; Hosea, J.; Wilson, R.

    1999-11-01

    Alcator C-Mod has been proposed as a test-bed for developing advanced tokamak scenarios owing to its strong shaping, relatively long pulse length capability at moderate field, e.g. t ~ L/R at B = 5T and T_eo ~ 7keV, and the availability of strong ICRF heating. We plan to exploit this capability by installing up to 4 MW RF power at 4.6 GHz for efficient off-axis current drive by lower hybrid waves. By launching LH waves with a grill whose n_xx spectrum can be dynamically controlled over the range 2 < n_xx < 3.5, the driven current profile can be modified so that, when combined with bootstrap current in high ɛβ_pol regimes, q_min > 2. Such reversed or nearly zero shear regimes have already been proposed as the basis of an advanced tokamak burning-plasma experiment-ATBX (M. Porkolab et al, IAEA-CN-69/FTP/13, IAEA,Yokohama 1998.), and could provide the basis for a demonstration power reactor. Theoretical and experimental basis for this advanced tokamak research program on C-Mod, including design of the lower hybrid coupler, its spectrum and current drive capabilities will be presented.

  5. Advances in the understanding of cuticular waxes in Arabidopsis thaliana and crop species.

    PubMed

    Lee, Saet Buyl; Suh, Mi Chung

    2015-04-01

    The aerial parts of plants are covered with a cuticle, a hydrophobic layer consisting of cutin polyester and cuticular waxes that protects them from various environmental stresses. Cuticular waxes mainly comprise very long chain fatty acids and their derivatives such as aldehydes, alkanes, secondary alcohols, ketones, primary alcohols, and wax esters that are also important raw materials for the production of lubricants, adhesives, cosmetics, and biofuels. The major function of cuticular waxes is to control non-stomatal water loss and gas exchange. In recent years, the in planta roles of many genes involved in cuticular wax biosynthesis have been characterized not only from model organisms like Arabidopsis thaliana and saltwater cress (Eutrema salsugineum), but also crop plants including maize, rice, wheat, tomato, petunia, Medicago sativa, Medicago truncatula, rapeseed, and Camelina sativa through genetic, biochemical, molecular, genomic, and cell biological approaches. In this review, we discuss recent advances in the understanding of the biological functions of genes involved in cuticular wax biosynthesis, transport, and regulation of wax deposition from Arabidopsis and crop species, provide information on cuticular wax amounts and composition in various organs of nine representative plant species, and suggest the important issues that need to be investigated in this field of study. PMID:25693495

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

    DOE PAGESBeta

    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

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

    NASA Astrophysics Data System (ADS)

    Murton, Julian B.; Lautridou, Jean-Pierre

    2003-02-01

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

  8. 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. PMID:17110089

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

    PubMed

    Brodersen, B W

    2014-03-01

    Bovine viral diarrhea virus (BVDV) continues to be of economic significance to the livestock industry in terms of acute disease and fetal loss. Many of the lesions relating to BVDV infection have been well described previously. The virus is perpetuated in herds through the presence of calves that are persistently infected. Relationships between various species and biotypes of BVDV and host defenses are increasingly understood. Understanding of the host defense mechanisms of innate immunity and adaptive immunity continues to improve, and the effects of the virus on these immune mechanisms are being used to explain how persistent infection develops. The noncytopathic biotype of BVDV plays the major role in its effects on the host defenses by inhibiting various aspects of the innate immune system and creation of immunotolerance in the fetus during early gestation. Recent advances have allowed for development of affordable test strategies to identify and remove persistently infected animals. With these improved tests and removal strategies, the livestock industry can begin more widespread effective control programs. PMID:24476940

  10. 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

  11. 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. PMID:26920883

  12. Godzilla Mullion: current understanding on the nature of the world’s largest oceanic core complex

    NASA Astrophysics Data System (ADS)

    Ohara, Y.; Snow, J. E.

    2009-12-01

    Oceanic core complex (OCC) provides a valuable opportunity to directly study the architecture of oceanic lithosphere, together with the tectono-magmatic processes that were associated with its formation and evolution. The world’s largest OCC, Godzilla Mullion, occurs along the Parece Vela Rift, extinct spreading center of the Parece Vela Basin in the Philippine Sea. Backarc basins are not in some way anomalous, but are in fact generating a significant fraction of the total oceanic crust. Therefore, the opportunity to explore the architecture of Godzilla Mullion is an important contribution to the overall understanding of oceanic lithosphere. In order to understand the different processes of OCC formation and the composition of the backarc mantle, and to provide a comparison of present day backarc mantle useful for the study of ophiolitic lower crustal and mantle sequences, we have conducted a series of cruises to the area in the last decade. In 2009, during YK09-05 cruise of R/V Yokosuka, we performed successful 9 dives of Shinkai 6500 and 3 dives of deep-towed camera, resulting in 12 new sample locations on the surface of Godzilla Mullion. The number of sample locations on the surface of Godzilla Mullion is now 36 different locations in total. Before YK09-05 cruise, we used a single name of “Godzilla Mullion” for its description. However, now that we have 36 sample locations, it has become difficult to describe the very enormous OCC with a single name. We thus have given 13 different names to the distinct topographic elements of Godzilla Mullion. In this contribution, we will introduce our current understanding of the nature of Godzilla Mullion, summarizing the recent results of geological mapping and its comparison with seismic tomography model. Godzilla Mullion has large lateral heterogeneity in the crust, varying from the region dominated with mantle peridotite overlain by a carapace of diabase and basalt, to the region with a massive gabbroic section

  13. 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.

  14. HIV transmission through breastmilk: the science behind the understanding of current trends and future research.

    PubMed

    Prameela, K K

    2012-12-01

    Breastmilk protects the infant from many diseases and many short- term and long- term benefits accrue. At the same time it is also known that breastfeeding acts as a vehicle for some infective agents. It is now accepted that breastmilk transmission of Human Immunodeficiency Virus- 1 (HIV-1) is an important mode of paediatric infection . Despite this fact, many researchers have observed that corresponding to the volume of milk consumed by the infant, maternal transmission via breastmilk is still comparatively low. Some have noted the long latency period of breastmilk HIV transmission with evidence of numerous anti-HIV factors in breastmilk. Although there are accepted standard guidelines on infant feeding in mothers who are HIV positive in many countries, it maybe equally important to realize gaps in our knowledge of mother- to -child HIV transmission. From an evolutionary perspective, the role of the mammary epithelial cell (MEC) and of breastmilk , in contributing to and possibly in influencing HIV-1 transmission is intriguing. The presence of HIV-1 or of other viruses in maternal milk seem to be a requisite to spur immunological defenses to optimize necessary protection to the infant. This article reviews some aspects of the science of HIV transmission through breastmilk and reflects the concept -based understanding of current policies on HIV and breastfeeding. At the same time, it highlights uncertainties in this field and the urgency for future research in this direction. Accepting current notions of breastmilk HIV transmission, greater deliberation by research may throw more light on why breastfeeding with its abundant advantages is fraught with the hazards of transmission of a deadly disease. PMID:23770969

  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. PMID:25295051

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

    PubMed Central

    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 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.

  18. 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

  19. 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

  20. 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. PMID:26776309

  1. 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

  2. Parathyroid Carcinoma: Current Understanding and New Insights into Gene Expression and Intraoperative Parathyroid Hormone Kinetics

    PubMed Central

    Abdelgadir Adam, Mohamed; Untch, Brian R.

    2010-01-01

    Parathyroid carcinoma is an indolent but ultimately life-threatening malignancy. Due to the lack of definitive diagnostic markers and overlapping clinical features of benign primary hyperparathyroidism (PHPT), this disease is often misdiagnosed as parathyroid adenoma. Therefore, a high index of suspicion preoperatively and early intraoperative recognition with en bloc surgical resection are crucial for favorable outcome. Owing to the rarity of the disease, little is known about the molecular pathogenesis of parathyroid carcinoma. Here, we review the literature to present current understanding of the disease and provide new information on gene expression and use of intraoperative parathyroid hormone (PTH) monitoring in the surgical management of this rare malignancy. Specifically, using microarray transcriptome analysis of an unequivocal case of parathyroid carcinoma and a biopsy from the same patient's normal parathyroid gland, we identify APP, CDH1, KCNJ16, and UCHL1 as differentially expressed genes in parathyroid carcinoma. Further, using case records from four cases of unequivocal parathyroid carcinoma, we compared intraoperative PTH kinetics of these patients to 475 patients with benign PHPT, and show that intraoperative PTH monitoring is accurate in predicting postoperative normocalcemia in initial en bloc operations for parathyroid carcinoma. PMID:20051478

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. Neoadjuvant treatment in advanced renal cell carcinoma: current situation and future perspectives.

    PubMed

    Timsit, Marc-Olivier; Albiges, Laurence; Méjean, Arnaud; Escudier, Bernard

    2012-12-01

    Neoadjuvant approaches in renal cell carcinoma are currently under investigation, following the demonstration of targeted therapy efficacy in the metastatic setting. It raises the issues of downsizing locally advanced or nonresectable tumor and offering organ-sparing surgery, safety and its potential role in early micrometastatic disease. Relevant studies of the neoadjuvant setting in renal cell carcinoma with targeted therapies were identified from the literature, clinical trial databases and conference abstracts. To date, a neoadjuvant approach appears feasible in terms of safety. Currently available drugs do not achieve major tumor downsizing with primary tumor diameters response rate of 10%. Neoadjuvants should only be considered in clinical trials or as a litmus test in locally advanced patients. PMID:23253222

  9. 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

  10. 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. PMID:26323825

  11. Current state-of-the-art of device therapy for advanced heart failure

    PubMed Central

    Lee, Lawrence S.; Shekar, Prem S.

    2014-01-01

    Heart failure remains one of the most common causes of morbidity and mortality worldwide. The advent of mechanical circulatory support devices has allowed significant improvements in patient survival and quality of life for those with advanced or end-stage heart failure. We provide a general overview of past and current mechanical circulatory support devices encompassing options for both short- and long-term ventricular support. PMID:25559828

  12. 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.

  13. 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

  14. 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

  15. Advances in Understanding Top-of-Atmosphere Radiation Variability from Satellite Observations

    NASA Astrophysics Data System (ADS)

    Loeb, Norman G.; Kato, Seiji; Su, Wenying; Wong, Takmeng; Rose, Fred G.; Doelling, David R.; Norris, Joel R.; Huang, Xianglei

    2012-07-01

    This paper highlights how the emerging record of satellite observations from the Earth Observation System (EOS) and A-Train constellation are advancing our ability to more completely document and understand the underlying processes associated with variations in the Earth's top-of-atmosphere (TOA) radiation budget. Large-scale TOA radiation changes during the past decade are observed to be within 0.5 Wm-2 per decade based upon comparisons between Clouds and the Earth's Radiant Energy System (CERES) instruments aboard Terra and Aqua and other instruments. Tropical variations in emitted outgoing longwave (LW) radiation are found to closely track changes in the El Niño-Southern Oscillation (ENSO). During positive ENSO phase (El Niño), outgoing LW radiation increases, and decreases during the negative ENSO phase (La Niña). The coldest year during the last decade occurred in 2008, during which strong La Nina conditions persisted throughout most of the year. Atmospheric Infrared Sounder (AIRS) observations show that the lower temperatures extended throughout much of the troposphere for several months, resulting in a reduction in outgoing LW radiation and an increase in net incoming radiation. At the global scale, outgoing LW flux anomalies are partially compensated for by decreases in midlatitude cloud fraction and cloud height, as observed by Moderate Resolution Imaging Spectrometer and Multi-angle Imaging SpectroRadiometer, respectively. CERES data show that clouds have a net radiative warming influence during La Niña conditions and a net cooling influence during El Niño, but the magnitude of the anomalies varies greatly from one ENSO event to another. Regional cloud-radiation variations among several Terra and A-Train instruments show consistent patterns and exhibit marked fluctuations at monthly timescales in response to tropical atmosphere-ocean dynamical processes associated with ENSO and Madden-Julian Oscillation.

  16. 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.

  17. 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.

  18. Pathophysiology of asthma: what has our current understanding taught us about new therapeutic approaches?

    PubMed

    Holgate, Stephen T

    2011-09-01

    Current asthma therapy is based on the use of adrenergic bronchodilator and anti-inflammatory drugs the specificity, efficacy, duration of action, and safety of which have been derived through classical pharmacology and medicinal chemistry. That asthma is a T(H)2-type inflammatory disorder frequently associated with atopy and allergic comorbidities has led to a concentrated effort to find treatments that act selectively on this pathway. A systematic literature review was undertaken, as well as a review of the Web site Clinicaltrials.gov for ongoing trials. Targets have included T cells themselves and their associated cytokines, chemokines, and receptors mostly targeted with biological agents. With the exception of anti-human IgE, none of these have met the expectations predicted from animal models and human in vitro tests. For most of these new therapies, only a very small subpopulation appears to respond. A case is made for a different approach to drug discovery based on acquiring a greater understanding of asthma stratification, the relevant pathways involved, and the development of appropriate diagnostic tests enabling the targeting of selective treatments to those asthmatic phenotypes most likely to respond. The recognition that asthma is more than allergy mandates improved predictive animal models and an appreciation that many of the environmental insults that initiate, consolidate, and exacerbate asthma operate through an epithelium functioning in a disorderly fashion. An integrated model that places the epithelium at the forefront of asthma pathogenesis suggests that greater emphasis should be placed on therapeutics that increase the airways' resistance against the inhaled environment rather than focusing only on suppression of inflammation. PMID:21807404

  19. 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

  20. 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...

  1. 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. PMID:25037625

  2. 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

  3. 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.

  4. Warfighter nutrition: current opportunities and advanced technologies report from a Department of Defense workshop.

    PubMed

    Deuster, Patricia A; Weinstein, Ali A; Sobel, Annette; Young, Andrew J

    2009-07-01

    The Uniformed Services University hosted a conference in July 2008 entitled "Warfighter Nutrition: Advanced Technologies and Opportunities" with Health Affairs and the Defense Advanced Research Projects Agency to develop strategic and tactical plans that could enhance Force Health Protection (FHP) by optimizing warfighter nutrition within the Department of Defense (DoD). The conference focused on three aspects of military nutrition: (1) fueling the forces, or garrison feeding; (2) performance optimization or operational feeding during deployment; and (3) nutritional interventions to support health reset and healing. Presentations by speakers addressed practical interventions (i.e., ready for implementation now) and advanced technologies (i.e., approaches meriting prioritized research and development efforts to transition into application). The conference concluded that nutritional optimization represents an integral and proactive approach to prevent illness, injury, and performance degradation throughout all phases of military service. The overarching consensus achieved was that warfighter nutrition, as a cornerstone of FHP, warrants the critical attention of both medical and line leadership to move quickly to support current initiatives and future advanced technologies. PMID:19685836

  5. 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.

  6. Current Advances in the Translation of Vascular Tissue Engineering to the Treatment of Pediatric Congenital Heart Disease

    PubMed Central

    Dean, Ethan W.; Udelsman, Brooks; Breuer, Christopher K.

    2012-01-01

    Tissue-engineered vascular grafts (TEVGs) hold great promise for the improvement of outcomes in pediatric patients with congenital cardiac anomalies. Currently used synthetic grafts have several limitations, including thrombogenicity, increased risk of infection, and lack of growth potential. The first pilot clinical trial of TEVGs demonstrated the feasibility of this new technology and revealed an excellent safety profile. However, long-term follow-up from this trial revealed the primary graft-related complication to be stenosis, affecting 16 percent of grafts within 7 years post-implantation. In order to determine the mechanism behind TEVG stenosis and ultimately to create improved second generation TEVGs, our group has returned to the bench to study vascular neotissue formation in a variety of large and small animal models. The purpose of this report is to review the recent advances in the understanding of neotissue formation and vascular tissue engineering. PMID:22737051

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

    NASA Technical Reports Server (NTRS)

    Hughes, William O.

    2003-01-01

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

  8. 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

  9. Stereotactic radiosurgery of glomus jugulare tumors: current concepts, recent advances and future perspectives.

    PubMed

    Sager, Omer; Dincoglan, Ferrat; Beyzadeoglu, Murat

    2015-01-01

    Stereotactic radiosurgery (SRS), a very highly focused form of therapeutic irradiation, has been widely recognized as a viable treatment option in the management of intracranial pathologies including benign tumors, malign tumors, vascular malformations and functional disorders. The applications of SRS are continuously expanding thanks to the ever-increasing advances and corresponding improvements in neuroimaging, radiation treatment techniques, equipment, treatment planning and delivery systems. In the context of glomus jugulare tumors (GJT), SRS is being more increasingly used both as the upfront management modality or as a complementary or salvage treatment option. As its safety and efficacy is being evident with compiling data from studies with longer follow-up durations, SRS appears to take the lead in the management of most patients with GJT. Herein, we address current concepts, recent advances and future perspectives in SRS of GJT in light of the literature. PMID:25768334

  10. The importance of Titan's current mass loss processes to understanding the evolution of Titan's atmosphere

    NASA Astrophysics Data System (ADS)

    Mandt, Kathleen; Waite, J. Hunter, Jr.; Bell, Jared; Mousis, Olivier

    2010-04-01

    Current isotopic ratios in planetary atmospheres have played an important role in determining how that atmosphere has evolved over geologic time scales (e.g. Donahue et al. 1997, Lunine et al. 1999). The current 12C/13C ratio in methane is a particularly useful indicator of Titan's atmospheric evolutionary history (Mandt et al. 2009). Primordial 12C/13C ratios throughout the solar system are limited to 89.01+4.45-2.67. (Alexander et al. 2007, Martins et al. 2008), while the methane 12C/13C ratio measured by GCMS and CIRS are 82.3+/-1.0 and 76.6+/-2.7 respectively (Niemann et al. 2005, Nixon et al. 2008). This is well below the primordial range, suggesting fractionation of the isotopes by atmospheric processes. A number of atmospheric mass loss processes can fractionate the isotopes over geologic time scales. Photochemistry and escape are of particular importance (Donahue et al 1997, Mandt et al. 2009). Measurements of the 12C/13C ratios in C2 hydrocarbons show evidence of fractionation due to photochemistry (Nixon et al. 2008) that is most likely due to a kinetic isotope effect (KIE). A KIE is a mildly efficient fractionating process in which reactions involving 12C occur 1.04 times faster than reactions involving 13C. A moderate time scale, on the order of 50 to 400 million years, is required to change the 12C/13C ratio of the atmospheric methane inventory. The exact length of this time scale depends directly on the methane photochemical loss rate. Titan's photochemistry is extremely complex, and although the total photochemical loss rate is photon-limited (Lorenz et al. 1997), the literature provides a range of loss rates between 4.9 x 10^9 cm-2s-1 (Wilson and Atreya 2004) and 3.4 x 10^10 cm-2s-1 (Lebonnois et al. 2003). This range can alter the time scale for fractionation in the carbon isotopes by as much as a factor of 8. INMS measurements of the methane 12C/13C ratio in the upper atmosphere show that atmospheric escape is a more efficient fractionating

  11. Advanced computational multi-fluid dynamics: a new model for understanding electrokinetic phenomena in porous media

    NASA Astrophysics Data System (ADS)

    Gulamali, M. Y.; Saunders, J. H.; Jackson, M. D.; Pain, C. C.

    2009-04-01

    We present results from a new computational multi-fluid dynamics code, designed to model the transport of heat, mass and chemical species during flow of single or multiple immiscible fluid phases through porous media, including gravitational effects and compressibility. The model also captures the electrical phenomena which may arise through electrokinetic, electrochemical and electrothermal coupling. Building on the advanced computational technology of the Imperial College Ocean Model, this new development leads the way towards a complex multiphase code using arbitrary unstructured and adaptive meshes, and domains decomposed to run in parallel over a cluster of workstations or a dedicated parallel computer. These facilities will allow efficient and accurate modelling of multiphase flows which capture large- and small-scale transport phenomena, while preserving the important geology and/or surface topology to make the results physically meaningful and realistic. Applications include modelling of contaminant transport in aquifers, multiphase flow during hydrocarbon production, migration of carbon dioxide during sequestration, and evaluation of the design and safety of nuclear reactors. Simulations of the streaming potential resulting from multiphase flow in laboratory- and field-scale models demonstrate that streaming potential signals originate at fluid fronts, and at geologic boundaries where fluid saturation changes. This suggests that downhole measurements of streaming potential may be used to inform production strategies in oil and gas reservoirs. As water encroaches on an oil production well, the streaming-potential signal associated with the water front encompasses the well even when the front is up to 100 m away, so the potential measured at the well starts to change significantly relative to a distant reference electrode. Variations in the geometry of the encroaching water front could be characterized using an array of electrodes positioned along the well

  12. 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

  13. 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.

  14. An update on current management of advanced renal cell cancer, biomarkers, and future directions

    PubMed Central

    Zhi, Wanqing Iris; Kim, Jenny J.

    2015-01-01

    In the past decade, metastatic renal cell carcinoma (mRCC) treatment underwent significant advancement that resulted in an unprecedented improvement in the prognosis of this disease. This review will provide an updated review of currently approved treatment options, namely antiangiogenic and immunotherapy, as well as treatment guideline recommended by the National Comprehensive Cancer Network (NCCN). We will summarize studies ongoing in determining prognostic and predictive biomarkers in maximizing therapeutic benefit in the treatment of this disease. Lastly, we will discuss promising agents in clinical testing. PMID:25722991

  15. 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.

  16. Recent Observational Advances in our Understanding of Magnetic Reconnection in Earth's Magnetosphere

    NASA Astrophysics Data System (ADS)

    Angelopoulos, V.

    2014-12-01

    The availability of multi-point observations through the ion diffusion region has provided a wealth of information on the workings of magnetic reconnection at the dayside magnetopause and at the nightside plasma sheet. Ion inertia and finite gyroradius result in clear Hall effects on ion inertial length scales that have been observed by single and multi-point spacecraft resulting in a fairly detailed understanding of that physics. The role of Hall dynamics on establishing the reconnection rate, and the outflow conditions is well understood. Electron violation of the frozen-in condition is much more subtle and rarely observed at the X-point; indirect evidence has been more frequently observed in parallel electric fields. The waves responsible for this violation and for resultant energy conversion are at the forefront of observational studies. The contraction of islands centered at multiple O-points could provide for rapid energy conversion. However, observations of in vivo FTEs at the dayside and classical plasmoids at the nightside, are rare even near the expected most probable location of reconnection. Rather, asymmetric proto-plasmoids and dipolarization (a.k.a reconnection) fronts at the nightside signify distinctly different evolution of the reconnection geometry from that of X and O points. Operating within meso-scale (1-3Re) flows the inherently kinetic (at electron inertial scales embeded in ion inertial scale current systems) processes at such fronts play a significant role in the dynamics and drive global magnetospheric energy conversion and flux transport. Recent studies suggest that the entire magnetosphere is, in fact, connected front-to-back by reconnection pulses resulting in meso-scale flows. The upcoming Heliophysics System Observatory, motivated by the launch of MMS and the coordinated observations of THEMIS, ARTEMIS, Van Allen probes and other space and ground assets will answer key questions on this subject locally, regionally and globally.

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

    PubMed Central

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

    2014-01-01

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

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. Recent advances in understanding/management of non-alcoholic steatohepatitis.

    PubMed

    Pacana, Tommy; Sanyal, Arun J

    2015-01-01

    Non-alcoholic steatohepatitis (NASH) can lead to advanced fibrosis, hepatocellular carcinoma, and end-stage liver disease requiring liver transplantation. A myriad of pathways and genetic influence contribute to NASH pathogenesis and liver disease progression. Diagnosing patients with NASH and advanced fibrosis is critical prior to treatment and prognostication. There has been ongoing interest in developing non-invasive biomarkers and tools for identifying NASH and advanced fibrosis. To date, there has been no approved therapy for NASH. Recently, the FLINT (Farnesoid X Receptor [FXR] Ligand Obeticholic Acid in NASH Treatment) trial provided promising results of the efficacy of obeticholic acid, a farnesoid X receptor agonist, in improving histological features of NASH and fibrosis. Long-term studies are needed to assess the safety of obeticholic acid and its effects on liver- and cardiovascular-related outcomes. PMID:25926979

  3. Challenges, current status and future perspectives of proteomics in improving understanding, diagnosis and treatment of vascular disease

    PubMed Central

    Moxon, Joseph V.; Padula, Matthew P.; Herbert, Ben R.; Golledge, Jonathan

    2009-01-01

    Technical advances have seen the rapid adoption of genomics and multiplex genetic polymorphism identification to research on vascular diseases. The utilization of proteomics for the study of vascular diseases has been limited by comparison. In this review we outline currently available proteomics techniques, the challenges to using these approaches and modifications which may improve the utilization of proteomics in the study of vascular diseases. PMID:19541510

  4. 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…

  5. 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…

  6. 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…

  7. 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

  8. 48 CFR 1552.215-74 - Advanced understanding-uncompensated time.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...-uncompensated time. 1552.215-74 Section 1552.215-74 Federal Acquisition Regulations System ENVIRONMENTAL... Clauses 1552.215-74 Advanced understanding—uncompensated time. As prescribed in 1515.408(b), insert the...—Uncompensated Time (AUG 1999) (a) The estimated cost of this contract is based upon the Contractor's...

  9. 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.…

  10. 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…

  11. 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…

  12. 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…

  13. A Study of Three Impoverished Preschoolers with Advanced Understanding of Literacy.

    ERIC Educational Resources Information Center

    Smith, Susan Robinson; Rotman, Molly

    A study examined factors that may foster advanced knowledge of literacy among impoverished preschoolers who are generally found to be academically at-risk in learning to read. Six preschoolers enrolled in a Head Start program were identified by teacher recommendation as showing profound interest in written language (looking at books, writing…

  14. 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.…

  15. 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…

  16. 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

  17. A survey to determine current practice patterns in the surgical treatment of advanced thumb carpometacarpal osteoarthrosis

    PubMed Central

    Brunton, Lance M.

    2010-01-01

    Background The purpose of this study was to determine current practice patterns and examine the influence of recent evidence in the surgical treatment of advanced thumb carpometacarpal (CMC) osteoarthrosis. Methods A survey was sent to 2,536 American Society for Surgery of the Hand members. Information regarding specialty training, years of experience, annual cases performed, treatment of choice, technique, and postoperative immobilization was collected. Respondents were asked whether their current treatment of choice differs from what they performed 5 years ago and about the importance of ligament reconstruction and “interposition” to thumb CMC arthroplasty success. Results One thousand twenty-four respondents completed the survey (40% response rate). Treatment of choice was trapeziectomy with ligament reconstruction and tendon interposition (68%), regardless of specialty training, years of experience, and annual cases performed. Over 70% favored treatment that was not different from what they performed 5 years ago. Less than 3% of respondents perform a trapeziectomy alone; only 14 surgeons have changed to this procedure in the last 5 years. Only 35% of the 822 respondents who perform a ligament reconstruction and 14% of the 764 respondents who perform an interposition believe those techniques are “extremely important” to thumb CMC arthroplasty success. Conclusions Despite recent evidence that suggests neither ligament reconstruction nor tendon interposition confers any additional benefit over trapeziectomy alone, few respondents have converted to the simpler procedure. Either the current evidence is not convincing enough to drastically change practice patterns, or other factors apart from this evidence have a greater influence on surgical decision-making for advanced thumb CMC osteoarthrosis. Electronic supplementary material The online version of this article (doi:10.1007/s11552-010-9275-7) contains supplementary material, which is available to

  18. 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

  19. 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.

  20. 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…

  1. 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…

  2. Sailing toward Understanding Surface Currents: A Science and Geography Integration Activity for Upper-Elementary Students

    ERIC Educational Resources Information Center

    Eidietis, Laura; Rutherford, Sandra

    2009-01-01

    In the activities presented in this article, students mimic real scientists while constructing predictions and scientific explanations about surface currents. The activities are inspired by and couched within true scientific inquiries regarding the ocean and the North American Great Lakes. Students engage in a classroom inquiry and use map-reading…

  3. [Current 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

  4. 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).

  5. Commentary: Advancing Our Understanding of Asian American Child Development: History, Context, and Culture as Essential Considerations.

    PubMed

    McLoyd, Vonnie C

    2016-07-01

    The Special Section will help scholars make informed choices about how to conceptualize developmental processes and assess contextually and culturally relevant variables in future research with Asian American children and youth. It undertakes tasks and addresses challenges that have broad relevance to the study of developmental processes and stands as a reminder of the vital role of interdisciplinary perspectives in the advancement of developmental science. PMID:27392798

  6. Status of Advanced Tokamak Scenario Modeling with Off-Axis Electron Cyclotron Current Drive in DIII-D

    SciTech Connect

    M. Murakami; H.E. St.John; T.A. Casper; M.S. Chu; J.C. DeBoo; C.M. Greenfield; J.E. Kinsey; L.L. Lao; R.J. La Haye; Y.R. Lin-Liu; T.C. Luce; P.A. Politzer; B.W. Rice; G.M. Staebler; T.S. Taylor; M.R. Wade

    1999-12-01

    The status of modeling work focused on developing the advanced tokamak scenarios in DIII-D is discussed. The objectives of the work are two-fold: (1) to develop AT scenarios with ECCD using time-dependent transport simulations, coupled with heating and current drive models, consistent with MHD equilibrium and stability; and (2) to use time-dependent simulations to help plan experiments and to understand the key physics involved. Time-dependent simulations based on transport coefficients derived from experimentally achieved target discharges are used to perform AT scenario modeling. The modeling indicates off-axis ECCD with approximately 3 MW absorbed power can maintain high-performance discharges with q{sub min} > 1 for 5 to 10 s. The resultant equilibria are calculated to be stable to n = 1 pressure driven modes. The plasma is well into the second stability regime for high-n ballooning modes over a large part of the plasma volume. The role of continuous localized ECCD is studied for stabilizing m/n = 2/1 tearing modes. The progress towards validating current drive and transport models, consistent with experimental results, and developing self-consistent, integrated high performance AT scenarios is discussed.

  7. 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.

  8. 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

  9. Acid deposition: atmospheric processes in eastern North America, a review of current scientific understanding

    SciTech Connect

    Not Available

    1983-01-01

    There is no observational evidence of a strong nonlinearity in the relationship between annual average total emissions and total deposition of sulfur in eastern North America. The finding is supported by theoretical calculations using the best available laboratory measurements of photochemical rate parameters. Currently available models of long-range atmospheric transport and transformation are not sufficiently developed to assess relationships between emissions from specific sources and deposition at specific receptor sites with high reliability.

  10. 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

  11. Carbon dynamics and changing winter conditions: a review of current understanding and future research directions

    NASA Astrophysics Data System (ADS)

    Haei, M.; Laudon, H.

    2015-09-01

    Despite the important role of winters for northern ecosystems, it remains the least understood of all the seasons. Here, we summarize existing empirical studies on winter climate and carbon dynamics and highlight some important future research directions. The existing studies include field-scale snow-cover manipulation experiments representing extreme soil climate conditions, laboratory soil incubations studying the influential factors, and time-series of climate and carbon data showing long-term natural variations and existing trends. Most of the field and laboratory experiments indicate an increased soil organic carbon loss due to soil frost. Long-term data demonstrate temporal changes in winter CO2 efflux and its important contribution to the annual fluxes. A number of research priorities to improve our understanding of winter conditions include (i) ecosystem processes in the fall-winter and winter-spring shoulder seasons, (ii) extreme events, (iii) partitioning into organic- and inorganic carbon, (iv) carry-over effects of winter and growing season on each other, (v) long-term cumulative impacts, and (vi) improved winter process modelling. These areas of research would enable an improved understanding of the role of the snow covered period for carbon cycling, and provide a basis for more realistic models that include winter processes.

  12. 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

  13. 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

  14. 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

  15. An eddy-current model for three-dimensional nondestructive evaluation of advanced composites

    NASA Astrophysics Data System (ADS)

    Sabbagh, Harold A.; Murphy, R. Kim; Sabbagh, Elias H.

    2015-03-01

    We have developed a rigorous electromagnetic model and an inversion algorithm for the three-dimensional NDE of advanced composite materials. This approach extends Victor Technologies' work in eddy-current NDE of conventional metals, and allows one to determine in localized regions the fiber-resin ratio in graphite-epoxy, and to determine those anomalies, e.g., delaminations, broken fibers, moisture content, etc., that can be reconstructed by our inversion method. In developing the model, we apply rigorous electromagnetic theory to determine a Green's function for a slab of anisotropic composite material, and then determine the integral relations for the forward and inverse problems using the Green's function. We will give examples of the solution of forward problems using this model.

  16. 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

  17. 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.

  18. 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. PMID:24351010

  19. 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

  20. 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

  1. Health in fragile and post-conflict states: a review of current understanding and challenges ahead.

    PubMed

    Haar, Rohini J; Rubenstein, Leonard S

    2012-01-01

    Health systems face enormous challenges in fragile and post-conflict states. This paper will review recent literature to better understand how, within a context of economic volatility, political instability, infrastructural collapse and human resource scarcity, population health deteriorates and requires significant attention and resources to rebuild. Classifications of fragile and post-conflict states differ among organizations and reviewing the basic consensus as well as differences will assist in clarifying how organizations use these terms and how statistics on these nations come about. Of particular interest is the increase in local conflicts within states that may not affect national mortality and morbidity but pose heavy burdens on regional populations. Recent research on sexual and reproductive health, children's health and mental health within fragile and post-conflict states highlights the effects of healthcare systems and their breakdown on communities. We propose a research agenda to further explore knowledge gaps concerning health in fragile and post-conflict states. PMID:23421305

  2. Does Titan have an ocean? A review of current understanding of Titan's surface

    NASA Astrophysics Data System (ADS)

    Lunine, J. I.

    1993-05-01

    An attempt is made to provide a balanced perspective regarding the knowledge of Titan's surface and how well current models address the various sets of data. Topics discussed include the Voyager data that led to the notion of a massive, global-scale hydrocarbon ocean; recent data sets including radar, radiometry, and NIR photometry that bear on the nature of the surface. Attention is also given to models of the surface that attempt to fit all of the constraints; and the Cassini investigations of Titan's surface. The surface and regolith of Titan are considered to be most likely a repository of liquid methane, other hydrocarbons, and dissolved nitrogen.

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

    ERIC Educational Resources Information Center

    Brechwald, Whitney A.; Prinstein, Mitchell J.

    2011-01-01

    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…

  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. Recent advances in the understanding of male lower urinary tract symptoms (LUTS)

    PubMed Central

    Kahokehr, Arman A.; Gilling, Peter J.

    2016-01-01

    In this review, we have looked at three important areas in understanding male lower urinary tract symptoms. These are improvement in terminology, detrusor underactivity, and nocturia. Benign prostatic hyperplasia leading to bladder outlet obstruction has been covered in a previous review. PMID:27134738

  6. Recent advances in the understanding of male lower urinary tract symptoms (LUTS).

    PubMed

    Kahokehr, Arman A; Gilling, Peter J

    2016-01-01

    In this review, we have looked at three important areas in understanding male lower urinary tract symptoms. These are improvement in terminology, detrusor underactivity, and nocturia. Benign prostatic hyperplasia leading to bladder outlet obstruction has been covered in a previous review. PMID:27134738

  7. Steep Electron Density Gradients in the Midlatitude Nighttime Ionosphere: Current Understanding and Future Directions

    NASA Astrophysics Data System (ADS)

    Makela, J. J.; Kelley, M. C.; Mathews, J. D.; Kintner, P. M.; Aponte, N.; Ledvina, B. M.; Nicolls, M. J.; Seker, I.

    2004-12-01

    The midlatitude nighttime ionosphere is generally considered to be a fairly quiet system. Indeed, when compared to the highly active low- and high-latitudes, this seems to be a valid description. However, observations in the 1990s, notably those conducted as part of the multi-instrument Combined Ionospheric Campaigns (CICs) carried out periodically from 1997 to 1999, have shown that disturbances can indeed occur in this region. For example, a relatively common feature seen in allsky images taken at 630.0 nm are bands of depleted intensity aligned from the northwest to southeast that propagate to the southwest (in the northern hemisphere). The general characteristics of these bands are now fairly well documented, as is the basic understanding of their underlying physics. The effects of these medium-scale traveling ionospheric disturbances, or electrobouyancy waves, is to produce gradients in the electron density and F-layer height. During quiet magnetic periods, these gradients are fairly small, of the order of a few TEC units. However, these structures seem to be amplified by high geomagnetic activity at which times the gradients can be of the order of 10 to 20 TEC units over distances as small as several 10s of kilometers. Although much was learned about these structures during the CICs of the late 1990s, there are still several unexplained features that warrant further investigation, notably their genesis region, Kp dependence, and effects (if any) on trans-ionospheric radio signals. We suggest the need for a new set of campaigns in the Caribbean to address these questions, modeled on the CICs but extending their spatial coverage and including additional instrumentation not available during the initial campaigns. It is only through such a comprehensive, multi-technique investigation that we will make further headway on understanding these phenomena.

  8. New test techniques and analytical procedures for understanding the behavior of advanced propellers

    NASA Technical Reports Server (NTRS)

    Stefko, G. L.; Bober, L. J.; Neumann, H. E.

    1983-01-01

    Analytical procedures and experimental techniques were developed to improve the capability to design advanced high speed propellers. Some results from the propeller lifting line and lifting surface aerodynamic analysis codes are compared with propeller force data, probe data and laser velocimeter data. In general, the code comparisons with data indicate good qualitative agreement. A rotating propeller force balance demonstrated good accuracy and reduced test time by 50 percent. Results from three propeller flow visualization techniques are shown which illustrate some of the physical phenomena occurring on these propellers.

  9. 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

  10. 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. PMID:26505539

  11. Understanding the catalyst-free transformation of amorphous carbon into graphene by current-induced annealing

    PubMed Central

    Barreiro, Amelia; Börrnert, Felix; Avdoshenko, Stanislav M.; Rellinghaus, Bernd; Cuniberti, Gianaurelio; Rümmeli, Mark H.; Vandersypen, Lieven M. K.

    2013-01-01

    We shed light on the catalyst-free growth of graphene from amorphous carbon (a–C) by current-induced annealing by witnessing the mechanism both with in-situ transmission electron microscopy and with molecular dynamics simulations. Both in experiment and in simulation, we observe that small a–C clusters on top of a graphene substrate rearrange and crystallize into graphene patches. The process is aided by the high temperatures involved and by the van der Waals interactions with the substrate. Furthermore, in the presence of a–C, graphene can grow from the borders of holes and form a seamless graphene sheet, a novel finding that has not been reported before and that is reproduced by the simulations as well. These findings open up new avenues for bottom-up engineering of graphene-based devices.

  12. 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.

  13. Entanglement in continuous-variable systems: recent advances and current perspectives

    NASA Astrophysics Data System (ADS)

    Adesso, Gerardo; Illuminati, Fabrizio

    2007-07-01

    We review the theory of continuous-variable entanglement with special emphasis on foundational aspects, conceptual structures and mathematical methods. Much attention is devoted to the discussion of separability criteria and entanglement properties of Gaussian states, for their great practical relevance in applications to quantum optics and quantum information, as well as for the very clean framework that they allow for the study of the structure of nonlocal correlations. We give a self-contained introduction to phase-space and symplectic methods in the study of Gaussian states of infinite-dimensional bosonic systems. We review the most important results on the separability and distillability of Gaussian states and discuss the main properties of bipartite entanglement. These include the extremal entanglement, minimal and maximal, of two-mode mixed Gaussian states, the ordering of two-mode Gaussian states according to different measures of entanglement, the unitary (reversible) localization and the scaling of bipartite entanglement in multimode Gaussian states. We then discuss recent advances in the understanding of entanglement sharing in multimode Gaussian states, including the proof of the monogamy inequality of distributed entanglement for all Gaussian states. Multipartite entanglement of Gaussian states is reviewed by discussing its qualification by different classes of separability, and the main consequences of the monogamy inequality, such as the quantification of genuine tripartite entanglement in three-mode Gaussian states, the promiscuous nature of entanglement sharing in symmetric Gaussian states and the possible coexistence of unlimited bipartite and multipartite entanglement. We finally review recent advances and discuss possible perspectives on the qualification and quantification of entanglement in non-Gaussian states, a field of research that is to a large extent yet to be explored.

  14. 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

  15. Targeting bone metabolism in patients with advanced prostate cancer: current options and controversies.

    PubMed

    Todenhöfer, Tilman; Stenzl, Arnulf; Hofbauer, Lorenz C; Rachner, Tilman D

    2015-01-01

    Maintaining bone health remains a clinical challenge in patients with prostate cancer (PC) who are at risk of developing metastatic bone disease and increased bone loss due to hormone ablation therapy. In patients with cancer-treatment induced bone loss (CTIBL), antiresorptive agents have been shown to improve bone mineral density (BMD) and to reduce the risk of fractures. For patients with bone metastases, both zoledronic acid and denosumab delay skeletal related events (SREs) in the castration resistant stage of disease. Novel agents targeting the Wnt inhibitors dickkopf-1 and sclerostin are currently under investigation for the treatment of osteoporosis and malignant bone disease. New antineoplastic drugs such as abiraterone, enzalutamide, and Radium-223 are capable of further delaying SREs in patients with advanced PC. The benefit of antiresorptive treatment for patients with castration sensitive PC appears to be limited. Recent trials on the use of zoledronic acid for the prevention of bone metastases failed to be successful, whereas denosumab delayed the occurrence of bone metastases by a median of 4.1 months. Currently, the use of antiresorptive drugs to prevent bone metastases still remains a field of controversies and further trials are needed to identify patient subgroups that may profit from early therapy. PMID:25802521

  16. High Current ESD Test of Advanced Triple Junction Solar Array Coupon

    NASA Technical Reports Server (NTRS)

    Wright, Kenneth H., Jr.; Schneider, Todd A.; Vaughn, Jason A.; Hoang, Bao; Wong, Frankie

    2014-01-01

    Testing was conducted on an Advanced Triple Junction (ATJ) coupon that was part of a risk reduction effort in the development of a high-powered solar array design by Space Systems Loral, LLC (SSL). The ATJ coupon was a small, 4-cell, two-string configuration 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.

  17. 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

  18. Current understanding of the mechanism of benzene-induced leukemia in humans: implications for risk assessment

    PubMed Central

    McHale, Cliona M.; Zhang, Luoping; Smith, Martyn T.

    2012-01-01

    Benzene causes acute myeloid leukemia and probably other hematological malignancies. As benzene also causes hematotoxicity even in workers exposed to levels below the US permissible occupational exposure limit of 1 part per million, further assessment of the health risks associated with its exposure, particularly at low levels, is needed. Here, we describe the probable mechanism by which benzene induces leukemia involving the targeting of critical genes and pathways through the induction of genetic, chromosomal or epigenetic abnormalities and genomic instability, in a hematopoietic stem cell (HSC); stromal cell dysregulation; apoptosis of HSCs and stromal cells and altered proliferation and differentiation of HSCs. These effects modulated by benzene-induced oxidative stress, aryl hydrocarbon receptor dysregulation and reduced immunosurveillance, lead to the generation of leukemic stem cells and subsequent clonal evolution to leukemia. A mode of action (MOA) approach to the risk assessment of benzene was recently proposed. This approach is limited, however, by the challenges of defining a simple stochastic MOA of benzene-induced leukemogenesis and of identifying relevant and quantifiable parameters associated with potential key events. An alternative risk assessment approach is the application of toxicogenomics and systems biology in human populations, animals and in vitro models of the HSC stem cell niche, exposed to a range of levels of benzene. These approaches will inform our understanding of the mechanisms of benzene toxicity and identify additional biomarkers of exposure, early effect and susceptibility useful for risk assessment. PMID:22166497

  19. 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

  20. 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.

  1. Current understanding of dysbiosis in disease in human and animal models

    PubMed Central

    DeGruttola, Arianna K.; Low, Daren; Mizoguchi, Atsushi; Mizoguchi, Emiko

    2016-01-01

    Inflammatory bowel disease (IBD) is an intestinal inflammatory condition that affects over two million people in the United States. Although the etiology and pathogenesis of IBD are still largely unknown, dysregulated host/enteric microbial interactions are requisite for the development of IBD. So far, many researchers have tried to identify a precise relationship between IBD and an imbalance of the intestinal microbiota, termed “dysbiosis”. In spite of the extensive efforts, it is still largely unknown about the interplay among microbes, their hosts, and their environments, and whether dysbiosis is a causal factor or an effect of IBD. Recently, deep-sequencing analyses of the microbiota in IBD patients have been instrumental in characterizing the strong association between dysbiosis and IBD development, although it is still unable to identify specific-associated species level changes in most cases. Based on many recent reports, dysbiosis of the commensal microbiota is implicated in the pathogenesis of several diseases, including IBD, obesity, and allergic disorders, in both human and animal models. In this review article, we have focused on explaining the multiple types of dysbiosis, as well as dysbiosis-related diseases and potential treatments in order to apply this knowledge to understand a possible cause and potentially find therapeutic strategies for IBD as well as the other dysbiosis-related diseases. PMID:27070911

  2. Current Understanding of Dysbiosis in Disease in Human and Animal Models.

    PubMed

    DeGruttola, Arianna K; Low, Daren; Mizoguchi, Atsushi; Mizoguchi, Emiko

    2016-05-01

    Inflammatory bowel disease (IBD) is an intestinal inflammatory condition that affects more than 2 million people in the United States. Although the etiology and pathogenesis of IBD are still largely unknown, dysregulated host/enteric microbial interactions are requisite for the development of IBD. So far, many researchers have tried to identify a precise relationship between IBD and an imbalance of the intestinal microbiota, termed "dysbiosis." Despite extensive efforts, it is still largely unknown about the interplay among microbes, their hosts, and their environments, and whether dysbiosis is a causal factor or an effect of IBD. Recently, deep-sequencing analyses of the microbiota in patients with IBD patients have been instrumental in characterizing the strong association between dysbiosis and IBD development, although it is still unable to identify specific-associated species level changes in most cases. Based on many recent reports, dysbiosis of the commensal microbiota is implicated in the pathogenesis of several diseases, including IBD, obesity, and allergic disorders, in both human and animal models. In this review article, the authors have focused on explaining the multiple types of dysbiosis, as well as dysbiosis-related diseases and potential treatments to apply this knowledge to understand a possible cause and potentially find therapeutic strategies for IBD as well as the other dysbiosis-related diseases. PMID:27070911

  3. 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. PMID:25694468

  4. Recent advances in understanding and managing cystic fibrosis transmembrane conductance regulator dysfunction

    PubMed Central

    Alton, Eric W.F.W.

    2015-01-01

    Cystic fibrosis is the most common autosomal recessive genetic disease in Caucasians and has been extensively studied for many decades. The cystic fibrosis transmembrane conductance regulator gene was identified in 1989. It encodes a complex protein which has numerous cellular functions. Our understanding of cystic fibrosis pathophysiology and genetics is constantly expanding and being refined, leading to improved management of the disease and increased life expectancy in affected individuals. PMID:26097737

  5. 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…

  6. Recent advances in understanding and managing cystic fibrosis transmembrane conductance regulator dysfunction.

    PubMed

    Griesenbach, Uta; Alton, Eric W F W

    2015-01-01

    Cystic fibrosis is the most common autosomal recessive genetic disease in Caucasians and has been extensively studied for many decades. The cystic fibrosis transmembrane conductance regulator gene was identified in 1989. It encodes a complex protein which has numerous cellular functions. Our understanding of cystic fibrosis pathophysiology and genetics is constantly expanding and being refined, leading to improved management of the disease and increased life expectancy in affected individuals. PMID:26097737

  7. 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

  8. 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...

  9. Sarcasm and advanced theory of mind understanding in children and adults with prelingual deafness.

    PubMed

    O'Reilly, Karin; Peterson, Candida C; Wellman, Henry M

    2014-07-01

    Two studies addressed key theoretical debates in theory of mind (ToM) development by comparing (a) deaf native signers (n = 18), (b) deaf late signers (n = 59), and (c) age-matched hearing persons (n = 74) in childhood (Study 1: n = 81) and adulthood (Study 2: n = 70) on tests of first- and second-order false belief and conversational sarcasm. Results showed ToM development to be a life span phenomenon for deaf and hearing people alike. Native and late signers were outperformed by hearing peers on advanced ToM in childhood (M = 9 years), but in adulthood (M = 40 years), native signers had caught up, whereas late signers had not. Findings highlight the extended importance of conversational interaction for ToM growth. PMID:24798505

  10. 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

  11. 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

  12. 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.

  13. Current understanding of contrast media reactions and implications for clinical management.

    PubMed

    Meth, Marc J; Maibach, Howard I

    2006-01-01

    Iodinated contrast media (CM) are an integral part of modern diagnostic medicine. Although these agents are considered to be relatively safe, adverse effects in the form of allergy-like reactions occur in a significant number of exposed patients. These reactions may be divided into immediate and delayed responses. Immediate (within 1 hour of administration) anaphylactic reactions range from urticaria and angioedema to laryngeal oedema, hypotension and even death. Delayed reactions to CM occur from 1 hour to 1 week after administration and usually have mostly cutaneous manifestations. History of prior CM reactions and atopy predispose patients to CM reactions. Despite intense research into the pathogenesis of the immediate anaphylactoid responses, new evidence shows that true IgE type I hypersensitivity mediation occurs only in rare, severe cases. The aetiology appears to be multifactorial in most individuals. There is strong evidence to conclude that type IV hypersensitivity is responsible for the delayed reactions to CM. Although switching to non-ionic agents significantly reduces the incidence of immediate reactions to CM, there is little consensus regarding corticosteroid prophylaxis in high-risk individuals. Skin testing and provocative challenges also provide little security. Therefore, physicians must be better prepared to treat immediate anaphylactoid responses. Preventing delayed CM reactions is best performed with patch and delayed intradermal testing in those with a history of prior reactions, although false-negative results have been reported. Corticosteroids and antihistamines may be required for treatment. Until newer agents are developed that negate these issues, healthcare providers must strive to better understand the risk factors associated with CM reactions, as well as the available prophylactic and treatment options. PMID:16454540

  14. Understanding the impact of deep brain stimulation on ambulatory activity in advanced Parkinson's disease.

    PubMed

    Rochester, Lynn; Chastin, Sebastien Francois Martin; Lord, Sue; Baker, Katherine; Burn, David John

    2012-06-01

    Whilst deep brain stimulation of the subthalamic nucleus (DBS-STN) improves the motor symptoms of Parkinson's disease (PD), its effect on daily activity is unknown. We aimed to quantify changes in ambulatory activity following DBS-STN in advanced PD using novel accelerometry based measures that describe changes to the volume and pattern of walking. Seventeen participants with advanced PD were measured over a 7-day period using an activPAL (™) activity monitor. Data were collected 6 weeks before and 6 months after surgery and included measures that describe the volume and pattern of ambulatory activity (number of steps per day, accumulation, diversity and variability of walking time), alongside standard measures for disease severity, freezing of gait, gait speed, and extended activities of daily living. Activity outcomes were compared pre- and 6 months post-surgery using linear mixed models and correlated with standard outcomes. The results of this study are despite significant improvements in motor symptoms after surgery, the volume of ambulatory activity (total number of steps per day) did not change (P = 0.468). However, significant increases in length and variability of walking bouts emerged, suggesting improvements in diversity and flexibility of walking patterns. Motor severity and extended activities of daily living scores were significantly correlated with walking bout variability but not with volume of walking. Thus, the conclusions are reduction in motor symptom severity after DBS-STN translated into selective improvements in daily activity. Novel measures derived from accelerometry provide a discrete measure of performance and allow closer interpretation of the impact of DBS-STN on real-world activity. PMID:22086738

  15. Nonampullary duodenal adenoma: Current understanding of its diagnosis, pathogenesis, and clinical management

    PubMed Central

    Lim, Chul-Hyun; Cho, Young-Seok

    2016-01-01

    Nonampullary duodenal adenomas are relatively common in familial adenomatous polyposis (FAP), but nonampullary sporadic duodenal adenomas (SDAs) are rare. Emerging evidence shows that duodenal adenomas, regardless of their anatomic location and whether they are sporadic or FAP-related, share morphologic and molecular features with colorectal adenomas. The available data suggest that duodenal adenomas develop to duodenal adenocarcinomas via similar mechanisms. The optimal approach for management of duodenal adenomas remains to be determined. The techniques for endoscopic resection of duodenal adenoma include snare polypectomy, endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and argon plasma coagulation ablation. EMR may facilitate removal of large duodenal polyps. Although several studies have reported cases of successful ESD for duodenal adenomas, the procedure is technically difficult to perform safely because of the anatomical properties of the duodenum. Although current clinical practice recommends endoscopic resection of all large duodenal adenomas in patients with FAP, endoscopic treatment is usually insufficient to guarantee a polyp-free duodenum. Surgery is indicated for FAP patients with severe polyposis or nonampullary SDAs or FAP-related polyps not amenable to endoscopic resection. Further studies are needed to develop newer endoscopic techniques to guide diagnostic and therapeutic decisions for future management of nonampullary duodenal adenomas. PMID:26811631

  16. 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

  17. Understanding the mental health of youth living with perinatal HIV infection: lessons learned and current challenges

    PubMed Central

    Mellins, Claude A; Malee, Kathleen M

    2013-01-01

    preclude both conclusions and full understanding of aetiology. Conversely, these limitations present opportunities for future research. Many PHIV+ youth experience adequate mental health despite vulnerabilities. However, the focus of research to date highlights the identification of risks rather than positive attributes, which could inform preventive interventions. Development and evaluation of mental health interventions and preventions are urgently needed to optimize mental health, particularly for PHIV+ youth growing up in low-and-middle income countries. PMID:23782478

  18. 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

  19. Recent advances in understanding stratospheric dynamics and transport processes - Application of satellite data to their interpretation

    NASA Technical Reports Server (NTRS)

    Grose, W. L.

    1984-01-01

    The present paper discusses the use of the transformed Eulerian (or 'residual') mean-flow formulation, the Eliassen-Palm flux, and Ertel's potential vorticity to provide an increased understanding of wave, mean-flow interactions, and constituent transport processes in the stratosphere. Temperature and ozone data retrieved from radiance profiles obtained by the LIMS instrument on the Nimbus 7 satellite are utilized in conjunction with these theoretical concepts for the interpretation of phenomena that occurred during the major and minor warmings of January-February 1979. The results illustrate the insight provided by these concepts and demonstrate that useful diagnostic quantities can be derived from global satellite temperature fields.

  20. The impact of recent advances in genetics in understanding disease mechanisms underlying the long QT syndromes.

    PubMed

    Harmer, Stephen C; Tinker, Andrew

    2016-07-01

    Long QT syndrome refers to a characteristic abnormality of the electrocardiogram and it is associated with a form of ventricular tachycardia known as torsade-de-pointes and sudden arrhythmic death. It can occur as part of a hereditary syndrome or can be acquired usually because of drug administration. Here we review recent genetic, molecular and cellular discoveries and outline how they have furthered our understanding of this disease. Specifically we focus on compound mutations, genome wide association studies of QT interval, modifier genes and the therapeutic implications of this recent work. PMID:26910742

  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. 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

  3. 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.

  4. Recent advances in understanding Kaposi’s sarcoma-associated herpesvirus

    PubMed Central

    Dissinger, Nathan J.; Damania, Blossom

    2016-01-01

    Kaposi’s sarcoma (KS)-associated herpesvirus (KSHV) is an oncogenic human herpesvirus. KSHV is associated with three cancers in the human population: KS, primary effusion lymphoma (PEL), and multicentric Castleman’s disease (MCD). KS is the leading cause of cancer in HIV-infected individuals. In this review, we discuss the most recent discoveries behind the mechanisms of KSHV latency maintenance and lytic replication. We also review current therapies for KSHV-associated cancers. PMID:27158465

  5. Advances in the understanding of delayed cerebral ischaemia after aneurysmal subarachnoid haemorrhage

    PubMed Central

    Flynn, Liam; Andrews, Peter

    2015-01-01

    Delayed cerebral ischaemia has been described as the single most important cause of morbidity and mortality in patients who survive the initial aneurysmal subarachnoid haemorrhage. Our understanding of the pathophysiology of delayed cerebral ischaemia is meagre at best and the calcium channel blocker nimodipine remains the only intervention to consistently improve functional outcome after aneurysmal subarachnoid haemorrhage. There is substantial evidence to support cerebral vessel narrowing as a causative factor in delayed cerebral ischaemia, but contemporary research demonstrating improvements in vessel narrowing has failed to show improved functional outcomes. This has encouraged researchers to investigate other potential causes of delayed cerebral ischaemia, such as early brain injury, microthrombosis, and cortical spreading depolarisation. Adherence to a common definition of delayed cerebral ischaemia is needed in order to allow easier assessment of studies using multiple different terms. Furthermore, improved recognition of delayed cerebral ischaemia would not only allow for faster treatment but also better assessment of interventions. Finally, understanding nimodipine’s mechanism of action may allow us to develop similar agents with improved efficacy. PMID:26937276

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Current Advances in Mathematical Modeling of Anti-Cancer Drug Penetration into Tumor Tissues

    PubMed Central

    Kim, MunJu; Gillies, Robert J.; Rejniak, Katarzyna A.

    2013-01-01

    Delivery of anti-cancer drugs to tumor tissues, including their interstitial transport and cellular uptake, is a complex process involving various biochemical, mechanical, and biophysical factors. Mathematical modeling provides a means through which to understand this complexity better, as well as to examine interactions between contributing components in a systematic way via computational simulations and quantitative analyses. In this review, we present the current state of mathematical modeling approaches that address phenomena related to drug delivery. We describe how various types of models were used to predict spatio-temporal distributions of drugs within the tumor tissue, to simulate different ways to overcome barriers to drug transport, or to optimize treatment schedules. Finally, we discuss how integration of mathematical modeling with experimental or clinical data can provide better tools to understand the drug delivery process, in particular to examine the specific tissue- or compound-related factors that limit drug penetration through tumors. Such tools will be important in designing new chemotherapy targets and optimal treatment strategies, as well as in developing non-invasive diagnosis to monitor treatment response and detect tumor recurrence. PMID:24303366

  12. 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. PMID:25286989

  13. Recent Advances in Understanding of NASH: MicroRNAs as Both Biochemical Markers and Players

    PubMed Central

    Vincent, Robert; Sanyal, Arun

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatis (NASH) are becoming the dominant liver diseases in the US and Western World. Extensive work is being done to diagnose, understand, and explore the pathogenesis of these multivariable complex diseases. Recently a new avenue of biologic regulation is being explored. MicroRNAs are non-coding RNAs that modulate the expression of multiple genes and have been implicated in multiple diseases. Recently there is a growing body of evidence supporting a significant role of microRNAs in NAFLD pathogenesis and progression to NASH, and hinting at their use as targets, biomarkers and potential therapeutic tools. This review is designed to highlight some of the recent work on a few of the key microRNAs involved in the pathogenesis of NAFLD and NASH. PMID:25574453

  14. 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

  15. 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. PMID:26631274

  16. 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

  17. 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

  18. 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

  19. Recent Advances in the Performance and Understanding of the SNS Ion Source

    NASA Astrophysics Data System (ADS)

    Welton, R. F.; Stockli, M. P.; Murray, S. N.; Keller, R.

    2005-04-01

    The ion source developed for the Spallation Neutron Source (SNS) by Lawrence Berkeley National Laboratory (LBNL), is a radio frequency, multi-cusp source designed to produce ˜ 40 mA of H- with a normalized rms emittance of less than 0.2 pi mm mrad. To date, the source has been utilized in the commissioning of the SNS accelerator and has already demonstrated stable, satisfactory operation at beam currents of ˜30 mA with duty-factors of ˜0.1% for operational periods of several weeks. Once the SNS is fully operational in 2008, a beam current duty-factor of 6% (1 ms pulse length, 60 Hz repetition rate) will be required in order to inject the accelerator. To ascertain the capability of the source to deliver beams at this high duty-factor over sustained time periods, several experimental runs have been conducted, each ˜1 week in length, in which the ion source was continuously operated on a dedicated test stand. The results of these tests are reported as well as a theory of the Cs release and transport processes which were derived from these data. The theory was then employed to develop a more effective source conditioning procedure as well as an improved Cs collar design. Initial results of tests employing a Cs collar with enhanced surface ionization geometry are also discussed.

  20. Imaging mass spectrometry of the visual system: Advancing the molecular understanding of retina degenerations.

    PubMed

    Bowrey, Hannah E; Anderson, David M; Pallitto, Patrick; Gutierrez, Danielle B; Fan, Jie; Crouch, Rosalie K; Schey, Kevin L; Ablonczy, Zsolt

    2016-04-01

    Visual sensation is fundamental for quality of life, and loss of vision to retinal degeneration is a debilitating condition. The eye is the only part of the central nervous system that can be noninvasively observed with optical imaging. In the clinics, various spectroscopic methods provide high spatial resolution images of the fundus and the developing degenerative lesions. However, the currently utilized tools are not specific enough to establish the molecular underpinnings of retinal diseases. In contrast, mass spectrometric imaging (MSI) is a powerful tool to identify molecularly specific disease indicators and classification markers. This technique is particularly well suited to the eye, where molecular information can be correlated with clinical data collected via noninvasive diagnostic imaging modalities. Recent studies during the last few recent years have uncovered a plethora of new spatially defined molecular information on several vision-threatening diseases, including age-related macular degeneration, Stargardt disease, glaucoma, cataract, as well as lipid disorders. Even though MS inside the eye cannot be performed noninvasively, by linking diagnostic and molecular information, these studies are the first step toward the development of smart ophthalmic diagnostic and surgical tools. Here, we provide an overview of current approaches applying MSI technology to ocular pathology. PMID:26586164

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. Eribulin in the Management of Advanced Breast Cancer: Implications of Current Research Findings.

    PubMed

    Kok, Victor C

    2015-01-01

    The search for cytotoxic agents from marine natural products ultimately led to the production of eribulin, which is a synthetic macrocyclic ketone analog of halichondrin B. Eribulin binds to tubulin to induce mitotic arrest and gained approval in Japan in May 2010; it was approved by the US Food and Drug Administration in November 2010 and the European Medicines Agency in March 2011 and was reimbursed by the Taiwan National Health Insurance in December 2014 for patients with metastatic breast cancer who had received at least one anthracycline and one taxane. The recommended regimen for eribulin mesylate comprises intravenous administration of 1.4 mg/m(2) (equivalent to 1.23 mg/m(2) eribulin) over two to five minutes on days 1 and 8 of a three-week cycle. Since 2011, various clinical investigations of eribulin monotherapy with dose or schedule modifications, combined use with other antineoplastic therapeutics, or head-to-head comparisons with specific agents have been performed in the management of advanced breast cancer. Ethnic-specific data from Japan and Korea indicate higher rates (>85%) of grade 3 or 4 neutropenia. Some anecdotal evidence suggests that eribulin can shrink brain and retinal metastases, which warrants further detailed studies. In this review, current observations of the effects of eribulin monotherapy are summarized and eribulin-backbone combination (bio-) chemotherapy is investigated. PMID:26691012

  7. Eribulin in the Management of Advanced Breast Cancer: Implications of Current Research Findings

    PubMed Central

    Kok, Victor C.

    2015-01-01

    The search for cytotoxic agents from marine natural products ultimately led to the production of eribulin, which is a synthetic macrocyclic ketone analog of halichondrin B. Eribulin binds to tubulin to induce mitotic arrest and gained approval in Japan in May 2010; it was approved by the US Food and Drug Administration in November 2010 and the European Medicines Agency in March 2011 and was reimbursed by the Taiwan National Health Insurance in December 2014 for patients with metastatic breast cancer who had received at least one anthracycline and one taxane. The recommended regimen for eribulin mesylate comprises intravenous administration of 1.4 mg/m2 (equivalent to 1.23 mg/m2 eribulin) over two to five minutes on days 1 and 8 of a three-week cycle. Since 2011, various clinical investigations of eribulin monotherapy with dose or schedule modifications, combined use with other antineoplastic therapeutics, or head-to-head comparisons with specific agents have been performed in the management of advanced breast cancer. Ethnic-specific data from Japan and Korea indicate higher rates (>85%) of grade 3 or 4 neutropenia. Some anecdotal evidence suggests that eribulin can shrink brain and retinal metastases, which warrants further detailed studies. In this review, current observations of the effects of eribulin monotherapy are summarized and eribulin-backbone combination (bio-) chemotherapy is investigated. PMID:26691012

  8. 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

  9. 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.

  10. Recent evidence, advances, and current practices in surgical treatment of lung cancer.

    PubMed

    Suda, Kenichi; Sato, Katsuaki; Mizuuchi, Hiroshi; Kobayashi, Yoshihisa; Shimoji, Masaki; Tomizawa, Kenji; Takemoto, Toshiki; Iwasaki, Takuya; Sakaguchi, Masahiro; Mitsudomi, Tetsuya

    2014-11-01

    In the last 10-15 years, strategies and modalities of lung cancer treatment have changed dramatically. Meanwhile, the treatment objectives, the lung cancers themselves, have also changed, probably owing to early detection by computed tomography and aging of the population. In particular, the proportions of smaller lung cancers, lung adenocarcinomas with ground-glass opacity, and lung cancers in older patients are increasing. Along with these changes, surgeons have innovated and evaluated novel procedures for pulmonary resection. These include the application of minimally invasive surgical techniques, such as video-assisted thoracoscopic surgery (VATS) and robotic surgery, and sub-lobar resection, such as wedge resection and segmentectomy, for small peripheral lung cancers. Currently, VATS has gained wide acceptance and several institutions in Japan have started using robotic surgery for lung cancers. Two important clinical trials of sub-lobar resection for small peripheral lung cancers are now underway in Japan. In addition, surgery itself is of growing importance in lung cancer treatment. In particular, recent evidence supports the use of surgery in strictly selected patients with locally advanced disease, lung cancers with N2 lymph node metastases, small cell lung cancers, recurrent oligo-metastasis after pulmonary resection, or relapsed tumors after drug treatment. Surgical treatment also provides abundant tumor samples for molecular analysis, which can be used for drug selection in the adjuvant setting or after disease relapse. In the era of personalized treatment, surgery is still one of the most important treatment modalities to combat lung cancer. PMID:25453375

  11. Advancing the application of systems thinking in health: understanding the dynamics of neonatal mortality in Uganda

    PubMed Central

    2014-01-01

    Background Of the three million newborns that die each year, Uganda ranks fifth highest in neonatal mortality rates, with 43,000 neonatal deaths each year. Despite child survival and safe motherhood programmes towards reducing child mortality, insufficient attention has been given to this critical first month of life. There is urgent need to innovatively employ alternative solutions that take into account the intricate complexities of neonatal health and the health systems. In this paper, we set out to empirically contribute to understanding the causes of the stagnating neonatal mortality by applying a systems thinking approach to explore the dynamics arising from the neonatal health complexity and non-linearity and its interplay with health systems factors, using Uganda as a case study. Methods Literature reviews and interviews were conducted in two divisions of Kampala district with high neonatal mortality rates with mothers at antenatal clinics and at home, village health workers, community leaders, healthcare decision and policy makers, and frontline health workers from both public and private health facilities. Data analysis and brainstorming sessions were used to develop causal loop diagrams (CLDs) depicting the causes of neonatal mortality, which were validated by local and international stakeholders. Results We developed two CLDs for demand and supply side issues, depicting the range of factors associated with neonatal mortality such as maternal health, level of awareness of maternal and newborn health, and availability and quality of health services, among others. Further, the reinforcing and balancing feedback loops that resulted from this complexity were also examined. The potential high leverage points include special gender considerations to ensure that girls receive essential education, thereby increasing maternal literacy rates, improved socioeconomic status enabling mothers to keep healthy and utilise health services, improved supervision, and

  12. 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

  13. Recent advances in the understanding of electrocatalysis and its relation to surface chemistry

    NASA Technical Reports Server (NTRS)

    Yeager, E.

    1977-01-01

    It is pointed out that electrosorption plays a key role in electrocatalysis. Little information is available, however, concerning the chemical nature of the interactions of the adsorbed species with the electrode and even less about the adsorption sites. The role of adsorbed species and surface layers in electrocatalysis is reviewed for several electrode systems. In recent years, some general insights have been achieved into the relationship of hydrogen electrode kinetics to hydrogen adsorption. For a given mechanism the exchange current density is related to the standard free energy of adsorption of the particular type of adsorbed hydrogen upon which the kinetics depend. The oxygen electrode reactions are less well understood than the reactions for the hydrogen electrode. The pronounced irreversibility of the oxygen electrode reactions at moderate temperatures has severely complicated mechanistic studies.

  14. 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

  15. 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

  16. Integrated Application of Active Controls (IAAC) technology to an advanced subsonic transport project: current and advanced act control system definition study

    SciTech Connect

    Not Available

    1982-04-01

    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.

  17. 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.

  18. Recent Advances in Understanding Radiation Belt Dynamics in the Earth's Inner Zone and Slot Region

    NASA Astrophysics Data System (ADS)

    Li, X.

    2015-12-01

    Comprehensive measurements of the inner belt protons from the Relativistic Electron and Proton Telescope (REPT) onboard Van Allen Probes, in a geo-transfer-like orbit, revealed new features of inner belt protons in terms of their spectrum distribution, spatial distribution, pitch angle distribution, and their different source populations. Concurrent measurements from the Relativistic Electron and Proton Telescope integrated little experiment (REPTile) on board Colorado Student Space Weather Experiment (CSSWE) CubeSat, in a highly inclined low Earth orbit, and REPT demonstrated that there exist sub-MeV electrons in the inner belt and their flux level is orders of magnitude higher than the background associated with the inner belt protons, while higher energy electron (>1.6 MeV) measurements cannot be distinguished from the background. Analysis on sub-MeV electrons data in the inner belt and slot region from the Magnetic Electron Ion Spectrometer (MagEIS) on board Van Allen Probes revealed rather complicated pitch angle distribution of these energetic electrons, with the 90 deg-minimum (butterfly) pitch angle distribution dominating near the magnetic equator. Furthermore, it is clearly shown from MagEIS measurements that 10s - 100s keV electrons are commonly seen penetrating into the inner belt region during geomagnetic active times while protons of similar energies are hardly seen there. These are part of a summary of the most recent measurements and understanding of the dynamics of energetic particles in the inner zone and slot region to be exhibited and discussed in this presentation.

  19. ADVANCED SIMULATION CAPABILITY FOR ENVIRONMENTAL MANAGEMENT – CURRENT STATUS AND PHASE II DEMONSTRATION RESULTS

    SciTech Connect

    Seitz, Roger; Freshley, Mark D.; Dixon, Paul; Hubbard, Susan S.; Freedman, Vicky L.; Flach, Gregory P.; Faybishenko, Boris; Gorton, Ian; Finsterle, Stefan A.; Moulton, John D.; Steefel, Carl I.; Marble, Justin

    2013-06-27

    The U.S. Department of Energy (USDOE) Office of Environmental Management (EM), Office of Soil and Groundwater, is supporting development of the Advanced Simulation Capability for Environmental Management (ASCEM). ASCEM is a state-of-the-art scientific tool and approach for understanding and predicting contaminant fate and transport in natural and engineered systems. The modular and open source high-performance computing tool facilitates integrated approaches to modeling and site characterization that enable robust and standardized assessments of performance and risk for EM cleanup and closure activities. The ASCEM project continues to make significant progress in development of computer software capabilities with an emphasis on integration of capabilities in FY12. Capability development is occurring for both the Platform and Integrated Toolsets and High-Performance Computing (HPC) Multiprocess Simulator. The Platform capabilities provide the user interface and tools for end-to-end model development, starting with definition of the conceptual model, management of data for model input, model calibration and uncertainty analysis, and processing of model output, including visualization. The HPC capabilities target increased functionality of process model representations, toolsets for interaction with Platform, and verification and model confidence testing. The Platform and HPC capabilities are being tested and evaluated for EM applications in a set of demonstrations as part of Site Applications Thrust Area activities. The Phase I demonstration focusing on individual capabilities of the initial toolsets was completed in 2010. The Phase II demonstration completed in 2012 focused on showcasing integrated ASCEM capabilities. For Phase II, the Hanford Site deep vadose zone (BC Cribs) served as an application site for an end-to-end demonstration of capabilities, with emphasis on integration and linkages between the Platform and HPC components. Other demonstrations

  20. 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

  1. 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

  2. Integrating movement in academic classrooms: understanding, applying and advancing the knowledge base.

    PubMed

    Webster, C A; Russ, L; Vazou, S; Goh, T L; Erwin, H

    2015-08-01

    In the context of comprehensive and coordinated approaches to school health, academic classrooms have gained attention as a promising setting for increasing physical activity and reducing sedentary time among children. The aims of this paper are to review the rationale and knowledge base related to movement integration in academic classrooms, consider the practical applications of current knowledge to interventions and teacher education, and suggest directions for future research. Specifically, this paper (i) situates movement integration amid policy and research related to children's health and the school as a health-promoting environment; (ii) highlights the benefits of movement integration; (iii) summarizes movement integration programs and interventions; (iv) examines factors associated with classroom teachers' movement integration; (v) offers strategies for translating research to practice and (vi) forwards recommendations for future inquiry related to the effectiveness and sustainability of efforts to integrate movement into classroom routines. This paper provides a comprehensive resource for developing state-of-the-art initiatives to maximize children's movement in academic classrooms as a key strategy for important goals in both education and public health. PMID:25904462

  3. Understanding STEM: Current Perceptions

    ERIC Educational Resources Information Center

    Brown, Ryan; Brown, Joshua; Reardon, Kristin; Merrill, Chris

    2011-01-01

    In many ways, the push for STEM (science, technology, engineering, and mathematics) education appears to have grown from a concern for the low number of future professionals to fill STEM jobs and careers and economic and educational competitiveness. The proponents of STEM education believe that by increasing math and science requirements in…

  4. Recent advances in understanding the assembly and repair of photosystem II

    PubMed Central

    Nixon, Peter J.; Michoux, Franck; Yu, Jianfeng; Boehm, Marko; Komenda, Josef

    2010-01-01

    Background Photosystem II (PSII) is the light-driven water:plastoquinone oxidoreductase of oxygenic photosynthesis and is found in the thylakoid membrane of chloroplasts and cyanobacteria. Considerable attention is focused on how PSII is assembled in vivo and how it is repaired following irreversible damage by visible light (so-called photoinhibition). Understanding these processes might lead to the development of plants with improved growth characteristics especially under conditions of abiotic stress. Scope Here we summarize recent results on the assembly and repair of PSII in cyanobacteria, which are excellent model organisms to study higher plant photosynthesis. Conclusions Assembly of PSII is highly co-ordinated and proceeds through a number of distinct assembly intermediates. Associated with these assembly complexes are proteins that are not found in the final functional PSII complex. Structural information and possible functions are beginning to emerge for several of these ‘assembly’ factors, notably Ycf48/Hcf136, Psb27 and Psb28. A number of other auxiliary proteins have been identified that appear to have evolved since the divergence of chloroplasts and cyanobacteria. The repair of PSII involves partial disassembly of the damaged complex, the selective replacement of the damaged sub-unit (predominantly the D1 sub-unit) by a newly synthesized copy, and reassembly. It is likely that chlorophyll released during the repair process is temporarily stored by small CAB-like proteins (SCPs). A model is proposed in which damaged D1 is removed in Synechocystis sp. PCC 6803 by a hetero-oligomeric complex composed of two different types of FtsH sub-unit (FtsH2 and FtsH3), with degradation proceeding from the N-terminus of D1 in a highly processive reaction. It is postulated that a similar mechanism of D1 degradation also operates in chloroplasts. Deg proteases are not required for D1 degradation in Synechocystis 6803 but members of this protease family might play a

  5. Recent Advances in Understanding the Sources of Methylmercury to Coastal Waters

    NASA Astrophysics Data System (ADS)

    Mason, R. P.; Balcom, P.; Chen, C.; Gosnell, K. J.; Jonsson, S.; Mazrui, N.; Ortiz, V.; Seelen, E.; Schartup, A. T.; Sunderland, E. M.

    2015-12-01

    Understanding the sources of methylmercury (MeHg) to the food chain in coastal waters is important given the related health concerns from consumption of seafood containing elevated MeHg. While water column dissolved or particulate MeHg is the best predictor of bioaccumulation into pelagic organisms in coastal waters, there is debate concerning the dominant sources of MeHg to the water column, and how the relative importance of these sources vary with ecosystem characteristics. Potential sources include both external inputs from the watershed and offshore waters and internal sources (net methylation in sediments and the associated flux of MeHg to the water column and/or net MeHg production in the water column). We will report the results from our various studies in estuarine and coastal waters which have examined the distribution and partitioning of sediment and water column MeHg, and its formation and degradation, across a geographic range from Labrador, Canada to the Chesapeake Bay, USA. The ecosystems studied vary from shallow estuarine bays to deeper systems, and from salt wedge to tidally-dynamic systems. Additionally, both pristine and contaminated environments were examined. The studies examined the factors controlling the net production of MeHg in sediments, and in our more recent work, the potential formation of MeHg in the oxic water column of coastal waters. Sediment measurements (core and grab samples) included both solid phase and porewater MeHg and total mercury (HgT) and important ancillary parameters. Water column parameters included dissolved and particulate MeHg and HgT, TSS, nutrients, and DOC. Stable Hg isotope tracer incubations were used to assess the degree of methylation and demethylation in sediments and surface waters. Average suspended particle MeHg ranged from <5 to 120 pmol/g, and was 1-8% of HgT across sites. Mass balance estimates provide insights into the importance of external MeHg sources to coastal waters. We will use the

  6. Advancing our understanding of plant adaptation to metal polluted environments - new insights from Biscutella laevigata

    NASA Astrophysics Data System (ADS)

    Babst-Kostecka, Alicja; Waldmann, Patrik; Frérot, Hélène; Vollenweider, Pierre

    2016-04-01

    The legacy of industrial pollution alters ecosystems, particularly at post-mining sites where metal trace elements have created toxic conditions that trigger rapid plant adaptation. Apart from the purely scientific merits, in-depth knowledge of the mechanisms underlying plant adaptation to metal contamination is beneficial for the economic and societal sectors because of its application in bioengineering (e.g. phytoremediation or biofortification). An important process is the evolution and/or enhancement of metal tolerance, a trait that has predominantly been studied by applying acute metal stress on species that allocate large quantities of certain metals to their foliage (so-called hyperaccumulators). As the vast majority of vascular plants does not hyperaccumulate metals, more efforts are needed to investigate non-hyperaccumulating species and thereby broaden understanding of biological mechanisms underlying metal tolerance. The pseudometallophyte Biscutella laevigata has shown potential in this respect, but its characteristics are insufficiently understood. We determined the zinc tolerance level and various plant responses to environmentally relevant zinc concentrations in ten metallicolous and non-metallicolous B. laevigata populations. In a two-phase hydroponic experiment, we scored multiple morphological and physiological traits (e.g. biomass, visible stress symptoms, element content in foliage) and assessed phenotypic variability within plant families. The structure of these quantitative traits was compared to that of neutral molecular markers to test, whether natural selection caused population differentiation in zinc tolerance. While all genotypes were tolerant compared to a zinc sensitive reference species, we found congruent trends toward higher tolerance in metallicolous compared to non-metallicolous plants. We identified the most indicative parameters for these differences and find that enhanced zinc tolerance in metallicolous populations is driven by

  7. Understanding what the public know and value about geoheritage sites in order to advance Earth science literacy

    NASA Astrophysics Data System (ADS)

    Vye, E. C.; Rose, W. I.

    2013-12-01

    With its impressive geology and rich cultural history, Michigan's Keweenaw Peninsula is ideally suited for Earth science education and geotourism initiatives, such as a Geopark. Geologic events that have shaped this region can be interpreted in such a way as to engage learners, not only through an intellectual connection to Earth science subject matter, but also through an emotional connection via culture, history, and sense of place. The notion that landscape is special because it is the sum total of all the interacting earth systems, including people as part of the biosphere, can be used to drive these initiatives as they affect one personally. It is speculated that most people in the Keweenaw have a basic understanding of the local cultural history and some understanding of geology. Advanced awareness and understanding of the geological significance of the Keweenaw stands to greatly enrich our community's sense of place and desire to advance further education and geotourism initiatives. It is anticipated that these initiatives will ultimately lead to increased Earth science literacy and understanding and recognition of one's own environs. This will aid in the further development of publications, teaching media, trails info, on-site museums, etc. Although the community has embraced geo-outreach thus far, it is germane to know what people value, what they know of the geology and how they connect to place. Results from semi-structured interviews administered with the aim and focus of determining what places are special to people, why they are special and how they formed will be presented in this paper. The results from this research will be used to direct the creation and continued development of geologic interpretation of our region. It is hoped that this understanding will reveal common misconceptions that can be used to improve interpretive material that not only addresses misconceptions but also connects the immediate past with the deep geologic past of the

  8. Advances in understanding, models and parameterizations of biosphere-atmosphere ammonia exchange

    NASA Astrophysics Data System (ADS)

    Flechard, C. R.; Massad, R.-S.; Loubet, B.; Personne, E.; Simpson, D.; Bash, J. O.; Cooter, E. J.; Nemitz, E.; Sutton, M. A.

    2013-07-01

    . Their level of complexity depends on their purpose, the spatial scale at which they are applied, the current level of parameterization, and the availability of the input data they require. State-of-the-art solutions for determining the emission/sink Γ potentials through the soil/canopy system include coupled, interactive chemical transport models (CTM) and soil/ecosystem modelling at the regional scale. However, it remains a matter for debate to what extent realistic options for future regional and global models should be based on process-based mechanistic versus empirical and regression-type models. Further discussion is needed on the extent and timescale by which new approaches can be used, such as integration with ecosystem models and satellite observations.

  9. Advances in understanding, models and parameterisations of biosphere-atmosphere ammonia exchange

    NASA Astrophysics Data System (ADS)

    Flechard, C. R.; Massad, R.-S.; Loubet, B.; Personne, E.; Simpson, D.; Bash, J. O.; Cooter, E. J.; Nemitz, E.; Sutton, M. A.

    2013-03-01

    -chemical species schemes. Their level of complexity depends on their purpose, the spatial scale at which they are applied, the current level of parameterisation, and the availability of the input data they require. State-of-the-art solutions for determining the emission/sink Γ potentials through the soil/canopy system include coupled, interactive chemical transport models (CTM) and soil/ecosystem modelling at the regional scale. However, it remains a matter for debate to what extent realistic options for future regional and global models should be based on process-based mechanistic versus empirical and regression-type models. Further discussion is needed on the extent and timescale by which new approaches can be used, such as integration with ecosystem models and satellite observations.

  10. Characteristics of the Low-Income Population: 1972. Current Population Reports, Consumer Income, Series P-60, No. 88, June 1973 (Advance Data From March 1973 Current Population Survey).

    ERIC Educational Resources Information Center

    Bureau of the Census (DOC), Suitland, MD. Population Div.

    This publication of advance data from the March 1973 Current Population Survey relates to consumer income: characteristics of the low-income population, 1972. About 24.5 million were below the low-income level in 1972, this figure being 1.1 million or 4.3 percent below the 1971 figure. The number of low-income whites declined by about 9 percent in…

  11. One View of the Current State of Understanding in Basal Ganglia Pathophysiology and What is Needed for the Future

    PubMed Central

    Montgomery, Erwin B.

    2011-01-01

    Deep Brain Stimulation (DBS), arguably, is the most dramatic development in movement disorders since the levodopa for Parkinson’s disease. Yet, its mechanisms of action of DBS are unknown. However, DBS related research already has demonstrated that current concepts of basal ganglia pathophysiology are wrong. Specifically, the notion that over-activity of the globus pallidus interna causes parkinsonism, the basis for the most current theories, is no longer tenable. The development of any new theory will be aided by an understanding of how current theories are wrong and why have these flawed theories persist. Many of the problems of current theories are more matters of inference, assumptions, presumptions, and the accepted level of ambiguity than they are of fact. Consequently, it is imperative that these issues be addressed. Just as the inappropriate use of a tool or method is grounds for criticism, methods of reasoning are tools that can be used inappropriately and should be subject to discussion just as misuse of any other tool. Thorough criticism can provide very important lesions though the process could be mistaken as harsh or personal; neither is the case here. At the least, such analyzes can point to potential pitfalls that could be avoided in the development of new theories. As will be discussed, theories are important for the development of therapies but perhaps most important, for the acceptance of new therapies, as was the case for the recent resurgence of interest in surgical therapies. PMID:24868387

  12. Integrated Application of Active Controls (IAAC) technology to an advanced subsonic transport project: Current and advanced act control system definition study. Volume 2: Appendices

    NASA Technical Reports Server (NTRS)

    Hanks, G. W.; Shomber, H. A.; Dethman, H. A.; Gratzer, L. B.; Maeshiro, A.; Gangsaas, D.; Blight, J. D.; Buchan, S. M.; Crumb, C. B.; Dorwart, R. J.

    1981-01-01

    The current status of the Active Controls Technology (ACT) for the advanced subsonic transport project is investigated through analysis of the systems technical data. Control systems technologies under examination include computerized reliability analysis, pitch axis fly by wire actuator, flaperon actuation system design trade study, control law synthesis and analysis, flutter mode control and gust load alleviation analysis, and implementation of alternative ACT systems. Extensive analysis of the computer techniques involved in each system is included.

  13. Advancing Our Understanding of the Link between Statistical Learning and Language Acquisition: The Need for Longitudinal Data

    PubMed Central

    Arciuli, Joanne; Torkildsen, Janne von Koss

    2012-01-01

    Mastery of language can be a struggle for some children. Amongst those that succeed in achieving this feat there is variability in proficiency. Cognitive scientists remain intrigued by this variation. A now substantial body of research suggests that language acquisition is underpinned by a child’s capacity for statistical learning (SL). Moreover, a growing body of research has demonstrated that variability in SL is associated with variability in language proficiency. Yet, there is a striking lack of longitudinal data. To date, there has been no comprehensive investigation of whether a capacity for SL in young children is, in fact, associated with language proficiency in subsequent years. Here we review key studies that have led to the need for this longitudinal research. Advancing the language acquisition debate via longitudinal research has the potential to transform our understanding of typical development as well as disorders such as autism, specific language impairment, and dyslexia. PMID:22969746

  14. Persons of Spanish Origin in the United States: March 1977 (Advance Report). Population Characteristics, Current Population Reports.

    ERIC Educational Resources Information Center

    Fernandez, Edward W.; And Others

    The report presents advance data from the March 1977 Current Population Survey on selected demographic, social, and economic characteristics of persons of Spanish origin. Persons of Spanish origin are divided into the subcategories of Mexican, Puerto Rican, Cuban, Central or South American, and other Spanish origin. Data pertain to such population…

  15. Advanced simulation technology used to reduce accident rates through a better understanding of human behaviors and human perception

    NASA Astrophysics Data System (ADS)

    Manser, Michael P.; Hancock, Peter A.

    1996-06-01

    Human beings and technology have attained a mutually dependent and symbiotic relationship. It is easy to recognize how each depends on the other for survival. It is also easy to see how technology advances due to human activities. However, the role technology plays in advancing humankind is seldom examined. This presentation examines two research areas where the role of advanced visual simulation systems play an integral and essential role in understanding human perception and behavior. The ultimate goal of this research is the betterment of humankind through reduced accident and death rates in transportation environments. The first research area examined involved the estimation of time-to-contact. A high-fidelity wrap-around simulator (RAS) was used to examine people's ability to estimate time-to- contact. The ability of people to estimate the amount of time before an oncoming vehicle will collide with them is a necessary skill for avoiding collisions. A vehicle approached participants at one of three velocities, and while en route to the participant, the vehicle disappeared. The participants' task was to respond when they felt the accuracy of time-to-contact estimates and the practical applications of the result. The second area of research investigates the effects of various visual stimuli on underground transportation tunnel walls for the perception of vehicle speed. A RAS is paramount in creating visual patterns in peripheral vision. Flat-screen or front-screen simulators do not have this ability. Results are discussed in terms of speed perception and the application of these results to real world environments.

  16. Socioscientific Issues: A Path Towards Advanced Scientific Literacy and Improved Conceptual Understanding of Socially Controversial Scientific Theories

    NASA Astrophysics Data System (ADS)

    Pinzino, Dean William

    This thesis investigates the use of socioscientific issues (SSI) in the high school science classroom as an introduction to argumentation and socioscientific reasoning, with the goal of improving students' scientific literacy (SL). Current research is reviewed that supports the likelihood of students developing a greater conceptual understanding of scientific theories as well as a deeper understanding of the nature of science (NOS), through participation in informal and formal forms of argumentation in the context of SSI. Significant gains in such understanding may improve a student's ability to recognize the rigor, legitimacy, and veracity of scientific claims and better discern science from pseudoscience. Furthermore, students that participate in significant SSI instruction by negotiating a range of science-related social issues can make significant gains in content knowledge and develop the life-long skills of argumentation and evidence-based reasoning, goals not possible in traditional lecture-based science instruction. SSI-based instruction may therefore help students become responsible citizens. This synthesis also suggests that that the improvements in science literacy and NOS understanding that develop from sustained engagement in SSI-based instruction will better prepare students to examine and scrutinize socially controversial scientific theories (i.e., evolution, global warming, and the Big Bang).

  17. Advanced Simulation Capability for Environmental Management - Current Status and Phase II Demonstration Results - 13161

    SciTech Connect

    Seitz, Roger R.; Flach, Greg; Freshley, Mark D.; Freedman, Vicky; Gorton, Ian; Dixon, Paul; Moulton, J. David; Hubbard, Susan S.; Faybishenko, Boris; Steefel, Carl I.; Finsterle, Stefan; Marble, Justin

    2013-07-01

    The U.S. Department of Energy (US DOE) 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 Tool-sets and High-Performance Computing (HPC) Multi-process Simulator. The Platform capabilities provide the user interface and tools for end-to-end model development, starting with definition of the conceptual model, management of data for model input, model calibration and uncertainty analysis, and processing of model output, including visualization. The HPC capabilities target increased functionality of process model representations, tool-sets for interaction with Platform, and verification and model confidence testing. The 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 tool-sets 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

  18. Application of advanced technologies to derivatives of current small transport aircraft

    NASA Technical Reports Server (NTRS)

    Renze, P. P.; Terry, J. E.

    1981-01-01

    Mission requirements of the derivative design were the same as the baseline to readily identify the advanced technology benefits achieved. Advanced technologies investigated were in the areas of propulsion, structures and aerodynamics and a direct operating cost benefit analysis conducted to identify the most promising. Engine improvements appear most promising and combined with propeller, airfoil, surface coating and composite advanced technologies give a 21-25 percent DOC savings. A 17 percent higher acquisition cost is offset by a 34 percent savings in fuel used.

  19. Advanced Model Compounds for Understanding Acid-Catalyzed Lignin Depolymerization: Identification of Renewable Aromatics and a Lignin-Derived Solvent.

    PubMed

    Lahive, Ciaran W; Deuss, Peter J; Lancefield, Christopher S; Sun, Zhuohua; Cordes, David B; Young, Claire M; Tran, Fanny; Slawin, Alexandra M Z; de Vries, Johannes G; Kamer, Paul C J; Westwood, Nicholas J; Barta, Katalin

    2016-07-20

    The development of fundamentally new approaches for lignin depolymerization is challenged by the complexity of this aromatic biopolymer. While overly simplified model compounds often lack relevance to the chemistry of lignin, the direct use of lignin streams poses significant analytical challenges to methodology development. Ideally, new methods should be tested on model compounds that are complex enough to mirror the structural diversity in lignin but still of sufficiently low molecular weight to enable facile analysis. In this contribution, we present a new class of advanced (β-O-4)-(β-5) dilinkage models that are highly realistic representations of a lignin fragment. Together with selected β-O-4, β-5, and β-β structures, these compounds provide a detailed understanding of the reactivity of various types of lignin linkages in acid catalysis in conjunction with stabilization of reactive intermediates using ethylene glycol. The use of these new models has allowed for identification of novel reaction pathways and intermediates and led to the characterization of new dimeric products in subsequent lignin depolymerization studies. The excellent correlation between model and lignin experiments highlights the relevance of this new class of model compounds for broader use in catalysis studies. Only by understanding the reactivity of the linkages in lignin at this level of detail can fully optimized lignin depolymerization strategies be developed. PMID:27310182

  20. Earth Observing-1 Advanced Land Imager Flight Performance Assessment: Noise and Dark Current Stability During the First Year on Orbit

    NASA Technical Reports Server (NTRS)

    Mendenhall, J. A.; Gibbs, M. D.

    2002-01-01

    The noise and dark current stability of the Advanced Land Imager during the first year on orbit (November 21, 2000 - November 21, 2001) are presented. Data have been separated into short-term and long-term periods. The analysis of short-term data indicate some SWIR detectors may drift up to ten digital numbers between the pre and post dark observations of a given data collection event. Analysis of long-term data suggest the SWIR dark current has deviated by less than ten digital numbers and some SCA SWIR dark Current have increased by up to 200 digital numbers during the first year on orbit.

  1. Current Understanding of the Pathways Involved in Adult Stem and Progenitor Cell Migration for Tissue Homeostasis and Repair.

    PubMed

    Goichberg, Polina

    2016-08-01

    With the advancements in the field of adult stem and progenitor cells grows the recognition that the motility of primitive cells is a pivotal aspect of their functionality. There is accumulating evidence that the recruitment of tissue-resident and circulating cells is critical for organ homeostasis and effective injury responses, whereas the pathobiology of degenerative diseases, neoplasm and aging, might be rooted in the altered ability of immature cells to migrate. Furthermore, understanding the biological machinery determining the translocation patterns of tissue progenitors is of great relevance for the emerging methodologies for cell-based therapies and regenerative medicine. The present article provides an overview of studies addressing the physiological significance and diverse modes of stem and progenitor cell trafficking in adult mammalian organs, discusses the major microenvironmental cues regulating cell migration, and describes the implementation of live imaging approaches for the exploration of stem cell movement in tissues and the factors dictating the motility of endogenous and transplanted cells with regenerative potential. PMID:27209167

  2. Greek primary school teachers' understanding of current environmental issues: An exploration of their environmental knowledge and images of nature

    NASA Astrophysics Data System (ADS)

    Michail, Sirmo; Stamou, Anastasia G.; Stamou, George P.

    2007-03-01

    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. Using the media as major environmental information sources, in which environmental issues are constructed as environmental risks, teachers are being environmentally educated in lay and not in scientific terms. Moreover, the image of nature emerging from their ideas about the three environmental issues is that of the romantic archetype, which prevails in postindustrial societies. Such a view, though, gives a conceptualization of nature as balance, under which the greenhouse effect and acid rain are seen as exclusively human-induced disturbances.

  3. Understanding the role of electron and hole trions on current transport in aluminium tris(8-hydroxyquinoline) using organic magnetoresistance

    SciTech Connect

    Zhang, Sijie; Gillin, W. P.; Willis, M.; Gotto, R.; Roy, K. A.; Kreouzis, T.; Rolfe, N. J.

    2014-01-27

    The change in current through an organic light emitting diode (OLED) when it is placed in a magnetic field has been dubbed organic magnetoresistance and provides a means to understand the spin interactions that are occurring in working devices. Whilst there are a wide range of interactions that have been proposed to be the cause of the measured effects, there is still a need to identify their individual roles and in particular how they respond to an applied magnetic field. In this work, we investigate the effect of changing the balance of electron and hole injection in a simple aluminium tris(8-hydroxyqinoline) based OLED and demonstrate that the triplet polaron interaction appears to be much stronger for electrons than for holes in this material.

  4. Metabolism-related pharmacokinetic drug−drug interactions with tyrosine kinase inhibitors: current understanding, challenges and recommendations

    PubMed Central

    Teo, Yi Ling; Ho, Han Kiat; Chan, Alexandre

    2015-01-01

    Drug−drug interactions (DDIs) occur when a patient's response to the drug is modified by administration or co-exposure to another drug. The main cytochrome P450 (CYP) enzyme, CYP3A4, is implicated in the metabolism of almost all of the tyrosine kinase inhibitors (TKIs). Therefore, there is a substantial potential for interaction between TKIs and other drugs that modulate the activity of this metabolic pathway. Cancer patients are susceptible to DDIs as they receive many medications, either for supportive care or for treatment of toxicity. Differences in DDI outcomes are generally negligible because of the wide therapeutic window of common drugs. However for anticancer agents, serious clinical consequences may occur from small changes in drug metabolism and pharmacokinetics. Therefore, the objective of this review is to highlight the current understanding of DDIs among TKIs, with a focus on metabolism, as well as to identify challenges in the prediction of DDIs and provide recommendations. PMID:25125025

  5. Fetal Microchimerism in Cancer Protection and Promotion: Current Understanding in Dogs and the Implications for Human Health.

    PubMed

    Bryan, Jeffrey N

    2015-05-01

    Fetal microchimerism is the co-existence of small numbers of cells from genetically distinct individuals living within a mother's body following pregnancy. During pregnancy, bi-directional exchange of cells occurs resulting in maternal microchimerism and even sibling microchimerism in offspring. The presence of fetal microchimerism has been identified with lower frequency in patients with cancers such as breast and lymphoma and with higher frequency in patients with colon cancer and autoimmune diseases. Microchimeric cells have been identified in healing and healed tissues as well as normal and tumor tissues. This has led to the hypothesis that fetal microchimerism may play a protective role in some cancers and may provoke other cancers or autoimmune disease. The long periods of risk for these diseases make it a challenge to prospectively study this phenomenon in human populations. Dogs get similar cancers as humans, share our homes and environmental exposures, and live compressed life-spans, allowing easier prospective study of disease development. This review describes the current state of understanding of fetal microchimerism in humans and dogs and highlights the similarities of the common cancers mammary carcinoma, lymphoma, and colon cancer between the two species. Study of fetal microchimerism in dogs might hold the key to characterization of the type and function of microchimeric cells and their role in health and disease. Such an understanding could then be applied to preventing and treating disease in humans. PMID:25693490

  6. Understanding the Racial and Ethnic Differences in Cost and Mortality Among Advanced Stage Prostate Cancer Patients (STROBE).

    PubMed

    Chhatre, Sumedha; Bruce Malkowicz, Stanley; Sanford Schwartz, J; Jayadevappa, Ravishankar

    2015-08-01

    The aims of the study were to understand the racial/ethnic differences in cost of care and mortality in Medicare elderly with advanced stage prostate cancer.This retrospective, observational study used SEER-Medicare data. Cohort consisted of 10,509 men aged 66 or older and diagnosed with advanced-stage prostate cancer between 2001and 2004. The cohort was followed retrospectively up to 2009. Racial/ethnic variation in cost was analyzed using 2 part-models and quantile regression. Step-wise GLM log-link and Cox regression was used to study the association between race/ethnicity and cost and mortality. Propensity score approach was used to minimize selection bias.Pattern of cost and mortality varies between racial/ethnic groups. Compared with other racial/ethnic groups, non-Hispanic white patients had higher unadjusted costs in treatment and follow-up phases. Quintile regression results indicated that in treatment phase, Hispanics had higher costs in the 95th quantile and non-Hispanic blacks had lower cost in the 95th quantile, compared with non-Hispanic white men. In terminal phase non-Hispanic blacks and Hispanics had higher cost. After controlling for treatment, all-cause and prostate cancer-specific mortality was not significant for non-Hispanic black men, compared with non-Hispanic white men. However, for Asians, mortality remained significantly lower compared with non-Hispanic white men.In conclusion, relationship between race/ethnicity, cost of care, and mortality is intricate. For non-Hispanic black men, disparity in mortality can be attributed to treatment differences. To reduce racial/ethnic disparities in prostate cancer care and outcomes, tailored policies to address underuse, overuse, and misuse of treatment and health services are necessary. PMID:26266389

  7. Feedbacks between geomorphology and biota controlling Earth surface processes and landforms: A review of foundation concepts and current understandings

    NASA Astrophysics Data System (ADS)

    Corenblit, Dov; Baas, Andreas C. W.; Bornette, Gudrun; Darrozes, José; Delmotte, Sébastien; Francis, Robert A.; Gurnell, Angela M.; Julien, Frédéric; Naiman, Robert J.; Steiger, Johannes

    2011-06-01

    This review article presents recent advances in the field of biogeomorphology related to the reciprocal coupling between Earth surface processes and landforms, and ecological and evolutionary processes. The aim is to present to the Earth Science community ecological and evolutionary concepts and associated recent conceptual developments for linking geomorphology and biota. The novelty of the proposed perspective is that (1) in the presence of geomorphologic-engineer species, which modify sediment and landform dynamics, natural selection operating at the scale of organisms may have consequences for the physical components of ecosystems, and particularly Earth surface processes and landforms; and (2) in return, these modifications of geomorphologic processes and landforms often feed back to the ecological characteristics of the ecosystem (structure and function) and thus to biological characteristics of engineer species and/or other species (adaptation and speciation). The main foundation concepts from ecology and evolutionary biology which have led only recently to an improved conception of landform dynamics in geomorphology are reviewed and discussed. The biogeomorphologic macroevolutionary insights proposed explicitly integrate geomorphologic niche-dimensions and processes within an ecosystem framework and reflect current theories of eco-evolutionary and ecological processes. Collectively, these lead to the definition of an integrated model describing the overall functioning of biogeomorphologic systems over ecological and evolutionary timescales.

  8. WinSRFR: Current Advances in Software for Surface Irrigation Simulation and Analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Significant advances have been made over the last decade in the development of software for surface irrigation analysis. WinSRFR is an integrated tool that combines unsteady flow simulation with tools for system evaluation/parameter estimation, system design, and for operational optimization. Ongoi...

  9. Coming of Age: The Advanced Writing Curriculum [and CD-ROM]. CrossCurrents.

    ERIC Educational Resources Information Center

    Shamoon, Linda K., Ed.; Howard, Rebecca Moore, Ed.; Jamieson, Sandra, Ed.; Schwegler, Robert A., Ed.

    Part book, part CD-ROM, this publication offers new ideas for transforming advanced writing courses. The 33 essays in the publication describe and offer concrete examples of curriculum that incorporates discipline-based theory and history, that situates writers in public discourse, and that fully prepares students for careers as writers. The…

  10. From technological advances to biological understanding: The main steps toward high-precision RT in breast cancer.

    PubMed

    Leonardi, Maria Cristina; Ricotti, Rosalinda; Dicuonzo, Samantha; Cattani, Federica; Morra, Anna; Dell'Acqua, Veronica; Orecchia, Roberto; Jereczek-Fossa, Barbara Alicja

    2016-10-01

    Radiotherapy improves local control in breast cancer (BC) patients which increases overall survival in the long term. Improvements in treatment planning and delivery and a greater understanding of BC behaviour have laid the groundwork for high-precision radiotherapy, which is bound to further improve the therapeutic index. Precise identification of target volumes, better coverage and dose homogeneity have had a positive impact on toxicity and local control. The conformity of treatment dose due to three-dimensional radiotherapy and new techniques such as intensity modulated radiotherapy makes it possible to spare surrounding normal tissue. The widespread use of dose-volume constraints and histograms have increased awareness of toxicity. Real time image guidance has improved geometric precision and accuracy, together with the implementation of quality assurance programs. Advances in the precision of radiotherapy is also based on the choice of the appropriate fractionation and approach. Adaptive radiotherapy is not only a technical concept, but is also a biological concept based on the knowledge that different types of BC have distinctive patterns of locoregional spread. A greater understanding of cancer biology helps in choosing the treatment best suited to a particular situation. Biomarkers predictive of response play a crucial role. The combination of radiotherapy with molecular targeted therapies may enhance radiosensitivity, thus increasing the cytotoxic effects and improving treatment response. The appropriateness of an alternative fractionation, partial breast irradiation, dose escalating/de-escalating approaches, the extent of nodal irradiation have been examined for all the BC subtypes. The broadened concept of adaptive radiotherapy is vital to high-precision treatments. PMID:27542556

  11. Utilizing LiDAR Datasets From Experimental Watersheds to Advance Ecohydrological Understanding in Seasonally Snow-Covered Forests

    NASA Astrophysics Data System (ADS)

    Harpold, A. A.; Broxton, P. D.; Guo, Q.; Barlage, M. J.; Gochis, D. J.

    2014-12-01

    The Western U.S. is strongly reliant on snowmelt from forested areas for ecosystem services and downstream populations. The ability to manage water resources from snow-covered forests faces major challenges from drought, disturbance, and regional changes in climate. An exciting avenue for improving ecohydrological process understanding is Light Detection and Ranging (LiDAR) because the technology simultaneously observes topography, forest properties, and snow/ice at high-resolution (<10 cm) and over large extents (>100 km2). The availability and quality of LiDAR datasets is increasing rapidly, however they remain under-utilized for process-based ecohydrology investigations. This presentation will illustrate how LiDAR datasets from the Critical Zone Observatory (CZO) network have been applied to advance ecohydrological understanding through direct empirical analysis, as well as model parameterization and verification. Direct analysis of the datasets has proved fruitful for pre- and post-disturbance snow distribution estimates and interpreting in-situ snow depth measurements across sites. In addition, we illustrate the potential value of LiDAR to parameterize and verify of physical models with two examples. First, we use LiDAR to parameterize a land surface model, Noah multi-parameterization (Noah-MP), to investigate the sensitivity of modeled water and energy fluxes to high-resolution forest information. Second, we present a Snow Physics and Laser Mapping (SnowPALM) model that is parameterized with LiDAR information at its native 1-m scale. Both modeling studies demonstrate the value of LiDAR for representing processes with greater fidelity. More importantly, the increased model fidelity led to different estimates of water and energy fluxes at larger, watershed scales. Creating a network of experimental watersheds with LiDAR datasets offers the potential to test theories and models in previously unexplored ways.

  12. Non-Inductive Current Drive Modeling Extending Advanced Tokamak Operation to Steady State

    SciTech Connect

    Casper, T.A.; Lodestro, L.L.; Pearlstein, L.D.; Porter, G.D.; Murakami, M.; Lao, L.L.; Lin-Lui, Y.R.; St. John, H.E.

    2000-06-06

    A critical issue for sustaining high performance, negative central shear (NCS) discharges is the ability to maintain current distributions that are maximum off axis. Sustaining such hollow current profiles in steady state requires the use of non-inductively driven current sources. On the DIII-D experiment, a combination of neutral beam current drive (NBCD) and bootstrap current have been used to create transient NCS discharges. The electron cyclotron heating (ECH) and current drive (ECCD) system is currently being upgraded from three gyrotrons to six to provide more than 3MW of absorbed power in long-pulse operation to help sustain the required off-axis current drive. This upgrade SuPporrs the long range goal of DIII-D to sustain high performance discharges with high values of normalized {beta}, {beta}{sub n} = {beta}/(I{sub p}/aB{sub T}), confinement enhancement factor, H, and neutron production rates while utilizing bootstrap current fraction, f{sub bs}, in excess of 50%. At these high performance levels, the likelihood of onset of MHD modes that spoil confinement indicates the need to control plasma profiles if we are to extend this operation to long pulse or steady state. To investigate the effectiveness of the EC system and to explore operating scenarios to sustain these discharges, we use time-dependent simulations of the equilibrium, transport and stability. We explore methods to directly alter the safety factor profile, q, through direct current drive or by localized electron heating to modify the bootstrap current profile. Time dependent simulations using both experimentally determined [1] and theory-based [2] energy transport models have been done. Here, we report on simulations exploring parametric dependencies of the heating, current drive, and profiles that affect our ability to sustain stable discharges.

  13. Adoptive T-cell therapies for refractory/relapsed leukemia and lymphoma: current strategies and recent advances

    PubMed Central

    McLaughlin, Lauren; Cruz, C. Russell; Bollard, Catherine M.

    2015-01-01

    Despite significant advancements in the treatment and outcome of hematologic malignancies, prognosis remains poor for patients who have relapsed or refractory disease. Adoptive T-cell immunotherapy offers novel therapeutics that attempt to utilize the noted graft versus leukemia effect. While CD19 chimeric antigen receptor (CAR)-modified T cells have thus far been the most clinically successful application of adoptive T immunotherapy, further work with antigen specific T cells and CARs that recognize other targets have helped diversify the field to treat a broad spectrum of hematologic malignancies. This article will focus primarily on therapies currently in the clinical trial phase as well as current downfalls or limitations. PMID:26622998

  14. Adoptive T-cell therapies for refractory/relapsed leukemia and lymphoma: current strategies and recent advances.

    PubMed

    McLaughlin, Lauren; Cruz, C Russell; Bollard, Catherine M

    2015-12-01

    Despite significant advancements in the treatment and outcome of hematologic malignancies, prognosis remains poor for patients who have relapsed or refractory disease. Adoptive T-cell immunotherapy offers novel therapeutics that attempt to utilize the noted graft versus leukemia effect. While CD19 chimeric antigen receptor (CAR)-modified T cells have thus far been the most clinically successful application of adoptive T immunotherapy, further work with antigen specific T cells and CARs that recognize other targets have helped diversify the field to treat a broad spectrum of hematologic malignancies. This article will focus primarily on therapies currently in the clinical trial phase as well as current downfalls or limitations. PMID:26622998

  15. Finite difference simulations of seismic wave propagation for understanding earthquake physics and predicting ground motions: Advances and challenges

    NASA Astrophysics Data System (ADS)

    Aochi, Hideo; Ulrich, Thomas; Ducellier, Ariane; Dupros, Fabrice; Michea, David

    2013-08-01

    Seismic waves radiated from an earthquake propagate in the Earth and the ground shaking is felt and recorded at (or near) the ground surface. Understanding the wave propagation with respect to the Earth's structure and the earthquake mechanisms is one of the main objectives of seismology, and predicting the strong ground shaking for moderate and large earthquakes is essential for quantitative seismic hazard assessment. The finite difference scheme for solving the wave propagation problem in elastic (sometimes anelastic) media has been more widely used since the 1970s than any other numerical methods, because of its simple formulation and implementation, and its easy scalability to large computations. This paper briefly overviews the advances in finite difference simulations, focusing particularly on earthquake mechanics and the resultant wave radiation in the near field. As the finite difference formulation is simple (interpolation is smooth), an easy coupling with other approaches is one of its advantages. A coupling with a boundary integral equation method (BIEM) allows us to simulate complex earthquake source processes.

  16. Long-Term Transcriptional Consequences of Drug Exposure as Cues to Understand Vulnerability to Relapse: Advances and Perspectives.

    PubMed

    Becker, Jerome A J; Le Merrer, Julie

    2016-09-01

    Quitting drug abuse represents a true challenge for addicted individuals because of the highly persistent vulnerability to relapse. Identifying long-lasting, drug-induced alterations in the brain-including at the transcriptome level-that underlie such vulnerability appears invaluable to improve relapse prevention. Despite substantial technological developments and research effort, however, the picture of drug-induced adaptations provided by high-throughput transcriptomics remains frustratingly partial, notably because of methodological issues. Major advances were made, however, regarding the time course and specificity of long-term transcriptional consequences of drug exposure as well as the recruitment of small, noncoding mRNAs (or miRNAs [microRNAs]) that were previously undetectable. Most importantly, high-throughput studies have benefited from systems biology approaches and shifted their interest toward regulations within functional gene networks rather than individual changes. Such network-based gene discovery approaches have proven informative to delineate the physiological processes, cellular signaling pathways, and neuronal populations altered by drug exposure. Provided the high-throughput effort will be pursued, together with the development of adapted bioinformatics tools, addiction transcriptomics should progressively integrate data across multiple scales (from epigenome to protein), allowing a better understanding of the genetics of drug abuse and opening novel therapeutic trails. PMID:27588526

  17. Advancing understanding of the fluvial export of organic matter through high-resolution profiling of dissolved organic carbon.

    NASA Astrophysics Data System (ADS)

    Waldron, S.; Drew, S.; Gilvear, D.; Murray, H.; Heal, K.

    2012-04-01

    Quantifying the natural variation (complexity) of a system remains an enduring scientific challenge in better understanding controls on surface water quality. This characterisation is needed in order to reveal controlling processes, such as dilution, and also to identify unusual load profiles. In trying to capture that natural variation we still rely largely on concentration time series (and associated export budgets) generated from manual spot sampling, or from samples collected by autosamplers - approaches which are unlikely to provide the high temporal resolution of parameter concentration required. Now however, advances in sensor technology are helping us address this challenge. Here we present detailed dissolved organic carbon (DOC) export profiles from a small upland river (9.4 km sq.), generated since June 2011 by semi-continuous logging of UV-vis absorption (200-750 nm, every 2.5 nm) every 30 minutes. Observed increases in the concentration of the DOC, [DOC], in freshwaters have prompted significant research to understand the cause and consequences of increased export: higher levels of DOC require additional water purification of potable sources; increased aquatic export may represent a reduction in terrestrial C-soil sequestration; changes in light penetration can affect the heterotrophic / autotrophic balance in surface waters and this has consequences for the food web structure; increased aquatic export may also result in increased carbon dioxide evasion. Additionally, C export is often linked to nutrient export: we have observed statistically significant stoichiometric relationships between DOC and soluble reactive phosphorus (SRP) concentrations, thus understanding better this parameters offers insight into export of other nutrient and the source of material from which these dissolved compounds are produced; this may be particulate. Our Scottish study site is interesting because there are multiple processes that can contribute to DOC and other nutrient

  18. Advances in Instrumental Analysis of Brominated Flame Retardants: Current Status and Future Perspectives

    PubMed Central

    2014-01-01

    This review aims to highlight the recent advances and methodological improvements in instrumental techniques applied for the analysis of different brominated flame retardants (BFRs). The literature search strategy was based on the recent analytical reviews published on BFRs. The main selection criteria involved the successful development and application of analytical methods for determination of the target compounds in various environmental matrices. Different factors affecting chromatographic separation and mass spectrometric detection of brominated analytes were evaluated and discussed. Techniques using advanced instrumentation to achieve outstanding results in quantification of different BFRs and their metabolites/degradation products were highlighted. Finally, research gaps in the field of BFR analysis were identified and recommendations for future research were proposed. PMID:27433482

  19. Anxiety and depression in patients with advanced macular degeneration: current perspectives

    PubMed Central

    Cimarolli, Verena R; Casten, Robin J; Rovner, Barry W; Heyl, Vera; Sörensen, Silvia; Horowitz, Amy

    2016-01-01

    Age-related macular degeneration (AMD) – despite advances in prevention and medical treatment options – remains prevalent among older adults, often resulting in functional losses that negatively affect the mental health of older adults. In particular, the prevalence of both anxiety and depression in patients with AMD is high. Along with medical treatment options, low vision rehabilitation and AMD-specific behavioral and self-management programs have been developed and have demonstrated effectiveness in improving the mental health of AMD patients. This article reviews the prevalence of anxiety and depression in patients with advanced AMD, discusses potential mechanisms accounting for the development of depression and anxiety in AMD patients, presents the state-of the-art of available interventions for addressing anxiety and depression in AMD patients, and delineates recommendations for eye care professionals regarding how to screen for these two prevalent mental health problems and how to facilitate appropriate treatment for patients with AMD. PMID:26766899

  20. Current advances and strategies towards fully automated sample preparation for regulated LC-MS/MS bioanalysis.

    PubMed

    Zheng, Naiyu; Jiang, Hao; Zeng, Jianing

    2014-09-01

    Robotic liquid handlers (RLHs) have been widely used in automated sample preparation for liquid chromatography-tandem mass spectrometry (LC-MS/MS) bioanalysis. Automated sample preparation for regulated bioanalysis offers significantly higher assay efficiency, better data quality and potential bioanalytical cost-savings. For RLHs that are used for regulated bioanalysis, there are additional requirements, including 21 CFR Part 11 compliance, software validation, system qualification, calibration verification and proper maintenance. This article reviews recent advances in automated sample preparation for regulated bioanalysis in the last 5 years. Specifically, it covers the following aspects: regulated bioanalysis requirements, recent advances in automation hardware and software development, sample extraction workflow simplification, strategies towards fully automated sample extraction, and best practices in automated sample preparation for regulated bioanalysis. PMID:25384595