Dopamine modulates hemocyte phagocytosis via a D1-like receptor in the rice stem borer, Chilo suppressalis

USDA-ARS?s Scientific Manuscript database

Dopamine (DA) is a signal moiety bridging the nervous and immune systems. DA dysregulation is linked to serious human diseases, including addiction, schizophrenia, and Parkinson's disease. However, DA actions in the immune system remain incompletely understood. In this study, we found that DA modula...

Internal Structure of Mini-CEX Scores for Internal Medicine Residents: Factor Analysis and Generalizability

ERIC Educational Resources Information Center

Cook, David A.; Beckman, Thomas J.; Mandrekar, Jayawant N.; Pankratz, V. Shane

2010-01-01

The mini-CEX is widely used to rate directly observed resident-patient encounters. Although several studies have explored the reliability of mini-CEX scores, the dimensionality of mini-CEX scores is incompletely understood. Objective: Explore the dimensionality of mini-CEX scores through factor analysis and generalizability analysis. Design:…

Enhanced mammary progesterone receptor-A isoform activity in the promotion of mammary tumor progression by dietary soy in rats

USDA-ARS?s Scientific Manuscript database

Dietary contribution to breast cancer risk, recurrence, and progression remains incompletely understood. Increased consumption of soy and soy isoflavones is associated with reduced mammary cancer susceptibility in women and in rodent models of carcinogenesis. In rats treated with N-Methyl-N-Nitrosou...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schreck, S.; Sant, T.; Micallef, D.

Wind turbine structures and components suffer excessive loads and premature failures when key aerodynamic phenomena are not well characterized, fail to be understood, or are inaccurately predicted. Turbine blade rotational augmentation remains incompletely characterized and understood, thus limiting robust prediction for design. Pertinent rotational augmentation research including experimental, theoretical, and computational work has been pursued for some time, but large scale wind tunnel testing is a relatively recent development for investigating wind turbine blade aerodynamics. Because of their large scale and complementary nature, the MEXICO and UAE Phase VI wind tunnel experiments offer unprecedented synergies to better characterize and understandmore » rotational augmentation of blade aerodynamics.« less

Characterization of apple replant disease-associated microbial communities over multiple growth periods using next-generation sequencing

USDA-ARS?s Scientific Manuscript database

Replant disease in apple occurs as a result of incompletely understood and variable complexes of soil-borne pathogens that can build up over time in orchard soil. This disease limits economic viability of newly established orchards on replant sites and results in reduced productivity for the life of...

Social and Non-Social Cueing of Visuospatial Attention in Autism and Typical Development

ERIC Educational Resources Information Center

Pruett, John R.; LaMacchia, Angela; Hoertel, Sarah; Squire, Emma; McVey, Kelly; Todd, Richard D.; Constantino, John N.; Petersen, Steven E.

2011-01-01

Three experiments explored attention to eye gaze, which is incompletely understood in typical development and is hypothesized to be disrupted in autism. Experiment 1 (n = 26 typical adults) involved covert orienting to box, arrow, and gaze cues at two probabilities and cue-target times to test whether reorienting for gaze is endogenous, exogenous,…

Such Stuff as Habits Are Made on: A Reply to Cooper and Shallice (2006)

ERIC Educational Resources Information Center

Botvinick, Matthew M.; Plaut, David C.

2006-01-01

The representations and mechanisms guiding everyday routine sequential action remain incompletely understood. In recent work, the authors proposed a computational model of routine sequential behavior that took the form of a recurrent neural network (M. Botvinick & D. C. Plaut, 2004). Subsequently, R. P. Cooper and T. Shallice (2006) put forth a…

The Origins of Mass

ScienceCinema

Lincoln, Don

2018-01-16

The Higgs boson was discovered in July of 2012 and is generally understood to be the origin of mass. While those statements are true, they are incomplete. It turns out that the Higgs boson is responsible for only about 2% of the mass of ordinary matter. In this dramatic new video, Dr. Don Lincoln of Fermilab tells us the rest of the story.

PD-L2 Elbows out PD-L1 to Rescue T Cell Immunity to Malaria.

PubMed

Crompton, Peter D; Pierce, Susan K

2016-08-16

How early interactions between innate and adaptive immune cells influence outcomes of acute infections is incompletely understood. In this issue of Immunity, Karunarathne et al. (2016) show that dendritic cells help CD4(+) T helper 1 cell immunity against malaria through PD-L2's competition with PD-L1. Published by Elsevier Inc.

Variation in offspring sex ratio of a long-lived sexually dimorphic raptor, the eastern imperial eagle (Aquila heliaca)

Treesearch

Todd E. Katzner; Daniel S. Jackson; Jamie Ivy; Evgeny A. Bragin; Andrew Dewoody

2014-01-01

Sex ratio theory attempts to explain observed variation in offspring sex ratio at both the population and the brood levels. In the context of low-fecundity organisms producing high-investment offspring, the drivers of adaptive variation in sex ratio are incompletely understood. For raptors that display reverse sexual dimorphism (RSD), preferential allocation of...

Chilled in Translation: Adapting to Bacterial Climate Change.

PubMed

Gottesman, Susan

2018-04-19

Cold-shocked bacteria transiently shut down protein translation, but the mechanisms whereby they adaptively restore translation were incompletely understood. Zhang et al. (2018) demonstrate a global increase in mRNA structure after cold shock and that, as structured RNA decreases, translation returns, dependent upon ribonuclease RNase R and cold shock protein CspA and its homologs. Published by Elsevier Inc.

S100A4 is a biomarker and regulator of glioma stem cells that is critical for mesenchymal transition in glioblastoma

USDA-ARS?s Scientific Manuscript database

Glioma stem cells (GSCs) and epithelial-mesenchymal transition (EMT) are strongly associated with therapy resistance and tumor recurrence, but the underlying mechanisms are incompletely understood. Here we show that S100A4 is a novel biomarker of GSCs. S100A4+ cells in gliomas are enriched with canc...

Transcriptome profiling of microRNA by next-gen deep sequencing reveals known and novel miRNA species in the lipid fraction of human breast milk

USDA-ARS?s Scientific Manuscript database

While breast milk has unique health advantages for infants, the mechanisms by which it regulates the physiology of newborns are incompletely understood. miRNAs have been described as functioning transcellularly, and have been previously isolated in cell-free and exosomal form from bodily liquids (se...

Increased Phosphoenolpyruvate Carboxykinase (PEPCK) Gene Expression and Steatosis During Hepatitis C Virus (HCV) Subgenome Replication: Role of Nonstructural Component-5A (NS5A) and CCAAT/Enhancer Binding Protein ß (C/EBPß)

USDA-ARS?s Scientific Manuscript database

Chronic hepatitis C virus (HCV) infection greatly increases the risk for type 2 diabetes and nonalcoholic steatohepatitis; however, the pathogenic mechanisms remain incompletely understood. Here we report gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) transcription and associated tra...

Time-dependent biodistribution and transgene expression of a recombinant human adenovirus serotype 5-luciferase vector as a surrogate agent for rAd5-FMDV vaccines in cattle

USDA-ARS?s Scientific Manuscript database

Replication-defective recombinant adenovirus 5 (rAd5) vectors carrying foot-and-mouth disease virus (FMDV) transgenes elicit a robust immune response to FMDV challenge in cattle; however vaccine function mechanisms are incompletely understood. Recent efforts addressing critical interactions of rAd5 ...

Safety assessment for In-service Pressure Bending Pipe Containing Incomplete Penetration Defects

NASA Astrophysics Data System (ADS)

Wang, M.; Tang, P.; Xia, J. F.; Ling, Z. W.; Cai, G. Y.

2017-12-01

Incomplete penetration defect is a common defect in the welded joint of pressure pipes. While the safety classification of pressure pipe containing incomplete penetration defects, according to periodical inspection regulations in present, is more conservative. For reducing the repair of incomplete penetration defect, a scientific and applicable safety assessment method for pressure pipe is needed. In this paper, the stress analysis model of the pipe system was established for the in-service pressure bending pipe containing incomplete penetration defects. The local finite element model was set up to analyze the stress distribution of defect location and the stress linearization. And then, the applicability of two assessment methods, simplified assessment and U factor assessment method, to the assessment of incomplete penetration defects located at pressure bending pipe were analyzed. The results can provide some technical supports for the safety assessment of complex pipelines in the future.

A Study of Incomplete Abortion Following Medical Method of Abortion (MMA).

PubMed

Pawde, Anuya A; Ambadkar, Arun; Chauhan, Anahita R

2016-08-01

Medical method of abortion (MMA) is a safe, efficient, and affordable method of abortion. However, incomplete abortion is a known side effect. To study incomplete abortion due to medication abortion and compare to spontaneous incomplete abortion and to study referral practices and prescriptions in cases of incomplete abortion following MMA. Prospective observational study of 100 women with first trimester incomplete abortion, divided into two groups (spontaneous or following MMA), was administered a questionnaire which included information regarding onset of bleeding, treatment received, use of medications for abortion, its prescription, and administration. Comparison of two groups was done using Fisher exact test (SPSS 21.0 software). Thirty percent of incomplete abortions were seen following MMA; possible reasons being self-administration or prescription by unregistered practitioners, lack of examination, incorrect dosage and drugs, and lack of follow-up. Complications such as collapse, blood requirement, and fever were significantly higher in these patients compared to spontaneous abortion group. The side effects of incomplete abortions following MMA can be avoided by the following standard guidelines. Self medication, over- the-counter use, and prescription by unregistered doctors should be discouraged and reported, and need of follow-up should be emphasized.

Epigenetics of prostate cancer and the prospect of identification of novel drug targets by RNAi screening of epigenetic enzymes.

PubMed

Björkman, Mari; Rantala, Juha; Nees, Matthias; Kallioniemi, Olli

2010-10-01

Alterations in epigenetic processes probably underlie most human malignancies. Novel genome-wide techniques, such as chromatin immunoprecipitation and high-throughput sequencing, have become state-of-the-art methods to map the epigenomic landscape of development and disease, such as in cancers. Despite these advances, the functional significance of epigenetic enzymes in cancer progression, such as prostate cancer, remain incompletely understood. A comprehensive mapping and functional understanding of the cancer epigenome will hopefully help to facilitate development of novel cancer therapy targets and improve future diagnostics. The authors have developed a novel cell microarray-based high-content siRNA screening technique suitable to address the putative functional role and impact of all known putative and novel epigenetic enzymes in cancer, including prostate cancer.

Influence of cold storage prior to and after ripening on quality factors and sensory attributes of ‘Hass’ avocados

USDA-ARS?s Scientific Manuscript database

Partially-ripened avocados are often held in cold storage in an attempt to enable the consistent delivery of ripe fruit to food service or retail outlets, although the effect on the quality of such fruit is incompletely understood. ‘Hass’ avocados were ripened to near ripeness (13.3 - 17.8 N) at 20 ...

Switch-Hitting Immune Cells: From Tumor Protection to Metastasis Promotion | Center for Cancer Research

Cancer.gov

The leading cause of death from cancer is not a primary tumor but is the metastases, or invasion of tumor cells into other locations in the body, that result from it. A complex and incompletely understood process, metastatic tumor formation is thought to require several steps in which tumor cells invade the tissue surrounding the primary tumor, enter local blood vessels,

[Gestalt theory of V. v. Weizsäcker from the viewpoint of the psychology emotions].

PubMed

Brunnhuber, S

2001-07-01

The "Gestaltkreis" represents an important part in the psychosomatic theory-discussion, which can be understood as an incomplete contribution towards a general theory of emotions. Especially the relationship between perception and motion requires further consideration. Instead of a causal attribution, cyclic complementaries are important. Furthermore different degrees of organisation within the body-scheme and the affect-apparatus are mentioned.

Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway* | Office of Cancer Genomics

Cancer.gov

Plasticity of the cell state has been proposed to drive resistance to multiple classes of cancer therapies, thereby limiting their effectiveness. A high-mesenchymal cell state observed in human tumors and cancer cell lines has been associated with resistance to multiple treatment modalities across diverse cancer lineages, but the mechanistic underpinning for this state has remained incompletely understood.

Modeling Aggressive Medulloblastoma Using Human Induced Pluripotent Stem Cells

DTIC Science & Technology

2017-09-01

and Myc in turn induces expression of AT1R creating a positive feedback loop and development of aggression tumor phenotype. The therapeutic...strengths are the relevant expertise of the applicant and his collaborating team, the novel paracrine positive feedback loop in EC-tumor cell...to as MYC-driven MB. The molecular mechanisms that drive MYC hyper -activation in MB remain incompletely understood. MB cells in actual tumors interact

Incomplete fusion analysis of the 7Li-induced reaction on 93Nb within 3-6.5 MeV/nucleon

NASA Astrophysics Data System (ADS)

Kumar, Deepak; Maiti, Moumita

2017-10-01

Background: It is understood from the recent experimental studies that prompt/resonant breakup, and transfer followed by breakup in the weakly bound Li,76-induced reactions play a significant role in the complete-incomplete fusion (CF-ICF), suppression/enhancement in the fusion cross section around the Coulomb barrier. Purpose: Investigation of ICF over CF by measuring cross sections of the populated residues, produced via different channels in the 7Li-induced reaction on a natNb target within the 3-6.5 MeV/nucleon energy region. Method: The 7Li beam was allowed to hit the self-supporting 93Nb targets, backed by the aluminium (Al) foil alternately, within 3-6.5 MeV/nucleon energy. Populated residues were identified by offline γ -ray spectrometry. Measured excitation functions of different channels were compared with different equilibrium and pre-equilibrium models. Result: The enhancement in cross sections in the proton (˜20 -30 MeV) and α -emitting channels, which may be ascribed to ICF, was observed in the measured energy range when compared to the Hauser-Feshbach and exciton model calculations using empire, which satisfactorily reproduces the neutron channels, compared to the Weisskopf-Ewing model and hybrid Monte Carlo calculations. The increment of the incomplete fusion fraction was observed with rising projectile energy. Conclusion: Contrary to the alice14, experimental results are well reproduced by the empire throughout the measured energy range. The signature of ICF over CF indicates that the breakup/transfer processes are involved in the weakly bound 7Li-induced reaction on 93Nb slightly above the Coulomb barrier.

Cooling Atomic Gases With Disorder

DOE PAGES

Paiva, Thereza; Khatami, Ehsan; Yang, Shuxiang; ...

2015-12-10

Cold atomic gases have proven capable of emulating a number of fundamental condensed matter phenomena including Bose-Einstein condensation, the Mott transition, Fulde-Ferrell-Larkin-Ovchinnikov pairing, and the quantum Hall effect. Cooling to a low enough temperature to explore magnetism and exotic superconductivity in lattices of fermionic atoms remains a challenge. Here in this paper, we propose a method to produce a low temperature gas by preparing it in a disordered potential and following a constant entropy trajectory to deliver the gas into a nondisordered state which exhibits these incompletely understood phases. We show, using quantum Monte Carlo simulations, that we can approachmore » the Néel temperature of the three-dimensional Hubbard model for experimentally achievable parameters. Recent experimental estimates suggest the randomness required lies in a regime where atom transport and equilibration are still robust.« less

Thermodynamics of inequalities: From precariousness to economic stratification

NASA Astrophysics Data System (ADS)

Smerlak, Matteo

2016-01-01

Growing economic inequalities are observed in several countries throughout the world. Following Pareto, the power-law structure of these inequalities has been the subject of much theoretical and empirical work. But their nonequilibrium dynamics, e.g. after a policy change, remains incompletely understood. Here we introduce a thermodynamical theory of inequalities based on the analogy between economic stratification and statistical entropy. Within this framework we identify the combination of upward mobility with precariousness as a fundamental driver of inequality. We formalize this statement by a "second-law" inequality displaying upward mobility and precariousness as thermodynamic conjugate variables. We estimate the time scale for the "relaxation" of the wealth distribution after a sudden change of the after-tax return on capital. Our method can be generalized to gain insight into the dynamics of inequalities in any Markovian model of socioeconomic interactions.

DNA curvature and flexibility in vitro and in vivo

PubMed Central

Peters, Justin P.; Maher, L. James

2014-01-01

It has been more than 50 years since the elucidation of the structure of double-helical DNA. Despite active research and progress in DNA biology and biochemistry, much remains to be learned in the field of DNA biophysics. Predicting the sequence-dependent curvature and flexibility of DNA is difficult. Applicability of the conventional worm-like chain polymer model of DNA has been challenged. The fundamental forces responsible for the remarkable resistance of DNA to bending and twisting remain controversial. The apparent “softening” of DNA measured in vivo in the presence of kinking proteins and superhelical strain is incompletely understood. New methods and insights are being applied to these problems. This review places current work on DNA biophysics in historical context and illustrates the ongoing interplay between theory and experiment in this exciting field. PMID:20478077

Nephrocalcinosis (Enamel Renal Syndrome) Caused by Autosomal Recessive FAM20A Mutations

PubMed Central

Jaureguiberry, Graciana; De la Dure-Molla, Muriel; Parry, David; Quentric, Mickael; Himmerkus, Nina; Koike, Toshiyasu; Poulter, James; Klootwijk, Enriko; Robinette, Steven L.; Howie, Alexander J.; Patel, Vaksha; Figueres, Marie-Lucile; Stanescu, Horia C.; Issler, Naomi; Nicholson, Jeremy K.; Bockenhauer, Detlef; Laing, Christopher; Walsh, Stephen B.; McCredie, David A.; Povey, Sue; Asselin, Audrey; Picard, Arnaud; Coulomb, Aurore; Medlar, Alan J.; Bailleul-Forestier, Isabelle; Verloes, Alain; Le Caignec, Cedric; Roussey, Gwenaelle; Guiol, Julien; Isidor, Bertrand; Logan, Clare; Shore, Roger; Johnson, Colin; Inglehearn, Christopher; Al-Bahlani, Suhaila; Schmittbuhl, Matthieu; Clauss, François; Huckert, Mathilde; Laugel, Virginie; Ginglinger, Emmanuelle; Pajarola, Sandra; Spartà, Giuseppina; Bartholdi, Deborah; Rauch, Anita; Addor, Marie-Claude; Yamaguti, Paulo M.; Safatle, Heloisa P.; Acevedo, Ana Carolina; Martelli-Júnior, Hercílio; dos Santos Netos, Pedro E.; Coletta, Ricardo D.; Gruessel, Sandra; Sandmann, Carolin; Ruehmann, Denise; Langman, Craig B.; Scheinman, Steven J.; Ozdemir-Ozenen, Didem; Hart, Thomas C.; Hart, P. Suzanne; Neugebauer, Ute; Schlatter, Eberhard; Houillier, Pascal; Gahl, William A.; Vikkula, Miikka; Bloch-Zupan, Agnès; Bleich, Markus; Kitagawa, Hiroshi; Unwin, Robert J.; Mighell, Alan; Berdal, Ariane; Kleta, Robert

2013-01-01

Background/Aims Calcium homeostasis requires regulated cellular and interstitial systems interacting to modulate the activity and movement of this ion. Disruption of these systems in the kidney results in nephrocalcinosis and nephrolithiasis, important medical problems whose pathogenesis is incompletely understood. Methods We investigated 25 patients from 16 families with unexplained nephrocalcinosis and characteristic dental defects (amelogenesis imperfecta, gingival hyperplasia, impaired tooth eruption). To identify the causative gene, we performed genome-wide linkage analysis, exome capture, next-generation sequencing, and Sanger sequencing. Results All patients had bi-allelic FAM20A mutations segregating with the disease; 20 different mutations were identified. Conclusions This au-tosomal recessive disorder, also known as enamel renal syndrome, of FAM20A causes nephrocalcinosis and amelogenesis imperfecta. We speculate that all individuals with biallelic FAM20A mutations will eventually show nephrocalcinosis. PMID:23434854

Leptin is associated with cardiopulmonary fitness independent of body-mass index and insulin sensitivity in adolescents with type 1 diabetes: a brief report from the EMERALD study.

PubMed

Bjornstad, Petter; Cree-Green, Melanie; Baumgartner, Amy; Coe, Gregory; Reyes, Yesenia Garcia; Schafer, Michal; Pyle, Laura; Regensteiner, Judith G; Reusch, Jane E B; Nadeau, Kristen J

2017-05-01

Cardiopulmonary fitness is decreased in type 1 diabetes for reasons that are incompletely understood. In this study, leptin was associated with exercise capacity independent of insulin sensitivity (IS) and body mass index (BMI), suggesting that leptin may relate to cardiopulmonary fitness by mechanisms beyond IS and/or obesity. Copyright © 2017 Elsevier Inc. All rights reserved.

A high-fat diet containing whole walnuts (Juglans regia) reduces tumour size and growth along with plasma insulin-like growth factor 1 in the transgenic adenocarcinoma of the mouse prostate model

USDA-ARS?s Scientific Manuscript database

Dietary fat is linked to prostate cancer (PCa), the most commonly diagnosed male cancer, but the nature and strength of the relationships between total fat, n-6 and n-3 fatty acids and PCa remain incompletely understood. Transgenic adenocarcinoma of the mouse prostate (TRAMP) mice (N=10-12 per grou...

Regional Seismic Methods of Identifying Explosions

NASA Astrophysics Data System (ADS)

Walter, W. R.; Ford, S. R.; Pasyanos, M.; Pyle, M. L.; Hauk, T. F.

2013-12-01

A lesson from the 2006, 2009 and 2013 DPRK declared nuclear explosion Ms:mb observations is that our historic collection of data may not be representative of future nuclear test signatures (e.g. Selby et al., 2012). To have confidence in identifying future explosions amongst the background of other seismic signals, we need to put our empirical methods on a firmer physical footing. Here we review the two of the main identification methods: 1) P/S ratios and 2) Moment Tensor techniques, which can be applied at the regional distance (200-1600 km) to very small events, improving nuclear explosion monitoring and confidence in verifying compliance with the Comprehensive Nuclear-Test-Ban Treaty (CTBT). Amplitude ratios of seismic P-to-S waves at sufficiently high frequencies (~>2 Hz) can identify explosions among a background of natural earthquakes (e.g. Walter et al., 1995). However the physical basis for the generation of explosion S-waves, and therefore the predictability of this P/S technique as a function of event properties such as size, depth, geology and path, remains incompletely understood. Calculated intermediate period (10-100s) waveforms from regional 1-D models can match data and provide moment tensor results that separate explosions from earthquakes and cavity collapses (e.g. Ford et al. 2009). However it has long been observed that some nuclear tests produce large Love waves and reversed Rayleigh waves that complicate moment tensor modeling. Again the physical basis for the generation of these effects from explosions remains incompletely understood. We are re-examining regional seismic data from a variety of nuclear test sites including the DPRK and the former Nevada Test Site (now the Nevada National Security Site (NNSS)). Newer relative amplitude techniques can be employed to better quantify differences between explosions and used to understand those differences in term of depth, media and other properties. We are also making use of the Source Physics Experiments (SPE) at NNSS. The SPE chemical explosions are explicitly designed to improve our understanding of emplacement and source material effects on the generation of shear and surface waves (e.g. Snelson et al., 2013). Our goal is to improve our explosion models and our ability to understand and predict where P/S and moment tensor methods of identifying explosions work, and any circumstances where they may not. This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

Dehydration upon admission is a risk factor for incomplete recovery of renal function in children with haemolytic uremic syndrome.

PubMed

Ojeda, José M; Kohout, Isolda; Cuestas, Eduardo

2013-01-01

Haemolytic uremic syndrome (HUS) is the most common cause of acute renal failure and the second leading cause of chronic renal failure in children. The factors that affect incomplete renal function recovery prior to hospital admission are poorly understood. To analyse the risk factors that determine incomplete recovery of renal function prior to hospitalisation in children with HUS. A retrospective case-control study. age, sex, duration of diarrhoea, bloody stools, vomiting, fever, dehydration, previous use of antibiotics, and incomplete recovery of renal function (proteinuria, hypertension, reduced creatinine clearance, and chronic renal failure during follow-up). Patients of both sexes under 15 years of age were included. Of 36 patients, 23 were males (65.3%; 95%CI: 45.8 to 80.9), with an average age of 2.5 ± 1.4 years. Twenty-one patients required dialysis (58%; 95% CI: 40.8 to 75.8), and 13 (36.1%; 95% CI: 19.0 to 53.1) did not recover renal function. In the bivariate model, the only significant risk factor was dehydration (defined as weight loss >5%) [(OR: 5.3; 95% CI: 1.4 to 12.3; P=.0220]. In the multivariate analysis (Cox multiple regression), only dehydration was marginally significant (HR: 95.823; 95% CI: 93.175 to 109.948; P=.085). Our data suggest that dehydration prior to admission may be a factor that increases the risk of incomplete recovery of renal function during long-term follow-up in children who develop HUS D+. Consequently, in patients with diarrhoea who are at risk of HUS, dehydration should be strongly avoided during outpatient care to preserve long-term renal function. These results must be confirmed by larger prospective studies.

Inflammation and hypoxia in the kidney: friends or foes?

PubMed

Haase, Volker H

2015-08-01

Hypoxic injury is commonly associated with inflammatory-cell infiltration, and inflammation frequently leads to the activation of cellular hypoxia response pathways. The molecular mechanisms underlying this cross-talk during kidney injury are incompletely understood. Yamaguchi and colleagues identify CCAAT/enhancer-binding protein δ as a cytokine- and hypoxia-regulated transcription factor that fine-tunes hypoxia-inducible factor-1 signaling in renal epithelial cells and thus provide a novel molecular link between hypoxia and inflammation in kidney injury.

The intersection of nonalcoholic fatty liver disease and obesity.

PubMed

Woo Baidal, Jennifer A; Lavine, Joel E

2016-01-27

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and recently emerged as the most rapidly increasing indication for liver transplant. Although obesity is a risk factor for NAFLD, overlap between these two entities is incompletely understood. We highlight recent insights into the pathogenesis of human NAFLD in relation to obesity and discuss advances in the diagnosis and treatment of NAFLD. Copyright © 2016, American Association for the Advancement of Science.

Stomach Dysfunction in Diabetes Mellitus: Emerging Technology and Pharmacology

PubMed Central

Szarka, Lawrence A.; Camilleri, Michael

2010-01-01

Gastroparesis and other types of gastric dysfunction result in substantial morbidity in diabetes patients. The pathophysiology of these disorders is incompletely understood. This article reviews techniques applicable to the assessment of gastric function in diabetes patients, including the measurement of emptying, accommodation, and contractility. Available treatment options are also reviewed, including novel yet unapproved serotonin 5-HT4 agonist pharmacological treatments, as well as the role of endoscopic, surgical, and device treatments of gastroparesis. PMID:20167183

Estimation of the KR20 Reliability Coefficient When Data Are Incomplete.

ERIC Educational Resources Information Center

Huynh, Huynh

Three techniques for estimating Kuder Richardson reliability (KR20) coefficients for incomplete data are contrasted. The methods are: (1) Henderson's Method 1 (analysis of variance, or ANOVA); (2) Henderson's Method 3 (FITCO); and (3) Koch's method of symmetric sums (SYSUM). A Monte Carlo simulation was used to assess the precision of the three…

COEXISTENCE OF CONSTIPATION AND INCONTINENCE IN CHILDREN AND ADULTS

PubMed Central

Nurko, S; Scott, SM

2011-01-01

The coexistence of constipation and fecal incontinence has long been recognized in pediatric and geriatric populations, but is grossly underappreciated in the rest of the adult population. In children, functional fecal incontinence is usually associated with constipation, stool retention and incomplete evacuation, and is frequently allied to urinary incontinence. Pathophysiology of the incontinence is incompletely understood, although both in children and adults, it is thought to be secondary to overflow, while in adults it may also be related to pelvic floor dysfunction and denervation. Incontinence has an important impact on quality of life and daily functioning, and in children may be associated with behavior problems. The treatment of underlying constipation usually results in improvement in incontinence. This review broadly addresses the epidemiology and pathophysiology of coexistent constipation and incontinence in both children and adults, and also reviews clinical presentation and treatment response in pediatrics. PMID:21382577

The Devil Is in the Details: Incomplete Reporting in Preclinical Animal Research.

PubMed

Avey, Marc T; Moher, David; Sullivan, Katrina J; Fergusson, Dean; Griffin, Gilly; Grimshaw, Jeremy M; Hutton, Brian; Lalu, Manoj M; Macleod, Malcolm; Marshall, John; Mei, Shirley H J; Rudnicki, Michael; Stewart, Duncan J; Turgeon, Alexis F; McIntyre, Lauralyn

2016-01-01

Incomplete reporting of study methods and results has become a focal point for failures in the reproducibility and translation of findings from preclinical research. Here we demonstrate that incomplete reporting of preclinical research is not limited to a few elements of research design, but rather is a broader problem that extends to the reporting of the methods and results. We evaluated 47 preclinical research studies from a systematic review of acute lung injury that use mesenchymal stem cells (MSCs) as a treatment. We operationalized the ARRIVE (Animal Research: Reporting of In Vivo Experiments) reporting guidelines for pre-clinical studies into 109 discrete reporting sub-items and extracted 5,123 data elements. Overall, studies reported less than half (47%) of all sub-items (median 51 items; range 37-64). Across all studies, the Methods Section reported less than half (45%) and the Results Section reported less than a third (29%). There was no association between journal impact factor and completeness of reporting, which suggests that incomplete reporting of preclinical research occurs across all journals regardless of their perceived prestige. Incomplete reporting of methods and results will impede attempts to replicate research findings and maximize the value of preclinical studies.

Rule Extracting based on MCG with its Application in Helicopter Power Train Fault Diagnosis

NASA Astrophysics Data System (ADS)

Wang, M.; Hu, N. Q.; Qin, G. J.

2011-07-01

In order to extract decision rules for fault diagnosis from incomplete historical test records for knowledge-based damage assessment of helicopter power train structure. A method that can directly extract the optimal generalized decision rules from incomplete information based on GrC was proposed. Based on semantic analysis of unknown attribute value, the granule was extended to handle incomplete information. Maximum characteristic granule (MCG) was defined based on characteristic relation, and MCG was used to construct the resolution function matrix. The optimal general decision rule was introduced, with the basic equivalent forms of propositional logic, the rules were extracted and reduction from incomplete information table. Combined with a fault diagnosis example of power train, the application approach of the method was present, and the validity of this method in knowledge acquisition was proved.

WE-AB-207A-02: John’s Equation Based Consistency Condition and Incomplete Projection Restoration Upon Circular Orbit CBCT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, J; Qi, H; Wu, S

Purpose: In transmitted X-ray tomography imaging, projections are sometimes incomplete due to a variety of reasons, such as geometry inaccuracy, defective detector cells, etc. To address this issue, we have derived a direct consistency condition based on John’s Equation, and proposed a method to effectively restore incomplete projections based on this consistency condition. Methods: Through parameter substitutions, we have derived a direct consistency condition equation from John’s equation, in which the left side is only projection derivative of view and the right side is projection derivative of other geometrical parameters. Based on this consistency condition, a projection restoration method ismore » proposed, which includes five steps: 1) Forward projecting reconstructed image and using linear interpolation to estimate the incomplete projections as the initial result; 2) Performing Fourier transform on the projections; 3) Restoring the incomplete frequency data using the consistency condition equation; 4) Performing inverse Fourier transform; 5) Repeat step 2)∼4) until our criteria is met to terminate the iteration. Results: A beam-blocking-based scatter correction case and a bad-pixel correction case were used to demonstrate the efficacy and robustness of our restoration method. The mean absolute error (MAE), signal noise ratio (SNR) and mean square error (MSE) were employed as our evaluation metrics of the reconstructed images. For the scatter correction case, the MAE is reduced from 63.3% to 71.7% with 4 iterations. Compared with the existing Patch’s method, the MAE of our method is further reduced by 8.72%. For the bad-pixel case, the SNR of the reconstructed image by our method is increased from 13.49% to 21.48%, with the MSE being decreased by 45.95%, compared with linear interpolation method. Conclusion: Our studies have demonstrated that our restoration method based on the new consistency condition could effectively restore the incomplete projections, especially for their high frequency component.« less

Getting older can be exhausting.

PubMed

Mittal, Rohit; Ford, Mandy L; Coopersmith, Craig M

2014-07-29

Sepsis is a disease that affects primarily the aged. Although mortality is higher in both older septic patients and aged septic mice, the mechanisms underlying decreased survival in older hosts are incompletely understood. New work by Inoue and colleagues demonstrates persistent inflammation and T-cell exhaustion in older septic patients and aged septic mice. The clinical significance of these findings is manifested not only in increased mortality but also in a marked difference in secondary infections in older patients as long as a month following ICU admission.

Pearling Instabilities of a Viscoelastic Thread

NASA Astrophysics Data System (ADS)

Deblais, A.; Velikov, K. P.; Bonn, D.

2018-05-01

Pearling instabilities of slender viscoelastic threads have received much attention, but remain incompletely understood. We study the instabilities in polymer solutions subject to uniaxial elongational flow. Two distinctly different instabilites are observed: beads on a string and blistering. The beads-on-a-string structure arises from a capillary instability whereas the blistering instability has a different origin: it is due to a coupling between stress and polymer concentration. By varying the temperature to change the solution properties we elucidate the interplay between flow and phase separation.

Perceived poisons.

PubMed

Nañagas, Kristine A; Kirk, Mark A

2005-11-01

Perceived poisoning may manifest in numerous ways; however, all cases share certain characteristics. All are fostered by the wide availability of unreliable information about chemical safety, poor understanding of scientific principles, and ineffective risk communication. Although this problem is still incompletely understood, some approaches have been demonstrated to be useful, such as education about risk, appropriate reassurance, and empathy on the part of the practitioner. Successful management may curtail the spread or exacerbation of symptoms, whereas unsuccessful treatment may cause the problems to escalate, with detrimental effects on both society and patient.

A new framework of statistical inferences based on the valid joint sampling distribution of the observed counts in an incomplete contingency table.

PubMed

Tian, Guo-Liang; Li, Hui-Qiong

2017-08-01

Some existing confidence interval methods and hypothesis testing methods in the analysis of a contingency table with incomplete observations in both margins entirely depend on an underlying assumption that the sampling distribution of the observed counts is a product of independent multinomial/binomial distributions for complete and incomplete counts. However, it can be shown that this independency assumption is incorrect and can result in unreliable conclusions because of the under-estimation of the uncertainty. Therefore, the first objective of this paper is to derive the valid joint sampling distribution of the observed counts in a contingency table with incomplete observations in both margins. The second objective is to provide a new framework for analyzing incomplete contingency tables based on the derived joint sampling distribution of the observed counts by developing a Fisher scoring algorithm to calculate maximum likelihood estimates of parameters of interest, the bootstrap confidence interval methods, and the bootstrap testing hypothesis methods. We compare the differences between the valid sampling distribution and the sampling distribution under the independency assumption. Simulation studies showed that average/expected confidence-interval widths of parameters based on the sampling distribution under the independency assumption are shorter than those based on the new sampling distribution, yielding unrealistic results. A real data set is analyzed to illustrate the application of the new sampling distribution for incomplete contingency tables and the analysis results again confirm the conclusions obtained from the simulation studies.

A Comparison of Maximum-Likelihood and Asymptotically Distribution-Free Methods of Treating Incomplete Nonnormal Data

ERIC Educational Resources Information Center

Gold, Michael S.; Bentler, Peter M.; Kim, Kevin H.

2003-01-01

This article describes a Monte Carlo study of 2 methods for treating incomplete nonnormal data. Skewed, kurtotic data sets conforming to a single structured model, but varying in sample size, percentage of data missing, and missing-data mechanism, were produced. An asymptotically distribution-free available-case (ADFAC) method and structured-model…

Incomplete Sparse Approximate Inverses for Parallel Preconditioning

DOE PAGES

Anzt, Hartwig; Huckle, Thomas K.; Bräckle, Jürgen; ...

2017-10-28

In this study, we propose a new preconditioning method that can be seen as a generalization of block-Jacobi methods, or as a simplification of the sparse approximate inverse (SAI) preconditioners. The “Incomplete Sparse Approximate Inverses” (ISAI) is in particular efficient in the solution of sparse triangular linear systems of equations. Those arise, for example, in the context of incomplete factorization preconditioning. ISAI preconditioners can be generated via an algorithm providing fine-grained parallelism, which makes them attractive for hardware with a high concurrency level. Finally, in a study covering a large number of matrices, we identify the ISAI preconditioner as anmore » attractive alternative to exact triangular solves in the context of incomplete factorization preconditioning.« less

Feeling Heard & Understood in the Hospital Environment: Benchmarking Communication Quality Among Patients with Advanced Cancer Before and After Palliative Care Consultation.

PubMed

Ingersoll, Luke T; Saeed, Fahad; Ladwig, Susan; Norton, Sally A; Anderson, Wendy; Alexander, Stewart C; Gramling, Robert

2018-05-02

Maximizing value in palliative care requires continued development and standardization of communication quality indicators. To describe the basic epidemiology of a newly-adopted patient-centered communication quality indicator for hospitalized palliative care patie9nts with advanced cancer. Cross-sectional analysis of 207 advanced cancer patients who received palliative care consultation at two medical centers in the United States. Participants completed the Heard & Understood quality indicator immediately before and the day following the initial palliative care consultation: "Over the past two days ["24 hours" for the post-consultation version], how much have you felt heard and understood by the doctors, nurses and hospital staff? Completely/Quite a Bit/Moderately/Slightly/Not at All". We categorized "Completely" as indicating ideal quality. Approximately one-third indicated ideal Heard & Understood quality before palliative care consultation. Age, financial security, emotional distress, preferences for comfort-longevity tradeoffs at end-of-life, and prognosis expectations were associated with pre-consultation quality. Among those with less-than-ideal quality at baseline, 56% rated feeling more Heard & Understood the day following palliative care consultation. The greatest pre-post improvement was among people who had unformed end-of-life treatment preferences or who reported having "no idea" about their prognosis at baseline. Most patients felt incompletely heard and understood at the time of referral to palliative care consultation and more than half improved following consultation. Feeling heard and understood is an important quality indicator sensitive to interventions to improve care and key variations in the patient experience. Copyright © 2018. Published by Elsevier Inc.

Cross-Sectional and Panel Data Analyses of an Incompletely Observed Variable Derived from the Nonrandomized Method for Surveying Sensitive Questions

ERIC Educational Resources Information Center

Yamaguchi, Kazuo

2016-01-01

This article describes (1) the survey methodological and statistical characteristics of the nonrandomized method for surveying sensitive questions for both cross-sectional and panel survey data and (2) the way to use the incompletely observed variable obtained from this survey method in logistic regression and in loglinear and log-multiplicative…

A Drosophila Toolkit for the Visualization and Quantification of Viral Replication Launched from Transgenic Genomes

PubMed Central

Wernet, Mathias F.; Klovstad, Martha; Clandinin, Thomas R.

2014-01-01

Arthropod RNA viruses pose a serious threat to human health, yet many aspects of their replication cycle remain incompletely understood. Here we describe a versatile Drosophila toolkit of transgenic, self-replicating genomes (‘replicons’) from Sindbis virus that allow rapid visualization and quantification of viral replication in vivo. We generated replicons expressing Luciferase for the quantification of viral replication, serving as useful new tools for large-scale genetic screens for identifying cellular pathways that influence viral replication. We also present a new binary system in which replication-deficient viral genomes can be activated ‘in trans’, through co-expression of an intact replicon contributing an RNA-dependent RNA polymerase. The utility of this toolkit for studying virus biology is demonstrated by the observation of stochastic exclusion between replicons expressing different fluorescent proteins, when co-expressed under control of the same cellular promoter. This process is analogous to ‘superinfection exclusion’ between virus particles in cell culture, a process that is incompletely understood. We show that viral polymerases strongly prefer to replicate the genome that encoded them, and that almost invariably only a single virus genome is stochastically chosen for replication in each cell. Our in vivo system now makes this process amenable to detailed genetic dissection. Thus, this toolkit allows the cell-type specific, quantitative study of viral replication in a genetic model organism, opening new avenues for molecular, genetic and pharmacological dissection of virus biology and tool development. PMID:25386852

Poorly Understood Aspects of Striated Muscle Contraction

PubMed Central

Månsson, Alf

2015-01-01

Muscle contraction results from cyclic interactions between the contractile proteins myosin and actin, driven by the turnover of adenosine triphosphate (ATP). Despite intense studies, several molecular events in the contraction process are poorly understood, including the relationship between force-generation and phosphate-release in the ATP-turnover. Different aspects of the force-generating transition are reflected in the changes in tension development by muscle cells, myofibrils and single molecules upon changes in temperature, altered phosphate concentration, or length perturbations. It has been notoriously difficult to explain all these events within a given theoretical framework and to unequivocally correlate observed events with the atomic structures of the myosin motor. Other incompletely understood issues include the role of the two heads of myosin II and structural changes in the actin filaments as well as the importance of the three-dimensional order. We here review these issues in relation to controversies regarding basic physiological properties of striated muscle. We also briefly consider actomyosin mutation effects in cardiac and skeletal muscle function and the possibility to treat these defects by drugs. PMID:25961006

Poorly understood aspects of striated muscle contraction.

PubMed

Månsson, Alf; Rassier, Dilson; Tsiavaliaris, Georgios

2015-01-01

Muscle contraction results from cyclic interactions between the contractile proteins myosin and actin, driven by the turnover of adenosine triphosphate (ATP). Despite intense studies, several molecular events in the contraction process are poorly understood, including the relationship between force-generation and phosphate-release in the ATP-turnover. Different aspects of the force-generating transition are reflected in the changes in tension development by muscle cells, myofibrils and single molecules upon changes in temperature, altered phosphate concentration, or length perturbations. It has been notoriously difficult to explain all these events within a given theoretical framework and to unequivocally correlate observed events with the atomic structures of the myosin motor. Other incompletely understood issues include the role of the two heads of myosin II and structural changes in the actin filaments as well as the importance of the three-dimensional order. We here review these issues in relation to controversies regarding basic physiological properties of striated muscle. We also briefly consider actomyosin mutation effects in cardiac and skeletal muscle function and the possibility to treat these defects by drugs.

Principle Component Analysis with Incomplete Data: A simulation of R pcaMethods package in Constructing an Environmental Quality Index with Missing Data

EPA Science Inventory

Missing data is a common problem in the application of statistical techniques. In principal component analysis (PCA), a technique for dimensionality reduction, incomplete data points are either discarded or imputed using interpolation methods. Such approaches are less valid when ...

Levels and trends of child and adult mortality rates in the Islamic Republic of Iran, 1990-2013; protocol of the NASBOD study.

PubMed

Mohammadi, Younes; Parsaeian, Mahboubeh; Farzadfar, Farshad; Kasaeian, Amir; Mehdipour, Parinaz; Sheidaei, Ali; Mansouri, Anita; Saeedi Moghaddam, Sahar; Djalalinia, Shirin; Mahmoudi, Mahmood; Khosravi, Ardeshir; Yazdani, Kamran

2014-03-01

Calculation of burden of diseases and risk factors is crucial to set priorities in the health care systems. Nevertheless, the reliable measurement of mortality rates is the main barrier to reach this goal. Unfortunately, in many developing countries the vital registration system (VRS) is either defective or does not exist at all. Consequently, alternative methods have been developed to measure mortality. This study is a subcomponent of NASBOD project, which is currently conducting in Iran. In this study, we aim to calculate incompleteness of the Death Registration System (DRS) and then to estimate levels and trends of child and adult mortality using reliable methods. In order to estimate mortality rates, first, we identify all possible data sources. Then, we calculate incompleteness of child and adult morality separately. For incompleteness of child mortality, we analyze summary birth history data using maternal age cohort and maternal age period methods. Then, we combine these two methods using LOESS regression. However, these estimates are not plausible for some provinces. We use additional information of covariates such as wealth index and years of schooling to make predictions for these provinces using spatio-temporal model. We generate yearly estimates of mortality using Gaussian process regression that covers both sampling and non-sampling errors within uncertainty intervals. By comparing the resulted estimates with mortality rates from DRS, we calculate child mortality incompleteness. For incompleteness of adult mortality, Generalized Growth Balance, Synthetic Extinct Generation and a hybrid of two mentioned methods are used. Afterwards, we combine incompleteness of three methods using GPR, and apply it to correct and adjust the number of deaths. In this study, we develop a conceptual framework to overcome the existing challenges for accurate measuring of mortality rates. The resulting estimates can be used to inform policy-makers about past, current and future mortality rates as a major indicator of health status of a population.

Co-amplification of phosphoinositide 3-kinase enhancer A and cyclin-dependent kinase 4 triggers glioblastoma progression | Office of Cancer Genomics

Cancer.gov

Glioblastoma (GBM) is the most common primary brain tumor and has a dismal prognosis. Amplification of chromosome 12q13-q15 (Cyclin-dependent kinase 4 (CDK4) amplicon) is frequently observed in numerous human cancers including GBM. Phosphoinositide 3-kinase enhancer (PIKE) is a group of GTP-binding proteins that belong to the subgroup of centaurin GTPase family, encoded by CENTG1 located in CDK4 amplicon. However, the pathological significance of CDK4 amplicon in GBM formation remains incompletely understood.

Bone-Immune Cell Crosstalk: Bone Diseases

PubMed Central

Mori, Giorgio; D'Amelio, Patrizia; Faccio, Roberta

2015-01-01

Bone diseases are associated with great morbidity; thus, the understanding of the mechanisms leading to their development represents a great challenge to improve bone health. Recent reports suggest that a large number of molecules produced by immune cells affect bone cell activity. However, the mechanisms are incompletely understood. This review aims to shed new lights into the mechanisms of bone diseases involving immune cells. In particular, we focused our attention on the major pathogenic mechanism underlying periodontal disease, psoriatic arthritis, postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, metastatic solid tumors, and multiple myeloma. PMID:26000310

Bone-immune cell crosstalk: bone diseases.

PubMed

Mori, Giorgio; D'Amelio, Patrizia; Faccio, Roberta; Brunetti, Giacomina

2015-01-01

Bone diseases are associated with great morbidity; thus, the understanding of the mechanisms leading to their development represents a great challenge to improve bone health. Recent reports suggest that a large number of molecules produced by immune cells affect bone cell activity. However, the mechanisms are incompletely understood. This review aims to shed new lights into the mechanisms of bone diseases involving immune cells. In particular, we focused our attention on the major pathogenic mechanism underlying periodontal disease, psoriatic arthritis, postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, metastatic solid tumors, and multiple myeloma.

Sleep Deprivation.

PubMed

Abrams, Robert M

2015-09-01

Sleep deprivation occurs when inadequate sleep leads to decreased performance, inadequate alertness, and deterioration in health. It is incompletely understood why humans need sleep, although some theories include energy conservation, restoration, and information processing. Sleep deprivation has many deleterious health effects. Residency programs have enacted strict work restrictions because of medically related errors due to sleep deprivation. Because obstetrics is an unpredictable specialty with long irregular hours, enacting a hospitalist program enhances patient safety, decreases malpractice risk, and improves the physician's quality of life by allowing obstetricians to get sufficient rest. Copyright © 2015 Elsevier Inc. All rights reserved.

Estimate of true incomplete exchanges using fluorescence in situ hybridization with telomere probes

NASA Technical Reports Server (NTRS)

Wu, H.; George, K.; Yang, T. C.

1998-01-01

PURPOSE: To study the frequency of true incomplete exchanges in radiation-induced chromosome aberrations. MATERIALS AND METHODS: Human lymphocytes were exposed to 2 Gy and 5 Gy of gamma-rays. Chromosome aberrations were studied using the fluorescence in situ hybridization (FISH) technique with whole chromosome-specific probes, together with human telomere probes. Chromosomes 2 and 4 were chosen in the present study. RESULTS: The percentage of incomplete exchanges was 27% when telomere signals were not considered. After excluding false incomplete exchanges identified by the telomere signals, the percentage of incomplete exchanges decreased to 11%. Since telomere signals appear on about 82% of the telomeres, the percentage of true incomplete exchanges should be even lower and was estimated to be 3%. This percentage was similar for chromosomes 2 and 4 and for doses of both 2 Gy and 5 Gy. CONCLUSIONS: The percentage of true incomplete exchanges is significantly lower in gamma-irradiated human lymphocytes than the frequencies reported in the literature.

Lengthening our perspective: morphological, cellular, and molecular responses to eccentric exercise.

PubMed

Hyldahl, Robert D; Hubal, Monica J

2014-02-01

The response of skeletal muscle to unaccustomed eccentric exercise has been studied widely, yet it is incompletely understood. This review is intended to provide an up-to-date overview of our understanding of how skeletal muscle responds to eccentric actions, with particular emphasis on the underlying molecular and cellular mechanisms of damage and recovery. This review begins by addressing the question of whether eccentric actions result in physical damage to muscle fibers and/or connective tissue. We next review the symptomatic manifestations of eccentric exercise (i.e., indirect damage markers, such as delayed onset muscle soreness), with emphasis on their relatively poorly understood molecular underpinnings. We then highlight factors that potentially modify the muscle damage response following eccentric exercise. Finally, we explore the utility of using eccentric training to improve muscle function in populations of healthy and aging individuals, as well as those living with neuromuscular disorders. Copyright © 2013 Wiley Periodicals, Inc.

Estimate of the frequency of true incomplete exchanges in human lymphocytes exposed to 1 GeV/u Fe ions in vitro

NASA Technical Reports Server (NTRS)

Wu, H.; George, K.; Yang, T. C.

1999-01-01

PURPOSE: To study the frequency of true incomplete exchanges induced by high-LET radiation. MATERIALS AND METHODS: Human lymphocytes were exposed to 1 GeV/u Fe ions (LET = 140 keV/microm). Chromosome aberrations were analysed by a fluorescence in situ hybridization using a combination of whole-chromosome-specific probes and human telomere probes. Chromosomes 1, 3 and 4 were investigated. RESULTS: The percentage of incomplete exchanges was between 23 and 29% if telomere signals were not considered. The percentage decreased to approximately 10% after ruling out false incomplete exchanges containing telomere signals. The final estimation of true incomplete exchanges was <10%. CONCLUSION: Within a degree of uncertainty, the percentage of true incomplete exchanges in 1 GeV/u Fe ion-irradiated human lymphocytes was similar to that induced by gamma rays.

Identity method to study chemical fluctuations in relativistic heavy-ion collisions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gazdzicki, Marek; Grebieszkow, Katarzyna; Mackowiak, Maja

Event-by-event fluctuations of the chemical composition of the hadronic final state of relativistic heavy-ion collisions carry valuable information on the properties of strongly interacting matter produced in the collisions. However, in experiments incomplete particle identification distorts the observed fluctuation signals. The effect is quantitatively studied and a new technique for measuring chemical fluctuations, the identity method, is proposed. The method fully eliminates the effect of incomplete particle identification. The application of the identity method to experimental data is explained.

Transcranial electric stimulation (tES) and NeuroImaging: the state-of-the-art, new insights and prospects in basic and clinical neuroscience.

PubMed

Soekadar, Surjo R; Herring, Jim Don; McGonigle, David

2016-10-15

Transcranial electric stimulation (tES) of the brain has attracted an increased interest in recent years. Yet, despite remarkable research efforts to date, the underlying neurobiological mechanisms of tES' effects are still incompletely understood. This Special Issue aims to provide a comprehensive and up-to-date overview of the state-of-the-art in studies combining tES and neuroimaging, while introducing most recent insights and outlining future prospects related to this new and rapidly growing field. The findings reported here combine methodological advancements with insights into the underlying mechanisms of tES itself. At the same time, they also point to the many caveats and specific challenges associated with such studies, which can arise from both technical and biological sources. Besides promising to advance basic neuroscience, combined tES and neuroimaging studies may also substantially change previous conceptions about the methods of action of electric or magnetic stimulation on the brain. Copyright © 2016. Published by Elsevier Inc.

Polymer physics of chromosome large-scale 3D organisation

NASA Astrophysics Data System (ADS)

Chiariello, Andrea M.; Annunziatella, Carlo; Bianco, Simona; Esposito, Andrea; Nicodemi, Mario

2016-07-01

Chromosomes have a complex architecture in the cell nucleus, which serves vital functional purposes, yet its structure and folding mechanisms remain still incompletely understood. Here we show that genome-wide chromatin architecture data, as mapped by Hi-C methods across mammalian cell types and chromosomes, are well described by classical scaling concepts of polymer physics, from the sub-Mb to chromosomal scales. Chromatin is a complex mixture of different regions, folded in the conformational classes predicted by polymer thermodynamics. The contact matrix of the Sox9 locus, a region linked to severe human congenital diseases, is derived with high accuracy in mESCs and its molecular determinants identified by the theory; Sox9 self-assembles hierarchically in higher-order domains, involving abundant many-body contacts. Our approach is also applied to the Bmp7 locus. Finally, the model predictions on the effects of mutations on folding are tested against available data on a deletion in the Xist locus. Our results can help progressing new diagnostic tools for diseases linked to chromatin misfolding.

Integrated Detection of Pathogens and Host Biomarkers for Wounds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jaing, C

2012-03-19

The increasing incidence and complications arising from combat wounds has necessitated a reassessment of methods for effective treatment. Infection, excessive inflammation, and incidence of drug-resistant organisms all contribute toward negative outcomes for afflicted individuals. The organisms and host processes involved in wound progression, however, are incompletely understood. We therefore set out, using our unique technical resources, to construct a profile of combat wounds which did or did not successfully resolve. We employed the Lawrence Livermore Microbial Detection Array and identified a number of nosocomial pathogens present in wound samples. Some of these identities corresponded with bacterial isolates previously cultured, whilemore » others were not obtained via standard microbiology. Further, we optimized proteomics protocols for the identification of host biomarkers indicative of various stages in wound progression. In combination with our pathogen data, our biomarker discovery efforts will provide a profile corresponding to wound complications, and will assist significantly in treatment of these complex cases.« less

An overview of structure, mechanical properties, and treatment for age-related tendinopathy.

PubMed

Zhou, B; Zhou, Y; Tang, K

2014-04-01

Tendons transfer tensile loads from muscle to bone, which enable joint motions and stabilize joints. Tendons sustain large mechanical loads in vivo and as a result, tendons were frequently injured. Aging has been confirmed as a predisposing factor of tendinopathy and bad recovery quality following tendon repair. Current treatment methods are generally not effective and involve either symptomatic relief with non-steroidal antiinflammatory drugs and physical therapy or surgery when conservative treatments failed. The limitation in treatment options is due to our incomplete knowledge of age-related tendinopathy. Studies over the past decades have uncovered a number of important mechanical and cellular changes of aging tendon. However, the basis of aging as a major risk factor for tendon injury and impaired tendon healing remained poorly understood. The objectives of this review are to provide an overview of the current knowledge about the aging-associated changes of structure, mechanical properties and treatment in tendon and highlight causes and therapies for age-related tendinopathy.

Treatment of Intravenous Leiomyomatosis with Cardiac Extension following Incomplete Resection.

PubMed

Doyle, Mathew P; Li, Annette; Villanueva, Claudia I; Peeceeyen, Sheen C S; Cooper, Michael G; Hanel, Kevin C; Fermanis, Gary G; Robertson, Greg

2015-01-01

Aim. Intravenous leiomyomatosis (IVL) with cardiac extension (CE) is a rare variant of benign uterine leiomyoma. Incomplete resection has a recurrence rate of over 30%. Different hormonal treatments have been described following incomplete resection; however no standard therapy currently exists. We review the literature for medical treatments options following incomplete resection of IVL with CE. Methods. Electronic databases were searched for all studies reporting IVL with CE. These studies were then searched for reports of patients with inoperable or incomplete resection and any further medical treatments. Our database was searched for patients with medical therapy following incomplete resection of IVL with CE and their results were included. Results. All studies were either case reports or case series. Five literature reviews confirm that surgery is the only treatment to achieve cure. The uses of progesterone, estrogen modulation, gonadotropin-releasing hormone antagonism, and aromatase inhibition have been described following incomplete resection. Currently no studies have reviewed the outcomes of these treatments. Conclusions. Complete surgical resection is the only means of cure for IVL with CE, while multiple hormonal therapies have been used with varying results following incomplete resection. Aromatase inhibitors are the only reported treatment to prevent tumor progression or recurrence in patients with incompletely resected IVL with CE.

Treatment of Intravenous Leiomyomatosis with Cardiac Extension following Incomplete Resection

PubMed Central

Doyle, Mathew P.; Li, Annette; Villanueva, Claudia I.; Peeceeyen, Sheen C. S.; Cooper, Michael G.; Hanel, Kevin C.; Fermanis, Gary G.; Robertson, Greg

2015-01-01

Aim. Intravenous leiomyomatosis (IVL) with cardiac extension (CE) is a rare variant of benign uterine leiomyoma. Incomplete resection has a recurrence rate of over 30%. Different hormonal treatments have been described following incomplete resection; however no standard therapy currently exists. We review the literature for medical treatments options following incomplete resection of IVL with CE. Methods. Electronic databases were searched for all studies reporting IVL with CE. These studies were then searched for reports of patients with inoperable or incomplete resection and any further medical treatments. Our database was searched for patients with medical therapy following incomplete resection of IVL with CE and their results were included. Results. All studies were either case reports or case series. Five literature reviews confirm that surgery is the only treatment to achieve cure. The uses of progesterone, estrogen modulation, gonadotropin-releasing hormone antagonism, and aromatase inhibition have been described following incomplete resection. Currently no studies have reviewed the outcomes of these treatments. Conclusions. Complete surgical resection is the only means of cure for IVL with CE, while multiple hormonal therapies have been used with varying results following incomplete resection. Aromatase inhibitors are the only reported treatment to prevent tumor progression or recurrence in patients with incompletely resected IVL with CE. PMID:26783463

The s-Ordered Fock Space Projectors Gained by the General Ordering Theorem

NASA Astrophysics Data System (ADS)

Farid, Shähandeh; Mohammad, Reza Bazrafkan; Mahmoud, Ashrafi

2012-09-01

Employing the general ordering theorem (GOT), operational methods and incomplete 2-D Hermite polynomials, we derive the t-ordered expansion of Fock space projectors. Using the result, the general ordered form of the coherent state projectors is obtained. This indeed gives a new integration formula regarding incomplete 2-D Hermite polynomials. In addition, the orthogonality relation of the incomplete 2-D Hermite polynomials is derived to resolve Dattoli's failure.

32 CFR 651.44 - Incomplete information.

Code of Federal Regulations, 2011 CFR

2011-07-01

... approaches or research methods generally accepted in the scientific community. ... 32 National Defense 4 2011-07-01 2011-07-01 false Incomplete information. 651.44 Section 651.44 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) ENVIRONMENTAL QUALITY...

32 CFR 651.44 - Incomplete information.

Code of Federal Regulations, 2010 CFR

2010-07-01

... approaches or research methods generally accepted in the scientific community. ... 32 National Defense 4 2010-07-01 2010-07-01 true Incomplete information. 651.44 Section 651.44 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) ENVIRONMENTAL QUALITY...

Review article: the pathophysiology, differential diagnosis and management of rumination syndrome.

PubMed

Tack, J; Blondeau, K; Boecxstaens, V; Rommel, N

2011-04-01

Rumination syndrome, characterised by the effortless, often repetitive, regurgitation of recently ingested food into the mouth, was originally described in children and in the developmentally disabled. It is now well-recognised that rumination syndrome occurs in patients of all ages and cognitive abilities. To review a scholarly review on our current understanding of the rumination syndrome. The review was conducted on the basis of a medline search to identify relevant publications pertaining to the pathophysiology, clinical diagnosis and management of rumination syndrome. The Rome III consensus established diagnostic criteria for rumination syndrome in adults, children and infants. A typical history can be highly suggestive but oesophageal (high resolution) manometry/impedance with ingestion of a meal may help to distinguish rumination syndrome from other belching/regurgitation disorders. The pathophysiology is incompletely understood, but involves a rise in intra-gastric pressure, generated by a voluntary, but often unintentional, contraction of the abdominal wall musculature, at a time of low pressure in the lower oesophageal sphincter, causing retrograde movement of gastric contents into the oesophagus. To date, controlled trials in the treatment rumination syndrome are lacking. The mainstay of treatment for rumination syndrome is explanation and behavioural treatment which consists of habit reversal techniques that compete with the urge to regurgitate. Chewing gum, prokinetics, baclofen and even antireflux surgery have been proposed as adjunctive therapies, but high quality studies are generally lacking. Rumination is an under-recognised condition with incompletely understood pathophysiology. Behavioural therapy seems effective, but controlled treatment trials are lacking. © 2011 Blackwell Publishing Ltd.

An incomplete assembly with thresholding algorithm for systems of reaction-diffusion equations in three space dimensions IAT for reaction-diffusion systems

NASA Astrophysics Data System (ADS)

Moore, Peter K.

2003-07-01

Solving systems of reaction-diffusion equations in three space dimensions can be prohibitively expensive both in terms of storage and CPU time. Herein, I present a new incomplete assembly procedure that is designed to reduce storage requirements. Incomplete assembly is analogous to incomplete factorization in that only a fixed number of nonzero entries are stored per row and a drop tolerance is used to discard small values. The algorithm is incorporated in a finite element method-of-lines code and tested on a set of reaction-diffusion systems. The effect of incomplete assembly on CPU time and storage and on the performance of the temporal integrator DASPK, algebraic solver GMRES and preconditioner ILUT is studied.

Teacher Ratings from Incomplete Student Ranking Data.

ERIC Educational Resources Information Center

Kaiser, Henry F.; Cerny, Barbara A.

1979-01-01

A method for obtaining teacher ratings from incomplete student ranking data is presented. The procedure involves finding the scores for the teachers on the first principal component of a student intercorrelation matrix, where the missing data are supplied by least squares. (Author)

Modeling the Metabolism of Arabidopsis thaliana: Application of Network Decomposition and Network Reduction in the Context of Petri Nets.

PubMed

Koch, Ina; Nöthen, Joachim; Schleiff, Enrico

2017-01-01

Motivation: Arabidopsis thaliana is a well-established model system for the analysis of the basic physiological and metabolic pathways of plants. Nevertheless, the system is not yet fully understood, although many mechanisms are described, and information for many processes exists. However, the combination and interpretation of the large amount of biological data remain a big challenge, not only because data sets for metabolic paths are still incomplete. Moreover, they are often inconsistent, because they are coming from different experiments of various scales, regarding, for example, accuracy and/or significance. Here, theoretical modeling is powerful to formulate hypotheses for pathways and the dynamics of the metabolism, even if the biological data are incomplete. To develop reliable mathematical models they have to be proven for consistency. This is still a challenging task because many verification techniques fail already for middle-sized models. Consequently, new methods, like decomposition methods or reduction approaches, are developed to circumvent this problem. Methods: We present a new semi-quantitative mathematical model of the metabolism of Arabidopsis thaliana . We used the Petri net formalism to express the complex reaction system in a mathematically unique manner. To verify the model for correctness and consistency we applied concepts of network decomposition and network reduction such as transition invariants, common transition pairs, and invariant transition pairs. Results: We formulated the core metabolism of Arabidopsis thaliana based on recent knowledge from literature, including the Calvin cycle, glycolysis and citric acid cycle, glyoxylate cycle, urea cycle, sucrose synthesis, and the starch metabolism. By applying network decomposition and reduction techniques at steady-state conditions, we suggest a straightforward mathematical modeling process. We demonstrate that potential steady-state pathways exist, which provide the fixed carbon to nearly all parts of the network, especially to the citric acid cycle. There is a close cooperation of important metabolic pathways, e.g., the de novo synthesis of uridine-5-monophosphate, the γ-aminobutyric acid shunt, and the urea cycle. The presented approach extends the established methods for a feasible interpretation of biological network models, in particular of large and complex models.

Modeling the Metabolism of Arabidopsis thaliana: Application of Network Decomposition and Network Reduction in the Context of Petri Nets

PubMed Central

Koch, Ina; Nöthen, Joachim; Schleiff, Enrico

2017-01-01

Motivation: Arabidopsis thaliana is a well-established model system for the analysis of the basic physiological and metabolic pathways of plants. Nevertheless, the system is not yet fully understood, although many mechanisms are described, and information for many processes exists. However, the combination and interpretation of the large amount of biological data remain a big challenge, not only because data sets for metabolic paths are still incomplete. Moreover, they are often inconsistent, because they are coming from different experiments of various scales, regarding, for example, accuracy and/or significance. Here, theoretical modeling is powerful to formulate hypotheses for pathways and the dynamics of the metabolism, even if the biological data are incomplete. To develop reliable mathematical models they have to be proven for consistency. This is still a challenging task because many verification techniques fail already for middle-sized models. Consequently, new methods, like decomposition methods or reduction approaches, are developed to circumvent this problem. Methods: We present a new semi-quantitative mathematical model of the metabolism of Arabidopsis thaliana. We used the Petri net formalism to express the complex reaction system in a mathematically unique manner. To verify the model for correctness and consistency we applied concepts of network decomposition and network reduction such as transition invariants, common transition pairs, and invariant transition pairs. Results: We formulated the core metabolism of Arabidopsis thaliana based on recent knowledge from literature, including the Calvin cycle, glycolysis and citric acid cycle, glyoxylate cycle, urea cycle, sucrose synthesis, and the starch metabolism. By applying network decomposition and reduction techniques at steady-state conditions, we suggest a straightforward mathematical modeling process. We demonstrate that potential steady-state pathways exist, which provide the fixed carbon to nearly all parts of the network, especially to the citric acid cycle. There is a close cooperation of important metabolic pathways, e.g., the de novo synthesis of uridine-5-monophosphate, the γ-aminobutyric acid shunt, and the urea cycle. The presented approach extends the established methods for a feasible interpretation of biological network models, in particular of large and complex models. PMID:28713420

Nanoparticle forming reactive plasmas: a multidiagnostic approach

NASA Astrophysics Data System (ADS)

Hinz, Alexander; Wahl, Erik von; Faupel, Franz; Strunskus, Thomas; Kersten, Holger

2018-05-01

With an ever increasing interest in functional materials based on nanoparticles a large amount of research in this field is dedicated to the development of new production methods for nanoparticles. A promising class of methods for the production of nanoparticles is reactive plasmas. However, since the particle formation process and the interaction between the particles and the plasma are so far not completely understood, it remains difficult to control the particle formation. As the interaction between the nanoparticles and the plasma in which they are dispersed is complex the use of one or two diagnostics often provides only an incomplete understanding of the involved processes. Thus a multidiagnostic approach is needed. This contribution reviews the latest results from the study of nanoparticle formation in a hydrocarbon-based reactive plasma by such a multidiagnostic approach. It is shown that the use of various diagnostics like an IV-probe, optical emission spectroscopy, and a multipole resonance probe in conjunction with an investigation of the particle formation provides a much more detailed picture of these interesting, yet challenging, systems. Contribution to the Topical Issue "Fundamentals of Complex Plasmas", edited by Jürgen Meichsner, Michael Bonitz, Holger Fehske, Alexander Piel.

Induction of belief decision trees from data

NASA Astrophysics Data System (ADS)

AbuDahab, Khalil; Xu, Dong-ling; Keane, John

2012-09-01

In this paper, a method for acquiring belief rule-bases by inductive inference from data is described and evaluated. Existing methods extract traditional rules inductively from data, with consequents that are believed to be either 100% true or 100% false. Belief rules can capture uncertain or incomplete knowledge using uncertain belief degrees in consequents. Instead of using singled-value consequents, each belief rule deals with a set of collectively exhaustive and mutually exclusive consequents. The proposed method extracts belief rules from data which contain uncertain or incomplete knowledge.

Double propensity-score adjustment: A solution to design bias or bias due to incomplete matching.

PubMed

Austin, Peter C

2017-02-01

Propensity-score matching is frequently used to reduce the effects of confounding when using observational data to estimate the effects of treatments. Matching allows one to estimate the average effect of treatment in the treated. Rosenbaum and Rubin coined the term "bias due to incomplete matching" to describe the bias that can occur when some treated subjects are excluded from the matched sample because no appropriate control subject was available. The presence of incomplete matching raises important questions around the generalizability of estimated treatment effects to the entire population of treated subjects. We describe an analytic solution to address the bias due to incomplete matching. Our method is based on using optimal or nearest neighbor matching, rather than caliper matching (which frequently results in the exclusion of some treated subjects). Within the sample matched on the propensity score, covariate adjustment using the propensity score is then employed to impute missing potential outcomes under lack of treatment for each treated subject. Using Monte Carlo simulations, we found that the proposed method resulted in estimates of treatment effect that were essentially unbiased. This method resulted in decreased bias compared to caliper matching alone and compared to either optimal matching or nearest neighbor matching alone. Caliper matching alone resulted in design bias or bias due to incomplete matching, while optimal matching or nearest neighbor matching alone resulted in bias due to residual confounding. The proposed method also tended to result in estimates with decreased mean squared error compared to when caliper matching was used.

Double propensity-score adjustment: A solution to design bias or bias due to incomplete matching

PubMed Central

2016-01-01

Propensity-score matching is frequently used to reduce the effects of confounding when using observational data to estimate the effects of treatments. Matching allows one to estimate the average effect of treatment in the treated. Rosenbaum and Rubin coined the term “bias due to incomplete matching” to describe the bias that can occur when some treated subjects are excluded from the matched sample because no appropriate control subject was available. The presence of incomplete matching raises important questions around the generalizability of estimated treatment effects to the entire population of treated subjects. We describe an analytic solution to address the bias due to incomplete matching. Our method is based on using optimal or nearest neighbor matching, rather than caliper matching (which frequently results in the exclusion of some treated subjects). Within the sample matched on the propensity score, covariate adjustment using the propensity score is then employed to impute missing potential outcomes under lack of treatment for each treated subject. Using Monte Carlo simulations, we found that the proposed method resulted in estimates of treatment effect that were essentially unbiased. This method resulted in decreased bias compared to caliper matching alone and compared to either optimal matching or nearest neighbor matching alone. Caliper matching alone resulted in design bias or bias due to incomplete matching, while optimal matching or nearest neighbor matching alone resulted in bias due to residual confounding. The proposed method also tended to result in estimates with decreased mean squared error compared to when caliper matching was used. PMID:25038071

Analysis of the incomplete Galerkin method for modelling of smoothly-irregular transition between planar waveguides

NASA Astrophysics Data System (ADS)

Divakov, D.; Sevastianov, L.; Nikolaev, N.

2017-01-01

The paper deals with a numerical solution of the problem of waveguide propagation of polarized light in smoothly-irregular transition between closed regular waveguides using the incomplete Galerkin method. This method consists in replacement of variables in the problem of reduction of the Helmholtz equation to the system of differential equations by the Kantorovich method and in formulation of the boundary conditions for the resulting system. The formulation of the boundary problem for the ODE system is realized in computer algebra system Maple. The stated boundary problem is solved using Maples libraries of numerical methods.

Switch-Hitting Immune Cells: From Tumor Protection to Metastasis Promotion | Center for Cancer Research

Cancer.gov

The leading cause of death from cancer is not a primary tumor but is the metastases, or invasion of tumor cells into other locations in the body, that result from it. A complex and incompletely understood process, metastatic tumor formation is thought to require several steps in which tumor cells invade the tissue surrounding the primary tumor, enter local blood vessels, navigate the circulation, exit the vasculature, and colonize a new site. Tumor cells do not, however, operate independently, and the role that the immune system plays in this metastatic process is beginning to be appreciated.

Identification of point mutations in clinical Staphylococcus aureus strains that produce small-colony variants auxotrophic for menadione.

PubMed

Dean, Melissa A; Olsen, Randall J; Long, S Wesley; Rosato, Adriana E; Musser, James M

2014-04-01

Staphylococcus aureus small-colony variants (SCVs) are implicated in chronic and relapsing infections that are difficult to diagnose and treat. Despite many years of study, the underlying molecular mechanisms and virulence effect of the small-colony phenotype remain incompletely understood. We sequenced the genomes of five S. aureus SCV strains recovered from human patients and discovered previously unidentified nonsynonymous point mutations in three genes encoding proteins in the menadione biosynthesis pathway. Analysis of genetic revertants and complementation with wild-type alleles confirmed that these mutations caused the SCV phenotype and decreased virulence for mice.

Alternative, Complementary, and Forgotten Remedies for Atopic Dermatitis

PubMed Central

Goddard, Allison L.; Lio, Peter A.

2015-01-01

Atopic dermatitis, perhaps more than other dermatologic diseases, has garnered much attention in the realm of alternative medicine. This may be because its etiopathogenesis is incompletely understood, it is increasingly common, and it waxes and wanes often without clear precipitants, opening up many opportunities for misinterpretation. Herein we explore the evidence for a number of different alternative and complementary therapies, from textiles to vitamin supplements. By definition, none have enough data to be deemed “effective” in a conventional sense, but it is hopeful that some show promising evidence that may one day lead to mainstream acceptance with further research. PMID:26257817

Use of metaknowledge in the verification of knowledge-based systems

NASA Technical Reports Server (NTRS)

Morell, Larry J.

1989-01-01

Knowledge-based systems are modeled as deductive systems. The model indicates that the two primary areas of concern in verification are demonstrating consistency and completeness. A system is inconsistent if it asserts something that is not true of the modeled domain. A system is incomplete if it lacks deductive capability. Two forms of consistency are discussed along with appropriate verification methods. Three forms of incompleteness are discussed. The use of metaknowledge, knowledge about knowledge, is explored in connection to each form of incompleteness.

NF-κB activating complex engaged in response to EGFR oncogene inhibition drives tumor cell survival and residual disease in lung cancer

PubMed Central

Blakely, Collin M.; Pazarentzos, Evangelos; Olivas, Victor; Asthana, Saurabh; Yan, Jenny Jiacheng; Tan, Irena; Hrustanovic, Gorjan; Chan, Elton; Lin, Luping; Neel, Dana S.; Newton, William; Bobb, Kathryn; Fouts, Timothy; Meshulam, Jeffrey; Gubens, Matthew A.; Jablons, David M.; Johnson, Jeffrey R.; Bandyopadhyay, Sourav; Krogan, Nevan J.; Bivona, Trever G.

2015-01-01

Summary Although oncogene-targeted therapy often elicits profound initial tumor responses in patients, responses are generally incomplete because some tumor cells survive initial therapy as residual disease that enables eventual acquired resistance. The mechanisms underlying tumor cell adaptation and survival during initial therapy are incompletely understood. Here, through the study of EGFR-mutant lung adenocarcinoma we show that NF-κB signaling is rapidly engaged upon initial EGFR inhibitor treatment to promote tumor cell survival and residual disease. EGFR oncogene inhibition induced an EGFR-TRAF2-RIP1-IKK complex that stimulated an NF-κB-mediated transcriptional survival program. The direct NF-κB inhibitor PBS-1086 suppressed this adaptive survival program and increased the magnitude and duration of initial EGFR inhibitor response in multiple NSCLC models, including a patient-derived xenograft. These findings unveil NF-κB activation as a critical adaptive survival mechanism engaged by EGFR oncogene inhibition and provide rationale for EGFR and NF-κB co-inhibition to eliminate residual disease and enhance patient responses. PMID:25843712

Plant Development, Auxin, and the Subsystem Incompleteness Theorem

PubMed Central

Niklas, Karl J.; Kutschera, Ulrich

2012-01-01

Plant morphogenesis (the process whereby form develops) requires signal cross-talking among all levels of organization to coordinate the operation of metabolic and genomic subsystems operating in a larger network of subsystems. Each subsystem can be rendered as a logic circuit supervising the operation of one or more signal-activated system. This approach simplifies complex morphogenetic phenomena and allows for their aggregation into diagrams of progressively larger networks. This technique is illustrated here by rendering two logic circuits and signal-activated subsystems, one for auxin (IAA) polar/lateral intercellular transport and another for IAA-mediated cell wall loosening. For each of these phenomena, a circuit/subsystem diagram highlights missing components (either in the logic circuit or in the subsystem it supervises) that must be identified experimentally if each of these basic plant phenomena is to be fully understood. We also illustrate the “subsystem incompleteness theorem,” which states that no subsystem is operationally self-sufficient. Indeed, a whole-organism perspective is required to understand even the most simple morphogenetic process, because, when isolated, every biological signal-activated subsystem is morphogenetically ineffective. PMID:22645582

Astroglial networks and implications for therapeutic neuromodulation of epilepsy.

PubMed

Witcher, Mark R; Ellis, Thomas L

2012-01-01

Epilepsy is a common chronic neurologic disorder affecting approximately 1% of the world population. More than one-third of all epilepsy patients have incompletely controlled seizures or debilitating medication side effects in spite of optimal medical management. Medically refractory epilepsy is associated with excess injury and mortality, psychosocial dysfunction, and significant cognitive impairment. Effective treatment options for these patients can be limited. The cellular mechanisms underlying seizure activity are incompletely understood, though we here describe multiple lines of evidence supporting the likely contribution of astroglia to epilepsy, with focus on individual astrocytes and their network functions. Of the emerging therapeutic modalities for epilepsy, one of the most intriguing is the field of neuromodulation. Neuromodulatory treatment, which consists of administering electrical pulses to neural tissue to modulate its activity leading to a beneficial effect, may be an option for these patients. Current modalities consist of vagal nerve stimulation, open and closed-loop stimulation, and transcranial magnetic stimulation. Due to their unique properties, we here present astrocytes as likely important targets for the developing field of neuromodulation in the treatment of epilepsy.

Link prediction boosted psychiatry disorder classification for functional connectivity network

NASA Astrophysics Data System (ADS)

Li, Weiwei; Mei, Xue; Wang, Hao; Zhou, Yu; Huang, Jiashuang

2017-02-01

Functional connectivity network (FCN) is an effective tool in psychiatry disorders classification, and represents cross-correlation of the regional blood oxygenation level dependent signal. However, FCN is often incomplete for suffering from missing and spurious edges. To accurate classify psychiatry disorders and health control with the incomplete FCN, we first `repair' the FCN with link prediction, and then exact the clustering coefficients as features to build a weak classifier for every FCN. Finally, we apply a boosting algorithm to combine these weak classifiers for improving classification accuracy. Our method tested by three datasets of psychiatry disorder, including Alzheimer's Disease, Schizophrenia and Attention Deficit Hyperactivity Disorder. The experimental results show our method not only significantly improves the classification accuracy, but also efficiently reconstructs the incomplete FCN.

Nonparametric Bayesian Dictionary Learning for Analysis of Noisy and Incomplete Images

PubMed Central

Zhou, Mingyuan; Chen, Haojun; Paisley, John; Ren, Lu; Li, Lingbo; Xing, Zhengming; Dunson, David; Sapiro, Guillermo; Carin, Lawrence

2013-01-01

Nonparametric Bayesian methods are considered for recovery of imagery based upon compressive, incomplete, and/or noisy measurements. A truncated beta-Bernoulli process is employed to infer an appropriate dictionary for the data under test and also for image recovery. In the context of compressive sensing, significant improvements in image recovery are manifested using learned dictionaries, relative to using standard orthonormal image expansions. The compressive-measurement projections are also optimized for the learned dictionary. Additionally, we consider simpler (incomplete) measurements, defined by measuring a subset of image pixels, uniformly selected at random. Spatial interrelationships within imagery are exploited through use of the Dirichlet and probit stick-breaking processes. Several example results are presented, with comparisons to other methods in the literature. PMID:21693421

Classifying with confidence from incomplete information.

DOE PAGES

Parrish, Nathan; Anderson, Hyrum S.; Gupta, Maya R.; ...

2013-12-01

For this paper, we consider the problem of classifying a test sample given incomplete information. This problem arises naturally when data about a test sample is collected over time, or when costs must be incurred to compute the classification features. For example, in a distributed sensor network only a fraction of the sensors may have reported measurements at a certain time, and additional time, power, and bandwidth is needed to collect the complete data to classify. A practical goal is to assign a class label as soon as enough data is available to make a good decision. We formalize thismore » goal through the notion of reliability—the probability that a label assigned given incomplete data would be the same as the label assigned given the complete data, and we propose a method to classify incomplete data only if some reliability threshold is met. Our approach models the complete data as a random variable whose distribution is dependent on the current incomplete data and the (complete) training data. The method differs from standard imputation strategies in that our focus is on determining the reliability of the classification decision, rather than just the class label. We show that the method provides useful reliability estimates of the correctness of the imputed class labels on a set of experiments on time-series data sets, where the goal is to classify the time-series as early as possible while still guaranteeing that the reliability threshold is met.« less

Assessment of predictive performance in incomplete data by combining internal validation and multiple imputation.

PubMed

Wahl, Simone; Boulesteix, Anne-Laure; Zierer, Astrid; Thorand, Barbara; van de Wiel, Mark A

2016-10-26

Missing values are a frequent issue in human studies. In many situations, multiple imputation (MI) is an appropriate missing data handling strategy, whereby missing values are imputed multiple times, the analysis is performed in every imputed data set, and the obtained estimates are pooled. If the aim is to estimate (added) predictive performance measures, such as (change in) the area under the receiver-operating characteristic curve (AUC), internal validation strategies become desirable in order to correct for optimism. It is not fully understood how internal validation should be combined with multiple imputation. In a comprehensive simulation study and in a real data set based on blood markers as predictors for mortality, we compare three combination strategies: Val-MI, internal validation followed by MI on the training and test parts separately, MI-Val, MI on the full data set followed by internal validation, and MI(-y)-Val, MI on the full data set omitting the outcome followed by internal validation. Different validation strategies, including bootstrap und cross-validation, different (added) performance measures, and various data characteristics are considered, and the strategies are evaluated with regard to bias and mean squared error of the obtained performance estimates. In addition, we elaborate on the number of resamples and imputations to be used, and adopt a strategy for confidence interval construction to incomplete data. Internal validation is essential in order to avoid optimism, with the bootstrap 0.632+ estimate representing a reliable method to correct for optimism. While estimates obtained by MI-Val are optimistically biased, those obtained by MI(-y)-Val tend to be pessimistic in the presence of a true underlying effect. Val-MI provides largely unbiased estimates, with a slight pessimistic bias with increasing true effect size, number of covariates and decreasing sample size. In Val-MI, accuracy of the estimate is more strongly improved by increasing the number of bootstrap draws rather than the number of imputations. With a simple integrated approach, valid confidence intervals for performance estimates can be obtained. When prognostic models are developed on incomplete data, Val-MI represents a valid strategy to obtain estimates of predictive performance measures.

Activation of Corticostriatal Circuitry Relieves Chronic Neuropathic Pain

PubMed Central

Lee, Michelle; Manders, Toby R.; Eberle, Sarah E.; Su, Chen; D'amour, James; Yang, Runtao; Lin, Hau Yueh; Deisseroth, Karl; Froemke, Robert C.

2015-01-01

Neural circuits that determine the perception and modulation of pain remain poorly understood. The prefrontal cortex (PFC) provides top-down control of sensory and affective processes. While animal and human imaging studies have shown that the PFC is involved in pain regulation, its exact role in pain states remains incompletely understood. A key output target for the PFC is the nucleus accumbens (NAc), an important component of the reward circuitry. Interestingly, recent human imaging studies suggest that the projection from the PFC to the NAc is altered in chronic pain. The function of this corticostriatal projection in pain states, however, is not known. Here we show that optogenetic activation of the PFC produces strong antinociceptive effects in a rat model (spared nerve injury model) of persistent neuropathic pain. PFC activation also reduces the affective symptoms of pain. Furthermore, we show that this pain-relieving function of the PFC is likely mediated by projections to the NAc. Thus, our results support a novel role for corticostriatal circuitry in pain regulation. PMID:25834050

Inhibiting platelet-derived growth factor beta reduces Ewing's sarcoma growth and metastasis in a novel orthotopic human xenograft model.

PubMed

Wang, Yong Xin; Mandal, Deendayal; Wang, Suizhau; Hughes, Dennis; Pollock, Raphael E; Lev, Dina; Kleinerman, Eugenie; Hayes-Jordan, Andrea

2009-01-01

Despite aggressive therapy, Ewing's sarcoma (ES) patients have a poor five-year overall survival of only 20-40%. Pulmonary metastasis is the most common form of demise in these patients. The pathogenesis of pulmonary metastasis is poorly understood and few orthotopic models exist that allow study of spontaneous pulmonary metastasis in ES. We have developed a novel orthotopic xenograft model in which spontaneous pulmonary metastases develop. While the underlying biology of ES is incompletely understood, in addition to the EWS-FLI-1 mutation, it is known that platelet-derived growth factor receptor beta (PDGFR-beta) is highly expressed in ES. Hypothesizing that PDGFR-beta expression is indicative of a specific role for this receptor protein in ES progression, the effect of PDGFR-beta inhibition on ES growth and metastasis was assessed in this novel orthotopic ES model. Silencing PDGFR-beta reduced spontaneous growth and metastasis in ES. Preclinical therapeutically relevant findings such as these may ultimately lead to new treatment initiatives in ES.

Rapid DNA Synthesis During Early Drosophila Embryogenesis Is Sensitive to Maternal Humpty Dumpty Protein Function.

PubMed

Lesly, Shera; Bandura, Jennifer L; Calvi, Brian R

2017-11-01

Problems with DNA replication cause cancer and developmental malformations. It is not fully understood how DNA replication is coordinated with development and perturbed in disease. We had previously identified the Drosophila gene humpty dumpty ( hd ), and showed that null alleles cause incomplete DNA replication, tissue undergrowth, and lethality. Animals homozygous for the missense allele, hd 272-9 , were viable, but adult females had impaired amplification of eggshell protein genes in the ovary, resulting in the maternal effects of thin eggshells and embryonic lethality. Here, we show that expression of an hd transgene in somatic cells of the ovary rescues amplification and eggshell synthesis but not embryo viability. The germline of these mothers remain mutant for the hd 272-9 allele, resulting in reduced maternal Hd protein and embryonic arrest during mitosis of the first few S/M nuclear cleavage cycles with chromosome instability and chromosome bridges. Epistasis analysis of hd with the rereplication mutation plutonium indicates that the chromosome bridges of hd embryos are the result of a failed attempt to segregate incompletely replicated sister chromatids. This study reveals that maternally encoded Humpty dumpty protein is essential for DNA replication and genome integrity during the little-understood embryonic S/M cycles. Moreover, the two hd 272-9 maternal-effect phenotypes suggest that ovarian gene amplification and embryonic cleavage are two time periods in development that are particularly sensitive to mild deficits in DNA replication function. This last observation has broader relevance for interpreting why mild mutations in the human ortholog of humpty dumpty and other DNA replication genes cause tissue-specific malformations of microcephalic dwarfisms. Copyright © 2017 by the Genetics Society of America.

Low Complexity Models to improve Incomplete Sensitivities for Shape Optimization

NASA Astrophysics Data System (ADS)

Stanciu, Mugurel; Mohammadi, Bijan; Moreau, Stéphane

2003-01-01

The present global platform for simulation and design of multi-model configurations treat shape optimization problems in aerodynamics. Flow solvers are coupled with optimization algorithms based on CAD-free and CAD-connected frameworks. Newton methods together with incomplete expressions of gradients are used. Such incomplete sensitivities are improved using reduced models based on physical assumptions. The validity and the application of this approach in real-life problems are presented. The numerical examples concern shape optimization for an airfoil, a business jet and a car engine cooling axial fan.

An improved swarm optimization for parameter estimation and biological model selection.

PubMed

Abdullah, Afnizanfaizal; Deris, Safaai; Mohamad, Mohd Saberi; Anwar, Sohail

2013-01-01

One of the key aspects of computational systems biology is the investigation on the dynamic biological processes within cells. Computational models are often required to elucidate the mechanisms and principles driving the processes because of the nonlinearity and complexity. The models usually incorporate a set of parameters that signify the physical properties of the actual biological systems. In most cases, these parameters are estimated by fitting the model outputs with the corresponding experimental data. However, this is a challenging task because the available experimental data are frequently noisy and incomplete. In this paper, a new hybrid optimization method is proposed to estimate these parameters from the noisy and incomplete experimental data. The proposed method, called Swarm-based Chemical Reaction Optimization, integrates the evolutionary searching strategy employed by the Chemical Reaction Optimization, into the neighbouring searching strategy of the Firefly Algorithm method. The effectiveness of the method was evaluated using a simulated nonlinear model and two biological models: synthetic transcriptional oscillators, and extracellular protease production models. The results showed that the accuracy and computational speed of the proposed method were better than the existing Differential Evolution, Firefly Algorithm and Chemical Reaction Optimization methods. The reliability of the estimated parameters was statistically validated, which suggests that the model outputs produced by these parameters were valid even when noisy and incomplete experimental data were used. Additionally, Akaike Information Criterion was employed to evaluate the model selection, which highlighted the capability of the proposed method in choosing a plausible model based on the experimental data. In conclusion, this paper presents the effectiveness of the proposed method for parameter estimation and model selection problems using noisy and incomplete experimental data. This study is hoped to provide a new insight in developing more accurate and reliable biological models based on limited and low quality experimental data.

A statistical approach to identify, monitor, and manage incomplete curated data sets.

PubMed

Howe, Douglas G

2018-04-02

Many biological knowledge bases gather data through expert curation of published literature. High data volume, selective partial curation, delays in access, and publication of data prior to the ability to curate it can result in incomplete curation of published data. Knowing which data sets are incomplete and how incomplete they are remains a challenge. Awareness that a data set may be incomplete is important for proper interpretation, to avoiding flawed hypothesis generation, and can justify further exploration of published literature for additional relevant data. Computational methods to assess data set completeness are needed. One such method is presented here. In this work, a multivariate linear regression model was used to identify genes in the Zebrafish Information Network (ZFIN) Database having incomplete curated gene expression data sets. Starting with 36,655 gene records from ZFIN, data aggregation, cleansing, and filtering reduced the set to 9870 gene records suitable for training and testing the model to predict the number of expression experiments per gene. Feature engineering and selection identified the following predictive variables: the number of journal publications; the number of journal publications already attributed for gene expression annotation; the percent of journal publications already attributed for expression data; the gene symbol; and the number of transgenic constructs associated with each gene. Twenty-five percent of the gene records (2483 genes) were used to train the model. The remaining 7387 genes were used to test the model. One hundred and twenty-two and 165 of the 7387 tested genes were identified as missing expression annotations based on their residuals being outside the model lower or upper 95% confidence interval respectively. The model had precision of 0.97 and recall of 0.71 at the negative 95% confidence interval and precision of 0.76 and recall of 0.73 at the positive 95% confidence interval. This method can be used to identify data sets that are incompletely curated, as demonstrated using the gene expression data set from ZFIN. This information can help both database resources and data consumers gauge when it may be useful to look further for published data to augment the existing expertly curated information.

Chemical kinetics and modeling of planetary atmospheres

NASA Technical Reports Server (NTRS)

Yung, Yuk L.

1990-01-01

A unified overview is presented for chemical kinetics and chemical modeling in planetary atmospheres. The recent major advances in the understanding of the chemistry of the terrestrial atmosphere make the study of planets more interesting and relevant. A deeper understanding suggests that the important chemical cycles have a universal character that connects the different planets and ultimately link together the origin and evolution of the solar system. The completeness (or incompleteness) of the data base for chemical kinetics in planetary atmospheres will always be judged by comparison with that for the terrestrial atmosphere. In the latter case, the chemistry of H, O, N, and Cl species is well understood. S chemistry is poorly understood. In the atmospheres of Jovian planets and Titan, the C-H chemistry of simple species (containing 2 or less C atoms) is fairly well understood. The chemistry of higher hydrocarbons and the C-N, P-N chemistry is much less understood. In the atmosphere of Venus, the dominant chemistry is that of chlorine and sulfur, and very little is known about C1-S coupled chemistry. A new frontier for chemical kinetics both in the Earth and planetary atmospheres is the study of heterogeneous reactions. The formation of the ozone hole on Earth, the ubiquitous photochemical haze on Venus and in the Jovian planets and Titan all testify to the importance of heterogeneous reactions. It remains a challenge to connect the gas phase chemistry to the production of aerosols.

Non-input analysis for incomplete trapping irreversible tracer with PET.

PubMed

Ohya, Tomoyuki; Kikuchi, Tatsuya; Fukumura, Toshimitsu; Zhang, Ming-Rong; Irie, Toshiaki

2013-07-01

When using metabolic trapping type tracers, the tracers are not always trapped in the target tissue; i.e., some are completely trapped in the target, but others can be eliminated from the target tissue at a measurable rate. The tracers that can be eliminated are termed 'incomplete trapping irreversible tracers'. These incomplete trapping irreversible tracers may be clinically useful when the tracer β-value, the ratio of the tracer (metabolite) elimination rate to the tracer efflux rate, is under approximately 0.1. In this study, we propose a non-input analysis for incomplete trapping irreversible tracers based on the shape analysis (Shape), a non-input analysis used for irreversible tracers. A Monte Carlo simulation study based on experimental monkey data with two actual PET tracers (a complete trapping irreversible tracer [(11)C]MP4A and an incomplete trapping irreversible tracer [(18)F]FEP-4MA) was performed to examine the effects of the environmental error and the tracer elimination rate on the estimation of the k3-parameter (corresponds to metabolic rate) using Shape (original) and modified Shape (M-Shape) analysis. The simulation results were also compared with the experimental results obtained with the two PET tracers. When the tracer β-value was over 0.03, the M-Shape method was superior to the Shape method for the estimation of the k3-parameter. The simulation results were also in reasonable agreement with the experimental ones. M-Shape can be used as the non-input analysis of incomplete trapping irreversible tracers for PET study. Copyright © 2013 Elsevier Inc. All rights reserved.

Thoracoscopic anterior ‘fissure first’ technique for left lung cancer with an incomplete fissure

PubMed Central

Samejima, Joji; Matsuura, Yosuke; Nakao, Masayuki; Uehara, Hirofumi; Nakagawa, Ken; Masuda, Munetaka; Okumura, Sakae

2016-01-01

Background Dealing with incomplete lung fissures during thoracoscopic surgery is difficult. Our objective was to evaluate the efficacy and safety of a thoracoscopic anterior ‘fissure first’ technique for dealing with incomplete left lung fissures. Methods One hundred and seventy patients underwent left upper lobectomy or left lower lobectomy between April 2008 and July 2014. Of these, 34 patients underwent surgery using a thoracoscopic anterior ‘fissure first’ technique for incomplete fissures (group A) and 136 underwent surgery using a conventional thoracoscopic method for unfused fissures (group B). A four-port complete thoracoscopic approach was used in all patients. After completion of the fissure, hilar lymphadenectomy was performed in the conventional manner. Results There were no significant differences between the two groups in operating time, blood loss, or duration of chest tube drainage. Patients in group A required more staple cartridges than those in group B (mean number of cartridges, 2.4 vs. 1.1; P<0.01). The two groups did not significantly differ with regard to the prevalence of air leaks (12% vs. 4%; P=0.11), either prolonged or delayed. Conclusions We found that a thoracoscopic anterior ‘fissure first’ technique for left lung cancer with an incomplete fissure enabled hilar lymphadenectomy to be performed in the conventional manner without any increase in the prevalence of air leaks, operating time, or duration of chest tube drainage. This technique should be considered for use in left upper lobectomy or left lower lobectomy in patients with an incomplete fissure. PMID:28066589

Avoidable waste related to inadequate methods and incomplete reporting of interventions: a systematic review of randomized trials performed in Sub-Saharan Africa.

PubMed

Ndounga Diakou, Lee Aymar; Ntoumi, Francine; Ravaud, Philippe; Boutron, Isabelle

2017-07-05

Randomized controlled trials (RCTs) are needed to improve health care in Sub-Saharan Africa (SSA). However, inadequate methods and incomplete reporting of interventions can prevent the transposition of research in practice which leads waste of research. The aim of this systematic review was to assess the avoidable waste in research related to inadequate methods and incomplete reporting of interventions in RCTs performed in SSA. We performed a methodological systematic review of RCTs performed in SSA and published between 1 January 2014 and 31 March 2015. We searched PubMed, the Cochrane library and the African Index Medicus to identify reports. We assessed the risk of bias using the Cochrane Risk of Bias tool, and for each risk of bias item, determined whether easy adjustments with no or minor cost could change the domain to low risk of bias. The reporting of interventions was assessed by using standardized checklists based on the Consolidated Standards for Reporting Trials, and core items of the Template for Intervention Description and Replication. Corresponding authors of reports with incomplete reporting of interventions were contacted to obtain additional information. Data were descriptively analyzed. Among 121 RCTs selected, 74 (61%) evaluated pharmacological treatments (PTs), including drugs and nutritional supplements; and 47 (39%) nonpharmacological treatments (NPTs) (40 participative interventions, 1 surgical procedure, 3 medical devices and 3 therapeutic strategies). Overall, the randomization sequence was adequately generated in 76 reports (62%) and the intervention allocation concealed in 48 (39%). The primary outcome was described as blinded in 46 reports (38%), and incomplete outcome data were adequately addressed in 78 (64%). Applying easy methodological adjustments with no or minor additional cost to trials with at least one domain at high risk of bias could have reduced the number of domains at high risk for 24 RCTs (19%). Interventions were completely reported for 73/121 (60%) RCTs: 51/74 (68%) of PTs and 22/47 (46%) of NPTs. Additional information was obtained from corresponding authors for 11/48 reports (22%). Inadequate methods and incomplete reporting of published SSA RCTs could be improved by easy and inexpensive methodological adjustments and adherence to reporting guidelines.

Current status of achalasia management: a review on diagnosis and treatment.

PubMed

Tuason, Joshua; Inoue, Haruhiro

2017-04-01

Achalasia is a rare esophageal motility disorder that is characterized by loss of peristalsis and failure of relaxation of the lower esophageal sphincter (LES), particularly during swallowing. This review focuses on the diagnosis of esophageal motility disorders as defined by the Chicago Classification ver 3.0, and presents management options with regard to per-oral endoscopic myotomy (POEM) as the treatment of choice. A concise review of literature was performed for articles related to the management of achalasia, and this was contrasted with our institution's current practice. Achalasia is still incompletely understood, and management is focused on establishing a proper diagnosis, and relieving the obstructive symptoms. Achalasia should be considered when dysphagia is present, and not otherwise caused by an obstruction or inflammation, and when criteria is met as per the Chicago Classification ver 3.0. Lowering LES tone and disruption of LES can be accomplished by various methods, most notably pneumatic balloon dilatation and surgical myotomy. POEM has been gaining momentum as a first line therapy for achalasia symptoms, and can be considered an important tool for motility disorders of the esophagus.

Mechanisms of action of ligands of potential-dependent sodium channels.

PubMed

Tikhonov, D B

2008-06-01

Potential-dependent sodium channels play a leading role in generating action potentials in excitable cells. Sodium channels are the site of action of a variety of modulator ligands. Despite numerous studies, the mechanisms of action of many modulators remain incompletely understood. The main reason that many important questions cannot be resolved is that there is a lack of precise data on the structures of the channels themselves. Structurally, potential-dependent sodium channels are members of the P-loop channel superfamily, which also include potassium and calcium channels and glutamate receptor channels. Crystallization of a series of potassium channels showed that it was possible to analyze the structures of different members of the superfamily using the "homologous modeling" method. The present study addresses model investigations of the actions of ligands of sodium channels, including tetrodotoxin and batrachotoxin, as well as local anesthetics. Comparison of experimental data on sodium channel ligands with x-ray analysis data allowed us to reach a new level of understanding of the mechanisms of channel modulation and to propose a series of experimentally verifiable hypotheses.

Reverse engineering systems models of regulation: discovery, prediction and mechanisms.

PubMed

Ashworth, Justin; Wurtmann, Elisabeth J; Baliga, Nitin S

2012-08-01

Biological systems can now be understood in comprehensive and quantitative detail using systems biology approaches. Putative genome-scale models can be built rapidly based upon biological inventories and strategic system-wide molecular measurements. Current models combine statistical associations, causative abstractions, and known molecular mechanisms to explain and predict quantitative and complex phenotypes. This top-down 'reverse engineering' approach generates useful organism-scale models despite noise and incompleteness in data and knowledge. Here we review and discuss the reverse engineering of biological systems using top-down data-driven approaches, in order to improve discovery, hypothesis generation, and the inference of biological properties. Copyright © 2011 Elsevier Ltd. All rights reserved.

Identification of Point Mutations in Clinical Staphylococcus aureus Strains That Produce Small-Colony Variants Auxotrophic for Menadione

PubMed Central

Dean, Melissa A.; Olsen, Randall J.; Long, S. Wesley; Rosato, Adriana E.

2014-01-01

Staphylococcus aureus small-colony variants (SCVs) are implicated in chronic and relapsing infections that are difficult to diagnose and treat. Despite many years of study, the underlying molecular mechanisms and virulence effect of the small-colony phenotype remain incompletely understood. We sequenced the genomes of five S. aureus SCV strains recovered from human patients and discovered previously unidentified nonsynonymous point mutations in three genes encoding proteins in the menadione biosynthesis pathway. Analysis of genetic revertants and complementation with wild-type alleles confirmed that these mutations caused the SCV phenotype and decreased virulence for mice. PMID:24452687

Simvastatin Potently Induces Calcium-dependent Apoptosis of Human Leiomyoma Cells*

PubMed Central

Borahay, Mostafa A.; Kilic, Gokhan S.; Yallampalli, Chandrasekha; Snyder, Russell R.; Hankins, Gary D. V.; Al-Hendy, Ayman; Boehning, Darren

2014-01-01

Statins are drugs commonly used for the treatment of high plasma cholesterol levels. Beyond these well known lipid-lowering properties, they possess broad-reaching effects in vivo, including antitumor effects. Statins inhibit the growth of multiple tumors. However, the mechanisms remain incompletely understood. Here we show that simvastatin inhibits the proliferation of human leiomyoma cells. This was associated with decreased mitogen-activated protein kinase signaling and multiple changes in cell cycle progression. Simvastatin potently stimulated leiomyoma cell apoptosis in a manner mechanistically dependent upon apoptotic calcium release from voltage-gated calcium channels. Therefore, simvastatin possesses antitumor effects that are dependent upon the apoptotic calcium release machinery. PMID:25359773

Vogt-Koyanagi-Harada disease.

PubMed

Burkholder, Bryn M

2015-11-01

The purpose of this article is to review the current literature on Vogt-Koyanagi-Harada (VKH) disease, including current treatment options and new research directions. Recent publications on VKH disease show an increased focus on the immunogenetics and immune pathways associated with the development of VKH disease. There have also been advances in imaging modalities and techniques that may help to better elucidate the disease process in eyes with VKH disease. VKH disease is an autoimmune, multisystem inflammatory disorder, the cause of which is still incompletely understood. Continued research may elucidate the causes and triggers of immune dysregulation in this disease, and in doing so, identify novel therapeutic targets.

Physiology and pathogenesis of gastroesophageal reflux disease.

PubMed

Mikami, Dean J; Murayama, Kenric M

2015-06-01

Gastroesophageal reflux disease (GERD) is one of the most common problems treated by primary care physicians. Almost 20% of the population in the United States experiences occasional regurgitation, heartburn, or retrosternal pain because of GERD. Reflux disease is complex, and the physiology and pathogenesis are still incompletely understood. However, abnormalities of any one or a combination of the three physiologic processes, namely, esophageal motility, lower esophageal sphincter function, and gastric motility or emptying, can lead to GERD. There are many diagnostic and therapeutic approaches to GERD today, but more studies are needed to better understand this complex disease process. Copyright © 2015 Elsevier Inc. All rights reserved.

Urbanization and kidney function decline in low and middle income countries.

PubMed

Jagannathan, Ram; Patzer, Rachel E

2017-08-29

Urbanization is expected to increase in low and middle-income countries (LMICs), and might contribute to the increased disease burden. The association between urbanization and CKD is incompletely understood among LMICs. Recently, Inoue et al., explored the association of urbanization on renal function from the China Health and Nutrition Survey. The study found that individuals living in an urban environment had a higher odds of reduced renal function independent of behavioral and cardiometabolic measures, and this effect increased in a dose dependent manner. In this commentary, we discuss the results of these findings and explain the need for more surveillance studies among LMICs.

Brain iron homeostasis, the choroid plexus, and localization of iron transport proteins.

PubMed

Rouault, Tracey A; Zhang, De-Liang; Jeong, Suh Young

2009-12-01

Maintenance of appropriate iron homeostasis in the brain is important, but the mechanisms involved in brain iron uptake are incompletely understood. Here, we have analyzed where messenger RNAs that encode iron transport proteins are expressed in the brain, using the Allen Brain atlas, and we conclude that several important iron transporters are highly expressed in the choroid plexus. Based on recent estimates of the surface area of the choroid plexus and on MRI imaging studies of manganese uptake in the brain, we propose that the choroid plexus may have a much greater role than has been previously appreciated in brain iron transport.

A Strategy for Urban Astronomical Observatory Site Preservation: The Southern Arizona Example (Abstract)

NASA Astrophysics Data System (ADS)

Craine, E. R.; Craine, B. L.; Craine, P. R.; Craine, E. M.; Fouts, S.

2014-12-01

(Abstract only) Urbanized observatories are under financial pressures for numerous and complex reasons, including concerns that increasing sky brightness will continue to erode their scientific viability. The history of urbanized observatories is one of steady decline and divestiture. We argue that light at night (LAN) impacts of urban growth are inadequately understood, that current measurement techniques are incomplete in scope, and that both limit the effectiveness of mitigation programs. We give examples of these factors for Pima County, Arizona, and propose techniques and a program that could provide focus and power to mitigation efforts, and could extend the longevity of southern Arizona observatories.

A Strategy for Urban Astronomical Observatory Site Preservation: The Southern Arizona Example

NASA Astrophysics Data System (ADS)

Craine, Eric R.; Craine, Brian L.; Craine, Patrick R.; Craine, Erin M.; Fouts, Scott

2014-05-01

Urbanized observatories are under financial pressures for numerous and complex reasons, including concerns that increasing sky brightness will continue to erode their scientific viability. The history of urbanized observatories is one of steady decline and divestiture. We argue that light at night (LAN) impacts of urban growth are inadequately understood, that current measurement techniques are incomplete in scope, and that both limit the effectiveness of mitigation programs. We give examples of these factors for Pima County, Arizona, and propose techniques and a program that could provide focus and power to mitigation efforts, and could extend the longevity of southern Arizona observatories.

Air Force Maintenance Technician Performance Measurement.

DTIC Science & Technology

1979-12-28

R G A N I Z A T IO N N A M E A N D A D R S A R E A P HO R U I T N U M B E R AFIT STUDENT AT: Arizona State Univ II. CONTROLLING OFFICE NAME AND...inflated, or provide incomplete and non -current coverage of maintenance organizations. The performance aopraisal method developed relies on subjective...highly inflated, or provided incomplete and non -current coverage of maintenance organizations. The performance appraisal method developed relied on

Incomplete Gröbner basis as a preconditioner for polynomial systems

NASA Astrophysics Data System (ADS)

Sun, Yang; Tao, Yu-Hui; Bai, Feng-Shan

2009-04-01

Precondition plays a critical role in the numerical methods for large and sparse linear systems. It is also true for nonlinear algebraic systems. In this paper incomplete Gröbner basis (IGB) is proposed as a preconditioner of homotopy methods for polynomial systems of equations, which transforms a deficient system into a system with the same finite solutions, but smaller degree. The reduced system can thus be solved faster. Numerical results show the efficiency of the preconditioner.

Workshop on Incomplete Network Data Held at Sandia National Labs – Livermore

DOE Office of Scientific and Technical Information (OSTI.GOV)

Soundarajan, Sucheta; Wendt, Jeremy D.

2016-06-01

While network analysis is applied in a broad variety of scientific fields (including physics, computer science, biology, and the social sciences), how networks are constructed and the resulting bias and incompleteness have drawn more limited attention. For example, in biology, gene networks are typically developed via experiment -- many actual interactions are likely yet to be discovered. In addition to this incompleteness, the data-collection processes can introduce significant bias into the observed network datasets. For instance, if you observe part of the World Wide Web network through a classic random walk, then high degree nodes are more likely to bemore » found than if you had selected nodes at random. Unfortunately, such incomplete and biasing data collection methods must be often used.« less

Incomplete fuzzy data processing systems using artificial neural network

NASA Technical Reports Server (NTRS)

Patyra, Marek J.

1992-01-01

In this paper, the implementation of a fuzzy data processing system using an artificial neural network (ANN) is discussed. The binary representation of fuzzy data is assumed, where the universe of discourse is decartelized into n equal intervals. The value of a membership function is represented by a binary number. It is proposed that incomplete fuzzy data processing be performed in two stages. The first stage performs the 'retrieval' of incomplete fuzzy data, and the second stage performs the desired operation on the retrieval data. The method of incomplete fuzzy data retrieval is proposed based on the linear approximation of missing values of the membership function. The ANN implementation of the proposed system is presented. The system was computationally verified and showed a relatively small total error.

Dynamic pattern matcher using incomplete data

NASA Technical Reports Server (NTRS)

Johnson, Gordon G. (Inventor); Wang, Lui (Inventor)

1993-01-01

This invention relates generally to pattern matching systems, and more particularly to a method for dynamically adapting the system to enhance the effectiveness of a pattern match. Apparatus and methods for calculating the similarity between patterns are known. There is considerable interest, however, in the storage and retrieval of data, particularly, when the search is called or initiated by incomplete information. For many search algorithms, a query initiating a data search requires exact information, and the data file is searched for an exact match. Inability to find an exact match thus results in a failure of the system or method.

Variational Quantum Tomography with Incomplete Information by Means of Semidefinite Programs

NASA Astrophysics Data System (ADS)

Maciel, Thiago O.; Cesário, André T.; Vianna, Reinaldo O.

We introduce a new method to reconstruct unknown quantum states out of incomplete and noisy information. The method is a linear convex optimization problem, therefore with a unique minimum, which can be efficiently solved with Semidefinite Programs. Numerical simulations indicate that the estimated state does not overestimate purity, and neither the expectation value of optimal entanglement witnesses. The convergence properties of the method are similar to compressed sensing approaches, in the sense that, in order to reconstruct low rank states, it needs just a fraction of the effort corresponding to an informationally complete measurement.

Modeling loosely annotated images using both given and imagined annotations

NASA Astrophysics Data System (ADS)

Tang, Hong; Boujemaa, Nozha; Chen, Yunhao; Deng, Lei

2011-12-01

In this paper, we present an approach to learn latent semantic analysis models from loosely annotated images for automatic image annotation and indexing. The given annotation in training images is loose due to: 1. ambiguous correspondences between visual features and annotated keywords; 2. incomplete lists of annotated keywords. The second reason motivates us to enrich the incomplete annotation in a simple way before learning a topic model. In particular, some ``imagined'' keywords are poured into the incomplete annotation through measuring similarity between keywords in terms of their co-occurrence. Then, both given and imagined annotations are employed to learn probabilistic topic models for automatically annotating new images. We conduct experiments on two image databases (i.e., Corel and ESP) coupled with their loose annotations, and compare the proposed method with state-of-the-art discrete annotation methods. The proposed method improves word-driven probability latent semantic analysis (PLSA-words) up to a comparable performance with the best discrete annotation method, while a merit of PLSA-words is still kept, i.e., a wider semantic range.

Incomplete colonoscopy: Maximizing completion rates of gastroenterologists

PubMed Central

Brahmania, Mayur; Park, Jei; Svarta, Sigrid; Tong, Jessica; Kwok, Ricky; Enns, Robert

2012-01-01

BACKGROUND Cecal intubation is one of the goals of a quality colonoscopy; however, many factors increasing the risk of incomplete colonoscopy have been implicated. The implications of missed pathology and the demand on health care resources for return colonoscopies pose a conundrum to many physicians. The optimal course of action after incomplete colonoscopy is unclear. OBJECTIVES: To assess endoscopic completion rates of previously incomplete colonoscopies, the methods used to complete them and the factors that led to the previous incomplete procedure. METHODS: All patients who previously underwent incomplete colonoscopy (2005 to 2010) and were referred to St Paul’s Hospital (Vancouver, British Columbia) were evaluated. Colonoscopies were re-attempted by a single endoscopist. Patient charts were reviewed retrospectively. RESULTS: A total of 90 patients (29 males) with a mean (± SD) age of 58±13.2 years were included in the analysis. Thirty patients (33%) had their initial colonoscopy performed by a gastroenterologist. Indications for initial colonoscopy included surveillance or screening (23%), abdominal pain (15%), gastrointestinal bleeding (29%), change in bowel habits or constitutional symptoms (18%), anemia (7%) and chronic diarrhea (8%). Reasons for incomplete colonoscopy included poor preparation (11%), pain or inadequate sedation (16%), tortuous colon (30%), diverticular disease (6%), obstructing mass (6%) and stricturing disease (10%). Reasons for incomplete procedures in the remaining 21% of patients were not reported by the referring physician. Eighty-seven (97%) colonoscopies were subsequently completed in a single attempt at the institution. Seventy-six (84%) colonoscopies were performed using routine manoeuvres, patient positioning and a variable-stiffness colonoscope (either standard or pediatric). A standard 160 or 180 series Olympus gastroscope (Olympus, Japan) was used in five patients (6%) to navigate through sigmoid diverticular disease; a pediatric colonoscope was used in six patients (7%) for similar reasons. Repeat colonoscopy on the remaining three patients (3%) failed: all three required surgery for strictures (two had obstructing malignant masses and one had a severe benign obstructing sigmoid diverticular stricture). CONCLUSION: Most patients with previous incomplete colonoscopy can undergo a successful repeat colonoscopy at a tertiary care centre with instruments that are readily available to most gastroenterologists. Other modalities for evaluation of the colon should be deferred until a second attempt is made at an expert centre. PMID:22993727

Composite Linear Models | Division of Cancer Prevention

Cancer.gov

By Stuart G. Baker The composite linear models software is a matrix approach to compute maximum likelihood estimates and asymptotic standard errors for models for incomplete multinomial data. It implements the method described in Baker SG. Composite linear models for incomplete multinomial data. Statistics in Medicine 1994;13:609-622. The software includes a library of thirty

Multi-task linear programming discriminant analysis for the identification of progressive MCI individuals.

PubMed

Yu, Guan; Liu, Yufeng; Thung, Kim-Han; Shen, Dinggang

2014-01-01

Accurately identifying mild cognitive impairment (MCI) individuals who will progress to Alzheimer's disease (AD) is very important for making early interventions. Many classification methods focus on integrating multiple imaging modalities such as magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET). However, the main challenge for MCI classification using multiple imaging modalities is the existence of a lot of missing data in many subjects. For example, in the Alzheimer's Disease Neuroimaging Initiative (ADNI) study, almost half of the subjects do not have PET images. In this paper, we propose a new and flexible binary classification method, namely Multi-task Linear Programming Discriminant (MLPD) analysis, for the incomplete multi-source feature learning. Specifically, we decompose the classification problem into different classification tasks, i.e., one for each combination of available data sources. To solve all different classification tasks jointly, our proposed MLPD method links them together by constraining them to achieve the similar estimated mean difference between the two classes (under classification) for those shared features. Compared with the state-of-the-art incomplete Multi-Source Feature (iMSF) learning method, instead of constraining different classification tasks to choose a common feature subset for those shared features, MLPD can flexibly and adaptively choose different feature subsets for different classification tasks. Furthermore, our proposed MLPD method can be efficiently implemented by linear programming. To validate our MLPD method, we perform experiments on the ADNI baseline dataset with the incomplete MRI and PET images from 167 progressive MCI (pMCI) subjects and 226 stable MCI (sMCI) subjects. We further compared our method with the iMSF method (using incomplete MRI and PET images) and also the single-task classification method (using only MRI or only subjects with both MRI and PET images). Experimental results show very promising performance of our proposed MLPD method.

Multi-Task Linear Programming Discriminant Analysis for the Identification of Progressive MCI Individuals

PubMed Central

Yu, Guan; Liu, Yufeng; Thung, Kim-Han; Shen, Dinggang

2014-01-01

Accurately identifying mild cognitive impairment (MCI) individuals who will progress to Alzheimer's disease (AD) is very important for making early interventions. Many classification methods focus on integrating multiple imaging modalities such as magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET). However, the main challenge for MCI classification using multiple imaging modalities is the existence of a lot of missing data in many subjects. For example, in the Alzheimer's Disease Neuroimaging Initiative (ADNI) study, almost half of the subjects do not have PET images. In this paper, we propose a new and flexible binary classification method, namely Multi-task Linear Programming Discriminant (MLPD) analysis, for the incomplete multi-source feature learning. Specifically, we decompose the classification problem into different classification tasks, i.e., one for each combination of available data sources. To solve all different classification tasks jointly, our proposed MLPD method links them together by constraining them to achieve the similar estimated mean difference between the two classes (under classification) for those shared features. Compared with the state-of-the-art incomplete Multi-Source Feature (iMSF) learning method, instead of constraining different classification tasks to choose a common feature subset for those shared features, MLPD can flexibly and adaptively choose different feature subsets for different classification tasks. Furthermore, our proposed MLPD method can be efficiently implemented by linear programming. To validate our MLPD method, we perform experiments on the ADNI baseline dataset with the incomplete MRI and PET images from 167 progressive MCI (pMCI) subjects and 226 stable MCI (sMCI) subjects. We further compared our method with the iMSF method (using incomplete MRI and PET images) and also the single-task classification method (using only MRI or only subjects with both MRI and PET images). Experimental results show very promising performance of our proposed MLPD method. PMID:24820966

Identification of Malassezia species in patients with seborrheic dermatitis in China.

PubMed

Zhang, Hao; Ran, Yuping; Xie, Zhen; Zhang, Ruifeng

2013-02-01

The causes of seborrheic dermatitis (SD) are complex and incompletely understood. Among the factors, Malassezia yeasts have been reported to play a major etiological role in SD. Many previous studies adopted conventional culture methods that were disadvantaged to detect Malassezia microflora in SD patients, resulting in a low detection rate for each species and high variance in types of microflora observed. This study analyzed Malassezia microflora in SD patients by applying a transparent dressing to the lesional skin and using direct detection of fungal DNA using nested PCR. We collected samples from the lesional skin of 146 SD patients in China and extracted fungal DNA directly from the lesional samples without culture. Specific primers for each Malassezia species were designed to amplify existing yeasts in each sample. Some samples were randomly selected to culture and identified by morphological and physiologic criteria. M. globosa and M. restricta were found in 87.0 and 81.5% of seborrheic dermatitis patients, respectively, which together accounted for more than 50% of Malassezia spp. recovered in these Chinese patients. The majority of SD patients (82.9%) showed co-colonization of two or more Malassezia species. M. globosa and M. restricta predominated in Malassezia colonization in Chinese SD patients. Compared with conventional culture, non-culture-based methods may more accurately reflect Malassezia microflora constitution.

Comparison of Extruded and Sonicated Vesicles for Planar Bilayer Self-Assembly

PubMed Central

Cho, Nam-Joon; Hwang, Lisa Y.; Solandt, Johan J.R.; Frank, Curtis W.

2013-01-01

Lipid vesicles are an important class of biomaterials that have a wide range of applications, including drug delivery, cosmetic formulations and model membrane platforms on solid supports. Depending on the application, properties of a vesicle population such as size distribution, charge and permeability need to be optimized. Preparation methods such as mechanical extrusion and sonication play a key role in controlling these properties, and yet the effects of vesicle preparation method on vesicular properties and integrity (e.g., shape, size, distribution and tension) remain incompletely understood. In this study, we prepared vesicles composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid by either extrusion or sonication, and investigated the effects on vesicle size distribution over time as well as the concomitant effects on the self-assembly of solid-supported planar lipid bilayers. Dynamic light scattering (DLS), quartz crystal microbalance with dissipation (QCM-D) monitoring, fluorescence recovery after photobleaching (FRAP) and atomic force microscopy (AFM) experiments were performed to characterize vesicles in solution as well as their interactions with silicon oxide substrates. Collectively, the data support that sonicated vesicles offer more robust control over the self-assembly of homogenous planar lipid bilayers, whereas extruded vesicles are vulnerable to aging and must be used soon after preparation. PMID:28811437

Epoxyeicosatrienoic acids enhance embryonic haematopoiesis and adult marrow engraftment.

PubMed

Li, Pulin; Lahvic, Jamie L; Binder, Vera; Pugach, Emily K; Riley, Elizabeth B; Tamplin, Owen J; Panigrahy, Dipak; Bowman, Teresa V; Barrett, Francesca G; Heffner, Garrett C; McKinney-Freeman, Shannon; Schlaeger, Thorsten M; Daley, George Q; Zeldin, Darryl C; Zon, Leonard I

2015-07-23

Haematopoietic stem and progenitor cell (HSPC) transplant is a widely used treatment for life-threatening conditions such as leukaemia; however, the molecular mechanisms regulating HSPC engraftment of the recipient niche remain incompletely understood. Here we develop a competitive HSPC transplant method in adult zebrafish, using in vivo imaging as a non-invasive readout. We use this system to conduct a chemical screen, and identify epoxyeicosatrienoic acids (EETs) as a family of lipids that enhance HSPC engraftment. The pro-haematopoietic effects of EETs were conserved in the developing zebrafish embryo, where 11,12-EET promoted HSPC specification by activating a unique activator protein 1 (AP-1) and runx1 transcription program autonomous to the haemogenic endothelium. This effect required the activation of the phosphatidylinositol-3-OH kinase (PI(3)K) pathway, specifically PI(3)Kγ. In adult HSPCs, 11,12-EET induced transcriptional programs, including AP-1 activation, which modulate several cellular processes, such as migration, to promote engraftment. Furthermore, we demonstrate that the EET effects on enhancing HSPC homing and engraftment are conserved in mammals. Our study establishes a new method to explore the molecular mechanisms of HSPC engraftment, and discovers a previously unrecognized, evolutionarily conserved pathway regulating multiple haematopoietic generation and regeneration processes. EETs may have clinical application in marrow or cord blood transplantation.

OGLE-2012-BLG-0455/MOA-2012-BLG-206: Microlensing Event with Ambiguity in Planetary Interpretations Caused by Incomplete Coverage of Planetary Signal

NASA Astrophysics Data System (ADS)

Park, H.; Han, C.; Gould, A.; Udalski, A.; Sumi, T.; Fouqué, P.; Choi, J.-Y.; Christie, G.; Depoy, D. L.; Dong, Subo; Gaudi, B. S.; Hwang, K.-H.; Jung, Y. K.; Kavka, A.; Lee, C.-U.; Monard, L. A. G.; Natusch, T.; Ngan, H.; Pogge, R. W.; Shin, I.-G.; Yee, J. C.; μFUN Collaboration; Szymański, M. K.; Kubiak, M.; Soszyński, I.; Pietrzyński, G.; Poleski, R.; Ulaczyk, K.; Pietrukowicz, P.; Kozłowski, S.; Skowron, J.; Wyrzykowski, Ł.; OGLE Collaboration; Abe, F.; Bennett, D. P.; Bond, I. A.; Botzler, C. S.; Chote, P.; Freeman, M.; Fukui, A.; Fukunaga, D.; Harris, P.; Itow, Y.; Koshimoto, N.; Ling, C. H.; Masuda, K.; Matsubara, Y.; Muraki, Y.; Namba, S.; Ohnishi, K.; Rattenbury, N. J.; Saito, To.; Sullivan, D. J.; Sweatman, W. L.; Suzuki, D.; Tristram, P. J.; Wada, K.; Yamai, N.; Yock, P. C. M.; Yonehara, A.; MOA Collaboration

2014-05-01

Characterizing a microlensing planet is done by modeling an observed lensing light curve. In this process, it is often confronted that solutions of different lensing parameters result in similar light curves, causing difficulties in uniquely interpreting the lens system, and thus understanding the causes of different types of degeneracy is important. In this work, we show that incomplete coverage of a planetary perturbation can result in degenerate solutions even for events where the planetary signal is detected with a high level of statistical significance. We demonstrate the degeneracy for an actually observed event OGLE-2012-BLG-0455/MOA-2012-BLG-206. The peak of this high-magnification event (A max ~ 400) exhibits very strong deviation from a point-lens model with Δχ2 >~ 4000 for data sets with a total of 6963 measurements. From detailed modeling of the light curve, we find that the deviation can be explained by four distinct solutions, i.e., two very different sets of solutions, each with a twofold degeneracy. While the twofold (so-called close/wide) degeneracy is well understood, the degeneracy between the radically different solutions is not previously known. The model light curves of this degeneracy differ substantially in the parts that were not covered by observation, indicating that the degeneracy is caused by the incomplete coverage of the perturbation. It is expected that the frequency of the degeneracy introduced in this work will be greatly reduced with the improvement of the current lensing survey and follow-up experiments and the advent of new surveys.

Bears in a Forest of Gene Trees: Phylogenetic Inference Is Complicated by Incomplete Lineage Sorting and Gene Flow

PubMed Central

Kutschera, Verena E.; Bidon, Tobias; Hailer, Frank; Rodi, Julia L.; Fain, Steven R.; Janke, Axel

2014-01-01

Ursine bears are a mammalian subfamily that comprises six morphologically and ecologically distinct extant species. Previous phylogenetic analyses of concatenated nuclear genes could not resolve all relationships among bears, and appeared to conflict with the mitochondrial phylogeny. Evolutionary processes such as incomplete lineage sorting and introgression can cause gene tree discordance and complicate phylogenetic inferences, but are not accounted for in phylogenetic analyses of concatenated data. We generated a high-resolution data set of autosomal introns from several individuals per species and of Y-chromosomal markers. Incorporating intraspecific variability in coalescence-based phylogenetic and gene flow estimation approaches, we traced the genealogical history of individual alleles. Considerable heterogeneity among nuclear loci and discordance between nuclear and mitochondrial phylogenies were found. A species tree with divergence time estimates indicated that ursine bears diversified within less than 2 My. Consistent with a complex branching order within a clade of Asian bear species, we identified unidirectional gene flow from Asian black into sloth bears. Moreover, gene flow detected from brown into American black bears can explain the conflicting placement of the American black bear in mitochondrial and nuclear phylogenies. These results highlight that both incomplete lineage sorting and introgression are prominent evolutionary forces even on time scales up to several million years. Complex evolutionary patterns are not adequately captured by strictly bifurcating models, and can only be fully understood when analyzing multiple independently inherited loci in a coalescence framework. Phylogenetic incongruence among gene trees hence needs to be recognized as a biologically meaningful signal. PMID:24903145

Eat, breathe, ROS: controlling stem cell fate through metabolism.

PubMed

Kubli, Dieter A; Sussman, Mark A

2017-05-01

Research reveals cardiac regeneration exists at levels previously deemed unattainable. Clinical trials using stem cells demonstrate promising cardiomyogenic and regenerative potential but insufficient contractile recovery. Incomplete understanding of the biology of administered cells likely contributes to inconsistent patient outcomes. Metabolism is a core component of many well-characterized stem cell types, and metabolic changes fundamentally alter stem cell fate from self-renewal to lineage commitment, and vice versa. However, the metabolism of stem cells currently studied for cardiac regeneration remains incompletely understood. Areas covered: Key metabolic features of stem cells are reviewed and unique stem cell metabolic characteristics are discussed. Metabolic changes altering stem cell fate are considered from quiescence and self-renewal to lineage commitment. Key metabolic concepts are applied toward examining cardiac regeneration through stem cell-based approaches, and clinical implications of current cell therapies are evaluated to identify potential areas of improvement. Expert commentary: The metabolism and biology of stem cells used for cardiac therapy remain poorly characterized. A growing appreciation for the fundamental relationship between stem cell functionality and metabolic phenotype is developing. Future studies unraveling links between cardiac stem cell metabolism and regenerative potential may considerably improve treatment strategies and therapeutic outcomes.

Culture as a variable in health research: perspectives and caveats.

PubMed

Al-Bannay, Hana; Jarus, Tal; Jongbloed, Lyn; Yazigi, Maya; Dean, Elizabeth

2014-09-01

To augment the rigor of health promotion research, this perspective article describes how cultural factors impact the outcomes of health promotion studies either intentionally or unintentionally. It proposes ways in which these factors can be addressed or controlled in designing studies and interpreting their results. We describe how variation within and across cultures can be considered within a study, e.g. the conceptualization of research questions or hypotheses, and the methodology including sampling, surveys and interviews. We provide multiple examples of how culture influences the interpretation of study findings. Inadequately accounting or controlling for cultural variations in health promotion studies, whether they are planned or unplanned, can lead to incomplete research questions, incomplete data gathering, spurious results and limited generalizability of the findings. In health promotion research, factors related to culture and cultural variations need to be considered, acknowledged or controlled irrespective of the purpose of the study, to maximize the reliability, validity and generalizability of study findings. These issues are particularly relevant in contemporary health promotion research focusing on global lifestyle-related conditions where cultural factors have a pivotal role and warrant being understood. © The Author (2013). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Eat, breathe, ROS: controlling stem cell fate through metabolism

PubMed Central

Kubli, Dieter A.; Sussman, Mark A.

2017-01-01

Introduction Research reveals cardiac regeneration exists at levels previously deemed unattainable. Clinical trials using stem cells demonstrate promising cardiomyogenic and regenerative potential but insufficient contractile recovery. Incomplete understanding of the biology of administered cells likely contributes to inconsistent patient outcomes. Metabolism is a core component of many well-characterized stem cell types, and metabolic changes fundamentally alter stem cell fate from self-renewal to lineage commitment, and vice versa. However, the metabolism of stem cells currently studied for cardiac regeneration remains incompletely understood. Areas covered Key metabolic features of stem cells are reviewed and unique stem cell metabolic characteristics are discussed. Metabolic changes altering stem cell fate are considered from quiescence and self-renewal to lineage commitment. Key metabolic concepts are applied toward examining cardiac regeneration through stem cell-based approaches, and clinical implications of current cell therapies are evaluated to identify potential areas of improvement. Expert commentary The metabolism and biology of stem cells used for cardiac therapy remain poorly characterized. A growing appreciation for the fundamental relationship between stem cell functionality and metabolic phenotype is developing. Future studies unraveling links between cardiac stem cell metabolism and regenerative potential may considerably improve treatment strategies and therapeutic outcomes. PMID:28406333

Mutations in HYAL2, Encoding Hyaluronidase 2, Cause a Syndrome of Orofacial Clefting and Cor Triatriatum Sinister in Humans and Mice

PubMed Central

Hasan, S. Naimul; Mark, Brian; Harlalka, Gaurav V.; Patton, Michael A.; Ishida, Miho; Sharma, Sanjay; Faqeih, Eissa; Blakley, Brian; Jackson, Mike; Lees, Melissa; Dolinsky, Vernon; Cross, Leroy; Stanier, Philip; Salter, Claire; Baple, Emma L.; Crosby, Andrew H.

2017-01-01

Orofacial clefting is amongst the most common of birth defects, with both genetic and environmental components. Although numerous studies have been undertaken to investigate the complexities of the genetic etiology of this heterogeneous condition, this factor remains incompletely understood. Here, we describe mutations in the HYAL2 gene as a cause of syndromic orofacial clefting. HYAL2, encoding hyaluronidase 2, degrades extracellular hyaluronan, a critical component of the developing heart and palatal shelf matrix. Transfection assays demonstrated that the gene mutations destabilize the molecule, dramatically reducing HYAL2 protein levels. Consistent with the clinical presentation in affected individuals, investigations of Hyal2-/- mice revealed craniofacial abnormalities, including submucosal cleft palate. In addition, cor triatriatum sinister and hearing loss, identified in a proportion of Hyal2-/- mice, were also found as incompletely penetrant features in affected humans. Taken together our findings identify a new genetic cause of orofacial clefting in humans and mice, and define the first molecular cause of human cor triatriatum sinister, illustrating the fundamental importance of HYAL2 and hyaluronan turnover for normal human and mouse development. PMID:28081210

Sample size considerations for paired experimental design with incomplete observations of continuous outcomes.

PubMed

Zhu, Hong; Xu, Xiaohan; Ahn, Chul

2017-01-01

Paired experimental design is widely used in clinical and health behavioral studies, where each study unit contributes a pair of observations. Investigators often encounter incomplete observations of paired outcomes in the data collected. Some study units contribute complete pairs of observations, while the others contribute either pre- or post-intervention observations. Statistical inference for paired experimental design with incomplete observations of continuous outcomes has been extensively studied in literature. However, sample size method for such study design is sparsely available. We derive a closed-form sample size formula based on the generalized estimating equation approach by treating the incomplete observations as missing data in a linear model. The proposed method properly accounts for the impact of mixed structure of observed data: a combination of paired and unpaired outcomes. The sample size formula is flexible to accommodate different missing patterns, magnitude of missingness, and correlation parameter values. We demonstrate that under complete observations, the proposed generalized estimating equation sample size estimate is the same as that based on the paired t-test. In the presence of missing data, the proposed method would lead to a more accurate sample size estimate comparing with the crude adjustment. Simulation studies are conducted to evaluate the finite-sample performance of the generalized estimating equation sample size formula. A real application example is presented for illustration.

Examining the Missing Completely at Random Mechanism in Incomplete Data Sets: A Multiple Testing Approach

ERIC Educational Resources Information Center

Raykov, Tenko; Lichtenberg, Peter A.; Paulson, Daniel

2012-01-01

A multiple testing procedure for examining implications of the missing completely at random (MCAR) mechanism in incomplete data sets is discussed. The approach uses the false discovery rate concept and is concerned with testing group differences on a set of variables. The method can be used for ascertaining violations of MCAR and disproving this…

Identifying Useful Auxiliary Variables for Incomplete Data Analyses: A Note on a Group Difference Examination Approach

ERIC Educational Resources Information Center

Raykov, Tenko; Marcoulides, George A.

2014-01-01

This research note contributes to the discussion of methods that can be used to identify useful auxiliary variables for analyses of incomplete data sets. A latent variable approach is discussed, which is helpful in finding auxiliary variables with the property that if included in subsequent maximum likelihood analyses they may enhance considerably…

State estimation with incomplete nonlinear constraint

NASA Astrophysics Data System (ADS)

Huang, Yuan; Wang, Xueying; An, Wei

2017-10-01

A problem of state estimation with a new constraints named incomplete nonlinear constraint is considered. The targets are often move in the curve road, if the width of road is neglected, the road can be considered as the constraint, and the position of sensors, e.g., radar, is known in advance, this info can be used to enhance the performance of the tracking filter. The problem of how to incorporate the priori knowledge is considered. In this paper, a second-order sate constraint is considered. A fitting algorithm of ellipse is adopted to incorporate the priori knowledge by estimating the radius of the trajectory. The fitting problem is transformed to the nonlinear estimation problem. The estimated ellipse function is used to approximate the nonlinear constraint. Then, the typical nonlinear constraint methods proposed in recent works can be used to constrain the target state. Monte-Carlo simulation results are presented to illustrate the effectiveness proposed method in state estimation with incomplete constraint.

Acute exposure to wood smoke from incomplete combustion--indications of cytotoxicity.

PubMed

Muala, Ala; Rankin, Gregory; Sehlstedt, Maria; Unosson, Jon; Bosson, Jenny A; Behndig, Annelie; Pourazar, Jamshid; Nyström, Robin; Pettersson, Esbjörn; Bergvall, Christoffer; Westerholm, Roger; Jalava, Pasi I; Happo, Mikko S; Uski, Oskari; Hirvonen, Maija-Riitta; Kelly, Frank J; Mudway, Ian S; Blomberg, Anders; Boman, Christoffer; Sandström, Thomas

2015-10-29

Smoke from combustion of biomass fuels is a major risk factor for respiratory disease, but the underlying mechanisms are poorly understood. The aim of this study was to determine whether exposure to wood smoke from incomplete combustion would elicit airway inflammation in humans. Fourteen healthy subjects underwent controlled exposures on two separate occasions to filtered air and wood smoke from incomplete combustion with PM1 concentration at 314 μg/m(3) for 3 h in a chamber. Bronchoscopy with bronchial wash (BW), bronchoalveolar lavage (BAL) and endobronchial mucosal biopsies was performed after 24 h. Differential cell counts and soluble components were analyzed, with biopsies stained for inflammatory markers using immunohistochemistry. In parallel experiments, the toxicity of the particulate matter (PM) generated during the chamber exposures was investigated in vitro using the RAW264.7 macrophage cell line. Significant reductions in macrophage, neutrophil and lymphocyte numbers were observed in BW (p < 0.01, <0.05, <0.05, respectively) following the wood smoke exposure, with a reduction in lymphocytes numbers in BAL fluid (<0.01. This unexpected cellular response was accompanied by decreased levels of sICAM-1, MPO and MMP-9 (p < 0.05, <0.05 and <0.01). In contrast, significant increases in submucosal and epithelial CD3+ cells, epithelial CD8+ cells and submucosal mast cells (p < 0.01, <0.05, <0.05 and <0.05, respectively), were observed after wood smoke exposure. The in vitro data demonstrated that wood smoke particles generated under these incomplete combustion conditions induced cell death and DNA damage, with only minor inflammatory responses. Short-term exposure to sooty PAH rich wood smoke did not induce an acute neutrophilic inflammation, a classic hallmark of air pollution exposure in humans. While minor proinflammatory lymphocytic and mast cells effects were observed in the bronchial biopsies, significant reductions in BW and BAL cells and soluble components were noted. This unexpected observation, combined with the in vitro data, suggests that wood smoke particles from incomplete combustion could be potentially cytotoxic. Additional research is required to establish the mechanism of this dramatic reduction in airway leukocytes and to clarify how this acute response contributes to the adverse health effects attributed to wood smoke exposure. NCT01488500.

Role of Stress Myocardial Scintigraphy in the Evaluation of Incompletely Revascularized Post-PCI Patients

PubMed Central

Galassi, Alfredo R.; Marzá, Francesco; Azzarelli, Salvatore; Tomasello, Salvatore D.

2011-01-01

Percutaneous coronary intervention (PCI) is actually the most used method of revascularization. Although complete revascularization remains a desirable goal, it may not be possible or not easy to plan in many patients. Thus, incomplete revascularization might be a preferred treatment strategy in selected patient categories. Stress myocardial scintigraphy, because of its high diagnostic accuracy and prognostic value and its ability to assess location and extent of myocardial ischemia regardless of symptoms as well as to evaluate patients who are unable to exercise or who have uninterpretable electrocardiogram, is of paramount importance for clinical decision making in patients with multivessel disease and incomplete revascularization. PMID:21941646

An Improved Swarm Optimization for Parameter Estimation and Biological Model Selection

PubMed Central

Abdullah, Afnizanfaizal; Deris, Safaai; Mohamad, Mohd Saberi; Anwar, Sohail

2013-01-01

One of the key aspects of computational systems biology is the investigation on the dynamic biological processes within cells. Computational models are often required to elucidate the mechanisms and principles driving the processes because of the nonlinearity and complexity. The models usually incorporate a set of parameters that signify the physical properties of the actual biological systems. In most cases, these parameters are estimated by fitting the model outputs with the corresponding experimental data. However, this is a challenging task because the available experimental data are frequently noisy and incomplete. In this paper, a new hybrid optimization method is proposed to estimate these parameters from the noisy and incomplete experimental data. The proposed method, called Swarm-based Chemical Reaction Optimization, integrates the evolutionary searching strategy employed by the Chemical Reaction Optimization, into the neighbouring searching strategy of the Firefly Algorithm method. The effectiveness of the method was evaluated using a simulated nonlinear model and two biological models: synthetic transcriptional oscillators, and extracellular protease production models. The results showed that the accuracy and computational speed of the proposed method were better than the existing Differential Evolution, Firefly Algorithm and Chemical Reaction Optimization methods. The reliability of the estimated parameters was statistically validated, which suggests that the model outputs produced by these parameters were valid even when noisy and incomplete experimental data were used. Additionally, Akaike Information Criterion was employed to evaluate the model selection, which highlighted the capability of the proposed method in choosing a plausible model based on the experimental data. In conclusion, this paper presents the effectiveness of the proposed method for parameter estimation and model selection problems using noisy and incomplete experimental data. This study is hoped to provide a new insight in developing more accurate and reliable biological models based on limited and low quality experimental data. PMID:23593445

Darwin and Genetics

PubMed Central

Charlesworth, Brian; Charlesworth, Deborah

2009-01-01

Darwin's theory of natural selection lacked an adequate account of inheritance, making it logically incomplete. We review the interaction between evolution and genetics, showing how, unlike Mendel, Darwin's lack of a model of the mechanism of inheritance left him unable to interpret his own data that showed Mendelian ratios, even though he shared with Mendel a more mathematical and probabilistic outlook than most biologists of his time. Darwin's own “pangenesis” model provided a mechanism for generating ample variability on which selection could act. It involved, however, the inheritance of characters acquired during an organism's life, which Darwin himself knew could not explain some evolutionary situations. Once the particulate basis of genetics was understood, it was seen to allow variation to be passed intact to new generations, and evolution could then be understood as a process of changes in the frequencies of stable variants. Evolutionary genetics subsequently developed as a central part of biology. Darwinian principles now play a greater role in biology than ever before, which we illustrate with some examples of studies of natural selection that use DNA sequence data and with some recent advances in answering questions first asked by Darwin. PMID:19933231

Protein tyrosine phosphatases as wardens of STAT signaling

PubMed Central

Böhmer, Frank-D; Friedrich, Karlheinz

2014-01-01

Signaling by signal transducers and activators of transcription (STATs) is controlled at many levels of the signaling cascade. Protein tyrosine phosphatases (PTPs) regulate STAT activation at several layers, including direct pSTAT dephosphorylation in both cytoplasm and nucleus. Despite the importance of this regulation mode, many aspects are still incompletely understood, e.g., the identity of PTPs acting on certain members of the STAT family. After a brief introduction into the STAT and PTP families, we discuss here the current knowledge on PTP mediated regulation of STAT activity, focusing on the interaction of individual STATs with specific PTPs. Finally, we highlight open questions and propose important tasks of future research. PMID:24778927

Targeting obesity-related adipose tissue dysfunction to prevent cancer development and progression

PubMed Central

Gucalp, Ayca; Iyengar, Neil M.; Hudis, Clifford A.; Dannenberg, Andrew J.

2016-01-01

The incidence of obesity, a leading modifiable risk factor for common solid tumors, is increasing. Effective interventions are needed to minimize the public health implications of obesity. Although the mechanisms linking increased adiposity to malignancy are incompletely understood, growing evidence points to complex interactions among multiple systemic and tissue-specific pathways including inflamed white adipose tissue. The metabolic and inflammatory consequences of white adipose tissue dysfunction collectively provide a plausible explanation for the link between overweight/obesity and carcinogenesis. Gaining a better understanding of these underlying molecular pathways and developing risk assessment tools that identify at-risk populations will be critical in implementing effective and novel cancer prevention and management strategies. PMID:26970134

Cerebral vasculopathy in children with sickle cell anemia.

PubMed

Fasano, Ross M; Meier, Emily R; Hulbert, Monica L

2015-01-01

Sickle cell anemia (SCA)-associated cerebral vasculopathy and moyamoya is a unique entity reflecting the abnormal interactions between sickled red blood cells (RBCs) and the cerebral arterial endothelium. Endothelial injury, coagulation activation, and the inflammatory response generated by sickled RBCs are implicated in the development of cerebral vasculopathy, but the pathophysiology remains incompletely understood. SCA-specific screening and treatment guidelines have successfully reduced the incidence of overt strokes in this high-risk population. However, despite aggressive hematological management, many children with cerebral vasculopathy due to SCA have progressive vasculopathy and recurrent strokes; therefore, more effective therapies, such as revascularization surgery and curative hematopoietic stem cell transplant, are urgently needed. Copyright © 2014 Elsevier Inc. All rights reserved.

Sulfate burial constraints on the Phanerozoic sulfur cycle.

PubMed

Halevy, Itay; Peters, Shanan E; Fischer, Woodward W

2012-07-20

The sulfur cycle influences the respiration of sedimentary organic matter, the oxidation state of the atmosphere and oceans, and the composition of seawater. However, the factors governing the major sulfur fluxes between seawater and sedimentary reservoirs remain incompletely understood. Using macrostratigraphic data, we quantified sulfate evaporite burial fluxes through Phanerozoic time. Approximately half of the modern riverine sulfate flux comes from weathering of recently deposited evaporites. Rates of sulfate burial are unsteady and linked to changes in the area of marine environments suitable for evaporite formation and preservation. By contrast, rates of pyrite burial and weathering are higher, less variable, and largely balanced, highlighting a greater role of the sulfur cycle in regulating atmospheric oxygen.

[Brain oedema and acute liver failure].

PubMed

Spahr, L

2003-04-01

Brain oedema leading to intracranial hypertension occurs in a significant proportion of patients with acute liver failure in whom it is a leading cause of death. Although precise pathogenic mechanisms associated to this severe complication remain incompletely understood, increasing evidence points to gut-derived neurotoxins including ammonia as key mediators in cerebral osmotic and perfusion disturbances. The management of brain oedema and intracranial hypertension requires a multidisciplinar approach in a center where liver transplantation is available, as this option is the only treatment modality that provides improvement in outcome. This article reviews the most common causes of acute liver failure and the standard of supportive care management, and describes future potential therapeutic aspects of brain oedema and intracranial hypertension.

Reconciling controversies about the ‘global warming hiatus’

NASA Astrophysics Data System (ADS)

Medhaug, Iselin; Stolpe, Martin B.; Fischer, Erich M.; Knutti, Reto

2017-05-01

Between about 1998 and 2012, a time that coincided with political negotiations for preventing climate change, the surface of Earth seemed hardly to warm. This phenomenon, often termed the ‘global warming hiatus’, caused doubt in the public mind about how well anthropogenic climate change and natural variability are understood. Here we show that apparently contradictory conclusions stem from different definitions of ‘hiatus’ and from different datasets. A combination of changes in forcing, uptake of heat by the oceans, natural variability and incomplete observational coverage reconciles models and data. Combined with stronger recent warming trends in newer datasets, we are now more confident than ever that human influence is dominant in long-term warming.

Reconciling controversies about the 'global warming hiatus'.

PubMed

Medhaug, Iselin; Stolpe, Martin B; Fischer, Erich M; Knutti, Reto

2017-05-03

Between about 1998 and 2012, a time that coincided with political negotiations for preventing climate change, the surface of Earth seemed hardly to warm. This phenomenon, often termed the 'global warming hiatus', caused doubt in the public mind about how well anthropogenic climate change and natural variability are understood. Here we show that apparently contradictory conclusions stem from different definitions of 'hiatus' and from different datasets. A combination of changes in forcing, uptake of heat by the oceans, natural variability and incomplete observational coverage reconciles models and data. Combined with stronger recent warming trends in newer datasets, we are now more confident than ever that human influence is dominant in long-term warming.

Advances in color science: from retina to behavior

PubMed Central

Chatterjee, Soumya; Field, Greg D.; Horwitz, Gregory D.; Johnson, Elizabeth N.; Koida, Kowa; Mancuso, Katherine

2010-01-01

Color has become a premier model system for understanding how information is processed by neural circuits, and for investigating the relationships among genes, neural circuits and perception. Both the physical stimulus for color and the perceptual output experienced as color are quite well characterized, but the neural mechanisms that underlie the transformation from stimulus to perception are incompletely understood. The past several years have seen important scientific and technical advances that are changing our understanding of these mechanisms. Here, and in the accompanying minisymposium, we review the latest findings and hypotheses regarding color computations in the retina, primary visual cortex and higher-order visual areas, focusing on non-human primates, a model of human color vision. PMID:21068298

Single molecule data under scrutiny. Comment on "Extracting physics of life at the molecular level: A review of single-molecule data analyses" by W. Colomb & S.K. Sarkar

NASA Astrophysics Data System (ADS)

Wohland, Thorsten

2015-06-01

Single Molecule Detection and Spectroscopy have grown from their first beginnings into mainstream, mature research areas that are widely applied in the biological sciences. However, despite the advances in technology and the application of many single molecule techniques even in in vivo settings, the data analysis of single molecule experiments is complicated by noise, systematic errors, and complex underlying processes that are only incompletely understood. Colomb and Sarkar provide in this issue an overview of single molecule experiments and the accompanying problems in data analysis, which have to be overcome for a proper interpretation of the experiments [1].

Development and validation of an algorithm to complete colonoscopy using standard endoscopes in patients with prior incomplete colonoscopy

PubMed Central

Rogers, Melinda C.; Gawron, Andrew; Grande, David; Keswani, Rajesh N.

2017-01-01

Background and study aims  Incomplete colonoscopy may occur as a result of colon angulation (adhesions or diverticulosis), endoscope looping, or both. Specialty endoscopes/devices have been shown to successfully complete prior incomplete colonoscopies, but may not be widely available. Radiographic or other image-based evaluations have been shown to be effective but may miss small or flat lesions, and colonoscopy is often still indicated if a large lesion is identified. The purpose of this study was to develop and validate an algorithm to determine the optimum endoscope to ensure completion of the examination in patients with prior incomplete colonoscopy. Patients and methods  This was a prospective cohort study of 175 patients with prior incomplete colonoscopy who were referred to a single endoscopist at a single academic medical center over a 3-year period from 2012 through 2015. Colonoscopy outcomes from the initial 50 patients were used to develop an algorithm to determine the optimal standard endoscope and technique to achieve cecal intubation. The algorithm was validated on the subsequent 125 patients. Results  The overall repeat colonoscopy success rate using a standard endoscope was 94 %. The initial standard endoscope specified by the algorithm was used and completed the colonoscopy in 90 % of patients. Conclusions  This study identifies an effective strategy for completing colonoscopy in patients with prior incomplete examination, using widely available standard endoscopes and an algorithm based on patient characteristics and reasons for prior incomplete colonoscopy. PMID:28924595

Correlation between compliance and brace treatment in juvenile and adolescent idiopathic scoliosis: SOSORT 2014 award winner

PubMed Central

2014-01-01

Background Over the last years, evidence has accumulated in support of bracing as an effective treatment option in patients with idiopathic scoliosis. Yet, little information is available on the impact of compliance on the outcome of conservative treatment in scoliotic subjects. The aim of the present study was to prospectively evaluate the association between compliance to brace treatment and the progression of scoliotic curve in patients with idiopathic adolescent (AIS) or juvenile scoliosis (JIS). Methods Among 1.424 patients treated for idiopathic scoliosis, 645 were eligible for inclusion criteria. Three outcomes were distinguished in agreement with the SRS criteria: curve correction, curve stabilization and curve progression. Brace wearing was assessed by one orthopaedic surgeon (LA) and scored on a standardized form. Compliance to treatment was categorized as complete (brace worn as prescribed), incomplete A (brace removed for 1 month), incomplete B (brace removed for 2 months), incomplete C (brace removed during school hours), and incomplete D (brace worn overnight only). Chi square test, T test or ANOVA and ANOVA for repeated measures tests were used as statistical tests. Results The results from our study showed that at follow-up the compliance was: Complete 61.1%; Incomplete A 5.2%; Incomplete B 10.7%; Incomplete C 14.2%; Incomplete D 8.8%. Curve correction was accomplished in 301/319 of Complete, 19/27 Incomplete A, 25/56 Incomplete B, 52/74 Incomplete C, 27/46 Incomplete D. Cobb mean value was 29.8 ± 7.5 SD at beginning and 17.1 ± 10.9 SD at follow-up. Both Cobb and Perdriolle degree amelioration was significantly higher in patients with complete compliance over all other groups, both in juvenile, both in adolescent scoliosis. In the intention-to-treat analysis, the rate of surgical treatment was 2.1% among patients with definite outcome and 12.1% among those with drop-out. Treatment compliance showed significant interactions with time. Conclusion Curve progression and referral to surgery are lower in patients with high brace compliance. Bracing discontinuation up to 1 month does not impact on the treatment outcome. Conversely, wearing the brace only overnight is associated with a high rate of curve progression. PMID:24995038

Estimation of Blood Flow Rates in Large Microvascular Networks

PubMed Central

Fry, Brendan C.; Lee, Jack; Smith, Nicolas P.; Secomb, Timothy W.

2012-01-01

Objective Recent methods for imaging microvascular structures provide geometrical data on networks containing thousands of segments. Prediction of functional properties, such as solute transport, requires information on blood flow rates also, but experimental measurement of many individual flows is difficult. Here, a method is presented for estimating flow rates in a microvascular network based on incomplete information on the flows in the boundary segments that feed and drain the network. Methods With incomplete boundary data, the equations governing blood flow form an underdetermined linear system. An algorithm was developed that uses independent information about the distribution of wall shear stresses and pressures in microvessels to resolve this indeterminacy, by minimizing the deviation of pressures and wall shear stresses from target values. Results The algorithm was tested using previously obtained experimental flow data from four microvascular networks in the rat mesentery. With two or three prescribed boundary conditions, predicted flows showed relatively small errors in most segments and fewer than 10% incorrect flow directions on average. Conclusions The proposed method can be used to estimate flow rates in microvascular networks, based on incomplete boundary data and provides a basis for deducing functional properties of microvessel networks. PMID:22506980

Empirical analysis shows reduced cost data collection may be an efficient method in economic clinical trials

PubMed Central

2012-01-01

Background Data collection for economic evaluation alongside clinical trials is burdensome and cost-intensive. Limiting both the frequency of data collection and recall periods can solve the problem. As a consequence, gaps in survey periods arise and must be filled appropriately. The aims of our study are to assess the validity of incomplete cost data collection and define suitable resource categories. Methods In the randomised KORINNA study, cost data from 234 elderly patients were collected quarterly over a 1-year period. Different strategies for incomplete data collection were compared with complete data collection. The sample size calculation was modified in response to elasticity of variance. Results Resource categories suitable for incomplete data collection were physiotherapy, ambulatory clinic in hospital, medication, consultations, outpatient nursing service and paid household help. Cost estimation from complete and incomplete data collection showed no difference when omitting information from one quarter. When omitting information from two quarters, costs were underestimated by 3.9% to 4.6%. With respect to the observed increased standard deviation, a larger sample size would be required, increased by 3%. Nevertheless, more time was saved than extra time would be required for additional patients. Conclusion Cost data can be collected efficiently by reducing the frequency of data collection. This can be achieved by incomplete data collection for shortened periods or complete data collection by extending recall windows. In our analysis, cost estimates per year for ambulatory healthcare and non-healthcare services in terms of three data collections was as valid and accurate as a four complete data collections. In contrast, data on hospitalisation, rehabilitation stays and care insurance benefits should be collected for the entire target period, using extended recall windows. When applying the method of incomplete data collection, sample size calculation has to be modified because of the increased standard deviation. This approach is suitable to enable economic evaluation with lower costs to both study participants and investigators. Trial registration The trial registration number is ISRCTN02893746 PMID:22978572

Review of Reliability-Based Design Optimization Approach and Its Integration with Bayesian Method

NASA Astrophysics Data System (ADS)

Zhang, Xiangnan

2018-03-01

A lot of uncertain factors lie in practical engineering, such as external load environment, material property, geometrical shape, initial condition, boundary condition, etc. Reliability method measures the structural safety condition and determine the optimal design parameter combination based on the probabilistic theory. Reliability-based design optimization (RBDO) is the most commonly used approach to minimize the structural cost or other performance under uncertainty variables which combines the reliability theory and optimization. However, it cannot handle the various incomplete information. The Bayesian approach is utilized to incorporate this kind of incomplete information in its uncertainty quantification. In this paper, the RBDO approach and its integration with Bayesian method are introduced.

Evaluation of Revascularization Subtypes in Octogenarians Undergoing Coronary Artery Bypass Grafting

PubMed Central

Aziz, Abdulhameed; Lee, Anson M.; Pasque, Michael K.; Lawton, Jennifer S.; Moazami, Nader; Damiano, Ralph J.; Moon, Marc R.

2009-01-01

Background Recent data suggest that octogenarians’ long-term survival after complete CABG revascularization is superior to incomplete revascularization. Discriminating between variable definitions of “complete” complicates interpretation of survival data. We aimed to clarify octogenarian long-term survival rates by stratifying revascularization subtypes. Methods and Results From 1986 to 2007, 580 patients 80 to 94 years of age underwent CABG. Functional complete revascularization was defined as at least one graft to all diseased coronary vessels with greater than 50% stenosis. Traditional complete revascularization was defined as one graft to each major arterial system with at least 50% stenosis. Incomplete revascularization was defined as leaving diseased, ungrafted regions. Revascularization was functional in 279 (48%), traditional in 181 (31%), and incomplete in 120 (21%). Long-term survival was evaluated by Kaplan-Meier analysis. Of 537 operative survivors, there were 402 late deaths. Cumulative long-term survival totaled 2,890 patient-years. Late survival (Kaplan-Meier) was similar between functional (6.8 years, mean) and traditional (6.7 years) groups (p=0.51), but diminished with incomplete (4.2 years) revascularization (p=0.007). Survival by group at 5 years was: 59±3% functional, 57±4% traditional, and 45±5% incomplete. Survival at 8 years was: 40±3% functional, 37±4% traditional, and 26±5% incomplete. To minimize selection bias in patients with limited life expectancy, Kaplan-Meier analysis was repeated including only patients with survival greater than 12 months. Survival was again impaired with incomplete revascularization (p=0.04), and there was no difference between functional and traditional complete revascularization (p=0.73). Conclusions Bypassing all diseased arterial vessels after revascularization does not afford significant long-term survival advantage compared to a traditional approach. Incomplete revascularization, related to more extensive disease, is associated with an 18% decline in survival. These data suggest that it is important to avoid incomplete revascularization in octogenarians, but the supplementary endeavor required to perform functional complete revascularization does not improve survival. PMID:19752388

Bears in a forest of gene trees: phylogenetic inference is complicated by incomplete lineage sorting and gene flow.

PubMed

Kutschera, Verena E; Bidon, Tobias; Hailer, Frank; Rodi, Julia L; Fain, Steven R; Janke, Axel

2014-08-01

Ursine bears are a mammalian subfamily that comprises six morphologically and ecologically distinct extant species. Previous phylogenetic analyses of concatenated nuclear genes could not resolve all relationships among bears, and appeared to conflict with the mitochondrial phylogeny. Evolutionary processes such as incomplete lineage sorting and introgression can cause gene tree discordance and complicate phylogenetic inferences, but are not accounted for in phylogenetic analyses of concatenated data. We generated a high-resolution data set of autosomal introns from several individuals per species and of Y-chromosomal markers. Incorporating intraspecific variability in coalescence-based phylogenetic and gene flow estimation approaches, we traced the genealogical history of individual alleles. Considerable heterogeneity among nuclear loci and discordance between nuclear and mitochondrial phylogenies were found. A species tree with divergence time estimates indicated that ursine bears diversified within less than 2 My. Consistent with a complex branching order within a clade of Asian bear species, we identified unidirectional gene flow from Asian black into sloth bears. Moreover, gene flow detected from brown into American black bears can explain the conflicting placement of the American black bear in mitochondrial and nuclear phylogenies. These results highlight that both incomplete lineage sorting and introgression are prominent evolutionary forces even on time scales up to several million years. Complex evolutionary patterns are not adequately captured by strictly bifurcating models, and can only be fully understood when analyzing multiple independently inherited loci in a coalescence framework. Phylogenetic incongruence among gene trees hence needs to be recognized as a biologically meaningful signal. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

OGLE-2012-BLG-0455/MOA-2012-BLG-206: Microlensing event with ambiguity in planetary interpretations caused by incomplete coverage of planetary signal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, H.; Han, C.; Choi, J.-Y.

2014-05-20

Characterizing a microlensing planet is done by modeling an observed lensing light curve. In this process, it is often confronted that solutions of different lensing parameters result in similar light curves, causing difficulties in uniquely interpreting the lens system, and thus understanding the causes of different types of degeneracy is important. In this work, we show that incomplete coverage of a planetary perturbation can result in degenerate solutions even for events where the planetary signal is detected with a high level of statistical significance. We demonstrate the degeneracy for an actually observed event OGLE-2012-BLG-0455/MOA-2012-BLG-206. The peak of this high-magnification eventmore » (A {sub max} ∼ 400) exhibits very strong deviation from a point-lens model with Δχ{sup 2} ≳ 4000 for data sets with a total of 6963 measurements. From detailed modeling of the light curve, we find that the deviation can be explained by four distinct solutions, i.e., two very different sets of solutions, each with a twofold degeneracy. While the twofold (so-called close/wide) degeneracy is well understood, the degeneracy between the radically different solutions is not previously known. The model light curves of this degeneracy differ substantially in the parts that were not covered by observation, indicating that the degeneracy is caused by the incomplete coverage of the perturbation. It is expected that the frequency of the degeneracy introduced in this work will be greatly reduced with the improvement of the current lensing survey and follow-up experiments and the advent of new surveys.« less

Reporting standards for Bland-Altman agreement analysis in laboratory research: a cross-sectional survey of current practice.

PubMed

Chhapola, Viswas; Kanwal, Sandeep Kumar; Brar, Rekha

2015-05-01

To carry out a cross-sectional survey of the medical literature on laboratory research papers published later than 2012 and available in the common search engines (PubMed, Google Scholar) on the quality of statistical reporting of method comparison studies using Bland-Altman (B-A) analysis. Fifty clinical studies were identified which had undertaken method comparison of laboratory analytes using B-A. The reporting of B-A was evaluated using a predesigned checklist with following six items: (1) correct representation of x-axis on B-A plot, (2) representation and correct definition of limits of agreement (LOA), (3) reporting of confidence interval (CI) of LOA, (4) comparison of LOA with a priori defined clinical criteria, (5) evaluation of the pattern of the relationship between difference (y-axis) and average (x-axis) and (6) measures of repeatability. The x-axis and LOA were presented correctly in 94%, comparison with a priori clinical criteria in 74%, CI reporting in 6%, evaluation of pattern in 28% and repeatability assessment in 38% of studies. There is incomplete reporting of B-A in published clinical studies. Despite its simplicity, B-A appears not to be completely understood by researchers, reviewers and editors of journals. There appear to be differences in the reporting of B-A between laboratory medicine journals and other clinical journals. A uniform reporting of B-A method will enhance the generalizability of results. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Medicolegal diagnostic value and clinical significance of traumatic incomplete tears of the basilar artery.

PubMed

Djokic, Vesna; Savic, Slobodan; Atanasijevic, Tatjana

2003-06-01

Ruptures of arteries of the vertebrobasilary system are relatively frequent in medicolegal practice, and their origin may be both natural and violent. Tears that affects the whole thickness of the basilar artery cause subarachnoid hemorrhage (SAH), with an often rapid fatal outcome. 1-3 However, in some situations, arterial tears may be incomplete, involving the intima or both the intima and the media, but with preserved adventitia. 1, 4 Although such incomplete tears are not the source of immediate subarachnoid bleeding, their presence may be important from both a medicolegal and a clinical point of view. The aim of this article is to point out the significance of incomplete tears of basilar artery as a possible diagnostic sign of traumatic origin of SAH as well as a certain mechanism of injury, which involves forcible hyperextension and rotational movements of the head. The authors also describe their method of performing longitudinal section of the basilar artery, both at autopsy and for histologic examination, which is convenient for identifying multiple transversal incomplete tears of this blood vessel. The article is based on the analysis of three cases from the autopsy material of the Institute of Forensic Medicine in Belgrade.

Reverse Engineering Validation using a Benchmark Synthetic Gene Circuit in Human Cells

PubMed Central

Kang, Taek; White, Jacob T.; Xie, Zhen; Benenson, Yaakov; Sontag, Eduardo; Bleris, Leonidas

2013-01-01

Multi-component biological networks are often understood incompletely, in large part due to the lack of reliable and robust methodologies for network reverse engineering and characterization. As a consequence, developing automated and rigorously validated methodologies for unraveling the complexity of biomolecular networks in human cells remains a central challenge to life scientists and engineers. Today, when it comes to experimental and analytical requirements, there exists a great deal of diversity in reverse engineering methods, which renders the independent validation and comparison of their predictive capabilities difficult. In this work we introduce an experimental platform customized for the development and verification of reverse engineering and pathway characterization algorithms in mammalian cells. Specifically, we stably integrate a synthetic gene network in human kidney cells and use it as a benchmark for validating reverse engineering methodologies. The network, which is orthogonal to endogenous cellular signaling, contains a small set of regulatory interactions that can be used to quantify the reconstruction performance. By performing successive perturbations to each modular component of the network and comparing protein and RNA measurements, we study the conditions under which we can reliably reconstruct the causal relationships of the integrated synthetic network. PMID:23654266

Reverse engineering validation using a benchmark synthetic gene circuit in human cells.

PubMed

Kang, Taek; White, Jacob T; Xie, Zhen; Benenson, Yaakov; Sontag, Eduardo; Bleris, Leonidas

2013-05-17

Multicomponent biological networks are often understood incompletely, in large part due to the lack of reliable and robust methodologies for network reverse engineering and characterization. As a consequence, developing automated and rigorously validated methodologies for unraveling the complexity of biomolecular networks in human cells remains a central challenge to life scientists and engineers. Today, when it comes to experimental and analytical requirements, there exists a great deal of diversity in reverse engineering methods, which renders the independent validation and comparison of their predictive capabilities difficult. In this work we introduce an experimental platform customized for the development and verification of reverse engineering and pathway characterization algorithms in mammalian cells. Specifically, we stably integrate a synthetic gene network in human kidney cells and use it as a benchmark for validating reverse engineering methodologies. The network, which is orthogonal to endogenous cellular signaling, contains a small set of regulatory interactions that can be used to quantify the reconstruction performance. By performing successive perturbations to each modular component of the network and comparing protein and RNA measurements, we study the conditions under which we can reliably reconstruct the causal relationships of the integrated synthetic network.

Exploring astrobiology using in silico molecular structure generation.

PubMed

Meringer, Markus; Cleaves, H James

2017-12-28

The origin of life is typically understood as a transition from inanimate or disorganized matter to self-organized, 'animate' matter. This transition probably took place largely in the context of organic compounds, and most approaches, to date, have focused on using the organic chemical composition of modern organisms as the main guide for understanding this process. However, it has gradually come to be appreciated that biochemistry, as we know it, occupies a minute volume of the possible organic 'chemical space'. As the majority of abiotic syntheses appear to make a large set of compounds not found in biochemistry, as well as an incomplete subset of those that are, it is possible that life began with a significantly different set of components. Chemical graph-based structure generation methods allow for exhaustive in silico enumeration of different compound types and different types of 'chemical spaces' beyond those used by biochemistry, which can be explored to help understand the types of compounds biology uses, as well as to understand the nature of abiotic synthesis, and potentially design novel types of living systems.This article is part of the themed issue 'Reconceptualizing the origins of life'. © 2017 The Authors.

Exploring astrobiology using in silico molecular structure generation

NASA Astrophysics Data System (ADS)

Meringer, Markus; Cleaves, H. James

2017-11-01

The origin of life is typically understood as a transition from inanimate or disorganized matter to self-organized, `animate' matter. This transition probably took place largely in the context of organic compounds, and most approaches, to date, have focused on using the organic chemical composition of modern organisms as the main guide for understanding this process. However, it has gradually come to be appreciated that biochemistry, as we know it, occupies a minute volume of the possible organic `chemical space'. As the majority of abiotic syntheses appear to make a large set of compounds not found in biochemistry, as well as an incomplete subset of those that are, it is possible that life began with a significantly different set of components. Chemical graph-based structure generation methods allow for exhaustive in silico enumeration of different compound types and different types of `chemical spaces' beyond those used by biochemistry, which can be explored to help understand the types of compounds biology uses, as well as to understand the nature of abiotic synthesis, and potentially design novel types of living systems. This article is part of the themed issue 'Reconceptualizing the origins of life'.

Shopping Problems among High School Students

PubMed Central

Grant, Jon E.; Potenza, Marc N.; Krishnan-Sarin, Suchitra; Cavallo, Dana A.; Desai, Rani A.

2010-01-01

Background Although shopping behavior among adolescents is normal, for some the shopping becomes problematic. An assessment of adolescent shopping behavior along a continuum of severity and its relationship to other behaviors and health issues is incompletely understood. Methods A large sample of high school students (n=3999) was examined using a self-report survey with 153 questions concerning demographic characteristics, shopping behaviors, other health behaviors including substance use, and functioning variables such as grades and violent behavior. Results The overall prevalence of problem shopping was 3.5% (95%CI: 2.93–4.07). Regular smoking, marijuana and other drug use, sadness and hopelessness, and antisocial behaviors (e.g., fighting, carrying weapons) were associated with problem shopping behavior in both boys and girls. Heavy alcohol use was significantly associated with problem shopping only in girls. Conclusion Problem shopping appears fairly common among high school students and is associated with symptoms of depression and a range of potentially addictive and antisocial behaviors. Significant distress and diminished behavioral control suggest that excessive shopping may often have significant associated morbidity. Additional research is needed to develop specific prevention and treatment strategies for adolescents who report problems with shopping. PMID:21497217

Prediction of microRNA target genes using an efficient genetic algorithm-based decision tree.

PubMed

Rabiee-Ghahfarrokhi, Behzad; Rafiei, Fariba; Niknafs, Ali Akbar; Zamani, Behzad

2015-01-01

MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression in almost all plants and animals. They play an important role in key processes, such as proliferation, apoptosis, and pathogen-host interactions. Nevertheless, the mechanisms by which miRNAs act are not fully understood. The first step toward unraveling the function of a particular miRNA is the identification of its direct targets. This step has shown to be quite challenging in animals primarily because of incomplete complementarities between miRNA and target mRNAs. In recent years, the use of machine-learning techniques has greatly increased the prediction of miRNA targets, avoiding the need for costly and time-consuming experiments to achieve miRNA targets experimentally. Among the most important machine-learning algorithms are decision trees, which classify data based on extracted rules. In the present work, we used a genetic algorithm in combination with C4.5 decision tree for prediction of miRNA targets. We applied our proposed method to a validated human datasets. We nearly achieved 93.9% accuracy of classification, which could be related to the selection of best rules.

Prediction of microRNA target genes using an efficient genetic algorithm-based decision tree

PubMed Central

Rabiee-Ghahfarrokhi, Behzad; Rafiei, Fariba; Niknafs, Ali Akbar; Zamani, Behzad

2015-01-01

MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression in almost all plants and animals. They play an important role in key processes, such as proliferation, apoptosis, and pathogen–host interactions. Nevertheless, the mechanisms by which miRNAs act are not fully understood. The first step toward unraveling the function of a particular miRNA is the identification of its direct targets. This step has shown to be quite challenging in animals primarily because of incomplete complementarities between miRNA and target mRNAs. In recent years, the use of machine-learning techniques has greatly increased the prediction of miRNA targets, avoiding the need for costly and time-consuming experiments to achieve miRNA targets experimentally. Among the most important machine-learning algorithms are decision trees, which classify data based on extracted rules. In the present work, we used a genetic algorithm in combination with C4.5 decision tree for prediction of miRNA targets. We applied our proposed method to a validated human datasets. We nearly achieved 93.9% accuracy of classification, which could be related to the selection of best rules. PMID:26649272

Management of incomplete abortion in South African public hospitals.

PubMed

Brown, H C; Jewkes, R; Levin, J; Dickson-Tetteh, K; Rees, H

2003-04-01

To describe the current management of incomplete abortion in South African public hospitals and to discuss the extent to which management is clinically appropriate. A multicentre, prospective descriptive study. South African public hospitals that manage gynaecological emergencies. Hospitals were selected using a stratified random sampling method. All women who presented to the above sampled hospitals with incomplete abortion during the three week data collection period in 2000 were included. A data collection sheet was completed at the time of discharge for each woman admitted with a diagnosis of incomplete, complete, missed or inevitable abortion during the study period. Information gathered included demographic data, clinical signs and symptoms at admission, medical management, surgical management, anaestetic management, use of blood products and antibiotics and complications. Three clinical severity categories were used for the purpose of data analysis and interpretation. Detail of medical management, detail of surgical management, use of blood products and antibiotics, methods of analgesia and anaesthesia used, and use of abortifacients. There is a trend towards low cost technology such as the use of manual vacuum aspiration and sedation anaesthesia; however, this is mainly limited to the better resourced tertiary hospitals linked to academic units. The use of antibiotics and blood products has decreased but much of the use is inappropriate. The use of abortifacients does include some use of misoprostol but merely as an adjunct to surgical evacuation. The management of incomplete abortion remains a problem in South Africa, a low income country that is still managing a common clinical problem with costly interventions. The evidence of a trend towards low cost technology is promising, albeit limited to tertiary centres. This study has given us information as how to best address this problem. More training in low cost methods is needed, targeting in particular the district and regional hospitals, and reinforced by skills training focussed mainly on undergraduates and midwife post-abortion care programmes.

Simulation-Based Evaluation of Hybridization Network Reconstruction Methods in the Presence of Incomplete Lineage Sorting

PubMed Central

Kamneva, Olga K; Rosenberg, Noah A

2017-01-01

Hybridization events generate reticulate species relationships, giving rise to species networks rather than species trees. We report a comparative study of consensus, maximum parsimony, and maximum likelihood methods of species network reconstruction using gene trees simulated assuming a known species history. We evaluate the role of the divergence time between species involved in a hybridization event, the relative contributions of the hybridizing species, and the error in gene tree estimation. When gene tree discordance is mostly due to hybridization and not due to incomplete lineage sorting (ILS), most of the methods can detect even highly skewed hybridization events between highly divergent species. For recent divergences between hybridizing species, when the influence of ILS is sufficiently high, likelihood methods outperform parsimony and consensus methods, which erroneously identify extra hybridizations. The more sophisticated likelihood methods, however, are affected by gene tree errors to a greater extent than are consensus and parsimony. PMID:28469378

Interaction between colloidal particles on an oil-water interface in dilute and dense phases.

PubMed

Parolini, Lucia; Law, Adam D; Maestro, Armando; Buzza, D Martin A; Cicuta, Pietro

2015-05-20

The interaction between micron-sized charged colloidal particles at polar/non-polar liquid interfaces remains surprisingly poorly understood for a relatively simple physical chemistry system. By measuring the pair correlation function g(r) for different densities of polystyrene particles at the decane-water interface, and using a powerful predictor-corrector inversion scheme, effective pair-interaction potentials can be obtained up to fairly high densities, and these reproduce the experimental g(r) in forward simulations, so are self consistent. While at low densities these potentials agree with published dipole-dipole repulsion, measured by various methods, an apparent density dependence and long range attraction are obtained when the density is higher. This condition is thus explored in an alternative fashion, measuring the local mobility of colloids when confined by their neighbors. This method of extracting interaction potentials gives results that are consistent with dipolar repulsion throughout the concentration range, with the same magnitude as in the dilute limit. We are unable to rule out the density dependence based on the experimental accuracy of our data, but we show that incomplete equilibration of the experimental system, which would be possible despite long waiting times due to the very strong repulsions, is a possible cause of artefacts in the inverted potentials. We conclude that to within the precision of these measurements, the dilute pair potential remains valid at high density in this system.

Intimal and medial contributions to the hydraulic resistance of the arterial wall at different pressures: a combined computational and experimental study.

PubMed

Chooi, K Y; Comerford, A; Sherwin, S J; Weinberg, P D

2016-06-01

The hydraulic resistances of the intima and media determine water flux and the advection of macromolecules into and across the arterial wall. Despite several experimental and computational studies, these transport processes and their dependence on transmural pressure remain incompletely understood. Here, we use a combination of experimental and computational methods to ascertain how the hydraulic permeability of the rat abdominal aorta depends on these two layers and how it is affected by structural rearrangement of the media under pressure. Ex vivo experiments determined the conductance of the whole wall, the thickness of the media and the geometry of medial smooth muscle cells (SMCs) and extracellular matrix (ECM). Numerical methods were used to compute water flux through the media. Intimal values were obtained by subtraction. A mechanism was identified that modulates pressure-induced changes in medial transport properties: compaction of the ECM leading to spatial reorganization of SMCs. This is summarized in an empirical constitutive law for permeability and volumetric strain. It led to the physiologically interesting observation that, as a consequence of the changes in medial microstructure, the relative contributions of the intima and media to the hydraulic resistance of the wall depend on the applied pressure; medial resistance dominated at pressures above approximately 93 mmHg in this vessel. © 2016 The Authors.

Proviral Latency, Persistent Human Immunodeficiency Virus Infection, and the Development of Latency Reversing Agents

PubMed Central

Archin, Nancie M.

2017-01-01

Abstract Quiescent proviral genomes that persist during human immunodeficiency virus type 1 (HIV-1) infection despite effective antiretroviral therapy (ART) can fuel rebound viremia after ART interruption and is a central obstacle to the cure of HIV infection. The induction of quiescent provirus is the goal of a new class of potential therapeutics, latency reversing agents (LRAs). The discovery, development, and testing of HIV LRAs is a key part of current efforts to develop latency reversal and viral clearance strategies to eradicate established HIV infection. The development of LRAs is burdened by many uncertainties that make drug discovery difficult. The biology of HIV latency is complex and incompletely understood. Potential targets for LRAs are host factors, and the potential toxicities of host-directed therapies in individuals that are otherwise clinically stable may be unacceptable. Assays to measure latency reversal and assess the effectiveness of potential therapeutics are complex and incompletely validated. Despite these obstacles, novel LRAs are under development and beginning to enter combination testing with viral clearance strategies. It is hoped that the steady advances in the development of LRAs now being paired with emerging immunotherapeutics to clear persistently infected cells will soon allow measurable clinical advances toward an HIV cure. PMID:28520964

Diagnoses of Depression and Anxiety Versus Current Symptoms and Quality of Life in Multiple Sclerosis.

PubMed

Marrie, Ruth Ann; Patten, Scott B; Berrigan, Lindsay I; Tremlett, Helen; Wolfson, Christina; Warren, Sharon; Leung, Stella; Fiest, Kirsten M; McKay, Kyla A; Fisk, John D

2018-01-01

Studies assessing the prevalence of depression and anxiety in multiple sclerosis (MS) have used various ascertainment methods that capture different constructs. The relationships between these methods are incompletely understood. Psychiatric comorbidity is associated with lower health-related quality of life (HRQOL) in MS, but the effects of past diagnoses of depression and anxiety on HRQOL are largely unknown. We compared the prevalence of depression and anxiety in persons with MS using administrative data, self-reported physician diagnoses, and symptom-based measures and compared characteristics of persons classified as depressed or anxious by each method. We evaluated whether HRQOL was most affected by previous diagnoses of depression or anxiety or by current symptoms. We linked clinical and administrative data for 859 participants with MS. HRQOL was measured by the Health Utilities Index Mark 3. We classified participants as depressed or anxious using administrative data, self-reported physician diagnoses, and the Hospital Anxiety and Depression Scale. Multivariable linear regression examined whether diagnosed depression or anxiety affected HRQOL after accounting for current symptoms. Lifetime prevalence estimates for depression were approximately 30% regardless of methods used, but 35.8% with current depressive symptoms were not captured by either administrative data or self-reported diagnoses. Prevalence estimates of anxiety ranged from 11% to 19%, but 65.6% with current anxiety were not captured by either administrative data or self-reported diagnoses. Previous diagnoses did not decrease HRQOL after accounting for current symptoms. Depression and, to a greater extent, anxiety remain underdiagnosed and undertreated in MS; both substantially contribute to reduced HRQOL in MS.

Investigation of complete and incomplete fusion in the 7Li+124Sn reaction near Coulomb barrier energies

NASA Astrophysics Data System (ADS)

Parkar, V. V.; Sharma, Sushil K.; Palit, R.; Upadhyaya, S.; Shrivastava, A.; Pandit, S. K.; Mahata, K.; Jha, V.; Santra, S.; Ramachandran, K.; Nag, T. N.; Rath, P. K.; Kanagalekar, Bhushan; Trivedi, T.

2018-01-01

The complete and incomplete fusion cross sections for the 7Li+124Sn reaction were measured using online and offline characteristic γ -ray detection techniques. The complete fusion (CF) cross sections at energies above the Coulomb barrier were found to be suppressed by ˜26 % compared to the coupled channel calculations. This suppression observed in complete fusion cross sections is found to be commensurate with the measured total incomplete fusion (ICF) cross sections. There is a distinct feature observed in the ICF cross sections, i.e., t capture is found to be dominant compared to α capture at all the measured energies. A simultaneous explanation of complete, incomplete, and total fusion (TF) data was also obtained from the calculations based on the continuum discretized coupled channel method with short range imaginary potentials. The cross section ratios of CF/TF and ICF/TF obtained from the data as well as the calculations showed the dominance of ICF at below-barrier energies and CF at above-barrier energies.

Recruitment of human aquaporin 3 to internal membranes in the Plasmodium falciparum infected erythrocyte.

PubMed

Bietz, Sven; Montilla, Irine; Külzer, Simone; Przyborski, Jude M; Lingelbach, Klaus

2009-09-01

The molecular mechanisms underlying the formation of the parasitophorous vacuolar membrane in Plasmodium falciparum infected erythrocytes are incompletely understood, and the protein composition of this membrane is still enigmatic. Although the differentiated mammalian erythrocyte lacks the machinery required for endocytosis, some reports have described a localisation of host cell membrane proteins at the parasitophorous vacuolar membrane. Aquaporin 3 is an abundant plasma membrane protein of various cells, including mammalian erythrocytes where it is found in distinct oligomeric states. Here we show that human aquaporin 3 is internalized into infected erythrocytes, presumably during or soon after invasion. It is integrated into the PVM where it is organized in novel oligomeric states which are not found in non-infected cells.

Gut failure in critical care: old school versus new school

PubMed Central

Sertaridou, Eleni; Papaioannou, Vasilios; Kolios, George; Pneumatikos, Ioannis

2015-01-01

The concept of bacterial translocation and gut-origin sepsis as causes of systemic infectious complications and multiple organ deficiency syndrome in surgical and critically ill patients has been a recurring issue over the last decades attracting the scientific interest. Although gastrointestinal dysfunction seemingly arises frequently in intensive care unit patients, it is usually underdiagnosed or underestimated, because the pathophysiology involved is incompletely understood and its exact clinical relevance still remains controversial with an unknown yet probably adverse impact on the patients’ outcome. The purpose of this review is to define gut-origin sepsis and related terms, to describe the mechanisms leading to gut-derived complications, and to illustrate the therapeutic options to prevent or limit these untoward processes. PMID:26130136

Mei-P26 Cooperates with Bam, Bgcn and Sxl to Promote Early Germline Development in the Drosophila Ovary

PubMed Central

Li, Yun; Zhang, Qiao; Carreira-Rosario, Arnaldo; Maines, Jean Z.; McKearin, Dennis M.; Buszczak, Michael

2013-01-01

In the Drosophila female germline, spatially and temporally specific translation of mRNAs governs both stem cell maintenance and the differentiation of their progeny. However, the mechanisms that control and coordinate different modes of translational repression within this lineage remain incompletely understood. Here we present data showing that Mei-P26 associates with Bam, Bgcn and Sxl and nanos mRNA during early cyst development, suggesting that this protein helps to repress the translation of nanos mRNA. Together with recently published studies, these data suggest that Mei-P26 mediates both GSC self-renewal and germline differentiation through distinct modes of translational repression depending on the presence of Bam. PMID:23526974

The importance of pro-inflammatory signaling in neonatal NEC

PubMed Central

Frost, Brandy L.; Jilling, Tamas; Caplan, Michael S.

2008-01-01

Despite modern medical advances, necrotizing enterocolitis (NEC) remains a significant cause of morbidity and mortality in neonatal intensive care units, affecting 10 percent of premature neonates born weighing less than 1500 grams. Although many advances have been made in the understanding of this disease, the etiology and pathophysiology remain incompletely understood, and treatment is limited to supportive care. In recent years, studies have focused on the role of the inflammatory cascade and its’ impact on the disease process, and investigators are evaluating strategies to attenuate inflammatory signaling that might prevent and/or ameliorate neonatal NEC. In this review, we examine the key points in the signaling pathways involved in NEC, and potential strategies for prevention and treatment of this dreaded disease. PMID:18346533

Anemia and heart failure: a cause of progression or only a consequence?

PubMed Central

METRA, MARCO; NODARI, SAVINA; BORDONALI, TANIA; BUGATTI, SILVIA; FONTANELLA, BENEDETTA; LOMBARDI, CARLO; SAPORETTI, ALBERTO; VERZURA, GIULIA; DANESI, ROSSELLA; DEI CAS, LIVIO

2007-01-01

Anemia is one of the most frequent co-morbidities in the patients with heart failure. Its prevalence increases from 4–7% in the subjects with asymptomatic left ventricular dysfunction to >30% in the patients with severe heart failure. Renal insufficiency, activation of inflammatory mediators, and treatment with renin-angiotensin antagonists seem to be its main determinants. The results of many studies agree in showing that anemia is a powerful independent determinant of survival in patients with heart failure. However, the mechanisms of this relation are still incompletely understood. Moreover a favourable effect on prognosis of the correction of anemia has not been shown, yet, and also controlled studies assessing its effects on exercise tolerance have yielded controversial results. PMID:21977269

Drowning stars: Reassessing the role of astrocytes in brain edema

PubMed Central

Thrane, Alexander S.; Thrane, Vinita Rangroo; Nedergaard, Maiken

2014-01-01

Edema formation frequently complicates brain infarction, tumors and trauma. Despite the significant mortality of this condition, current treatment options are often ineffective or incompletely understood. Recent studies have revealed the existence of a brain-wide paravascular pathway for cerebrospinal (CSF) and interstitial fluid (ISF) exchange. The current review critically examines the contribution of this ‘glymphatic’ system to the main types of brain edema. We propose that in cytotoxic edema, energy depletion enhances glymphatic CSF influx, whilst suppressing ISF efflux. We also argue that paravascular inflammation or ‘paravasculitis’ plays a critical role in vasogenic edema. Finally, recent advances in diagnostic imaging of glymphatic function may hold the key to defining the edema profile of individual patients and thus enable more targeted therapy. PMID:25236348

Programming of Essential Hypertension: What Pediatric Cardiologists Need to Know.

PubMed

Morgado, Joana; Sanches, Bruno; Anjos, Rui; Coelho, Constança

2015-10-01

Hypertension is recognized as one of the major contributing factors to cardiovascular disease, but its etiology remains incompletely understood. Known genetic and environmental influences can only explain a small part of the variability in cardiovascular disease risk. The missing heritability is currently one of the most important challenges in blood pressure and hypertension genetics. Recently, some promising approaches have emerged that move beyond the DNA sequence and focus on identification of blood pressure genes regulated by epigenetic mechanisms such as DNA methylation, histone modification and microRNAs. This review summarizes information on gene-environmental interactions that lead toward the developmental programming of hypertension with specific reference to epigenetics and provides pediatricians and pediatric cardiologists with a more complete understanding of its pathogenesis.

Chromatin Constrains the Initiation and Elongation of DNA Replication.

PubMed

Devbhandari, Sujan; Jiang, Jieqing; Kumar, Charanya; Whitehouse, Iestyn; Remus, Dirk

2017-01-05

Eukaryotic chromosomal DNA is faithfully replicated in a complex series of cell-cycle-regulated events that are incompletely understood. Here we report the reconstitution of DNA replication free in solution with purified proteins from the budding yeast Saccharomyces cerevisiae. The system recapitulates regulated bidirectional origin activation; synthesis of leading and lagging strands by the three replicative DNA polymerases Pol α, Pol δ, and Pol ε; and canonical maturation of Okazaki fragments into continuous daughter strands. We uncover a dual regulatory role for chromatin during DNA replication: promoting origin dependence and determining Okazaki fragment length by restricting Pol δ progression. This system thus provides a functional platform for the detailed mechanistic analysis of eukaryotic chromosome replication. Copyright © 2017 Elsevier Inc. All rights reserved.

Diabetic cardiomyopathy: Where are we 40 years later?

PubMed Central

Sharma, Vijay; McNeill, John H

2006-01-01

Diabetic cardiomyopathy is a cardiac disease that arises as a result of the diabetic state, independent of vascular or valvular pathology. It manifests initially as asymptomatic diastolic dysfunction, which progresses to symptomatic heart failure. The compliance of the heart wall is decreased and contractile function is impaired. The pathophysiology is incompletely understood, but appears to be initiated both by hyperglycemia and changes in cardiac metabolism. These changes induce oxidative stress and activate a number of secondary messenger pathways, leading to cardiac hypertrophy, fibrosis and cell death. Alterations in contractile proteins and intracellular ions impair excitation-contraction coupling, while decreased autonomic responsiveness and autonomic neuropathy impair its regulation. Extensive structural abnormalities also occur, which have deleterious mechanical and functional consequences. PMID:16568154

Interleukin-22 Signaling in the Regulation of Intestinal Health and Disease

PubMed Central

Parks, Olivia B.; Pociask, Derek A.; Hodzic, Zerina; Kolls, Jay K.; Good, Misty

2016-01-01

Interleukin (IL)-22 is a member of the IL-10 family of cytokines that has been extensively studied since its discovery in 2000. This review article aims to describe the cellular sources and signaling pathways of this cytokine as well as the functions of IL-22 in the intestine. In addition, this article describes the roles of IL-22 in the pathogenesis of several gastrointestinal diseases, including inhibition of inflammation and barrier defense against pathogens within the intestine. Since many of the functions of IL-22 in the intestine are incompletely understood, this review is meant to assess our current understanding of the roles of IL-22 and provide new opportunities for inquiry to improve human intestinal health and disease. PMID:26793707

A novel ALS-associated variant in UBQLN4 regulates motor axon morphogenesis.

PubMed

Edens, Brittany M; Yan, Jianhua; Miller, Nimrod; Deng, Han-Xiang; Siddique, Teepu; Ma, Yongchao C

2017-05-02

The etiological underpinnings of amyotrophic lateral sclerosis (ALS) are complex and incompletely understood, although contributions to pathogenesis by regulators of proteolytic pathways have become increasingly apparent. Here, we present a novel variant in UBQLN4 that is associated with ALS and show that its expression compromises motor axon morphogenesis in mouse motor neurons and in zebrafish. We further demonstrate that the ALS-associated UBQLN4 variant impairs proteasomal function, and identify the Wnt signaling pathway effector beta-catenin as a UBQLN4 substrate. Inhibition of beta-catenin function rescues the UBQLN4 variant-induced motor axon phenotypes. These findings provide a strong link between the regulation of axonal morphogenesis and a new ALS-associated gene variant mediated by protein degradation pathways.

“The Mind Is Its Own Place”: Amelioration of Claustrophobia in Semantic Dementia

PubMed Central

Clark, Camilla N.; Downey, Laura E.; Golden, Hannah L.; Fletcher, Phillip D.; Cifelli, Alberto; Warren, Jason D.

2014-01-01

Phobias are among the few intensely fearful experiences we regularly have in our everyday lives, yet the brain basis of phobic responses remains incompletely understood. Here we describe the case of a 71-year-old patient with a typical clinicoanatomical syndrome of semantic dementia led by selective (predominantly right-sided) temporal lobe atrophy, who showed striking amelioration of previously disabling claustrophobia following onset of her cognitive syndrome. We interpret our patient's newfound fearlessness as an interaction of damaged limbic and autonomic responsivity with loss of the cognitive meaning of previously threatening situations. This case has implications for our understanding of brain network disintegration in semantic dementia and the neurocognitive basis of phobias more generally. PMID:24825962

Repeated Assessments of Informed Consent Comprehension among HIV-Infected Participants of a Three-Year Clinical Trial in Botswana

PubMed Central

Chaisson, Lelia H.; Kass, Nancy E.; Chengeta, Bafanana; Mathebula, Unami; Samandari, Taraz

2011-01-01

Background Informed consent (IC) has been an international standard for decades for the ethical conduct of clinical trials. Yet frequently study participants have incomplete understanding of key issues, a problem exacerbated by language barriers or lack of familiarity with research concepts. Few investigators measure participant comprehension of IC, while even fewer conduct interim assessments once a trial is underway. Methods and Findings We assessed comprehension of IC using a 20-question true/false quiz administered in 6-month intervals in the context of a placebo-controlled, randomized trial for the prevention of tuberculosis among HIV-infected adults in Botswana (2004–2009). Quizzes were offered in both Setswana and English. To enroll in the TB trial, participants were required to have ≥16/20 correct responses. We examined concepts understood and the degree to which understanding changed over three-years. We analyzed 5,555 quizzes from 1,835 participants. The participants' highest education levels were: 28% primary, 59% secondary, 9% tertiary and 7% no formal education. Eighty percent of participants passed the enrollment quiz (Quiz1) on their first attempt and the remainder passed on their second attempt. Those having higher than primary education and those who took the quiz in English were more likely to receive a passing score on their first attempt (adjusted odds ratios and 95% confidence intervals, 3.1 (2.4–4.0) and 1.5 (1.2, 1.9), respectively). The trial's purpose or procedures were understood by 90–100% of participants, while 44–77% understood randomization, placebos, or risks. Participants who failed Quiz1 on their initial attempt were more likely to fail quizzes later in the trial. Pass rates improved with quiz re-administration in subsequent years. Conclusions Administration of a comprehension quiz at enrollment and during follow-up was feasible in a large, international collaboration and efficiently determined IC comprehension by trial participants. Strategies to improve understanding of concepts like placebos and randomization are needed. Comprehension assessments throughout a study may reinforce key concepts. PMID:22046230

Backfitting in Smoothing Spline Anova, with Application to Historical Global Temperature Data

NASA Astrophysics Data System (ADS)

Luo, Zhen

In the attempt to estimate the temperature history of the earth using the surface observations, various biases can exist. An important source of bias is the incompleteness of sampling over both time and space. There have been a few methods proposed to deal with this problem. Although they can correct some biases resulting from incomplete sampling, they have ignored some other significant biases. In this dissertation, a smoothing spline ANOVA approach which is a multivariate function estimation method is proposed to deal simultaneously with various biases resulting from incomplete sampling. Besides that, an advantage of this method is that we can get various components of the estimated temperature history with a limited amount of information stored. This method can also be used for detecting erroneous observations in the data base. The method is illustrated through an example of modeling winter surface air temperature as a function of year and location. Extension to more complicated models are discussed. The linear system associated with the smoothing spline ANOVA estimates is too large to be solved by full matrix decomposition methods. A computational procedure combining the backfitting (Gauss-Seidel) algorithm and the iterative imputation algorithm is proposed. This procedure takes advantage of the tensor product structure in the data to make the computation feasible in an environment of limited memory. Various related issues are discussed, e.g., the computation of confidence intervals and the techniques to speed up the convergence of the backfitting algorithm such as collapsing and successive over-relaxation.

Semi-Supervised Tripled Dictionary Learning for Standard-dose PET Image Prediction using Low-dose PET and Multimodal MRI

PubMed Central

Wang, Yan; Ma, Guangkai; An, Le; Shi, Feng; Zhang, Pei; Lalush, David S.; Wu, Xi; Pu, Yifei; Zhou, Jiliu; Shen, Dinggang

2017-01-01

Objective To obtain high-quality positron emission tomography (PET) image with low-dose tracer injection, this study attempts to predict the standard-dose PET (S-PET) image from both its low-dose PET (L-PET) counterpart and corresponding magnetic resonance imaging (MRI). Methods It was achieved by patch-based sparse representation (SR), using the training samples with a complete set of MRI, L-PET and S-PET modalities for dictionary construction. However, the number of training samples with complete modalities is often limited. In practice, many samples generally have incomplete modalities (i.e., with one or two missing modalities) that thus cannot be used in the prediction process. In light of this, we develop a semi-supervised tripled dictionary learning (SSTDL) method for S-PET image prediction, which can utilize not only the samples with complete modalities (called complete samples) but also the samples with incomplete modalities (called incomplete samples), to take advantage of the large number of available training samples and thus further improve the prediction performance. Results Validation was done on a real human brain dataset consisting of 18 subjects, and the results show that our method is superior to the SR and other baseline methods. Conclusion This work proposed a new S-PET prediction method, which can significantly improve the PET image quality with low-dose injection. Significance The proposed method is favorable in clinical application since it can decrease the potential radiation risk for patients. PMID:27187939

New Onset of Constipation during Long-Term Physical Inactivity: A Proof-of-Concept Study on the Immobility-Induced Bowel Changes

PubMed Central

Iovino, Paola; Chiarioni, Giuseppe; Bilancio, Giancarlo; Cirillo, Massimo; Mekjavic, Igor B.; Pisot, Rado; Ciacci, Carolina

2013-01-01

Background The pathophysiological mechanisms underlining constipation are incompletely understood, but prolonged bed rest is commonly considered a relevant determinant. Aims Our primary aim was to study the effect of long-term physical inactivity on determining a new onset of constipation. Secondary aim were the evaluation of changes in stool frequency, bowel function and symptoms induced by this prolonged physical inactivity. Methods Ten healthy men underwent a 7-day run-in followed by 35-day study of experimentally-controlled bed rest. The study was sponsored by the Italian Space Agency. The onset of constipation was evaluated according to Rome III criteria for functional constipation. Abdominal bloating, flatulence, pain and urgency were assessed by a 100mm Visual Analog Scales and bowel function by adjectival scales (Bristol Stool Form Scale, ease of passage of stool and sense of incomplete evacuation). Daily measurements of bowel movements was summarized on a weekly score. Pre and post bed rest Quality of Life (SF-36), general health (Goldberg’s General Health) and depression mood (Zung scale) questionnaires were administered. Results New onset of functional constipation fulfilling Rome III criteria was found in 60% (6/10) of participants (p=0.03). The score of flatulence significantly increased whilst the stool frequency significantly decreased during the week-by-week comparisons period (repeated-measures ANOVA, p=0.02 and p=0.001, respectively). Stool consistency and bowel symptoms were not influenced by prolonged physical inactivity. In addition, no significant changes were observed in general health, in mood state and in quality of life at the end of bed rest Conclusions Our results provide evidence that prolonged physical inactivity is relevant etiology in functional constipation in healthy individuals. The common clinical suggestion of early mobilization in bedridden patients is supported as well. PMID:23977327

Pak2 is required for actin cytoskeleton remodeling, TCR signaling, and normal thymocyte development and maturation

PubMed Central

Phee, Hyewon; Au-Yeung, Byron B; Pryshchep, Olga; O'Hagan, Kyle Leonard; Fairbairn, Stephanie Grace; Radu, Maria; Kosoff, Rachelle; Mollenauer, Marianne; Cheng, Debra; Chernoff, Jonathan; Weiss, Arthur

2014-01-01

The molecular mechanisms that govern thymocyte development and maturation are incompletely understood. The P21-activated kinase 2 (Pak2) is an effector for the Rho family GTPases Rac and Cdc42 that regulate actin cytoskeletal remodeling, but its role in the immune system remains poorly understood. In this study, we show that T-cell specific deletion of Pak2 gene in mice resulted in severe T cell lymphopenia accompanied by marked defects in development, maturation, and egress of thymocytes. Pak2 was required for pre-TCR β-selection and positive selection. Surprisingly, Pak2 deficiency in CD4 single positive thymocytes prevented functional maturation and reduced expression of S1P1 and KLF2. Mechanistically, Pak2 is required for actin cytoskeletal remodeling triggered by TCR. Failure to induce proper actin cytoskeletal remodeling impaired PLCγ1 and Erk1/2 signaling in the absence of Pak2, uncovering the critical function of Pak2 as an essential regulator that governs the actin cytoskeleton-dependent signaling to ensure normal thymocyte development and maturation. DOI: http://dx.doi.org/10.7554/eLife.02270.001 PMID:24843022

TOPSIS-based consensus model for group decision-making with incomplete interval fuzzy preference relations.

PubMed

Liu, Fang; Zhang, Wei-Guo

2014-08-01

Due to the vagueness of real-world environments and the subjective nature of human judgments, it is natural for experts to estimate their judgements by using incomplete interval fuzzy preference relations. In this paper, based on the technique for order preference by similarity to ideal solution method, we present a consensus model for group decision-making (GDM) with incomplete interval fuzzy preference relations. To do this, we first define a new consistency measure for incomplete interval fuzzy preference relations. Second, a goal programming model is proposed to estimate the missing interval preference values and it is guided by the consistency property. Third, an ideal interval fuzzy preference relation is constructed by using the induced ordered weighted averaging operator, where the associated weights of characterizing the operator are based on the defined consistency measure. Fourth, a similarity degree between complete interval fuzzy preference relations and the ideal one is defined. The similarity degree is related to the associated weights, and used to aggregate the experts' preference relations in such a way that more importance is given to ones with the higher similarity degree. Finally, a new algorithm is given to solve the GDM problem with incomplete interval fuzzy preference relations, which is further applied to partnership selection in formation of virtual enterprises.

Sparse reconstruction for quantitative bioluminescence tomography based on the incomplete variables truncated conjugate gradient method.

PubMed

He, Xiaowei; Liang, Jimin; Wang, Xiaorui; Yu, Jingjing; Qu, Xiaochao; Wang, Xiaodong; Hou, Yanbin; Chen, Duofang; Liu, Fang; Tian, Jie

2010-11-22

In this paper, we present an incomplete variables truncated conjugate gradient (IVTCG) method for bioluminescence tomography (BLT). Considering the sparse characteristic of the light source and insufficient surface measurement in the BLT scenarios, we combine a sparseness-inducing (ℓ1 norm) regularization term with a quadratic error term in the IVTCG-based framework for solving the inverse problem. By limiting the number of variables updated at each iterative and combining a variable splitting strategy to find the search direction more efficiently, it obtains fast and stable source reconstruction, even without a priori information of the permissible source region and multispectral measurements. Numerical experiments on a mouse atlas validate the effectiveness of the method. In vivo mouse experimental results further indicate its potential for a practical BLT system.

Bayesian Inference of Natural Rankings in Incomplete Competition Networks

PubMed Central

Park, Juyong; Yook, Soon-Hyung

2014-01-01

Competition between a complex system's constituents and a corresponding reward mechanism based on it have profound influence on the functioning, stability, and evolution of the system. But determining the dominance hierarchy or ranking among the constituent parts from the strongest to the weakest – essential in determining reward and penalty – is frequently an ambiguous task due to the incomplete (partially filled) nature of competition networks. Here we introduce the “Natural Ranking,” an unambiguous ranking method applicable to a round robin tournament, and formulate an analytical model based on the Bayesian formula for inferring the expected mean and error of the natural ranking of nodes from an incomplete network. We investigate its potential and uses in resolving important issues of ranking by applying it to real-world competition networks. PMID:25163528

Measuring treatment compliance of men with non-gonococcal urethritis receiving oxytetracycline combined with low dose phenobarbitone.

PubMed Central

Bignell, C J; Mulcahy, F M; Peaker, S; Pullar, T; Feely, M P

1988-01-01

Of 62 men with non-gonococcal urethritis who entered a study to assess compliance with treatment with oxytetracycline, only 33 could be evaluated. Traditional methods (interview and the absence of oxytetracycline in the urine) showed incomplete compliance in nine. Use of low dose phenobarbitone as a pharmacological marker showed incomplete compliance in a further five patients. In addition, phenobarbitone concentrations gave information on the extent to which individual patients had omitted treatment and provided direct, as opposed to circumstantial, evidence of good compliance by most (18) of those studied. Only three of the 33 patients whose compliance was assessed had evidence of continuing infection at follow up, and there was evidence of incomplete compliance in only one of these patients. PMID:3203931

Bayesian Inference of Natural Rankings in Incomplete Competition Networks

NASA Astrophysics Data System (ADS)

Park, Juyong; Yook, Soon-Hyung

2014-08-01

Competition between a complex system's constituents and a corresponding reward mechanism based on it have profound influence on the functioning, stability, and evolution of the system. But determining the dominance hierarchy or ranking among the constituent parts from the strongest to the weakest - essential in determining reward and penalty - is frequently an ambiguous task due to the incomplete (partially filled) nature of competition networks. Here we introduce the ``Natural Ranking,'' an unambiguous ranking method applicable to a round robin tournament, and formulate an analytical model based on the Bayesian formula for inferring the expected mean and error of the natural ranking of nodes from an incomplete network. We investigate its potential and uses in resolving important issues of ranking by applying it to real-world competition networks.

Weighted graph based ordering techniques for preconditioned conjugate gradient methods

NASA Technical Reports Server (NTRS)

Clift, Simon S.; Tang, Wei-Pai

1994-01-01

We describe the basis of a matrix ordering heuristic for improving the incomplete factorization used in preconditioned conjugate gradient techniques applied to anisotropic PDE's. Several new matrix ordering techniques, derived from well-known algorithms in combinatorial graph theory, which attempt to implement this heuristic, are described. These ordering techniques are tested against a number of matrices arising from linear anisotropic PDE's, and compared with other matrix ordering techniques. A variation of RCM is shown to generally improve the quality of incomplete factorization preconditioners.

A novel multisensor traffic state assessment system based on incomplete data.

PubMed

Zeng, Yiliang; Lan, Jinhui; Ran, Bin; Jiang, Yaoliang

2014-01-01

A novel multisensor system with incomplete data is presented for traffic state assessment. The system comprises probe vehicle detection sensors, fixed detection sensors, and traffic state assessment algorithm. First of all, the validity checking of the traffic flow data is taken as preprocessing of this method. And then a new method based on the history data information is proposed to fuse and recover the incomplete data. According to the characteristics of space complementary of data based on the probe vehicle detector and fixed detector, a fusion model of space matching is presented to estimate the mean travel speed of the road. Finally, the traffic flow data include flow, speed and, occupancy rate, which are detected between Beijing Deshengmen bridge and Drum Tower bridge, are fused to assess the traffic state of the road by using the fusion decision model of rough sets and cloud. The accuracy of experiment result can reach more than 98%, and the result is in accordance with the actual road traffic state. This system is effective to assess traffic state, and it is suitable for the urban intelligent transportation system.

A Novel Multisensor Traffic State Assessment System Based on Incomplete Data

PubMed Central

Zeng, Yiliang; Lan, Jinhui; Ran, Bin; Jiang, Yaoliang

2014-01-01

A novel multisensor system with incomplete data is presented for traffic state assessment. The system comprises probe vehicle detection sensors, fixed detection sensors, and traffic state assessment algorithm. First of all, the validity checking of the traffic flow data is taken as preprocessing of this method. And then a new method based on the history data information is proposed to fuse and recover the incomplete data. According to the characteristics of space complementary of data based on the probe vehicle detector and fixed detector, a fusion model of space matching is presented to estimate the mean travel speed of the road. Finally, the traffic flow data include flow, speed and, occupancy rate, which are detected between Beijing Deshengmen bridge and Drum Tower bridge, are fused to assess the traffic state of the road by using the fusion decision model of rough sets and cloud. The accuracy of experiment result can reach more than 98%, and the result is in accordance with the actual road traffic state. This system is effective to assess traffic state, and it is suitable for the urban intelligent transportation system. PMID:25162055

Results From Spain's 2016 Report Card on Physical Activity for Children and Youth.

PubMed

Roman-Viñas, Blanca; Marin, Jorge; Sánchez-López, Mairena; Aznar, Susana; Leis, Rosaura; Aparicio-Ugarriza, Raquel; Schroder, Helmut; Ortiz-Moncada, Rocío; Vicente, German; González-Gross, Marcela; Serra-Majem, Lluís

2016-11-01

The first Active Healthy Kids Spanish Report Card aims to gather the most robust information about physical activity (PA) and sedentary behavior of children and adolescents. A Research Working Group of experts on PA and sport sciences was convened. A comprehensive data search, based on a review of the literature, dissertations, gray literature, and experts' nonpublished data, was conducted to identify the best sources to grade each indicator following the procedures and methodology outlined by the Active Healthy Kids Canada Report Card model. Overall PA (based on objective and self-reported methods) was graded as D-, Organized Sports Participation as B, Active Play as C+, Active Transportation as C, Sedentary Behavior as D, School as C, and Family and Peers as Incomplete, Community and the Built Environment as Incomplete, and Government as Incomplete. Spanish children and adolescents showed low levels of adherence to PA and sedentary behavior guidelines, especially females and adolescents. There is a need to achieve consensus and harmonize methods to evaluate PA and sedentary behavior to monitor changes over time and to evaluate the effectiveness of policies to promote PA.

The Relative Effectiveness of Expository Methods of Teaching Science

ERIC Educational Resources Information Center

Babikian, Elijah

1973-01-01

Two methods of instruction (question-answer and question-incomplete-answer) are utilized in teaching a unit on thermal energy. Effectiveness, as measured by a posttest, confirmed significant differences in the two modes of instruction. (DF)

A consensus reaching model for 2-tuple linguistic multiple attribute group decision making with incomplete weight information

NASA Astrophysics Data System (ADS)

Zhang, Wancheng; Xu, Yejun; Wang, Huimin

2016-01-01

The aim of this paper is to put forward a consensus reaching method for multi-attribute group decision-making (MAGDM) problems with linguistic information, in which the weight information of experts and attributes is unknown. First, some basic concepts and operational laws of 2-tuple linguistic label are introduced. Then, a grey relational analysis method and a maximising deviation method are proposed to calculate the incomplete weight information of experts and attributes respectively. To eliminate the conflict in the group, a weight-updating model is employed to derive the weights of experts based on their contribution to the consensus reaching process. After conflict elimination, the final group preference can be obtained which will give the ranking of the alternatives. The model can effectively avoid information distortion which is occurred regularly in the linguistic information processing. Finally, an illustrative example is given to illustrate the application of the proposed method and comparative analysis with the existing methods are offered to show the advantages of the proposed method.

Surgical versus expectant management in women with an incomplete evacuation of the uterus after treatment with misoprostol for miscarriage: the MisoREST trial

PubMed Central

2013-01-01

Background Medical treatment with misoprostol is a non-invasive and inexpensive treatment option in first trimester miscarriage. However, about 30% of women treated with misoprostol have incomplete evacuation of the uterus. Despite being relatively asymptomatic in most cases, this finding often leads to additional surgical treatment (curettage). A comparison of effectiveness and cost-effectiveness of surgical management versus expectant management is lacking in women with incomplete miscarriage after misoprostol. Methods/Design The proposed study is a multicentre randomized controlled trial that assesses the costs and effects of curettage versus expectant management in women with incomplete evacuation of the uterus after misoprostol treatment for first trimester miscarriage. Eligible women will be randomized, after informed consent, within 24 hours after identification of incomplete evacuation of the uterus by ultrasound scanning. Women are randomly allocated to surgical or expectant management. Curettage is performed within three days after randomization. Primary outcome is the sonographic finding of an empty uterus (maximal diameter of any contents of the uterine cavity < 10 millimeters) six weeks after study entry. Secondary outcomes are patients’ quality of life, surgical outcome parameters, the type and number of re-interventions during the first three months and pregnancy rates and outcome 12 months after study entry. Discussion This trial will provide evidence for the (cost) effectiveness of surgical versus expectant management in women with incomplete evacuation of the uterus after misoprostol treatment for first trimester miscarriage. Trial registration Dutch Trial Register: NTR3110 PMID:23638956

Fitting models of continuous trait evolution to incompletely sampled comparative data using approximate Bayesian computation.

PubMed

Slater, Graham J; Harmon, Luke J; Wegmann, Daniel; Joyce, Paul; Revell, Liam J; Alfaro, Michael E

2012-03-01

In recent years, a suite of methods has been developed to fit multiple rate models to phylogenetic comparative data. However, most methods have limited utility at broad phylogenetic scales because they typically require complete sampling of both the tree and the associated phenotypic data. Here, we develop and implement a new, tree-based method called MECCA (Modeling Evolution of Continuous Characters using ABC) that uses a hybrid likelihood/approximate Bayesian computation (ABC)-Markov-Chain Monte Carlo approach to simultaneously infer rates of diversification and trait evolution from incompletely sampled phylogenies and trait data. We demonstrate via simulation that MECCA has considerable power to choose among single versus multiple evolutionary rate models, and thus can be used to test hypotheses about changes in the rate of trait evolution across an incomplete tree of life. We finally apply MECCA to an empirical example of body size evolution in carnivores, and show that there is no evidence for an elevated rate of body size evolution in the pinnipeds relative to terrestrial carnivores. ABC approaches can provide a useful alternative set of tools for future macroevolutionary studies where likelihood-dependent approaches are lacking. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

A novel deep learning algorithm for incomplete face recognition: Low-rank-recovery network.

PubMed

Zhao, Jianwei; Lv, Yongbiao; Zhou, Zhenghua; Cao, Feilong

2017-10-01

There have been a lot of methods to address the recognition of complete face images. However, in real applications, the images to be recognized are usually incomplete, and it is more difficult to realize such a recognition. In this paper, a novel convolution neural network frame, named a low-rank-recovery network (LRRNet), is proposed to conquer the difficulty effectively inspired by matrix completion and deep learning techniques. The proposed LRRNet first recovers the incomplete face images via an approach of matrix completion with the truncated nuclear norm regularization solution, and then extracts some low-rank parts of the recovered images as the filters. With these filters, some important features are obtained by means of the binaryzation and histogram algorithms. Finally, these features are classified with the classical support vector machines (SVMs). The proposed LRRNet method has high face recognition rate for the heavily corrupted images, especially for the images in the large databases. The proposed LRRNet performs well and efficiently for the images with heavily corrupted, especially in the case of large databases. Extensive experiments on several benchmark databases demonstrate that the proposed LRRNet performs better than some other excellent robust face recognition methods. Copyright © 2017 Elsevier Ltd. All rights reserved.

High-resolution imaging of the low velocity layer in Alaskan subduction zone with scattered waves and interferometry

NASA Astrophysics Data System (ADS)

Kim, D.; Keranen, K. M.; Abers, G. A.; Kim, Y.; Li, J.; Shillington, D. J.; Brown, L. D.

2017-12-01

The physical factors that control the rupture process of great earthquakes at convergent plate boundaries remain incompletely understood. While recent developments in imaging using the teleseismic wavefield have led to marked advances at wavelengths of a couple kilometers to tens of kilometers, higher resolution imaging of the rupture zone would improve the resolution of imaging and thus provide improved parameter estimation, as the teleseismic wavefield is fundamentally limited by its low frequency content. This study compares and evaluates two seismic imaging techniques using the high-frequency signals from teleseismic coda versus earthquake scattered waves to image the subducting Yakutat oceanic plateau in the Alaska subduction zone. We use earthquakes recorded by the MOOS PASSCAL broadband deployment in southern Alaska. In our first method, we select local earthquakes that lie directly beneath and laterally near the recording array for imaging, and extract body wave information via a simple autocorrelation and stacking. Profiles analogous to seismic reflection profile are constructed using the near-vertically travelling waves. In our second method, we compute teleseismic receiver functions within the 0.02-1.0 Hz frequency band. Both results image interfaces that we associate with the subducting oceanic plate in Alaska-Aleutian system, with greater resolution than commonly used methods with teleseismic sources. Structural details from our results can further our understanding of the conditions and materials that characterize the subduction megathrusts, and the techniques can be employed in other regions along the Alaska-Aleutian system and at other convergent margins with suitable seismic arrays.

Clustering Genes of Common Evolutionary History

PubMed Central

Gori, Kevin; Suchan, Tomasz; Alvarez, Nadir; Goldman, Nick; Dessimoz, Christophe

2016-01-01

Phylogenetic inference can potentially result in a more accurate tree using data from multiple loci. However, if the loci are incongruent—due to events such as incomplete lineage sorting or horizontal gene transfer—it can be misleading to infer a single tree. To address this, many previous contributions have taken a mechanistic approach, by modeling specific processes. Alternatively, one can cluster loci without assuming how these incongruencies might arise. Such “process-agnostic” approaches typically infer a tree for each locus and cluster these. There are, however, many possible combinations of tree distance and clustering methods; their comparative performance in the context of tree incongruence is largely unknown. Furthermore, because standard model selection criteria such as AIC cannot be applied to problems with a variable number of topologies, the issue of inferring the optimal number of clusters is poorly understood. Here, we perform a large-scale simulation study of phylogenetic distances and clustering methods to infer loci of common evolutionary history. We observe that the best-performing combinations are distances accounting for branch lengths followed by spectral clustering or Ward’s method. We also introduce two statistical tests to infer the optimal number of clusters and show that they strongly outperform the silhouette criterion, a general-purpose heuristic. We illustrate the usefulness of the approach by 1) identifying errors in a previous phylogenetic analysis of yeast species and 2) identifying topological incongruence among newly sequenced loci of the globeflower fly genus Chiastocheta. We release treeCl, a new program to cluster genes of common evolutionary history (http://git.io/treeCl). PMID:26893301

SOCIAL AND NON-SOCIAL CUEING OF VISUOSPATIAL ATTENTION IN AUTISM AND TYPICAL DEVELOPMENT

PubMed Central

Pruett, John R.; LaMacchia, Angela; Hoertel, Sarah; Squire, Emma; McVey, Kelly; Todd, Richard D.; Constantino, John N.; Petersen, Steven E.

2013-01-01

Three experiments explored attention to eye gaze, which is incompletely understood in typical development and is hypothesized to be disrupted in autism. Experiment 1 (n=26 typical adults) involved covert orienting to box, arrow, and gaze cues at two probabilities and cue-target times to test whether reorienting for gaze is endogenous, exogenous, or unique; experiment 2 (total n=80: male and female children and adults) studied age and sex effects on gaze cueing. Gaze cueing appears endogenous and may strengthen in typical development. Experiment 3 tested exogenous, endogenous, and/or gaze-based orienting in 25 typical and 27 Autistic Spectrum Disorder (ASD) children. ASD children made more saccades, slowing their reaction times; however, exogenous and endogenous orienting, including gaze cueing, appear intact in ASD. PMID:20809377

Case of Primary Central Nervous System Lymphoma Arising at Site of Remote Herpes Encephalitis.

PubMed

Li, Victor; Levine, Adrian B; Gooderham, Peter A; Yip, Stephen; Chew, Jason

2018-05-01

Primary central nervous system lymphoma (PCNSL) is a rare malignancy that usually arises in the context of severe immunosuppression but has incompletely understood etiology, limiting effective treatments. We present the case of an 81-year-old immunocompetent man who developed a PCNSL in the right temporal lobe, at the site of a remote episode of herpes simplex virus (HSV) encephalitis 8 years prior. There are numerous viruses with known oncogenic associations; however, to our knowledge, this is the first reported case of PCNSL with an antecedent HSV infection. We discuss this case in the context of our current understandings of the pathogenesis of HSV encephalitis and PCNSL and postulate mechanisms through which the 2 could be associated. Copyright © 2018 Elsevier Inc. All rights reserved.

Human Polyomavirus Reactivation: Disease Pathogenesis and Treatment Approaches

PubMed Central

De Gascun, Cillian F.; Carr, Michael J.

2013-01-01

JC and BK polyomaviruses were discovered over 40 years ago and have become increasingly prevalent causes of morbidity and mortality in a variety of distinct, immunocompromised patient cohorts. The recent discoveries of eight new members of the Polyomaviridae family that are capable of infecting humans suggest that there are more to be discovered and raise the possibility that they may play a more significant role in human disease than previously understood. In spite of this, there remains a dearth of specific therapeutic options for human polyomavirus infections and an incomplete understanding of the relationship between the virus and the host immune system. This review summarises the human polyomaviruses with particular emphasis on pathogenesis in those directly implicated in disease aetiology and the therapeutic options available for treatment in the immunocompromised host. PMID:23737811

Role of adapter function in oncoprotein-mediated activation of NF-kappaB. Human T-cell leukemia virus type I Tax interacts directly with IkappaB kinase gamma.

PubMed

Jin, D Y; Giordano, V; Kibler, K V; Nakano, H; Jeang, K T

1999-06-18

Mechanisms by which the human T-cell leukemia virus type I Tax oncoprotein activates NF-kappaB remain incompletely understood. Although others have described an interaction between Tax and a holo-IkappaB kinase (IKK) complex, the exact details of protein-protein contact are not fully defined. Here we show that Tax binds to neither IKK-alpha nor IKK-beta but instead complexes directly with IKK-gamma, a newly characterized component of the IKK complex. This direct interaction with IKK-gamma correlates with Tax-induced IkappaB-alpha phosphorylation and NF-kappaB activation. Thus, our findings establish IKK-gamma as a key molecule for adapting an oncoprotein-specific signaling to IKK-alpha and IKK-beta.

Red blood cell dynamics: from cell deformation to ATP release.

PubMed

Wan, Jiandi; Forsyth, Alison M; Stone, Howard A

2011-10-01

The mechanisms of red blood cell (RBC) deformation under both static and dynamic, i.e., flow, conditions have been studied extensively since the mid 1960s. Deformation-induced biochemical reactions and possible signaling in RBCs, however, were proposed only fifteen years ago. Therefore, the fundamental relationship between RBC deformation and cellular signaling dynamics i.e., mechanotransduction, remains incompletely understood. Quantitative understanding of the mechanotransductive pathways in RBCs requires integrative studies of physical models of RBC deformation and cellular biochemical reactions. In this article we review the physical models of RBC deformation, spanning from continuum membrane mechanics to cellular skeleton dynamics under both static and flow conditions, and elaborate the mechanistic links involved in deformation-induced ATP release. This journal is © The Royal Society of Chemistry 2011

Bacterial vaginosis and preterm birth.

PubMed

Manns-James, Laura

2011-01-01

Although it has been clear for more than 2 decades that bacterial vaginosis increases the risk for preterm birth in some women, it is not yet fully understood why this association exists or how best to modify the risk. Incomplete understanding of this polymicrobial condition and difficulties in classification contribute to the challenge. The relationship between altered vaginal microflora and preterm birth is likely mediated by host immune responses. Because treatment of bacterial vaginosis during pregnancy does not improve preterm birth rates, and may in fact increase them, screening and treatment of asymptomatic pregnant women is discouraged. Symptomatic women should be treated for symptom relief. This article reviews the pathophysiology of bacterial vaginosis and controversy surrounding management during pregnancy. Agents currently recommended for treatment of this condition are reviewed. © 2011 by the American College of Nurse-Midwives.

Epigenetic control of CD8+ T cell differentiation.

PubMed

Henning, Amanda N; Roychoudhuri, Rahul; Restifo, Nicholas P

2018-05-01

Upon stimulation, small numbers of naive CD8 + T cells proliferate and differentiate into a variety of memory and effector cell types. CD8 + T cells can persist for years and kill tumour cells and virally infected cells. The functional and phenotypic changes that occur during CD8 + T cell differentiation are well characterized, but the epigenetic states that underlie these changes are incompletely understood. Here, we review the epigenetic processes that direct CD8 + T cell differentiation and function. We focus on epigenetic modification of DNA and associated histones at genes and their regulatory elements. We also describe structural changes in chromatin organization that affect gene expression. Finally, we examine the translational potential of epigenetic interventions to improve CD8 + T cell function in individuals with chronic infections and cancer.

Taste receptors in the gastrointestinal tract. I. Bitter taste receptors and alpha-gustducin in the mammalian gut.

PubMed

Rozengurt, Enrique

2006-08-01

Molecular sensing by gastrointestinal (GI) cells plays a critical role in the control of multiple fundamental functions in digestion and also initiates hormonal and/or neural pathways leading to the regulation of caloric intake, pancreatic insulin secretion, and metabolism. Molecular sensing in the GI tract is also responsible for the detection of ingested harmful drugs and toxins, thereby initiating responses critical for survival. The initial recognition events and mechanism(s) involved remain incompletely understood. The notion to be discussed in this article is that there are important similarities between the chemosensory machinery elucidated in specialized neuroepithelial taste receptor cells of the lingual epithelium and the molecular transducers localized recently in enteroendocrine open GI cells that sense the chemical composition of the luminal contents of the gut.

The application and use of chemical space mapping to interpret crystallization screening results

PubMed Central

Snell, Edward H.; Nagel, Ray M.; Wojtaszcyk, Ann; O’Neill, Hugh; Wolfley, Jennifer L.; Luft, Joseph R.

2008-01-01

Macromolecular crystallization screening is an empirical process. It often begins by setting up experiments with a number of chemically diverse cocktails designed to sample chemical space known to promote crystallization. Where a potential crystal is seen a refined screen is set up, optimizing around that condition. By using an incomplete factorial sampling of chemical space to formulate the cocktails and presenting the results graphically, it is possible to readily identify trends relevant to crystallization, coarsely sample the phase diagram and help guide the optimization process. In this paper, chemical space mapping is applied to both single macromolecules and to a diverse set of macromolecules in order to illustrate how visual information is more readily understood and assimilated than the same information presented textually. PMID:19018100

The application and use of chemical space mapping to interpret crystallization screening results.

PubMed

Snell, Edward H; Nagel, Ray M; Wojtaszcyk, Ann; O'Neill, Hugh; Wolfley, Jennifer L; Luft, Joseph R

2008-12-01

Macromolecular crystallization screening is an empirical process. It often begins by setting up experiments with a number of chemically diverse cocktails designed to sample chemical space known to promote crystallization. Where a potential crystal is seen a refined screen is set up, optimizing around that condition. By using an incomplete factorial sampling of chemical space to formulate the cocktails and presenting the results graphically, it is possible to readily identify trends relevant to crystallization, coarsely sample the phase diagram and help guide the optimization process. In this paper, chemical space mapping is applied to both single macromolecules and to a diverse set of macromolecules in order to illustrate how visual information is more readily understood and assimilated than the same information presented textually.

Non-alcoholic steatohepatitis pathogenesis: sublethal hepatocyte injury as a driver of liver inflammation

PubMed Central

Ibrahim, Samar H; Hirsova, Petra; Gores, Gregory J

2018-01-01

A subset of patients with non-alcoholic fatty liver disease develop an inflammatory condition, termed nonalcoholic steatohepatitis (NASH). NASH is characterised by hepatocellular injury, innate immune cell-mediated inflammation and progressive liver fibrosis. The mechanisms whereby hepatic inflammation occurs in NASH remain incompletely understood, but appear to be linked to the proinflammatory microenvironment created by toxic lipid-induced hepatocyte injury, termed lipotoxicity. In this review, we discuss the signalling pathways induced by sublethal hepatocyte lipid overload that contribute to the pathogenesis of NASH. Furthermore, we will review the role of proinflammatory, proangiogenic and profibrotic hepatocyte-derived extracellular vesicles as disease biomarkers and pathogenic mediators during lipotoxicity. We also review the potential therapeutic strategies to block the feed-forward loop between sublethal hepatocyte injury and liver inflammation. PMID:29367207

Resolving Single Molecule Lysozyme Dynamics with a Carbon Nanotube Electronic Circuit

NASA Astrophysics Data System (ADS)

Choi, Yongki; Moody, Issa S.; Perez, Israel; Sheps, Tatyana; Weiss, Gregory A.; Collins, Philip G.

2011-03-01

High resolution, real-time monitoring of a single lysozyme molecule is demonstrated by fabricating nanoscale electronic devices based on single-walled carbon nanotubes (SWCNT). In this sensor platform, a biomolecule of interest is attached to a single SWCNT device. The electrical conductance transduces chemical events with single molecule sensitivity and 10 microsecond resolution. In this work, enzymatic turnover by lysozyme is investigated, because the mechanistic details for its processivity and dynamics remain incompletely understood. Stochastically distributed binding events between a lysozyme and its binding substrate, peptidoglycan, are monitored via the sensor conductance. Furthermore, the magnitude and repetition rate of these events varies with pH and the presence of inhibitors or denaturation agents. Changes in the conductance signal are analyzed in terms of lysozyme's internal hinge motion, binding events, and enzymatic processing.

Towards understanding the guessing game: a dynamical systems’ perspective

NASA Astrophysics Data System (ADS)

Reimann, Stefan

2004-08-01

The so-called “Guessing Game” or α-Beauty Contest serves as a paradigmatic conceptual framework for competitive price formation on financial markets beyond traditional equilibrium finance. It highlights features that are reasonable to consider when dealing with price formation on real markets. Nonetheless this game is still poorly understood. We propose a model which is essentially based on two assumptions: (1) players consider intervals rather than exact numbers to cope with incomplete knowledge and (2) players iteratively update their recent guesses. It provides an explanation for typical patterns observed in real data, such as the strict positivity of outcomes in the 1-shot setting, the skew background distribution of guessed numbers, as well as the polynomial convergence towards the game-theoretic Nash equilibrium in the iterative setting.

Evolving Concepts of Pulmonary Hypertension Secondary to Left Heart Disease.

PubMed

Ramu, Bhavadharini; Thenappan, Thenappan

2016-04-01

Pulmonary hypertension associated with left heart disease is the most common form of pulmonary hypertension. Although its pathophysiology remains incompletely understood, it is now well recognized that the presence of pulmonary hypertension is associated with a worse prognosis. Right ventricular failure has independent and additive prognostic value over pulmonary hypertension for adverse outcomes in left heart disease. Recently, several new terminologies have been introduced to better define and characterize the nature and severity of pulmonary hypertension. Several new treatment options including the use of pulmonary arterial hypertension specific therapies are being considered, but there is lack of evidence. Here, we review the recent advances in this field and summarize the diagnostic and therapeutic modalities of use in the management of pulmonary hypertension associated with left heart disease.

Intravascular Papillary Endothelial Hyperplasia (Masson’s Tumor) of the Radial Artery: A Case Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stark, Christopher, E-mail: Christopher.stark@uvmhealth.org; Olsen, Daniel; Morris, Christopher

Intravascular papillary endothelial hyperplasia (IPEH), often referred to as Masson’s tumor, is a benign non-neoplastic vascular lesion of the skin and subcutaneous tissues. Although it is rare, knowledge of the existence of IPEH is important as it can mimic other benign and malignant tumors, most notably angiosarcoma. IPEH remains an incompletely understood entity; however, most consider it to be the result of reactive endothelial proliferation following thrombus formation within a vessel, vascular malformation, or adjacent to a vessel. In this article, we report a case of IPEH arising within an arteriovenous malformation of the radial artery and present accompanying multimodalitymore » imaging and pathology figures. We will also describe the clinical presentation, pathophysiology, histology, imaging features, and management of IPEH.« less

Drowning stars: reassessing the role of astrocytes in brain edema.

PubMed

Thrane, Alexander S; Rangroo Thrane, Vinita; Nedergaard, Maiken

2014-11-01

Edema formation frequently complicates brain infarction, tumors, and trauma. Despite the significant mortality of this condition, current treatment options are often ineffective or incompletely understood. Recent studies have revealed the existence of a brain-wide paravascular pathway for cerebrospinal (CSF) and interstitial fluid (ISF) exchange. The current review critically examines the contribution of this 'glymphatic' system to the main types of brain edema. We propose that in cytotoxic edema, energy depletion enhances glymphatic CSF influx, whilst suppressing ISF efflux. We also argue that paravascular inflammation or 'paravasculitis' plays a critical role in vasogenic edema. Finally, recent advances in diagnostic imaging of glymphatic function may hold the key to defining the edema profile of individual patients, and thus enable more targeted therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

The role of calcium and predation on plate morph evolution in the three-spined stickleback (Gasterosteus aculeatus).

PubMed

Smith, Carl; Spence, Rowena; Barber, Iain; Przybylski, Mirosław; Wootton, Robert J

2014-09-01

While the genetic basis to plate morph evolution of the three-spined stickleback (Gasterosteus aculeatus) is well described, the environmental variables that select for different plate and spine morphs are incompletely understood. Using replicate populations of three-spined sticklebacks on North Uist, Scotland, we previously investigated the role of predation pressure and calcium limitation on the adaptive evolution of stickleback morphology and behavior. While dissolved calcium proved a significant predictor of plate and spine morph, predator abundance did not. Ecol. Evol., xxx, 2014 and xxx performed a comparable analysis to our own to address the same question. They failed to detect a significant effect of dissolved calcium on morphological evolution, but did establish a significant effect of predation; albeit in the opposite direction to their prediction.

Nature Disaster Risk Evaluation with a Group Decision Making Method Based on Incomplete Hesitant Fuzzy Linguistic Preference Relations.

PubMed

Tang, Ming; Liao, Huchang; Li, Zongmin; Xu, Zeshui

2018-04-13

Because the natural disaster system is a very comprehensive and large system, the disaster reduction scheme must rely on risk analysis. Experts' knowledge and experiences play a critical role in disaster risk assessment. The hesitant fuzzy linguistic preference relation is an effective tool to express experts' preference information when comparing pairwise alternatives. Owing to the lack of knowledge or a heavy workload, information may be missed in the hesitant fuzzy linguistic preference relation. Thus, an incomplete hesitant fuzzy linguistic preference relation is constructed. In this paper, we firstly discuss some properties of the additive consistent hesitant fuzzy linguistic preference relation. Next, the incomplete hesitant fuzzy linguistic preference relation, the normalized hesitant fuzzy linguistic preference relation, and the acceptable hesitant fuzzy linguistic preference relation are defined. Afterwards, three procedures to estimate the missing information are proposed. The first one deals with the situation in which there are only n-1 known judgments involving all the alternatives; the second one is used to estimate the missing information of the hesitant fuzzy linguistic preference relation with more known judgments; while the third procedure is used to deal with ignorance situations in which there is at least one alternative with totally missing information. Furthermore, an algorithm for group decision making with incomplete hesitant fuzzy linguistic preference relations is given. Finally, we illustrate our model with a case study about flood disaster risk evaluation. A comparative analysis is presented to testify the advantage of our method.

Handling incomplete correlated continuous and binary outcomes in meta-analysis of individual participant data.

PubMed

Gomes, Manuel; Hatfield, Laura; Normand, Sharon-Lise

2016-09-20

Meta-analysis of individual participant data (IPD) is increasingly utilised to improve the estimation of treatment effects, particularly among different participant subgroups. An important concern in IPD meta-analysis relates to partially or completely missing outcomes for some studies, a problem exacerbated when interest is on multiple discrete and continuous outcomes. When leveraging information from incomplete correlated outcomes across studies, the fully observed outcomes may provide important information about the incompleteness of the other outcomes. In this paper, we compare two models for handling incomplete continuous and binary outcomes in IPD meta-analysis: a joint hierarchical model and a sequence of full conditional mixed models. We illustrate how these approaches incorporate the correlation across the multiple outcomes and the between-study heterogeneity when addressing the missing data. Simulations characterise the performance of the methods across a range of scenarios which differ according to the proportion and type of missingness, strength of correlation between outcomes and the number of studies. The joint model provided confidence interval coverage consistently closer to nominal levels and lower mean squared error compared with the fully conditional approach across the scenarios considered. Methods are illustrated in a meta-analysis of randomised controlled trials comparing the effectiveness of implantable cardioverter-defibrillator devices alone to implantable cardioverter-defibrillator combined with cardiac resynchronisation therapy for treating patients with chronic heart failure. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Identity method for particle number fluctuations and correlations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gorenstein, M. I.

An incomplete particle identification distorts the observed event-by-event fluctuations of the hadron chemical composition in nucleus-nucleus collisions. A new experimental technique called the identity method was recently proposed. It eliminated the misidentification problem for one specific combination of the second moments in a system of two hadron species. In the present paper, this method is extended to calculate all the second moments in a system with an arbitrary number of hadron species. Special linear combinations of the second moments are introduced. These combinations are presented in terms of single-particle variables and can be found experimentally from the event-by-event averaging. Themore » mathematical problem is then reduced to solving a system of linear equations. The effect of incomplete particle identification is fully eliminated from the final results.« less

Using DNA fingerprints to infer familial relationships within NHANES III households

PubMed Central

Katki, Hormuzd A.; Sanders, Christopher L.; Graubard, Barry I.; Bergen, Andrew W.

2009-01-01

Developing, targeting, and evaluating genomic strategies for population-based disease prevention require population-based data. In response to this urgent need, genotyping has been conducted within the Third National Health and Nutrition Examination (NHANES III), the nationally-representative household-interview health survey in the U.S. However, before these genetic analyses can occur, family relationships within households must be accurately ascertained. Unfortunately, reported family relationships within NHANES III households based on questionnaire data are incomplete and inconclusive with regards to actual biological relatedness of family members. We inferred family relationships within households using DNA fingerprints (Identifiler®) that contain the DNA loci used by law enforcement agencies for forensic identification of individuals. However, performance of these loci for relationship inference is not well understood. We evaluated two competing statistical methods for relationship inference on pairs of household members: an exact likelihood ratio relying on allele frequencies to an Identical By State (IBS) likelihood ratio that only requires matching alleles. We modified these methods to account for genotyping errors and population substructure. The two methods usually agree on the rankings of the most likely relationships. However, the IBS method underestimates the likelihood ratio by not accounting for the informativeness of matching rare alleles. The likelihood ratio is sensitive to estimates of population substructure, and parent-child relationships are sensitive to the specified genotyping error rate. These loci were unable to distinguish second-degree relationships and cousins from being unrelated. The genetic data is also useful for verifying reported relationships and identifying data quality issues. An important by-product is the first explicitly nationally-representative estimates of allele frequencies at these ubiquitous forensic loci. PMID:20664713

Analyzing and synthesizing phylogenies using tree alignment graphs.

PubMed

Smith, Stephen A; Brown, Joseph W; Hinchliff, Cody E

2013-01-01

Phylogenetic trees are used to analyze and visualize evolution. However, trees can be imperfect datatypes when summarizing multiple trees. This is especially problematic when accommodating for biological phenomena such as horizontal gene transfer, incomplete lineage sorting, and hybridization, as well as topological conflict between datasets. Additionally, researchers may want to combine information from sets of trees that have partially overlapping taxon sets. To address the problem of analyzing sets of trees with conflicting relationships and partially overlapping taxon sets, we introduce methods for aligning, synthesizing and analyzing rooted phylogenetic trees within a graph, called a tree alignment graph (TAG). The TAG can be queried and analyzed to explore uncertainty and conflict. It can also be synthesized to construct trees, presenting an alternative to supertrees approaches. We demonstrate these methods with two empirical datasets. In order to explore uncertainty, we constructed a TAG of the bootstrap trees from the Angiosperm Tree of Life project. Analysis of the resulting graph demonstrates that areas of the dataset that are unresolved in majority-rule consensus tree analyses can be understood in more detail within the context of a graph structure, using measures incorporating node degree and adjacency support. As an exercise in synthesis (i.e., summarization of a TAG constructed from the alignment trees), we also construct a TAG consisting of the taxonomy and source trees from a recent comprehensive bird study. We synthesized this graph into a tree that can be reconstructed in a repeatable fashion and where the underlying source information can be updated. The methods presented here are tractable for large scale analyses and serve as a basis for an alternative to consensus tree and supertree methods. Furthermore, the exploration of these graphs can expose structures and patterns within the dataset that are otherwise difficult to observe.

Analyzing and Synthesizing Phylogenies Using Tree Alignment Graphs

PubMed Central

Smith, Stephen A.; Brown, Joseph W.; Hinchliff, Cody E.

2013-01-01

Phylogenetic trees are used to analyze and visualize evolution. However, trees can be imperfect datatypes when summarizing multiple trees. This is especially problematic when accommodating for biological phenomena such as horizontal gene transfer, incomplete lineage sorting, and hybridization, as well as topological conflict between datasets. Additionally, researchers may want to combine information from sets of trees that have partially overlapping taxon sets. To address the problem of analyzing sets of trees with conflicting relationships and partially overlapping taxon sets, we introduce methods for aligning, synthesizing and analyzing rooted phylogenetic trees within a graph, called a tree alignment graph (TAG). The TAG can be queried and analyzed to explore uncertainty and conflict. It can also be synthesized to construct trees, presenting an alternative to supertrees approaches. We demonstrate these methods with two empirical datasets. In order to explore uncertainty, we constructed a TAG of the bootstrap trees from the Angiosperm Tree of Life project. Analysis of the resulting graph demonstrates that areas of the dataset that are unresolved in majority-rule consensus tree analyses can be understood in more detail within the context of a graph structure, using measures incorporating node degree and adjacency support. As an exercise in synthesis (i.e., summarization of a TAG constructed from the alignment trees), we also construct a TAG consisting of the taxonomy and source trees from a recent comprehensive bird study. We synthesized this graph into a tree that can be reconstructed in a repeatable fashion and where the underlying source information can be updated. The methods presented here are tractable for large scale analyses and serve as a basis for an alternative to consensus tree and supertree methods. Furthermore, the exploration of these graphs can expose structures and patterns within the dataset that are otherwise difficult to observe. PMID:24086118

Fast angular synchronization for phase retrieval via incomplete information

NASA Astrophysics Data System (ADS)

Viswanathan, Aditya; Iwen, Mark

2015-08-01

We consider the problem of recovering the phase of an unknown vector, x ∈ ℂd, given (normalized) phase difference measurements of the form xjxk*/|xjxk*|, j,k ∈ {1,...,d}, and where xj* denotes the complex conjugate of xj. This problem is sometimes referred to as the angular synchronization problem. This paper analyzes a linear-time-in-d eigenvector-based angular synchronization algorithm and studies its theoretical and numerical performance when applied to a particular class of highly incomplete and possibly noisy phase difference measurements. Theoretical results are provided for perfect (noiseless) measurements, while numerical simulations demonstrate the robustness of the method to measurement noise. Finally, we show that this angular synchronization problem and the specific form of incomplete phase difference measurements considered arise in the phase retrieval problem - where we recover an unknown complex vector from phaseless (or magnitude) measurements.

How often do condoms fail? : A cross-sectional study exploring incomplete use of condoms, condom failures, and other condom problems among Black and White MSM in the Southern U.S

PubMed Central

Hernández-Romieu, Alfonso C.; Siegler, Aaron; Sullivan, Patrick S.; Crosby, Richard; Rosenberg, Eli S.

2015-01-01

Objectives Compare the occurrence of risk-inducing condom events (condom failures and incomplete use) and the frequency of their antecedents (condom errors, fit/feel problems, and erection problems) between Black and White MSM, and determine the associations between risk-inducing condom events and their antecedents. Methods We studied cross-sectional data of 475 MSM who indicated using a condom as an insertive partner in the previous 6 months enrolled in a cohort study in Atlanta, GA. Results Nearly 40% of Black MSM reported breakage or incomplete use, and they were more likely to report breakage, early removal, and delayed application of a condom than White MSM. Only 31% and 54% of MSM reported correct condom use and suboptimal fit/feel of a condom respectively. The use of oil-based lubricants and suboptimal fit/feel were associated with higher odds of reporting breakage (P = 0.009). Suboptimal fit/feel was also associated with higher odds of incomplete use of condoms (P <0.0001). Conclusions Incomplete use of condoms and condom failures were especially common among Black MSM. Our findings indicate that condoms likely offered them less protection against HIV/STI when compared to White MSM. More interventions are needed, particularly addressing the use of oil-based lubricants and suboptimal fit/feel of condoms. PMID:25080511

Assessing Mediational Models: Testing and Interval Estimation for Indirect Effects.

PubMed

Biesanz, Jeremy C; Falk, Carl F; Savalei, Victoria

2010-08-06

Theoretical models specifying indirect or mediated effects are common in the social sciences. An indirect effect exists when an independent variable's influence on the dependent variable is mediated through an intervening variable. Classic approaches to assessing such mediational hypotheses ( Baron & Kenny, 1986 ; Sobel, 1982 ) have in recent years been supplemented by computationally intensive methods such as bootstrapping, the distribution of the product methods, and hierarchical Bayesian Markov chain Monte Carlo (MCMC) methods. These different approaches for assessing mediation are illustrated using data from Dunn, Biesanz, Human, and Finn (2007). However, little is known about how these methods perform relative to each other, particularly in more challenging situations, such as with data that are incomplete and/or nonnormal. This article presents an extensive Monte Carlo simulation evaluating a host of approaches for assessing mediation. We examine Type I error rates, power, and coverage. We study normal and nonnormal data as well as complete and incomplete data. In addition, we adapt a method, recently proposed in statistical literature, that does not rely on confidence intervals (CIs) to test the null hypothesis of no indirect effect. The results suggest that the new inferential method-the partial posterior p value-slightly outperforms existing ones in terms of maintaining Type I error rates while maximizing power, especially with incomplete data. Among confidence interval approaches, the bias-corrected accelerated (BC a ) bootstrapping approach often has inflated Type I error rates and inconsistent coverage and is not recommended; In contrast, the bootstrapped percentile confidence interval and the hierarchical Bayesian MCMC method perform best overall, maintaining Type I error rates, exhibiting reasonable power, and producing stable and accurate coverage rates.

Thermal and Chemical Characterization of Composite Materials. MSFC Center Director's Discretionary Fund Final Report, Project No. ED36-18

NASA Technical Reports Server (NTRS)

Stanley, D. C.; Huff, T. L.

2003-01-01

The purpose of this research effort was to: (1) provide a concise and well-defined property profile of current and developing composite materials using thermal and chemical characterization techniques and (2) optimize analytical testing requirements of materials. This effort applied a diverse array of methodologies to ascertain composite material properties. Often, a single method of technique will provide useful, but nonetheless incomplete, information on material composition and/or behavior. To more completely understand and predict material properties, a broad-based analytical approach is required. By developing a database of information comprised of both thermal and chemical properties, material behavior under varying conditions may be better understood. THis is even more important in the aerospace community, where new composite materials and those in the development stage have little reference data. For example, Fourier transform infrared (FTIR) spectroscopy spectral databases available for identification of vapor phase spectra, such as those generated during experiments, generally refer to well-defined chemical compounds. Because this method renders a unique thermal decomposition spectral pattern, even larger, more diverse databases, such as those found in solid and liquid phase FTIR spectroscopy libraries, cannot be used. By combining this and other available methodologies, a database specifically for new materials and materials being developed at Marshall Space Flight Center can be generated . In addition, characterizing materials using this approach will be extremely useful in the verification of materials and identification of anomalies in NASA-wide investigations.

Incomplete Mixing and Reactions - A Lagrangian Approach in a Pure Shear Flow

NASA Astrophysics Data System (ADS)

Paster, A.; Aquino, T.; Bolster, D.

2014-12-01

Incomplete mixing of reactive solutes is well known to slow down reaction rates relative to what would be expected from assuming perfect mixing. As reactions progress in a system and deplete reactant concentrations, initial fluctuations in the concentrations of reactions can be amplified relative to mean background concentrations and lead to spatial segregation of reactants. As the system evolves, in the absence of sufficient mixing, this segregation will increase, leading to a persistence of incomplete mixing that fundamentally changes the effective rate at which overall reactions will progress. On the other hand, non-uniform fluid flows are known to affect mixing between interacting solutes. Thus a natural question arises: Can non-uniform flows sufficiently enhance mixing to suppress incomplete mixing effects, and if so, under what conditions? In this work we address this question by considering one of the simplest possible flows, a laminar pure shear flow, which is known to significantly enhance mixing relative to diffusion alone. To study this system we adapt a novel Lagrangian particle-based random walk method, originally designed to simulate reactions in purely diffusive systems, to the case of advection and diffusion in a shear flow. To interpret the results we develop a semi-analytical solution, by proposing a closure approximation that aims to capture the effect of incomplete mixing. The results obtained via the Lagrangian model and the semi-analytical solutions consistently highlight that if shear effects in the system are not sufficiently strong, incomplete mixing effects initially similar to purely diffusive systems will occur, slowing down the overall reaction rate. Then, at some later time, dependent on the strength of the shear, the system will return to behaving as if it were well-mixed, but represented by a reduced effective reaction rate. If shear effects are sufficiently strong, the incomplete mixing regime never emerges and the system can behave as well-mixed at all times.

Incomplete Mixing and Reactions - A Lagrangian Approach in a Pure Shear Flow

NASA Astrophysics Data System (ADS)

Paster, Amir; Bolster, Diogo; Aquino, Tomas

2015-04-01

Incomplete mixing of reactive solutes is well known to slow down reaction rates relative to what would be expected from assuming perfect mixing. As reactions progress in a system and deplete reactant concentrations, initial fluctuations in the concentrations of reactions can be amplified relative to mean background concentrations and lead to spatial segregation of reactants. As the system evolves, in the absence of sufficient mixing, this segregation will increase, leading to a persistence of incomplete mixing that fundamentally changes the effective rate at which overall reactions will progress. On the other hand, nonuniform fluid flows are known to affect mixing between interacting solutes. Thus a natural question arises: Can non-uniform flows sufficiently enhance mixing to suppress incomplete mixing effects, and if so, under what conditions? In this work we address this question by considering one of the simplest possible flows, a laminar pure shear flow, which is known to significantly enhance mixing relative to diffusion alone. To study this system we adapt a novel Lagrangian particle-based random walk method, originally designed to simulate reactions in purely diffusive systems, to the case of advection and diffusion in a shear flow. To interpret the results we develop a semi-analytical solution, by proposing a closure approximation that aims to capture the effect of incomplete mixing. The results obtained via the Lagrangian model and the semi-analytical solutions consistently highlight that if shear effects in the system are not sufficiently strong, incomplete mixing effects initially similar to purely diffusive systems will occur, slowing down the overall reaction rate. Then, at some later time, dependent on the strength of the shear, the system will return to behaving as if it were well-mixed, but represented by a reduced effective reaction rate. If shear effects are sufficiently strong, the incomplete mixing regime never emerges and the system can behave as well-mixed at all times.

Mass spectrometry as a tool for studying autism spectrum disorder.

PubMed

Woods, Alisa G; Ngounou Wetie, Armand G; Sokolowska, Izabela; Russell, Stefanie; Ryan, Jeanne P; Michel, Tanja Maria; Thome, Johannes; Darie, Costel C

2013-01-01

Autism spectrum disorders (ASDs) are increasing in incidence but have an incompletely understood etiology. Tools for uncovering clues to the cause of ASDs and means for diagnoses are valuable to the field. Mass Spectrometry (MS) has been a useful method for evaluating differences between individuals with ASDs versus matched controls. Different biological substances can be evaluated using MS, including urine, blood, saliva, and hair. This technique has been used to evaluate relatively unsupported hypotheses based on introduction of exogenous factors, such as opiate and heavy metal excretion theories of ASDs. MS has also been used to support disturbances in serotonin-related molecules, which have been more consistently observed in ASDs. Serotonergic system markers, markers for oxidative stress, cholesterol system disturbances, peptide hypo-phosphorylation and methylation have been measured using MS in ASDs, although further analyses with larger numbers of subjects are needed (as well as consideration of behavioral data). Refinements in MS and data analysis are ongoing, allowing for the possibility that future studies examining body fluids and specimens from ASD subjects could continue to yield novel insights. This review summarizes MS investigations that have been conducted to study ASD to date and provides insight into future promising applications for this technique, with focus on proteomic studies.

Statistical imprints of CMB B -type polarization leakage in an incomplete sky survey analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Santos, Larissa; Wang, Kai; Hu, Yangrui

2017-01-01

One of the main goals of modern cosmology is to search for primordial gravitational waves by looking on their imprints in the B -type polarization in the cosmic microwave background radiation. However, this signal is contaminated by various sources, including cosmic weak lensing, foreground radiations, instrumental noises, as well as the E -to- B leakage caused by the partial sky surveys, which should be well understood to avoid the misinterpretation of the observed data. In this paper, we adopt the E / B decomposition method suggested by Smith in 2006, and study the imprints of E -to- B leakage residualsmore » in the constructed B -type polarization maps, B( n-circumflex ), by employing various statistical tools. We find that the effects of E -to- B leakage are negligible for the B-mode power spectrum, as well as the skewness and kurtosis analyses of B-maps. However, if employing the morphological statistical tools, including Minkowski functionals and/or Betti numbers, we find the effect of leakage can be detected at very high confidence level, which shows that in the morphological analysis, the leakage can play a significant role as a contaminant for measuring the primordial B -mode signal and must be taken into account for a correct explanation of the data.« less

An Overview of Biofield Devices

PubMed Central

Muehsam, David; Chevalier, Gaétan; Barsotti, Tiffany

2015-01-01

Advances in biophysics, biology, functional genomics, neuroscience, psychology, psychoneuroimmunology, and other fields suggest the existence of a subtle system of “biofield” interactions that organize biological processes from the subatomic, atomic, molecular, cellular, and organismic to the interpersonal and cosmic levels. Biofield interactions may bring about regulation of biochemical, cellular, and neurological processes through means related to electromagnetism, quantum fields, and perhaps other means of modulating biological activity and information flow. The biofield paradigm, in contrast to a reductionist, chemistry-centered viewpoint, emphasizes the informational content of biological processes; biofield interactions are thought to operate in part via low-energy or “subtle” processes such as weak, nonthermal electromagnetic fields (EMFs) or processes potentially related to consciousness and nonlocality. Biofield interactions may also operate through or be reflected in more well-understood informational processes found in electroencephalographic (EEG) and electrocardiographic (ECG) data. Recent advances have led to the development of a wide variety of therapeutic and diagnostic biofield devices, defined as physical instruments best understood from the viewpoint of a biofield paradigm. Here, we provide a broad overview of biofield devices, with emphasis on those devices for which solid, peer-reviewed evidence exists. A subset of these devices, such as those based upon EEG- and ECG-based heart rate variability, function via mechanisms that are well understood and are widely employed in clinical settings. Other device modalities, such a gas discharge visualization and biophoton emission, appear to operate through incompletely understood mechanisms and have unclear clinical significance. Device modes of operation include EMF-light, EMF-heat, EMF-nonthermal, electrical current, vibration and sound, physical and mechanical, intentionality and nonlocality, gas and plasma, and other (mode of operation not well-understood). Methodological issues in device development and interfaces for future interdisciplinary research are discussed. Devices play prominent cultural and scientific roles in our society, and it is likely that device technologies will be one of the most influential access points for the furthering of biofield research and the dissemination of biofield concepts. This developing field of study presents new areas of research that have many important implications for both basic science and clinical medicine. PMID:26665041

An Overview of Biofield Devices.

PubMed

Muehsam, David; Chevalier, Gaétan; Barsotti, Tiffany; Gurfein, Blake T

2015-11-01

Advances in biophysics, biology, functional genomics, neuroscience, psychology, psychoneuroimmunology, and other fields suggest the existence of a subtle system of "biofield" interactions that organize biological processes from the subatomic, atomic, molecular, cellular, and organismic to the interpersonal and cosmic levels. Biofield interactions may bring about regulation of biochemical, cellular, and neurological processes through means related to electromagnetism, quantum fields, and perhaps other means of modulating biological activity and information flow. The biofield paradigm, in contrast to a reductionist, chemistry-centered viewpoint, emphasizes the informational content of biological processes; biofield interactions are thought to operate in part via low-energy or "subtle" processes such as weak, nonthermal electromagnetic fields (EMFs) or processes potentially related to consciousness and nonlocality. Biofield interactions may also operate through or be reflected in more well-understood informational processes found in electroencephalographic (EEG) and electrocardiographic (ECG) data. Recent advances have led to the development of a wide variety of therapeutic and diagnostic biofield devices, defined as physical instruments best understood from the viewpoint of a biofield paradigm. Here, we provide a broad overview of biofield devices, with emphasis on those devices for which solid, peer-reviewed evidence exists. A subset of these devices, such as those based upon EEG- and ECG-based heart rate variability, function via mechanisms that are well understood and are widely employed in clinical settings. Other device modalities, such a gas discharge visualization and biophoton emission, appear to operate through incompletely understood mechanisms and have unclear clinical significance. Device modes of operation include EMF-light, EMF-heat, EMF-nonthermal, electrical current, vibration and sound, physical and mechanical, intentionality and nonlocality, gas and plasma, and other (mode of operation not well-understood). Methodological issues in device development and interfaces for future interdisciplinary research are discussed. Devices play prominent cultural and scientific roles in our society, and it is likely that device technologies will be one of the most influential access points for the furthering of biofield research and the dissemination of biofield concepts. This developing field of study presents new areas of research that have many important implications for both basic science and clinical medicine.

Assessment of volcanic hazards, vulnerability, risk and uncertainty (Invited)

NASA Astrophysics Data System (ADS)

Sparks, R. S.

2009-12-01

A volcanic hazard is any phenomenon that threatens communities . These hazards include volcanic events like pyroclastic flows, explosions, ash fall and lavas, and secondary effects such as lahars and landslides. Volcanic hazards are described by the physical characteristics of the phenomena, by the assessment of the areas that they are likely to affect and by the magnitude-dependent return period of events. Volcanic hazard maps are generated by mapping past volcanic events and by modelling the hazardous processes. Both these methods have their strengths and limitations and a robust map should use both approaches in combination. Past records, studied through stratigraphy, the distribution of deposits and age dating, are typically incomplete and may be biased. Very significant volcanic hazards, such as surge clouds and volcanic blasts, are not well-preserved in the geological record for example. Models of volcanic processes are very useful to help identify hazardous areas that do not have any geological evidence. They are, however, limited by simplifications and incomplete understanding of the physics. Many practical volcanic hazards mapping tools are also very empirical. Hazards maps are typically abstracted into hazards zones maps, which are some times called threat or risk maps. Their aim is to identify areas at high levels of threat and the boundaries between zones may take account of other factors such as roads, escape routes during evacuation, infrastructure. These boundaries may change with time due to new knowledge on the hazards or changes in volcanic activity levels. Alternatively they may remain static but implications of the zones may change as volcanic activity changes. Zone maps are used for planning purposes and for management of volcanic crises. Volcanic hazards maps are depictions of the likelihood of future volcanic phenomena affecting places and people. Volcanic phenomena are naturally variable, often complex and not fully understood. There are many sources of uncertainty in forecasting the areas that volcanic activity will effect and the severity of the effects. Uncertainties arise from: natural variability, inadequate data, biased data, incomplete data, lack of understanding of the processes, limitations to predictive models, ambiguity, and unknown unknowns. The description of volcanic hazards is thus necessarily probabilistic and requires assessment of the attendant uncertainties. Several issues arise from the probabilistic nature of volcanic hazards and the intrinsic uncertainties. Although zonation maps require well-defined boundaries for administrative pragmatism, such boundaries cannot divide areas that are completely safe from those that are unsafe. Levels of danger or safety need to be defined to decide on and justify boundaries through the concepts of vulnerability and risk. More data, better observations, improved models may reduce uncertainties, but can increase uncertainties and may lead to re-appraisal of zone boundaries. Probabilities inferred by statistical techniques are hard to communicate. Expert elicitation is an emerging methodology for risk assessment and uncertainty evaluation. The method has been applied at one major volcanic crisis (Soufrière Hills Volcano, Montserrat), and is being applied in planning for volcanic crises at Vesuvius.

High school incompletion and childhood maltreatment among street-involved young people in Vancouver, Canada.

PubMed

Barker, Brittany; Kerr, Thomas; Dong, Huiru; Wood, Evan; DeBeck, Kora

2017-03-01

While the link between educational attainment and future health and wellness is well understood, little investigation has considered the potential impacts of distinct forms of childhood maltreatment on high school completion. In the present study, the relationship between five categories of childhood maltreatment (physical, emotional, and sexual abuse, and physical and emotional neglect) and completion of high school education were examined using the Childhood Trauma Questionnaire (CTQ). From September 2005 to May 2013, data were collected for the At-Risk Youth Study (ARYS), a cohort of street-involved young people who use illicit drugs in Vancouver, Canada. We used logistic regression to examine the relationship between childhood maltreatment and high school completion, while controlling for a range of potential confounding variables. Specifically, five separate models for each category of maltreatment and two combined models were employed to examine the relative associations between, and cumulative impact of, different forms of childhood maltreatment and educational attainment. Among 974 young people, 737 (76%) reported not completing high school. In separate multivariable analyses physical abuse, emotional abuse, physical neglect, and emotional neglect remained positively and independently associated with an incomplete high school education. In a combined multivariable model with all forms of childhood maltreatment considered together, emotional abuse (adjusted odds ratio = 2.08; 95% confidence interval: 1.51-2.86) was the only form of maltreatment that remained significantly associated with an incomplete high school education. The cumulative impact assessment indicated a moderate dose-dependent trend where the greater the number of different forms of childhood maltreatment the greater the risk of not completing a high school education. These findings point to the need for trauma-informed interventions to improve educational attainment among vulnerable young people, as well as evidence-based prevention programmes, such as the Nurse-Family Partnership, aimed at supporting at-risk families before maltreatment occurs. © 2015 John Wiley & Sons Ltd.

Analytical solution for reactive solute transport considering incomplete mixing within a reference elementary volume

NASA Astrophysics Data System (ADS)

Chiogna, Gabriele; Bellin, Alberto

2013-05-01

The laboratory experiments of Gramling et al. (2002) showed that incomplete mixing at the pore scale exerts a significant impact on transport of reactive solutes and that assuming complete mixing leads to overestimation of product concentration in bimolecular reactions. Successively, several attempts have been made to model this experiment, either considering spatial segregation of the reactants, non-Fickian transport applying a Continuous Time Random Walk (CTRW) or an effective upscaled time-dependent kinetic reaction term. Previous analyses of these experimental results showed that, at the Darcy scale, conservative solute transport is well described by a standard advection dispersion equation, which assumes complete mixing at the pore scale. However, reactive transport is significantly affected by incomplete mixing at smaller scales, i.e., within a reference elementary volume (REV). We consider here the family of equilibrium reactions for which the concentration of the reactants and the product can be expressed as a function of the mixing ratio, the concentration of a fictitious non reactive solute. For this type of reactions we propose, in agreement with previous studies, to model the effect of incomplete mixing at scales smaller than the Darcy scale assuming that the mixing ratio is distributed within an REV according to a Beta distribution. We compute the parameters of the Beta model by imposing that the mean concentration is equal to the value that the concentration assumes at the continuum Darcy scale, while the variance decays with time as a power law. We show that our model reproduces the concentration profiles of the reaction product measured in the Gramling et al. (2002) experiments using the transport parameters obtained from conservative experiments and an instantaneous reaction kinetic. The results are obtained applying analytical solutions both for conservative and for reactive solute transport, thereby providing a method to handle the effect of incomplete mixing on multispecies reactive solute transport, which is simpler than other previously developed methods.

Unenhanced MR Angiography of Uterine and Ovarian Arteries after Uterine Artery Embolization: Differences between Patients with Incomplete and Complete Fibroid Infarction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mori, Kensaku, E-mail: moriken@md.tsukuba.ac.jp; Saida, Tsukasa; Shibuya, Yoko

Purpose: To compare the status of uterine and ovarian arteries after uterine artery embolization (UAE) in patients with incomplete and complete fibroid infarction via unenhanced 3D time-of-flight magnetic resonance (MR) angiography. Materials and Methods: Thirty-five consecutive women (mean age 43 years; range 26-52 years) with symptomatic uterine fibroids underwent UAE and MR imaging before and within 2 months after UAE. The patients were divided into incomplete and complete fibroid infarction groups on the basis of the postprocedural gadolinium-enhanced MR imaging findings. Two independent observers reviewed unenhanced MR angiography before and after UAE to determine bilateral uterine and ovarian arterial flowmore » scores. The total arterial flow scores were calculated by summing the scores of the 4 arteries. All scores were compared with the Mann-Whitney test. Results: Fourteen and 21 patients were assigned to the incomplete and complete fibroid infarction groups, respectively. The total arterial flow score in the incomplete fibroid infarction group was significantly greater than that in the complete fibroid infarction group (P = 0.019 and P = 0.038 for observers 1 and 2, respectively). In 3 patients, additional therapy was recommended for insufficient fibroid infarction. In 1 of the 3 patients, bilateral ovarian arteries were invisible before UAE but seemed enlarged after UAE. Conclusion: The total arterial flow from bilateral uterine and ovarian arteries in patients with incomplete fibroid infarction is less well reduced than in those with complete fibroid infarction. Postprocedural MR angiography provides useful information to estimate the cause of insufficient fibroid infarction in individual cases.« less

MULTI-SOURCE FEATURE LEARNING FOR JOINT ANALYSIS OF INCOMPLETE MULTIPLE HETEROGENEOUS NEUROIMAGING DATA

PubMed Central

Yuan, Lei; Wang, Yalin; Thompson, Paul M.; Narayan, Vaibhav A.; Ye, Jieping

2012-01-01

Analysis of incomplete data is a big challenge when integrating large-scale brain imaging datasets from different imaging modalities. In the Alzheimer’s Disease Neuroimaging Initiative (ADNI), for example, over half of the subjects lack cerebrospinal fluid (CSF) measurements; an independent half of the subjects do not have fluorodeoxyglucose positron emission tomography (FDG-PET) scans; many lack proteomics measurements. Traditionally, subjects with missing measures are discarded, resulting in a severe loss of available information. In this paper, we address this problem by proposing an incomplete Multi-Source Feature (iMSF) learning method where all the samples (with at least one available data source) can be used. To illustrate the proposed approach, we classify patients from the ADNI study into groups with Alzheimer’s disease (AD), mild cognitive impairment (MCI) and normal controls, based on the multi-modality data. At baseline, ADNI’s 780 participants (172 AD, 397 MCI, 211 NC), have at least one of four data types: magnetic resonance imaging (MRI), FDG-PET, CSF and proteomics. These data are used to test our algorithm. Depending on the problem being solved, we divide our samples according to the availability of data sources, and we learn shared sets of features with state-of-the-art sparse learning methods. To build a practical and robust system, we construct a classifier ensemble by combining our method with four other methods for missing value estimation. Comprehensive experiments with various parameters show that our proposed iMSF method and the ensemble model yield stable and promising results. PMID:22498655

The extraction of drug-disease correlations based on module distance in incomplete human interactome.

PubMed

Yu, Liang; Wang, Bingbo; Ma, Xiaoke; Gao, Lin

2016-12-23

Extracting drug-disease correlations is crucial in unveiling disease mechanisms, as well as discovering new indications of available drugs, or drug repositioning. Both the interactome and the knowledge of disease-associated and drug-associated genes remain incomplete. We present a new method to predict the associations between drugs and diseases. Our method is based on a module distance, which is originally proposed to calculate distances between modules in incomplete human interactome. We first map all the disease genes and drug genes to a combined protein interaction network. Then based on the module distance, we calculate the distances between drug gene sets and disease gene sets, and take the distances as the relationships of drug-disease pairs. We also filter possible false positive drug-disease correlations by p-value. Finally, we validate the top-100 drug-disease associations related to six drugs in the predicted results. The overlapping between our predicted correlations with those reported in Comparative Toxicogenomics Database (CTD) and literatures, and their enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways demonstrate our approach can not only effectively identify new drug indications, but also provide new insight into drug-disease discovery.

Predictors of seizure freedom after incomplete resection in children.

PubMed

Perry, M S; Dunoyer, C; Dean, P; Bhatia, S; Bavariya, A; Ragheb, J; Miller, I; Resnick, T; Jayakar, P; Duchowny, M

2010-10-19

Incomplete resection of the epileptogenic zone (EZ) is the most important predictor of poor outcome after resective surgery for intractable epilepsy. We analyzed the contribution of preoperative and perioperative variables including MRI and EEG data as predictors of seizure-free (SF) outcome after incomplete resection. We retrospectively reviewed patients <18 years of age with incomplete resection for epilepsy with 2 years of follow-up. Fourteen preoperative and perioperative variables were compared in SF and non-SF (NSF) patients. We compared lesional patients, categorized by reason for incompleteness, to lesional patients with complete resection. We analyzed for effect of complete EEG resection on SF outcome in patients with incompletely resected MRI lesions and vice versa. Eighty-three patients with incomplete resection were included with 41% becoming SF. Forty-eight lesional patients with complete resection were included. Thirty-eight percent (57/151) of patients with incomplete resection and 34% (47/138) with complete resection were excluded secondary to lack of follow-up or incomplete records. Contiguous MRI lesions were predictive of seizure freedom after incomplete resection. Fifty-seven percent of patients incomplete by MRI alone, 52% incomplete by EEG alone, and 24% incomplete by both became SF compared to 77% of patients with complete resection (p = 0.0005). Complete resection of the MRI- and EEG-defined EZ is the best predictor of seizure freedom, though patients incomplete by EEG or MRI alone have better outcome compared to patients incomplete by both. More than one-third of patients with incomplete resection become SF, with contiguous MRI lesions a predictor of SF outcome.

Sensitivity to imputation models and assumptions in receiver operating characteristic analysis with incomplete data

PubMed Central

Karakaya, Jale; Karabulut, Erdem; Yucel, Recai M.

2015-01-01

Modern statistical methods using incomplete data have been increasingly applied in a wide variety of substantive problems. Similarly, receiver operating characteristic (ROC) analysis, a method used in evaluating diagnostic tests or biomarkers in medical research, has also been increasingly popular problem in both its development and application. While missing-data methods have been applied in ROC analysis, the impact of model mis-specification and/or assumptions (e.g. missing at random) underlying the missing data has not been thoroughly studied. In this work, we study the performance of multiple imputation (MI) inference in ROC analysis. Particularly, we investigate parametric and non-parametric techniques for MI inference under common missingness mechanisms. Depending on the coherency of the imputation model with the underlying data generation mechanism, our results show that MI generally leads to well-calibrated inferences under ignorable missingness mechanisms. PMID:26379316

High-Density Signal Interface Electromagnetic Radiation Prediction for Electromagnetic Compatibility Evaluation.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Halligan, Matthew

Radiated power calculation approaches for practical scenarios of incomplete high- density interface characterization information and incomplete incident power information are presented. The suggested approaches build upon a method that characterizes power losses through the definition of power loss constant matrices. Potential radiated power estimates include using total power loss information, partial radiated power loss information, worst case analysis, and statistical bounding analysis. A method is also proposed to calculate radiated power when incident power information is not fully known for non-periodic signals at the interface. Incident data signals are modeled from a two-state Markov chain where bit state probabilities aremore » derived. The total spectrum for windowed signals is postulated as the superposition of spectra from individual pulses in a data sequence. Statistical bounding methods are proposed as a basis for the radiated power calculation due to the statistical calculation complexity to find a radiated power probability density function.« less

Krylov subspace methods on supercomputers

NASA Technical Reports Server (NTRS)

Saad, Youcef

1988-01-01

A short survey of recent research on Krylov subspace methods with emphasis on implementation on vector and parallel computers is presented. Conjugate gradient methods have proven very useful on traditional scalar computers, and their popularity is likely to increase as three-dimensional models gain importance. A conservative approach to derive effective iterative techniques for supercomputers has been to find efficient parallel/vector implementations of the standard algorithms. The main source of difficulty in the incomplete factorization preconditionings is in the solution of the triangular systems at each step. A few approaches consisting of implementing efficient forward and backward triangular solutions are described in detail. Polynomial preconditioning as an alternative to standard incomplete factorization techniques is also discussed. Another efficient approach is to reorder the equations so as to improve the structure of the matrix to achieve better parallelism or vectorization. An overview of these and other ideas and their effectiveness or potential for different types of architectures is given.

Inference and sample size calculation for clinical trials with incomplete observations of paired binary outcomes.

PubMed

Zhang, Song; Cao, Jing; Ahn, Chul

2017-02-20

We investigate the estimation of intervention effect and sample size determination for experiments where subjects are supposed to contribute paired binary outcomes with some incomplete observations. We propose a hybrid estimator to appropriately account for the mixed nature of observed data: paired outcomes from those who contribute complete pairs of observations and unpaired outcomes from those who contribute either pre-intervention or post-intervention outcomes. We theoretically prove that if incomplete data are evenly distributed between the pre-intervention and post-intervention periods, the proposed estimator will always be more efficient than the traditional estimator. A numerical research shows that when the distribution of incomplete data is unbalanced, the proposed estimator will be superior when there is moderate-to-strong positive within-subject correlation. We further derive a closed-form sample size formula to help researchers determine how many subjects need to be enrolled in such studies. Simulation results suggest that the calculated sample size maintains the empirical power and type I error under various design configurations. We demonstrate the proposed method using a real application example. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

3D numerical simulation of flow field with incompletely flaring gate pier in large unit discharge and deep tail water project

NASA Astrophysics Data System (ADS)

Zhao, Zhou; Junxing, Wang

2018-06-01

Limited by large unit discharge above the overflow weir and deep tail water inside the stilling basin, the incoming flow inside stilling basin is seriously short of enough energy dissipation and outgoing flow still carries much energy with large velocity, bound to result in secondary hydraulic jump outside stilling basin and scour downstream river bed. Based on the RNG k-ɛ turbulence model and the VOF method, this paper comparatively studies flow field between the conventional flat gate pier program and the incompletely flaring gate pier program to reveal energy dissipation mechanism of incomplete flaring gate pier. Results show that incompletely flaring gate pier can greatly promote the longitudinally stretched water jet to laterally diffuse and collide in the upstream region of stilling basin due to velocity gradients between adjacent inflow from each chamber through shrinking partial overflow flow chamber weir chamber, which would lead to large scale vertical axis vortex from the bottom to the surface and enhance mutual shear turbulence dissipation. This would significantly increase energy dissipation inside stilling basin to reduce outgoing velocity and totally solve the common hydraulic problems in large unit discharge and deep tail water projects.

A comparative study of prebiotic and present day translational models

NASA Technical Reports Server (NTRS)

Rein, R.; Raghunathan, G.; Mcdonald, J.; Shibata, M.; Srinivasan, S.

1986-01-01

It is generally recognized that the understanding of the molecular basis of primitive translation is a fundamental step in developing a theory of the origin of life. However, even in modern molecular biology, the mechanism for the decoding of messenger RNA triplet codons into an amino acid sequence of a protein on the ribosome is understood incompletely. Most of the proposed models for prebiotic translation lack, not only experimental support, but also a careful theoretical scrutiny of their compatibility with well understood stereochemical and energetic principles of nucleic acid structure, molecular recognition principles, and the chemistry of peptide bond formation. Present studies are concerned with comparative structural modelling and mechanistic simulation of the decoding apparatus ranging from those proposed for prebiotic conditions to the ones involved in modern biology. Any primitive decoding machinery based on nucleic acids and proteins, and most likely the modern day system, has to satisfy certain geometrical constraints. The charged amino acyl and the peptidyl termini of successive adaptors have to be adjacent in space in order to satisfy the stereochemical requirements for amide bond formation. Simultaneously, the same adaptors have to recognize successive codons on the messenger. This translational complex has to be realized by components that obey nucleic acid conformational principles, stabilities, and specificities. This generalized condition greatly restricts the number of acceptable adaptor structures.

Complications associated with prone positioning in elective spinal surgery.

PubMed

DePasse, J Mason; Palumbo, Mark A; Haque, Maahir; Eberson, Craig P; Daniels, Alan H

2015-04-18

Complications associated with prone surgical positioning during elective spine surgery have the potential to cause serious patient morbidity. Although many of these complications remain uncommon, the range of possible morbidities is wide and includes multiple organ systems. Perioperative visual loss (POVL) is a well described, but uncommon complication that may occur due to ischemia to the optic nerve, retina, or cerebral cortex. Closed-angle glaucoma and amaurosis have been reported as additional etiologies for vision loss following spinal surgery. Peripheral nerve injuries, such as those caused by prolonged traction to the brachial plexus, are more commonly encountered postoperative events. Myocutaneous complications including pressure ulcers and compartment syndrome may also occur after prone positioning, albeit rarely. Other uncommon positioning complications such as tongue swelling resulting in airway compromise, femoral artery ischemia, and avascular necrosis of the femoral head have also been reported. Many of these are well-understood and largely avoidable through thoughtful attention to detail. Other complications, such as POVL, remain incompletely understood and thus more difficult to predict or prevent. Here, the current literature on the complications of prone positioning for spine surgery is reviewed to increase awareness of the spectrum of potential complications and to inform spine surgeons of strategies to minimize the risk of prone patient morbidity.

Complications associated with prone positioning in elective spinal surgery

PubMed Central

DePasse, J Mason; Palumbo, Mark A; Haque, Maahir; Eberson, Craig P; Daniels, Alan H

2015-01-01

Complications associated with prone surgical positioning during elective spine surgery have the potential to cause serious patient morbidity. Although many of these complications remain uncommon, the range of possible morbidities is wide and includes multiple organ systems. Perioperative visual loss (POVL) is a well described, but uncommon complication that may occur due to ischemia to the optic nerve, retina, or cerebral cortex. Closed-angle glaucoma and amaurosis have been reported as additional etiologies for vision loss following spinal surgery. Peripheral nerve injuries, such as those caused by prolonged traction to the brachial plexus, are more commonly encountered postoperative events. Myocutaneous complications including pressure ulcers and compartment syndrome may also occur after prone positioning, albeit rarely. Other uncommon positioning complications such as tongue swelling resulting in airway compromise, femoral artery ischemia, and avascular necrosis of the femoral head have also been reported. Many of these are well-understood and largely avoidable through thoughtful attention to detail. Other complications, such as POVL, remain incompletely understood and thus more difficult to predict or prevent. Here, the current literature on the complications of prone positioning for spine surgery is reviewed to increase awareness of the spectrum of potential complications and to inform spine surgeons of strategies to minimize the risk of prone patient morbidity. PMID:25893178

A double-cusp type electrostatic analyzer for high-cadence ring current ion measurements

NASA Astrophysics Data System (ADS)

Ogasawara, K.; Allegrini, F.; Burch, J. L.; Desai, M. I.; Ebert, R. W.; Goldstein, J.; John, J. M.; Livi, S. A.; McComas, D. J.

2015-12-01

Detailed observations of a variety of ion species at a sufficiently high temporal resolution are essential to understanding the loss and acceleration processes of ring current ions. For example, CRESS/MICS observations indicated that the energy density of suprathermal O+ exceeds that of H+ in large magnetic storms (Daglis et al., 1997), while the H+ energy density dominates under quiet conditions. However, the primary ion loss processes during the storm recovery phase are still incompletely understood. The mechanisms to accelerate upflowing ions, regularly observed with energies of a few keV at ~1000 km altitude, up to the 100s-keV range in the geospace are also not fully understood. Our novel electrostatic analyzer (ESA) employs a toroidal double-shell structure to cover the entire ring current ion range of ~3-250 keV/Q with high temporal resolution (<1 minute with a necessary counting statistics for the quiet time), while saving significant resources in mass and size. In this presentation, we discuss the operation principle and the proof of concept study of the ESA in terms of numerical calculations and ion beam calibration activities. This presentation comprehensively covers the expected sensor performance important for the in-flight capabilities, such as sensor parameters (G-factor, K-factor, and energy resolution), cross-shell contaminations, and UV background counts.

Analytical Solution for Reactive Solute Transport Considering Incomplete Mixing

NASA Astrophysics Data System (ADS)

Bellin, A.; Chiogna, G.

2013-12-01

The laboratory experiments of Gramling et al. (2002) showed that incomplete mixing at the pore scale exerts a significant impact on transport of reactive solutes and that assuming complete mixing leads to overestimation of product concentration in bimolecular reactions. We consider here the family of equilibrium reactions for which the concentration of the reactants and the product can be expressed as a function of the mixing ratio, the concentration of a fictitious non reactive solute. For this type of reactions we propose, in agreement with previous studies, to model the effect of incomplete mixing at scales smaller than the Darcy scale assuming that the mixing ratio is distributed within an REV according to a Beta distribution. We compute the parameters of the Beta model by imposing that the mean concentration is equal to the value that the concentration assumes at the continuum Darcy scale, while the variance decays with time as a power law. We show that our model reproduces the concentration profiles of the reaction product measured in the Gramling et al. (2002) experiments using the transport parameters obtained from conservative experiments and an instantaneous reaction kinetic. The results are obtained applying analytical solutions both for conservative and for reactive solute transport, thereby providing a method to handle the effect of incomplete mixing on multispecies reactive solute transport, which is simpler than other previously developed methods. Gramling, C. M., C. F. Harvey, and L. C. Meigs (2002), Reactive transport in porous media: A comparison of model prediction with laboratory visualization, Environ. Sci. Technol., 36(11), 2508-2514.

Negotiating identity and self-image: perceptions of falls in ambulatory individuals with spinal cord injury – a qualitative study

PubMed Central

Jørgensen, Vivien; Roaldsen, Kirsti Skavberg

2016-01-01

Objective: Explore and describe experiences and perceptions of falls, risk of falling, and fall-related consequences in individuals with incomplete spinal cord injury (SCI) who are still walking. Design: A qualitative interview study applying interpretive content analysis with an inductive approach. Setting: Specialized rehabilitation hospital. Subjects: A purposeful sample of 15 individuals (10 men), 23 to 78 years old, 2-34 years post injury with chronic incomplete traumatic SCI, and walking ⩾75% of time for mobility needs. Methods: Individual, semi-structured face-to-face interviews were recorded, condensed, and coded to find themes and subthemes. Results: One overarching theme was revealed: “Falling challenges identity and self-image as normal” which comprised two main themes “Walking with incomplete SCI involves minimizing fall risk and fall-related concerns without compromising identity as normal” and “Walking with incomplete SCI implies willingness to increase fall risk in order to maintain identity as normal”. Informants were aware of their increased fall risk and took precautions, but willingly exposed themselves to risky situations when important to self-identity. All informants expressed some conditional fall-related concerns, and a few experienced concerns limiting activity and participation. Conclusion: Ambulatory individuals with incomplete SCI considered falls to be a part of life. However, falls interfered with the informants’ identities and self-images as normal, healthy, and well-functioning. A few expressed dysfunctional concerns about falling, and interventions should target these. PMID:27170274

Gut-kidney crosstalk in septic acute kidney injury.

PubMed

Zhang, Jingxiao; Ankawi, Ghada; Sun, Jian; Digvijay, Kumar; Yin, Yongjie; Rosner, Mitchell H; Ronco, Claudio

2018-05-03

Sepsis is the leading cause of acute kidney injury (AKI) in the intensive care unit (ICU). Septic AKI is a complex and multifactorial process that is incompletely understood. During sepsis, the disruption of the mucus membrane barrier, a shift in intestinal microbial flora, and microbial translocation may lead to systemic inflammation, which further alters host immune and metabolic homeostasis. This altered homeostasis may promote and potentiate the development of AKI. As part of this vicious cycle, when AKI develops, the clearance of inflammatory mediators and metabolic products is decreased. This will lead to further gut injury and breakdown in mucous membrane barriers. Thus, changes in the gut during sepsis can initiate and propagate septic AKI. This deleterious gut-kidney crosstalk may be a potential target for therapeutic maneuvers. This review analyses the underlying mechanisms in gut-kidney crosstalk in septic AKI.

The Role of Esophageal Hypersensitivity in Functional Esophageal Disorders.

PubMed

Farmer, Adam D; Ruffle, James K; Aziz, Qasim

2017-02-01

The Rome IV diagnostic criteria delineates 5 functional esophageal disorders which include functional chest pain, functional heartburn, reflux hypersensitivity, globus, and functional dysphagia. These are a heterogenous group of disorders which, despite having characteristic symptom profiles attributable to esophageal pathology, fail to demonstrate any structural, motility or inflammatory abnormalities on standard clinical testing. These disorders are associated with a marked reduction in patient quality of life, not least considerable healthcare resources. Furthermore, the pathophysiology of these disorders is incompletely understood. In this narrative review we provide the reader with an introductory primer to the structure and function of esophageal perception, including nociception that forms the basis of the putative mechanisms that may give rise to symptoms in functional esophageal disorders. We also discuss the provocative techniques and outcome measures by which esophageal hypersensitivity can be established.

Upper gastrointestinal sensory-motor dysfunction in diabetes mellitus

PubMed Central

Zhao, Jing-Bo; Frøkjær, Jens Brøndum; Drewes, Asbjørn Mohr; Ejskjaer, Niels

2006-01-01

Gastrointestinal (GI) sensory-motor abnormalities are common in patients with diabetes mellitus and may involve any part of the GI tract. Abnormalities are frequently sub-clinical, and fortunately only rarely do severe and life-threatening problems occur. The pathogenesis of abnormal upper GI sensory-motor function in diabetes is incompletely understood and is most likely multi-factorial of origin. Diabetic autonomic neuropathy as well as acute suboptimal control of diabetes has been shown to impair GI motor and sensory function. Morphological and biomechanical remodeling of the GI wall develops during the duration of diabetes, and may contribute to motor and sensory dysfunction. In this review sensory and motility disorders of the upper GI tract in diabetes is discussed; and the morphological changes and biomechanical remodeling related to the sensory-motor dysfunction is also addressed. PMID:16718808

Steps in Prostate Cancer Progression that lead to Bone Metastasis

PubMed Central

Jin, Jung-Kang; Dayyani, Farshid; Gallick, Gary E.

2011-01-01

Prostate cancer is a complex disease in which metastasis to the bone is the main cause of death. Initial stages of metastasis are generally similar to those for most solid tumors; however, the mechanisms that underlie the homing of prostate tumor cells to the bone remain incompletely understood. Prostate cancer bone metastasis is also a microenvironment-driven disease, involving bi-directional interactions between the tumor and the bone microenvironment. In this review, we discuss the current understanding of the biologic processes and regulatory factors involved in the metastasis of prostate cancer cells, and their specific properties that promote growth in bone. Although many of these processes still need to be fully elucidated, a better understanding of the complex tumor/microenvironment interplay is slowly leading to more effective therapies for patients with prostate cancer bone metastases. PMID:21365645

The Origins of Scintillator Non-Proportionality

NASA Astrophysics Data System (ADS)

Moses, W. W.; Bizarri, G. A.; Williams, R. T.; Payne, S. A.; Vasil'ev, A. N.; Singh, J.; Li, Q.; Grim, J. Q.; Choong, W.-S.

2012-10-01

Recent years have seen significant advances in both theoretically understanding and mathematically modeling the underlying causes of scintillator non-proportionality. The core cause is that the interaction of radiation with matter invariably leads to a non-uniform ionization density in the scintillator, coupled with the fact that the light yield depends on the ionization density. The mechanisms that lead to the luminescence dependence on ionization density are incompletely understood, but several important features have been identified, notably Auger-like processes (where two carriers of excitation interact with each other, causing one to de-excite non-radiatively), the inability of excitation carriers to recombine (caused either by trapping or physical separation), and the carrier mobility. This paper reviews the present understanding of the fundamental origins of scintillator non-proportionality, specifically the various theories that have been used to explain non-proportionality.

Spectrum of MRI findings in clinical athletic pubalgia.

PubMed

Zajick, Donald C; Zoga, Adam C; Omar, Imran M; Meyers, William C

2008-03-01

Athletic pubalgia is a frequently encountered syndrome for clinicians who treat active patients participating in a wide variety of athletic endeavors worldwide. Pathologies associated with this clinical scenario span anatomically from the pubic symphysis to the hip and include a myriad of poorly understood and incompletely described musculoskeletal entities, many of which are centered about the pubic symphysis and its tendinous attachments. In this article, we discuss the relevant anatomy and pathophysiology for the most frequently encountered of these disorders, using magnetic resonance (MR) images as a guide. We describe an MR imaging protocol tailored to clinical athletic pubalgia. We then review reproducible MRI patterns of pathology about the pubic symphysis, the rectus abdominis/adductor aponeurosis and the inguinal ring, as well as a group of clinically confounding entities remote from the symphysis but visible by MRI.

Endothelial Response to Glucocorticoids in Inflammatory Diseases

PubMed Central

Zielińska, Karolina A.; Van Moortel, Laura; Opdenakker, Ghislain; De Bosscher, Karolien; Van den Steen, Philippe E.

2016-01-01

The endothelium plays a crucial role in inflammation. A balanced control of inflammation requires the action of glucocorticoids (GCs), steroidal hormones with potent cell-specific anti-inflammatory properties. Besides the classic anti-inflammatory effects of GCs on leukocytes, recent studies confirm that endothelial cells also represent an important target for GCs. GCs regulate different aspects of endothelial physiology including expression of adhesion molecules, production of pro-inflammatory cytokines and chemokines, and maintenance of endothelial barrier integrity. However, the regulation of endothelial GC sensitivity remains incompletely understood. In this review, we specifically examine the endothelial response to GCs in various inflammatory diseases ranging from multiple sclerosis, stroke, sepsis, and vasculitis to atherosclerosis. Shedding more light on the cross talk between GCs and endothelium will help to improve existing therapeutic strategies and develop new therapies better tailored to the needs of patients. PMID:28018358

Abdominal Sepsis.

PubMed

De Waele, Jan J

2016-08-01

Abdominal infections are an important challenge for the intensive care physician. In an era of increasing antimicrobial resistance, selecting the appropriate regimen is important and, with new drugs coming to the market, correct use is important more than ever before and abdominal infections are an excellent target for antimicrobial stewardship programs. Biomarkers may be helpful, but their exact role in managing abdominal infections remains incompletely understood. Source control also remains an ongoing conundrum, and evidence is increasing that its importance supersedes the impact of antibiotic therapy. New strategies such as open abdomen management may offer added benefit in severely ill patients, but more data are needed to identify its exact role. The role of fungi and the need for antifungal coverage, on the other hand, have been investigated extensively in recent years, but at this point, it remains unclear who requires empirical as well as directed therapy.

Pathophysiological Mechanisms of Chronic Venous Disease and Implications for Venoactive Drug Therapy.

PubMed

Mansilha, Armando; Sousa, Joel

2018-06-05

Chronic venous disease (CVD) is a common pathology, with significant physical and psychological impacts for patients and high economic costs for national healthcare systems. Throughout the last decades, several risk factors for this condition have been identified, but only recently, have the roles of inflammation and endothelial dysfunction been properly assessed. Although still incompletely understood, current knowledge of the pathophysiological mechanisms of CVD reveals several potential targets and strategies for therapeutic intervention, some of which are addressable by currently available venoactive drugs. The roles of these drugs in the clinical improvement of venous tone and contractility, reduction of edema and inflammation, as well as in improved microcirculation and venous ulcer healing have been studied extensively, with favorable results reported in the literature. Here, we aim to review these pathophysiological mechanisms and their implications regarding currently available venoactive drug therapies.

The skeletal consequences of thyrotoxicosis.

PubMed

Nicholls, Jonathan J; Brassill, Mary Jane; Williams, Graham R; Bassett, J H Duncan

2012-06-01

Euthyroid status is essential for normal skeletal development and the maintenance of adult bone structure and strength. Established thyrotoxicosis has long been recognised as a cause of high bone turnover osteoporosis and fracture but more recent studies have suggested that subclinical hyperthyroidism and long-term suppressive doses of thyroxine (T4) may also result in decreased bone mineral density (BMD) and an increased risk of fragility fracture, particularly in postmenopausal women. Furthermore, large population studies of euthyroid individuals have demonstrated that a hypothalamic-pituitary-thyroid axis set point at the upper end of the normal reference range is associated with reduced BMD and increased fracture susceptibility. Despite these findings, the cellular and molecular mechanisms of thyroid hormone action in bone remain controversial and incompletely understood. In this review, we discuss the role of thyroid hormones in bone and the skeletal consequences of hyperthyroidism.

PNUTS functions as a proto-oncogene by sequestering PTEN

PubMed Central

Kavela, Sridhar; Shinde, Swapnil R; Ratheesh, Raman; Viswakalyan, Kotapalli; Bashyam, Murali D; Gowrishankar, Swarnalata; Vamsy, Mohana; Pattnaik, Sujit; Rao, Subramanyeshwar; Sastry, Regulagadda A; Srinivasulu, Mukta; Chen, Junjie; Maddika, Subbareddy

2012-01-01

PTEN is a well-defined tumor suppressor gene that antagonizes the PI3K/Akt pathway to regulate a multitude of cellular processes such as survival, growth, motility, invasiveness and angiogenesis. While the functions of PTEN have been studied extensively, the regulation of its activity during normal and disease conditions still remains incompletely understood. In this study, we identified the protein phosphatase-1 nuclear targeting subunit PNUTS (PPP1R10) as a PTEN associated protein. PNUTS directly interacted with the lipid-binding domain (C2 domain) of PTEN and sequestered it in the nucleus. Depletion of PNUTS leads to increased apoptosis and reduced cellular proliferation in a PTEN-dependent manner. PNUTS expression was elevated in certain cancers compared to matched normal tissues. Collectively, our studies reveal PNUTS as a novel PTEN regulator and a likely oncogene. PMID:23117887

MicroRNAs enriched in hematopoietic stem cells differentially regulate long-term hematopoietic output.

PubMed

O'Connell, Ryan M; Chaudhuri, Aadel A; Rao, Dinesh S; Gibson, William S J; Balazs, Alejandro B; Baltimore, David

2010-08-10

The production of blood cells depends on a rare hematopoietic stem-cell (HSC) population, but the molecular mechanisms underlying HSC biology remain incompletely understood. Here, we identify a subset of microRNAs (miRNAs) that is enriched in HSCs compared with other bone-marrow cells. An in vivo gain-of-function screen found that three of these miRNAs conferred a competitive advantage to engrafting hematopoietic cells, whereas other HSC miRNAs attenuated production of blood cells. Overexpression of the most advantageous miRNA, miR-125b, caused a dose-dependent myeloproliferative disorder that progressed to a lethal myeloid leukemia in mice and also enhanced hematopoietic engraftment in human immune system mice. Our study identifies an evolutionarily conserved subset of miRNAs that is expressed in HSCs and functions to modulate hematopoietic output.

SERCA directs cell migration and branching across species and germ layers

PubMed Central

Lansdale, Nick; Navarro, Sonia; Truong, Thai V.; Bower, Dan J.; Featherstone, Neil C.; Connell, Marilyn G.; Al Alam, Denise; Frey, Mark R.; Trinh, Le A.; Fernandez, G. Esteban; Warburton, David; Fraser, Scott E.; Bennett, Daimark; Jesudason, Edwin C.

2017-01-01

ABSTRACT Branching morphogenesis underlies organogenesis in vertebrates and invertebrates, yet is incompletely understood. Here, we show that the sarco-endoplasmic reticulum Ca2+ reuptake pump (SERCA) directs budding across germ layers and species. Clonal knockdown demonstrated a cell-autonomous role for SERCA in Drosophila air sac budding. Live imaging of Drosophila tracheogenesis revealed elevated Ca2+ levels in migratory tip cells as they form branches. SERCA blockade abolished this Ca2+ differential, aborting both cell migration and new branching. Activating protein kinase C (PKC) rescued Ca2+ in tip cells and restored cell migration and branching. Likewise, inhibiting SERCA abolished mammalian epithelial budding, PKC activation rescued budding, while morphogens did not. Mesoderm (zebrafish angiogenesis) and ectoderm (Drosophila nervous system) behaved similarly, suggesting a conserved requirement for cell-autonomous Ca2+ signaling, established by SERCA, in iterative budding. PMID:28821490

Patent Ductus Arteriosus Ligation and Adverse Outcomes: Causality or Bias?

PubMed Central

Weisz, Dany E.; McNamara, Patrick J.

2014-01-01

Observational studies have associated patent ductus arteriosus (PDA) ligation in preterm infants with increased chronic lung disease (CLD), retinopathy of prematurity, and neurodevelopmental impairment at long-term follow-up. Although the biological rationale for this association is incompletely understood, there is an emerging secular trend toward a permissive approach to the PDA. However, insufficient adjustment for postnatal, pre-ligation confounders, such as intraventricular hemorrhage and the duration and intensity of mechanical ventilation, suggests the presence of residual bias due to confounding by indication, and obliges caution in interpreting the ligation-morbidity relationship. A period of conservative management after failure of medical PDA closure may be considered to reduce the number of infants treated with surgery. Increased mortality and CLD in infants with persistent symptomatic PDA suggests that surgical ligation remains an important treatment modality for preterm infants. PMID:25024972

A novel ALS-associated variant in UBQLN4 regulates motor axon morphogenesis

PubMed Central

Edens, Brittany M; Yan, Jianhua; Miller, Nimrod; Deng, Han-Xiang; Siddique, Teepu; Ma, Yongchao C

2017-01-01

The etiological underpinnings of amyotrophic lateral sclerosis (ALS) are complex and incompletely understood, although contributions to pathogenesis by regulators of proteolytic pathways have become increasingly apparent. Here, we present a novel variant in UBQLN4 that is associated with ALS and show that its expression compromises motor axon morphogenesis in mouse motor neurons and in zebrafish. We further demonstrate that the ALS-associated UBQLN4 variant impairs proteasomal function, and identify the Wnt signaling pathway effector beta-catenin as a UBQLN4 substrate. Inhibition of beta-catenin function rescues the UBQLN4 variant-induced motor axon phenotypes. These findings provide a strong link between the regulation of axonal morphogenesis and a new ALS-associated gene variant mediated by protein degradation pathways. DOI: http://dx.doi.org/10.7554/eLife.25453.001 PMID:28463112

Visualizing uncertainty about the future.

PubMed

Spiegelhalter, David; Pearson, Mike; Short, Ian

2011-09-09

We are all faced with uncertainty about the future, but we can get the measure of some uncertainties in terms of probabilities. Probabilities are notoriously difficult to communicate effectively to lay audiences, and in this review we examine current practice for communicating uncertainties visually, using examples drawn from sport, weather, climate, health, economics, and politics. Despite the burgeoning interest in infographics, there is limited experimental evidence on how different types of visualizations are processed and understood, although the effectiveness of some graphics clearly depends on the relative numeracy of an audience. Fortunately, it is increasingly easy to present data in the form of interactive visualizations and in multiple types of representation that can be adjusted to user needs and capabilities. Nonetheless, communicating deeper uncertainties resulting from incomplete or disputed knowledge--or from essential indeterminacy about the future--remains a challenge.

Adrenomedullin and endocrine control of immune cells during pregnancy.

PubMed

Matson, Brooke C; Caron, Kathleen M

2014-09-01

The immunology of pregnancy is complex and incompletely understood. Aberrant immune activity in the decidua and in the placenta is believed to play a role in diseases of pregnancy, such as infertility, miscarriage, fetal growth restriction and preeclampsia. Here, we briefly review the endocrine control of uterine natural killer cell populations and their functions by the peptide hormone adrenomedullin. Studies in genetic animal models have revealed the critical importance of adrenomedullin dosage at the maternal-fetal interface, with cells from both the maternal and fetal compartments contributing to essential aspects underlying appropriate uterine receptivity, implantation and vascular remodeling of spiral arteries. These basic insights into the crosstalk between the endocrine and immune systems within the maternal-fetal interface may ultimately translate to a better understanding of the functions and consequences of dysregulated adrenomedullin levels in clinically complicated pregnancies.

Mammalian autophagy and the plasma membrane.

PubMed

Pavel, Mariana; Rubinsztein, David C

2017-03-01

Autophagy (literally 'self-eating') is an evolutionarily conserved degradation process where cytoplasmic components are engulfed by vesicles called autophagosomes, which are then delivered to lysosomes, where their contents are degraded. Under stress conditions, such as starvation or oxidative stress, autophagy is upregulated in order to degrade macromolecules and restore the nutrient balance. The source of membranes that participate in the initial formation of phagophores is still incompletely understood and many intracellular structures have been shown to act as lipid donors, including the endoplasmic reticulum, Golgi, nucleus, mitochondria and the plasma membrane. Here, we focus on the contributions of the plasma membrane to autophagosome biogenesis governed by ATG16L1 and ATG9A trafficking, and summarize the physiological and pathological implications of this macroautophagy route, from development and stem cell fate to neurodegeneration and cancer. © 2016 Federation of European Biochemical Societies.

The role of calcium and predation on plate morph evolution in the three-spined stickleback (Gasterosteus aculeatus)

PubMed Central

Smith, Carl; Spence, Rowena; Barber, Iain; Przybylski, Mirosław; Wootton, Robert J

2014-01-01

While the genetic basis to plate morph evolution of the three-spined stickleback (Gasterosteus aculeatus) is well described, the environmental variables that select for different plate and spine morphs are incompletely understood. Using replicate populations of three-spined sticklebacks on North Uist, Scotland, we previously investigated the role of predation pressure and calcium limitation on the adaptive evolution of stickleback morphology and behavior. While dissolved calcium proved a significant predictor of plate and spine morph, predator abundance did not. Ecol. Evol., xxx, 2014 and xxx performed a comparable analysis to our own to address the same question. They failed to detect a significant effect of dissolved calcium on morphological evolution, but did establish a significant effect of predation; albeit in the opposite direction to their prediction. PMID:25478147

Arc expression identifies the lateral amygdala fear memory trace

PubMed Central

Gouty-Colomer, L A; Hosseini, B; Marcelo, I M; Schreiber, J; Slump, D E; Yamaguchi, S; Houweling, A R; Jaarsma, D; Elgersma, Y; Kushner, S A

2016-01-01

Memories are encoded within sparsely distributed neuronal ensembles. However, the defining cellular properties of neurons within a memory trace remain incompletely understood. Using a fluorescence-based Arc reporter, we were able to visually identify the distinct subset of lateral amygdala (LA) neurons activated during auditory fear conditioning. We found that Arc-expressing neurons have enhanced intrinsic excitability and are preferentially recruited into newly encoded memory traces. Furthermore, synaptic potentiation of thalamic inputs to the LA during fear conditioning is learning-specific, postsynaptically mediated and highly localized to Arc-expressing neurons. Taken together, our findings validate the immediate-early gene Arc as a molecular marker for the LA neuronal ensemble recruited during fear learning. Moreover, these results establish a model of fear memory formation in which intrinsic excitability determines neuronal selection, whereas learning-related encoding is governed by synaptic plasticity. PMID:25802982

On the uncertainty of interdisciplinarity measurements due to incomplete bibliographic data.

PubMed

Calatrava Moreno, María Del Carmen; Auzinger, Thomas; Werthner, Hannes

The accuracy of interdisciplinarity measurements is directly related to the quality of the underlying bibliographic data. Existing indicators of interdisciplinarity are not capable of reflecting the inaccuracies introduced by incorrect and incomplete records because correct and complete bibliographic data can rarely be obtained. This is the case for the Rao-Stirling index, which cannot handle references that are not categorized into disciplinary fields. We introduce a method that addresses this problem. It extends the Rao-Stirling index to acknowledge missing data by calculating its interval of uncertainty using computational optimization. The evaluation of our method indicates that the uncertainty interval is not only useful for estimating the inaccuracy of interdisciplinarity measurements, but it also delivers slightly more accurate aggregated interdisciplinarity measurements than the Rao-Stirling index.

Protein structure estimation from NMR data by matrix completion.

PubMed

Li, Zhicheng; Li, Yang; Lei, Qiang; Zhao, Qing

2017-09-01

Knowledge of protein structures is very important to understand their corresponding physical and chemical properties. Nuclear Magnetic Resonance (NMR) spectroscopy is one of the main methods to measure protein structure. In this paper, we propose a two-stage approach to calculate the structure of a protein from a highly incomplete distance matrix, where most data are obtained from NMR. We first randomly "guess" a small part of unobservable distances by utilizing the triangle inequality, which is crucial for the second stage. Then we use matrix completion to calculate the protein structure from the obtained incomplete distance matrix. We apply the accelerated proximal gradient algorithm to solve the corresponding optimization problem. Furthermore, the recovery error of our method is analyzed, and its efficiency is demonstrated by several practical examples.

Integrated Force Method for Indeterminate Structures

NASA Technical Reports Server (NTRS)

Hopkins, Dale A.; Halford, Gary R.; Patnaik, Surya N.

2008-01-01

Two methods of solving indeterminate structural-mechanics problems have been developed as products of research on the theory of strain compatibility. In these methods, stresses are considered to be the primary unknowns (in contrast to strains and displacements being considered as the primary unknowns in some prior methods). One of these methods, denoted the integrated force method (IFM), makes it possible to compute stresses, strains, and displacements with high fidelity by use of modest finite-element models that entail relatively small amounts of computation. The other method, denoted the completed Beltrami Mitchell formulation (CBMF), enables direct determination of stresses in an elastic continuum with general boundary conditions, without the need to first calculate displacements as in traditional methods. The equilibrium equation, the compatibility condition, and the material law are the three fundamental concepts of the theory of structures. For almost 150 years, it has been commonly supposed that the theory is complete. However, until now, the understanding of the compatibility condition remained incomplete, and the compatibility condition was confused with the continuity condition. Furthermore, the compatibility condition as applied to structures in its previous incomplete form was inconsistent with the strain formulation in elasticity.

The geometry of protein hydration

NASA Astrophysics Data System (ADS)

Persson, Filip; Söderhjelm, Pär; Halle, Bertil

2018-06-01

Based on molecular dynamics simulations of four globular proteins in dilute aqueous solution, with three different water models, we examine several, essentially geometrical, aspects of the protein-water interface that remain controversial or incompletely understood. First, we compare different hydration shell definitions, based on spatial or topological proximity criteria. We find that the best method for constructing monolayer shells with nearly complete coverage is to use a 5 Å water-carbon cutoff and a 4 Å water-water cutoff. Using this method, we determine a mean interfacial water area of 11.1 Å2 which appears to be a universal property of the protein-water interface. We then analyze the local coordination and packing density of water molecules in the hydration shells and in subsets of the first shell. The mean polar water coordination number in the first shell remains within 1% of the bulk-water value, and it is 5% lower in the nonpolar part of the first shell. The local packing density is obtained from additively weighted Voronoi tessellation, arguably the most physically realistic method for allocating space between protein and water. We find that water in all parts of the first hydration shell, including the nonpolar part, is more densely packed than in the bulk, with a shell-averaged density excess of 6% for all four proteins. We suggest reasons why this value differs from previous experimental and computational results, emphasizing the importance of a realistic placement of the protein-water dividing surface and the distinction between spatial correlation and packing density. The protein-induced perturbation of water coordination and packing density is found to be short-ranged, with an exponential decay "length" of 0.6 shells. We also compute the protein partial volume, analyze its decomposition, and argue against the relevance of electrostriction.

Estimating gene gain and loss rates in the presence of error in genome assembly and annotation using CAFE 3.

PubMed

Han, Mira V; Thomas, Gregg W C; Lugo-Martinez, Jose; Hahn, Matthew W

2013-08-01

Current sequencing methods produce large amounts of data, but genome assemblies constructed from these data are often fragmented and incomplete. Incomplete and error-filled assemblies result in many annotation errors, especially in the number of genes present in a genome. This means that methods attempting to estimate rates of gene duplication and loss often will be misled by such errors and that rates of gene family evolution will be consistently overestimated. Here, we present a method that takes these errors into account, allowing one to accurately infer rates of gene gain and loss among genomes even with low assembly and annotation quality. The method is implemented in the newest version of the software package CAFE, along with several other novel features. We demonstrate the accuracy of the method with extensive simulations and reanalyze several previously published data sets. Our results show that errors in genome annotation do lead to higher inferred rates of gene gain and loss but that CAFE 3 sufficiently accounts for these errors to provide accurate estimates of important evolutionary parameters.

Sparse subspace clustering for data with missing entries and high-rank matrix completion.

PubMed

Fan, Jicong; Chow, Tommy W S

2017-09-01

Many methods have recently been proposed for subspace clustering, but they are often unable to handle incomplete data because of missing entries. Using matrix completion methods to recover missing entries is a common way to solve the problem. Conventional matrix completion methods require that the matrix should be of low-rank intrinsically, but most matrices are of high-rank or even full-rank in practice, especially when the number of subspaces is large. In this paper, a new method called Sparse Representation with Missing Entries and Matrix Completion is proposed to solve the problems of incomplete-data subspace clustering and high-rank matrix completion. The proposed algorithm alternately computes the matrix of sparse representation coefficients and recovers the missing entries of a data matrix. The proposed algorithm recovers missing entries through minimizing the representation coefficients, representation errors, and matrix rank. Thorough experimental study and comparative analysis based on synthetic data and natural images were conducted. The presented results demonstrate that the proposed algorithm is more effective in subspace clustering and matrix completion compared with other existing methods. Copyright © 2017 Elsevier Ltd. All rights reserved.

3D Characteristics

NASA Technical Reports Server (NTRS)

Holt, Maurice

1998-01-01

Contributions to the Method of Characteristics in Three Dimensions, which previously received incomplete recognition, are reviewed. They mostly follow from a fundamental paper by Rusanov which led to several developments in Russia, described by Chushkin.

Bone marrow stimulation of the medial femoral condyle produces inferior cartilage and bone repair compared to the trochlea in a rabbit surgical model.

PubMed

Chen, Hongmei; Chevrier, Anik; Hoemann, Caroline D; Sun, Jun; Picard, Genevieve; Buschmann, Michael D

2013-11-01

The influence of the location of cartilage lesions on cartilage repair outcome is incompletely understood. This study compared cartilage and bone repair in medial femoral condylar (MFC) versus femoral trochlear (TR) defects 3 months after bone marrow stimulation in mature rabbits. Intact femurs from adult rabbits served as controls. Results from quantitative histomorphometry and histological scoring showed that bone marrow stimulation produced inferior soft tissue repair in MFC versus TR defects, as indicated by significantly lower % Fill (p = 0.03), a significant increase in collagen type I immunostaining (p < 0.00001) and lower O'Driscoll scores (p < 0.05). 3D micro-CT analysis showed that repaired TR defects regained normal un-operated values of bone volume fraction, trabecular thickness, and trabecular number, whereas in MFC defects the repaired bone architecture appeared immature and less dense compared to intact un-operated MFC controls (p < 0.0001). Severe medial meniscal damage was found in 28% of operated animals and was strongly correlated with (i) low cartilage defect fill, (ii) incomplete bone repair in MFC, and (iii) with a more posterior defect placement in the weight-bearing region. We conclude that the location of cartilage lesions influences cartilage repair, with better outcome in TR versus MFC defects in rabbits. Meniscal degeneration is associated with cartilage damage. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

The Diagnostic Value of Anti-Müllerian Hormone in Early Post Menarche Adolescent Girls with Polycystic Ovarian Syndrome.

PubMed

Kocaay, Pınar; Siklar, Zeynep; Buyukfirat, Sema; Berberoglu, Merih

2018-02-17

Polycystic ovarian syndrome (PCOS) is a common endocrine disorder characterized by hyperandrogenism and chronic anovulation, which affects 5%-10% of reproductive-age women. Diagnosis of adult patients with PCOS is made easily with clinical and laboratory methods and the anti-Müllerian hormone (AMH) level are accepted as a good indicator. However, there is still no complete consensus on the diagnosis of PCOS in adolescents. Prospective cohort study, December 2013 to November 2014. The study was conducted on adolescent girls with oligomenorrhea, with at least 2 years since menarche. The study group consisted of adolescent girls with complete PCOS and incomplete PCOS. A control group was formed of healthy adolescent girls. Complete PCOS was diagnosed according to the Rotterdam criteria, as the presence of all the following characteristics: oligomenorrhea, hyperandrogenism, and polycystic ovarian morphology on ultrasound image. Incomplete PCOS was accepted as "oligomenorrhea and polycystic ovarian morphology," or "oligomenorrhea and hyperandrogenism." All patients underwent a physical examination and the anthropometric assessments, insulin resistance, and acanthosis nigricans were recorded. It was also noted whether or not the patient had an acne score. The Ferriman-Gallwey score was applied to evaluate hirsutism. The results of this study showed that no statistically significant difference was found between the PCOS and incomplete PCOS groups and the control group with respect to AMH levels. The use of adult-specific diagnostic methods in adolescence might result in an incomplete diagnosis and inadequate treatment plan. Although the serum AMH level clearly facilitates the diagnosis of PCOS, the use of the AMH level in adolescence in PCOS diagnosis is still controversial and further studies are needed. Copyright © 2018 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Matriculation Research Report: Incomplete Grades; Data & Analysis.

ERIC Educational Resources Information Center

Gerda, Joe

The policy on incomplete grades at California's College of the Canyons states that incompletes may only be given under circumstances beyond students' control and that students must make arrangements with faculty prior to the end of the semester to clear the incomplete. Failure to complete an incomplete may result in an "F" grade. While…

Clinical antibacterial effectiveness and biocompatibility of gaseous ozone after incomplete caries removal.

PubMed

Krunić, Jelena; Stojanović, Nikola; Đukić, Ljiljana; Roganović, Jelena; Popović, Branka; Simić, Ivana; Stojić, Dragica

2018-06-01

To evaluate local effect of gaseous ozone on bacteria in deep carious lesions after incomplete caries removal, using chlorhexidine as control, and to investigate its effect on pulp vascular endothelial growth factor (VEGF), neuronal nitric oxide synthase (nNOS), and superoxide dismutase (SOD). Antibacterial effect was evaluated in 48 teeth with diagnosed deep carious lesion. After incomplete caries removal, teeth were randomly allocated into two groups regarding the cavity disinfectant used: ozone (open system) or 2% chlorhexidine. Dentin samples were analyzed for the presence of total bacteria and Lactobacillus spp. by real-time quantitative polymerase chain reaction. For evaluation of ozone effect on dental pulp, 38 intact permanent teeth indicated for pulp removal/tooth extraction were included. After cavity preparation, teeth were randomly allocated into two groups: ozone group and control group. VEGF/nNOS level and SOD activity in dental pulp were determined by enzyme-linked immunosorbent assay and spectrophotometric method, respectively. Ozone application decreased number of total bacteria (p = 0.001) and Lactobacillus spp. (p < 0.001), similarly to chlorhexidine. The VEGF (p < 0.001) and nNOS (p = 0.012) levels in dental pulp after ozone application were higher, while SOD activity was lower (p = 0.001) comparing to those in control pulp. Antibacterial effect of ozone on residual bacteria after incomplete caries removal was similar to that of 2% chlorhexidine. Effect of ozone on pulp VEGF, nNOS, and SOD indicated its biocompatibility. Ozone appears as effective and biocompatible cavity disinfectant in treatment of deep carious lesions by incomplete caries removal technique.

Changes in Body Temperature in Incomplete Spinal Cord Injury by Digital Infrared Thermographic Imaging

PubMed Central

Song, Yun-Gyu; Won, Yu Hui; Park, Sung-Hee; Ko, Myoung-Hwan

2015-01-01

Objective To investigate changes in the core temperature and body surface temperature in patients with incomplete spinal cord injuries (SCI). In incomplete SCI, the temperature change is difficult to see compared with complete spinal cord injuries. The goal of this study was to better understand thermal regulation in patients with incomplete SCI. Methods Fifty-six SCI patients were enrolled, and the control group consisted of 20 healthy persons. The spinal cord injuries were classified according to International Standards for Neurological Classification of Spinal Cord Injury. The patients were classified into two groups: upper (neurological injury level T6 or above) and lower (neurological injury level T7 or below) SCIs. Body core temperature was measured using an oral thermometer, and body surface temperature was measured using digital infrared thermographic imaging. Results Twenty-nine patients had upper spinal cord injuries, 27 patients had lower SCIs, and 20 persons served as the normal healthy persons. Comparing the skin temperatures of the three groups, the temperatures at the lower abdomen, anterior thigh and anterior tibia in the patients with upper SCIs were lower than those of the normal healthy persons and the patients with lower SCIs. No significant temperature differences were observed between the normal healthy persons and the patients with lower SCIs. Conclusion In our study, we found thermal dysregulation in patients with incomplete SCI. In particular, body surface temperature regulation was worse in upper SCIs than in lower injuries. Moreover, cord injury severity affected body surface temperature regulation in SCI patients. PMID:26605167

Risk factors for massive postpartum bleeding in pregnancies in which incomplete placenta previa are located on the posterior uterine wall

PubMed Central

Lee, Hyun Jung; Lee, Young Jai; Ahn, Eun Hee; Kim, Hyeon Chul; Jung, Sang Hee; Chang, Sung Woon

2017-01-01

Objective To identify factors associated with massive postpartum bleeding in pregnancies complicated by incomplete placenta previa located on the posterior uterine wall. Methods A retrospective case-control study was performed. We identified 210 healthy singleton pregnancies with incomplete placenta previa located on the posterior uterine wall, who underwent elective or emergency cesarean section after 24 weeks of gestation between January 2006 and April 2016. The cases with intraoperative blood loss (≥2,000 mL) or transfusion of packed red blood cells (≥4) or uterine artery embolization or hysterectomy were defined as massive bleeding. Results Twenty-three women experienced postpartum profuse bleeding (11.0%). After multivariable analysis, 4 variables were associated with massive postpartum hemorrhage (PPH): experience of 2 or more prior uterine curettage (adjusted odds ratio [aOR], 4.47; 95% confidence interval [CI], 1.29 to 15.48; P=0.018), short cervical length before delivery (<2.0 cm) (aOR, 7.13; 95% CI, 1.01 to 50.25; P=0.049), fetal non-cephalic presentation (aOR, 12.48; 95% CI, 1.29 to 121.24; P=0.030), and uteroplacental hypervascularity (aOR, 6.23; 95% CI, 2.30 to 8.83; P=0.001). Conclusion This is the first study of cases with incomplete placenta previa located on the posterior uterine wall, which were complicated by massive PPH. Our findings might be helpful to guide obstetric management and provide useful information for prediction of massive PPH in pregnancies with incomplete placenta previa located on the posterior uterine wall. PMID:29184859

Changes in hemodynamics and light scattering during cortical spreading depression

NASA Astrophysics Data System (ADS)

Li, Pengcheng; Yang, Yuanyuan; Luo, Qingming

2005-01-01

Cortical spreading depression (CSD) has been known to play an important role in the mechanism of migraine, stroke and brain injure. Optical imaging of intrinsic signals has been shown a powerful method for characterizing the spatial and temporal pattern of the propagation of CSD. However, the possible physiological mechanisms underlying the intrinsic optical signal (IOS) during CSD still remain incompletely understood. In this study, a spectroscopic recording of the change in optical intrinsic signal during CSD was performed and an analysis method based on the modified Beer-Lambert law was used to estimate the changes in the concentration of HbO2 and Hb, and changes in light scattering from the spectra data. The CSD were induced by pinprick in 10 α-chloralose/urethane anesthetized Sprague-Dawley rats. In all experiments, four-phasic changes in optical reflectance were observed at 450 nm ~ 570 nm, and triphasic changes in optical reflectance were observed in the range of 570 nm ~750 nm. But at 750 nm ~ 850 nm, only biphasic changes of optical signal were detected. Converting the spectra data to the changes in light scattering and concentration of Hb and HbO2, we found that the CSD induced an initial increase in concentration of HbO2 (amplitude: 9.0+/-3.7%), which was 26.2+/-18.6 s earlier than the onset of increase of Hb concentration. Furthermore, the concentration of HbO2 showed a four-phasic change, whereas the concentration of Hb only showed a biphasic change. For the changes in light scattering during CSD, a triphasic change was observed.

Cardiovascular Redox and Ox Stress Proteomics

PubMed Central

Kumar, Vikas; Calamaras, Timothy Dean; Haeussler, Dagmar; Colucci, Wilson Steven; Cohen, Richard Alan; McComb, Mark Errol; Pimentel, David

2012-01-01

Abstract Significance: Oxidative post-translational modifications (OPTMs) have been demonstrated as contributing to cardiovascular physiology and pathophysiology. These modifications have been identified using antibodies as well as advanced proteomic methods, and the functional importance of each is beginning to be understood using transgenic and gene deletion animal models. Given that OPTMs are involved in cardiovascular pathology, the use of these modifications as biomarkers and predictors of disease has significant therapeutic potential. Adequate understanding of the chemistry of the OPTMs is necessary to determine what may occur in vivo and which modifications would best serve as biomarkers. Recent Advances: By using mass spectrometry, advanced labeling techniques, and antibody identification, OPTMs have become accessible to a larger proportion of the scientific community. Advancements in instrumentation, database search algorithms, and processing speed have allowed MS to fully expand on the proteome of OPTMs. In addition, the role of enzymatically reversible OPTMs has been further clarified in preclinical models. Critical Issues: The identification of OPTMs suffers from limitations in analytic detection based on the methodology, instrumentation, sample complexity, and bioinformatics. Currently, each type of OPTM requires a specific strategy for identification, and generalized approaches result in an incomplete assessment. Future Directions: Novel types of highly sensitive MS instrumentation that allow for improved separation and detection of modified proteins and peptides have been crucial in the discovery of OPTMs and biomarkers. To further advance the identification of relevant OPTMs in advanced search algorithms, standardized methods for sample processing and depository of MS data will be required. Antioxid. Redox Signal. 17, 1528–1559. PMID:22607061

Surgical excision of skin cancer: the importance of training.

PubMed

Salmon, P; Mortimer, N; Rademaker, M; Adams, L; Stanway, A; Hill, S

2010-01-01

Background Skin cancers are the most common malignancy in New Zealand and their treatment imparts a huge burden on the healthcare system both in terms of the cost of surgical intervention and in treatment delivery (estimates are in excess of NZ$33 million per annum for the year 2000). Currently in New Zealand, skin cancers are excised by dermatologists, general practitioners (GPs), GPs with a special interest in skin surgery (GPSIs) and specialist surgeons with diverse training backgrounds including ear, nose and throat, ophthalmic and general surgeons. To date there is scant literature evaluating complete excision rates following surgical treatment of skin cancer between these vocational groups. Objectives To review retrospectively pathology reports from all skin excisions sent to one private pathology laboratory over three consecutive months. The aim was to investigate the margins of excision and completeness of skin cancer surgery performed by each vocational group. Methods A retrospective analysis of skin pathology reports was undertaken for a 3-month period between April and June 2007. Raw data obtained from the pathology reports included diagnosis, completeness of excision, size of specimens, body site and vocational group of the medical practitioner performing the surgery. Results In total, 1532 lesions were excised: 432 benign and 1100 malignant. Six hundred and seven were from the head and neck. Dermatologists excised 276 lesions of which 93% were malignant, 55% were from the head and neck, and 0% were incompletely excised. GPs excised 633 lesions: 63% malignant, 30% head and neck, 23% incomplete excision of malignant lesions. GPSIs excised 368 lesions: 71% malignant, 35% head and neck, 21.5% incomplete malignant excision. Specialist surgeons excised 255 lesions: 72% malignant, 53% head and neck, 20% incomplete malignant excision. Conclusion GPs and GPSIs excised more benign lesions and had higher incomplete excision rates of skin cancer surgery than dermatologists. Incomplete excision rates for the vocational groups ranged from 0% to 45% depending on site and pathology.

Prognosis of complete versus incomplete revascularisation of patients with STEMI with multivessel coronary artery disease: an observational study

PubMed Central

Dimitriu-Leen, Aukelien C; Hermans, Maaike P J; Veltman, Caroline E; van der Hoeven, Bas L; van Rosendael, Alexander R; van Zwet, Erik W; Schalij, Martin J; Delgado, Victoria; Bax, Jeroen J; Scholte, Arthur J H A

2017-01-01

Objective The best strategy in patients with acute ST-segment elevation myocardial infarction (STEMI) with multivessel coronary artery disease (CAD) regarding completeness of revascularisation of the non-culprit lesion(s) is still unclear. To establish which strategy should be followed, survival rates over a longer period should be evaluated. The aim of this study was to investigate whether complete revascularisation, compared with incomplete revascularisation, is associated with reduced short-term and long-term all-cause mortality in patients with first STEMI and multivessel CAD. Methods This retrospective study consisted of 518 patients with first STEMI with multivessel CAD. Complete revascularisation (45%) was defined as the treatment of any significant coronary artery stenosis (≥70% luminal narrowing) during primary or staged percutaneous coronary intervention prior to discharge. The primary end point was all-cause mortality. Results Incomplete revascularisation was not independently associated with 30-day all-cause mortality in patients with acute first STEMI and multivessel CAD (OR 1.98; 95% CI 0.62to6.37; p=0.25). During a median long-term follow-up of 6.7 years, patients with STEMI with multivessel CAD and incomplete revascularisation showed higher mortality rates compared with patients who received complete revascularisation (24% vs 12%, p<0.001), and these differences remained after excluding the first 30 days. However, in multivariate analysis, incomplete revascularisation was not independently associated with increased all-cause mortality during long-term follow-up in the group of patients with STEMI who survived the first 30 days post-STEMI (HR 1.53 95% CI 0.89-2.61, p=0.12). Conclusion In patients with acute first STEMI and multivessel CAD, incomplete revascularisation compared with complete revascularisation was not independently associated with increased short-term and long-term all-cause mortality. PMID:28409009

Type and Location of Placenta Previa Affect Preterm Delivery Risk Related to Antepartum Hemorrhage

PubMed Central

Sekiguchi, Atsuko; Nakai, Akihito; Kawabata, Ikuno; Hayashi, Masako; Takeshita, Toshiyuki

2013-01-01

Purpose: To evaluate whether type and location of placenta previa affect risk of antepartum hemorrhage-related preterm delivery. Methods: We retrospectively studied 162 women with singleton pregnancies presenting placenta previa. Through observation using transvaginal ultrasound the women were categorized into complete or incomplete placenta previa, and then assigned to anterior and posterior groups. Complete placenta previa was defined as a placenta that completely covered the internal cervical os, with the placental margin >2 cm from the os. Incomplete placenta previa comprised marginal placenta previa whose margin adjacent to the internal os and partial placenta previa which covered the os but the margin situated within 2 cm of the os. Maternal characteristics and perinatal outcomes in complete and incomplete placenta previa were compared, and the differences between the anterior and the posterior groups were evaluated. Results: Antepartum hemorrhage was more prevalent in women with complete placenta previa than in those with incomplete placenta previa (59.1% versus 17.6%), resulting in the higher incidence of preterm delivery in women with complete than in those with incomplete placenta previa [45.1% versus 8.8%; odds ratio (OR) 8.51; 95% confidence interval (CI) 3.59-20.18; p < 0.001]. In complete placenta previa, incidence of antepartum hemorrhage did not significantly differ between the anterior and the posterior groups. However, gestational age at bleeding onset was lower in the anterior group than in the posterior group, and the incidence of preterm delivery was higher in the anterior group than in the posterior group (76.2% versus 32.0%; OR 6.8; 95% CI 2.12-21.84; p = 0.002). In incomplete placenta previa, gestational age at delivery did not significantly differ between the anterior and posterior groups. Conclusion: Obstetricians should be aware of the increased risk of preterm delivery related to antepartum hemorrhage in women with complete placenta previa, particularly when the placenta is located on the anterior wall. PMID:24151440

PoMo: An Allele Frequency-Based Approach for Species Tree Estimation

PubMed Central

De Maio, Nicola; Schrempf, Dominik; Kosiol, Carolin

2015-01-01

Incomplete lineage sorting can cause incongruencies of the overall species-level phylogenetic tree with the phylogenetic trees for individual genes or genomic segments. If these incongruencies are not accounted for, it is possible to incur several biases in species tree estimation. Here, we present a simple maximum likelihood approach that accounts for ancestral variation and incomplete lineage sorting. We use a POlymorphisms-aware phylogenetic MOdel (PoMo) that we have recently shown to efficiently estimate mutation rates and fixation biases from within and between-species variation data. We extend this model to perform efficient estimation of species trees. We test the performance of PoMo in several different scenarios of incomplete lineage sorting using simulations and compare it with existing methods both in accuracy and computational speed. In contrast to other approaches, our model does not use coalescent theory but is allele frequency based. We show that PoMo is well suited for genome-wide species tree estimation and that on such data it is more accurate than previous approaches. PMID:26209413

Generalized Cross Entropy Method for estimating joint distribution from incomplete information

NASA Astrophysics Data System (ADS)

Xu, Hai-Yan; Kuo, Shyh-Hao; Li, Guoqi; Legara, Erika Fille T.; Zhao, Daxuan; Monterola, Christopher P.

2016-07-01

Obtaining a full joint distribution from individual marginal distributions with incomplete information is a non-trivial task that continues to challenge researchers from various domains including economics, demography, and statistics. In this work, we develop a new methodology referred to as ;Generalized Cross Entropy Method; (GCEM) that is aimed at addressing the issue. The objective function is proposed to be a weighted sum of divergences between joint distributions and various references. We show that the solution of the GCEM is unique and global optimal. Furthermore, we illustrate the applicability and validity of the method by utilizing it to recover the joint distribution of a household profile of a given administrative region. In particular, we estimate the joint distribution of the household size, household dwelling type, and household home ownership in Singapore. Results show a high-accuracy estimation of the full joint distribution of the household profile under study. Finally, the impact of constraints and weight on the estimation of joint distribution is explored.

Intrauterine growth restriction and hypospadias: is there a connection?

PubMed Central

2014-01-01

Hypospadias is one of the most common congenital malformations of the genitourinary tract in males. It is an incomplete fusion of urethral folds early in fetal development and may be associated with other malformations of the genital tract. The etiology is poorly understood and may be hormonal, genetic, or environmental, but most often is idiopathic or multifactorial. Among many possible risk factors identified, of particular importance is low birth weight, which is defined in various ways in the literature. No mechanism has been identified for the association of low birth weight and hypospadias, but some authors propose placental insufficiency as a common inciting factor. Currently, there is no standardized approach for evaluating children with hypospadias in the setting of intrauterine growth restriction. We reviewed the available published literature on the association of hypospadias and growth restriction to determine whether it should be considered a separate entity within the category of disorders of sexual differentiation. PMID:25337123

Optical Imaging and Control of Neurons

NASA Astrophysics Data System (ADS)

Song, Yoon-Kyu

Although remarkable progress has been made in our understanding of the function, organization, and development of the brain by various approaches of modern science and technology, how the brain performs its marvelous function remains unsolved or incompletely understood. This is mainly attributed to the insufficient capability of currently available research tools and conceptual frameworks to deal with enormous complexity of the brain. Hence, in the last couple of decades, a significant effort has been made to crack the complexity of brain by utilizing research tools from diverse scientific areas. The research tools include the optical neurotechnology which incorporates the exquisite characteristics of optics, such as multi-parallel access and non-invasiveness, in sensing and stimulating the excitable membrane of a neuron, the basic functional unit of the brain. This chapter is aimed to serve as a short introduction to the optical neurotechnology for those who wish to use optical techniques as one of their brain research tools.

High expression of A-type lamin in the leading front is required for Drosophila thorax closure.

PubMed

Kosakamoto, Hina; Fujisawa, Yuya; Obata, Fumiaki; Miura, Masayuki

2018-05-05

Tissue closure involves the coordinated unidirectional movement of a group of cells without loss of cell-cell contact. However, the molecular mechanisms controlling the tissue closure are not fully understood. Here, we demonstrate that Lamin C, the sole A-type lamin in Drosophila, contributes to the process of thorax closure in pupa. High expression of Lamin C was observed at the leading front of the migrating wing imaginal discs. Live imaging analysis revealed that knockdown of Lamin C in the thorax region affected the coordinated movement of the leading front, resulting in incomplete tissue fusion required for formation of the adult thorax. The closure defect due to knockdown of Lamin C correlated with insufficient accumulation of F-actin at the front. Our study indicates a link between A-type lamin and the cell migration behavior during tissue closure. Copyright © 2018 Elsevier Inc. All rights reserved.

Antibiotic-induced changes in the microbiota disrupt redox dynamics in the gut

PubMed Central

Reese, Aspen T; Cho, Eugenia H; Klitzman, Bruce; Nichols, Scott P; Wisniewski, Natalie A; Villa, Max M; Durand, Heather K; Jiang, Sharon; Midani, Firas S; Nimmagadda, Sai N; O'Connell, Thomas M; Wright, Justin P; Deshusses, Marc A

2018-01-01

How host and microbial factors combine to structure gut microbial communities remains incompletely understood. Redox potential is an important environmental feature affected by both host and microbial actions. We assessed how antibiotics, which can impact host and microbial function, change redox state and how this contributes to post-antibiotic succession. We showed gut redox potential increased within hours of an antibiotic dose in mice. Host and microbial functioning changed under treatment, but shifts in redox potentials could be attributed specifically to bacterial suppression in a host-free ex vivo human gut microbiota model. Redox dynamics were linked to blooms of the bacterial family Enterobacteriaceae. Ecological succession to pre-treatment composition was associated with recovery of gut redox, but also required dispersal from unaffected gut communities. As bacterial competition for electron acceptors can be a key ecological factor structuring gut communities, these results support the potential for manipulating gut microbiota through managing bacterial respiration. PMID:29916366

Hyaline-Vascular Type Castleman's Disease, Sarcoidosis, and Crohns Disease.

PubMed

Gupta, Arjun; Ayyar, Balaji; Zia, Hamid; Chen, Weina; Harris, Samar; Naina, Harris V

2016-06-01

Sarcoidosis and Crohns disease have been associated with increased long term risk of lymphoproliferative disorders, including lymphomas. Newly developed lymphadenopathy in a patient with these disorders should prompt pathological evaluation. Castleman's disease is a lymphoproliferative disorder characterized by enlarged hyperplastic lymph nodes with regressed follicles surrounded by expanded mantle zones of small lymphocytes, and interfollicular vascular proliferation in the hyaline-vascular type. Similar to sarcoidosis and Crohns disease, its etiology is incompletely understood, although immune dysregulation, genetic factors and infectious and environmental factors are thought to play a role in all three diseases. Interleukin-6 is a possible pathological common factor between these three disease processed. Unicentric, hyaline-vascular type Castleman's disease can be treated successfully with complete surgical resection. We report a patient with long history of sarcoidosis and Crohns disease with newly developed lymphadenopathy which was found to be due to Castleman's disease.

Cardiac myofilaments: mechanics and regulation

NASA Technical Reports Server (NTRS)

de Tombe, Pieter P.; Bers, D. M. (Principal Investigator)

2003-01-01

The mechanical properties of the cardiac myofilament are an important determinant of pump function of the heart. This report is focused on the regulation of myofilament function in cardiac muscle. Calcium ions form the trigger that induces activation of the thin filament which, in turn, allows for cross-bridge formation, ATP hydrolysis, and force development. The structure and protein-protein interactions of the cardiac sarcomere that are responsible for these processes will be reviewed. The molecular mechanism that underlies myofilament activation is incompletely understood. Recent experimental approaches have been employed to unravel the mechanism and regulation of myofilament mechanics and energetics by activator calcium and sarcomere length, as well as contractile protein phosphorylation mediated by protein kinase A. Central to these studies is the question whether such factors impact on muscle function simply by altering thin filament activation state, or whether modulation of cross-bridge cycling also plays a part in the responses of muscle to these stimuli.

The origin, function, and diagnostic potential of extracellular microRNAs in human body fluids.

PubMed

Liang, Hongwei; Gong, Fei; Zhang, Suyang; Zhang, Chen-Yu; Zen, Ke; Chen, Xi

2014-01-01

Recently, numerous studies have documented the importance of microRNAs (miRNAs) as an essential cornerstone of the genetic system. Although RNA is usually considered an unstable molecule because of the ubiquitous ribonuclease, miRNAs are now known to circulate in the bloodstream and other body fluids in a stable, cell-free form. Importantly, extracellular miRNAs are aberrantly present in plasma, serum, and other body fluids during the pathogenesis of many diseases and, thus, are promising noninvasive or minimally invasive biomarkers to assess the pathological status of the body. However, the origin and biological function of extracellular miRNAs remains incompletely understood. In this review, we summarize the recent literature on the biogenesis and working models of extracellular miRNAs, and we highlight the impact of extending these ongoing extracellular miRNA studies to clinical applications. © 2013 John Wiley & Sons, Ltd.

Glaucoma surgery and induced astigmatism: a systematic review.

PubMed

Chan, Helen H L; Kong, Yu Xiang G

2017-01-01

The refractive outcomes of glaucoma surgeries, particularly their effect on astigmatism, are incompletely understood. Trabeculectomy is associated with a considerable amount of with-the-rule astigmatic change in the immediate postoperative period. This is followed by a gradual against-the-rule shift. These changes are altered with the use of mitomycin C (MMC). Non-penetrating surgery such as deep sclerectomy is also associated with a similar or smaller degree of induced astigmatism. Minimally invasive glaucoma surgery appears to be astigmatically neutral. There is no clear evidence regarding refractive outcomes of glaucoma drainage device surgery. Induced astigmatism may account for a reduction in unaided visual acuity in the early postoperative period following a successful trabeculectomy. These changes appear to stabilise at 3 months, and it would be prudent to defer the prescription of new glasses until this time. If sequential cataract surgery is to be performed, toric intraocular lenses can be a useful option for astigmatic correction.

Decision Making: from Neuroscience to Psychiatry

PubMed Central

Lee, Daeyeol

2013-01-01

Adaptive behaviors increase the likelihood of survival and reproduction and improve the quality of life. However, it is often difficult to identify optimal behaviors in real life due to the complexity of the decision maker’s environment and social dynamics. As a result, although many different brain areas and circuits are involved in decision making, evolutionary and learning solutions adopted by individual decision makers sometimes produce suboptimal outcomes. Although these problems are exacerbated in numerous neurological and psychiatric disorders, their underlying neurobiological causes remain incompletely understood. In this review, theoretical frameworks in economics and machine learning and their applications in recent behavioral and neurobiological studies are summarized. Examples of such applications in clinical domains are also discussed for substance abuse, Parkinson’s disease, attention-deficit/hyperactivity disorder, schizophrenia, mood disorders, and autism. Findings from these studies have begun to lay the foundations necessary to improve diagnostics and treatment for various neurological and psychiatric disorders. PMID:23622061

Poreless eggshells

PubMed Central

Lin, Haifan; Matzuk, Martin M.

2015-01-01

The oocyte is the sole source of the female genetic material that will be fertilized by sperm to form an embryo. Many extrinsic and intrinsic factors are critical for oocyte development and survival; however, these mediators are incompletely understood. In this issue of the JCI, Weinberg-Shukron et al. uncover a novel recessive missense mutation in the gene encoding nucleoporin-107 (NUP107) that results in abnormal ovarian development. Recapitulation of the human mutation in the Drosophila NUP107 ortholog resulted in poor follicular development and demonstrated an evolutionarily conserved and ovary-specific role of NUP107. While NUP107 is required for nuclear pore complex function in somatic cells of flies and women, this specific amino acid change appears only to be disruptive in the ovary. All together, these findings imply that missense mutations in other genes could be specifically disruptive of ovarian or testicular function, while leaving extragonadal function intact. PMID:26485282

Aquaporins-2 and -4 regulate glycogen metabolism and survival during hyposmotic-anoxic stress in Caenorhabditis elegans

PubMed Central

LaMacchia, John C.

2015-01-01

Periods of oxygen deprivation can lead to ion and water imbalances in affected tissues that manifest as swelling (edema). Although oxygen deprivation-induced edema is a major contributor to injury in clinical ischemic diseases such as heart attack and stroke, the pathophysiology of this process is incompletely understood. In the present study we investigate the impact of aquaporin-mediated water transport on survival in a Caenorhabditis elegans model of edema formation during complete oxygen deprivation (anoxia). We find that nematodes lacking aquaporin water channels in tissues that interface with the surrounding environment display decreased edema formation and improved survival rates in anoxia. We also find that these animals have significantly reduced demand for glycogen as an energetic substrate during anoxia. Together, our data suggest that reductions in membrane water permeability may be sufficient to induce a hypometabolic state during oxygen deprivation that reduces injury and extends survival limits. PMID:26017147

Therapeutic targeting of HES1 transcriptional programs in T-ALL

PubMed Central

Schnell, Stephanie A.; Ambesi-Impiombato, Alberto; Sanchez-Martin, Marta; Belver, Laura; Xu, Luyao; Qin, Yue; Kageyama, Ryoichiro

2015-01-01

Oncogenic activation of NOTCH1 signaling plays a central role in the pathogenesis of T-cell acute lymphoblastic leukemia, with mutations on this signaling pathway affecting more than 60% of patients at diagnosis. However, the transcriptional regulatory circuitries driving T-cell transformation downstream of NOTCH1 remain incompletely understood. Here we identify Hairy and Enhancer of Split 1 (HES1), a transcriptional repressor controlled by NOTCH1, as a critical mediator of NOTCH1-induced leukemogenesis strictly required for tumor cell survival. Mechanistically, we demonstrate that HES1 directly downregulates the expression of BBC3, the gene encoding the PUMA BH3-only proapoptotic factor in T-cell acute lymphoblastic leukemia. Finally, we identify perhexiline, a small-molecule inhibitor of mitochondrial carnitine palmitoyltransferase-1, as a HES1-signature antagonist drug with robust antileukemic activity against NOTCH1-induced leukemias in vitro and in vivo. PMID:25784680

Adenosine and Ischemic Preconditioning

PubMed Central

Liang, Bruce T.; Swierkosz, Tomasz A.; Herrmann, Howard C.; Kimmel, Stephen; Jacobson, Kenneth A.

2012-01-01

Adenosine is released in large amounts during myocardial ischemia and is capable of exerting potent cardioprotective effects in the heart. Although these observations on adenosine have been known for a long time, how adenosine acts to achieve its anti-ischemic effect remains incompletely understood. However, recent advances on the chemistry and pharmacology of adenosine receptor ligands have provided important and novel information on the function of adenosine receptor subtypes in the cardiovascular system. The development of model systems for the cardiac actions of adenosine has yielded important insights into its mechanism of action and have begun to elucidate the sequence of signalling events from receptor activation to the actual exertion of its cardioprotective effect. The present review will focus on the adenosine receptors that mediate the potent anti-ischemic effect of adenosine, new ligands at the receptors, potential molecular signalling mechanisms downstream of the receptor, mediators for cardioprotection, and possible clinical applications in cardiovascular disorders. PMID:10607860

Poroelastic Mechanical Effects of Hemicelluloses on Cellulosic Hydrogels under Compression

PubMed Central

Lopez-Sanchez, Patricia; Cersosimo, Julie; Wang, Dongjie; Flanagan, Bernadine; Stokes, Jason R.; Gidley, Michael J.

2015-01-01

Hemicelluloses exhibit a range of interactions with cellulose, the mechanical consequences of which in plant cell walls are incompletely understood. We report the mechanical properties of cell wall analogues based on cellulose hydrogels to elucidate the contribution of xyloglucan or arabinoxylan as examples of two hemicelluloses displaying different interactions with cellulose. We subjected the hydrogels to mechanical pressures to emulate the compressive stresses experienced by cell walls in planta. Our results revealed that the presence of either hemicellulose increased the resistance to compression at fast strain rates. However, at slow strain rates, only xyloglucan increased composite strength. This behaviour could be explained considering the microstructure and the flow of water through the composites confirming their poroelastic nature. In contrast, small deformation oscillatory rheology showed that only xyloglucan decreased the elastic moduli. These results provide evidence for contrasting roles of different hemicelluloses in plant cell wall mechanics and man-made cellulose-based composite materials. PMID:25794048

Exosomes from Glioma-Associated Mesenchymal Stem Cells Increase the Tumorigenicity of Glioma Stem-like Cells via Transfer of miR-1587.

PubMed

Figueroa, Javier; Phillips, Lynette M; Shahar, Tal; Hossain, Anwar; Gumin, Joy; Kim, Hoon; Bean, Andrew J; Calin, George A; Fueyo, Juan; Walters, Edgar T; Kalluri, Raghu; Verhaak, Roel G; Lang, Frederick F

2017-11-01

Tumor-stromal communications impact tumorigenesis in ways that are incompletely understood. Here, we show that glioma-associated human mesenchymal stem cells (GA-hMSC), a newly identified stromal component of glioblastoma, release exosomes that increase the proliferation and clonogenicity of tumor-initiating glioma stem-like cells (GSC). This event leads to a significantly greater tumor burden and decreased host survival compared with untreated GSCs in orthotopic xenografts. Analysis of the exosomal content identified miR-1587 as a mediator of the exosomal effects on GSCs, in part via downregulation of the tumor-suppressive nuclear receptor corepressor NCOR1. Our results illuminate the tumor-supporting role for GA-hMSCs by identifying GA-hMSC-derived exosomes in the intercellular transfer of specific miRNA that enhance the aggressiveness of glioblastoma. Cancer Res; 77(21); 5808-19. ©2017 AACR . ©2017 American Association for Cancer Research.

Protective Efficacy of Serially Up-Ranked Subdominant CD8+ T Cell Epitopes against Virus Challenges

PubMed Central

Roshorm, Yaowaluck; Bridgeman, Anne; Létourneau, Sven; Liljeström, Peter; Potash, Mary Jane; Volsky, David J.; McMichael, Andrew J.; Hanke, Tomáš

2011-01-01

Immunodominance in T cell responses to complex antigens like viruses is still incompletely understood. Some data indicate that the dominant responses to viruses are not necessarily the most protective, while other data imply that dominant responses are the most important. The issue is of considerable importance to the rational design of vaccines, particularly against variable escaping viruses like human immunodeficiency virus type 1 and hepatitis C virus. Here, we showed that sequential inactivation of dominant epitopes up-ranks the remaining subdominant determinants. Importantly, we demonstrated that subdominant epitopes can induce robust responses and protect against whole viruses if they are allowed at least once in the vaccination regimen to locally or temporally dominate T cell induction. Therefore, refocusing T cell immune responses away from highly variable determinants recognized during natural virus infection towards subdominant, but conserved regions is possible and merits evaluation in humans. PMID:21625575

Bacterial pneumonia as an influenza complication.

PubMed

Martin-Loeches, Ignacio; van Someren Gréve, Frank; Schultz, Marcus J

2017-04-01

The pathogenesis and impact of coinfection, in particular bacterial coinfection, in influenza are incompletely understood. This review summarizes results from studies on bacterial coinfection in the recent pandemic influenza outbreak. Systemic immune mechanisms play a key role in the development of coinfection based on the complexity of the interaction of the host and the viral and bacterial pathogens. Several studies were performed to determine the point prevalence of bacterial coinfection in influenza. Coinfection in influenza is frequent in critically ill patients with Streptococcus pneumoniae being the most frequent bacterial pathogen and higher rates of potentially resistant pathogens over the years. Bacterial pneumonia is certainly an influenza complication. The recent epidemiology findings have helped to partially resolve the contribution of different pathogens. Immunosuppression is a risk factor for bacterial coinfection in influenza, and the epidemiology of coinfection has changed over the years during the last influenza pandemic, and these recent findings should be taken into account during present outbreaks.

Lack of involvement of lipocortin 1 in dexamethasone suppression of IL-1 release

PubMed Central

Rickard, D.; Goulding, N. J.

1993-01-01

The annexin lipocortin 1 is reported to mediate some anti-inflammatory effects of glucocorticoids, but the mechanisms of this mediation are incompletely understood. The involvement of lipocortin 1 in glucocorticoid inhibition of monocyte interleukin 1β (IL-1β) release has been investigated. Treatment of peripheral blood monocytes with 2 μg/ml lipopolysaccharide potently increased IL–1β release (p = 0.001) and dexamethasone (10−7 M) significantly reduced both resting and stimulated IL-1β release (p = 0.009). A neutralizing monoclonal antibody to lipocortin 1 (0.5–50.0 μg/ml) was unable to inhibit this effect and recombinant lipocortin 1 (2 × 10−6 M) and 188aa lipocortin 1 fragment (10−8−10−6 M) had no effect. It is concluded that lipocortin 1 is not involved in the inhibition of monocyte IL-1β release by glucocorticoids. PMID:18475502

Identification of genetic elements in metabolism by high-throughput mouse phenotyping.

PubMed

Rozman, Jan; Rathkolb, Birgit; Oestereicher, Manuela A; Schütt, Christine; Ravindranath, Aakash Chavan; Leuchtenberger, Stefanie; Sharma, Sapna; Kistler, Martin; Willershäuser, Monja; Brommage, Robert; Meehan, Terrence F; Mason, Jeremy; Haselimashhadi, Hamed; Hough, Tertius; Mallon, Ann-Marie; Wells, Sara; Santos, Luis; Lelliott, Christopher J; White, Jacqueline K; Sorg, Tania; Champy, Marie-France; Bower, Lynette R; Reynolds, Corey L; Flenniken, Ann M; Murray, Stephen A; Nutter, Lauryl M J; Svenson, Karen L; West, David; Tocchini-Valentini, Glauco P; Beaudet, Arthur L; Bosch, Fatima; Braun, Robert B; Dobbie, Michael S; Gao, Xiang; Herault, Yann; Moshiri, Ala; Moore, Bret A; Kent Lloyd, K C; McKerlie, Colin; Masuya, Hiroshi; Tanaka, Nobuhiko; Flicek, Paul; Parkinson, Helen E; Sedlacek, Radislav; Seong, Je Kyung; Wang, Chi-Kuang Leo; Moore, Mark; Brown, Steve D; Tschöp, Matthias H; Wurst, Wolfgang; Klingenspor, Martin; Wolf, Eckhard; Beckers, Johannes; Machicao, Fausto; Peter, Andreas; Staiger, Harald; Häring, Hans-Ulrich; Grallert, Harald; Campillos, Monica; Maier, Holger; Fuchs, Helmut; Gailus-Durner, Valerie; Werner, Thomas; Hrabe de Angelis, Martin

2018-01-18

Metabolic diseases are a worldwide problem but the underlying genetic factors and their relevance to metabolic disease remain incompletely understood. Genome-wide research is needed to characterize so-far unannotated mammalian metabolic genes. Here, we generate and analyze metabolic phenotypic data of 2016 knockout mouse strains under the aegis of the International Mouse Phenotyping Consortium (IMPC) and find 974 gene knockouts with strong metabolic phenotypes. 429 of those had no previous link to metabolism and 51 genes remain functionally completely unannotated. We compared human orthologues of these uncharacterized genes in five GWAS consortia and indeed 23 candidate genes are associated with metabolic disease. We further identify common regulatory elements in promoters of candidate genes. As each regulatory element is composed of several transcription factor binding sites, our data reveal an extensive metabolic phenotype-associated network of co-regulated genes. Our systematic mouse phenotype analysis thus paves the way for full functional annotation of the genome.

APOBEC3A cytidine deaminase induces RNA editing in monocytes and macrophages

PubMed Central

Sharma, Shraddha; Patnaik, Santosh K.; Thomas Taggart, R.; Kannisto, Eric D.; Enriquez, Sally M.; Gollnick, Paul; Baysal, Bora E.

2015-01-01

The extent, regulation and enzymatic basis of RNA editing by cytidine deamination are incompletely understood. Here we show that transcripts of hundreds of genes undergo site-specific C>U RNA editing in macrophages during M1 polarization and in monocytes in response to hypoxia and interferons. This editing alters the amino acid sequences for scores of proteins, including many that are involved in pathogenesis of viral diseases. APOBEC3A, which is known to deaminate cytidines of single-stranded DNA and to inhibit viruses and retrotransposons, mediates this RNA editing. Amino acid residues of APOBEC3A that are known to be required for its DNA deamination and anti-retrotransposition activities were also found to affect its RNA deamination activity. Our study demonstrates the cellular RNA editing activity of a member of the APOBEC3 family of innate restriction factors and expands the understanding of C>U RNA editing in mammals. PMID:25898173

Neurons for hunger and thirst transmit a negative-valence teaching signal.

PubMed

Betley, J Nicholas; Xu, Shengjin; Cao, Zhen Fang Huang; Gong, Rong; Magnus, Christopher J; Yu, Yang; Sternson, Scott M

2015-05-14

Homeostasis is a biological principle for regulation of essential physiological parameters within a set range. Behavioural responses due to deviation from homeostasis are critical for survival, but motivational processes engaged by physiological need states are incompletely understood. We examined motivational characteristics of two separate neuron populations that regulate energy and fluid homeostasis by using cell-type-specific activity manipulations in mice. We found that starvation-sensitive AGRP neurons exhibit properties consistent with a negative-valence teaching signal. Mice avoided activation of AGRP neurons, indicating that AGRP neuron activity has negative valence. AGRP neuron inhibition conditioned preference for flavours and places. Correspondingly, deep-brain calcium imaging revealed that AGRP neuron activity rapidly reduced in response to food-related cues. Complementary experiments activating thirst-promoting neurons also conditioned avoidance. Therefore, these need-sensing neurons condition preference for environmental cues associated with nutrient or water ingestion, which is learned through reduction of negative-valence signals during restoration of homeostasis.

CaMKII in Vascular Signalling: "Friend or Foe"?

PubMed

Ebenebe, Obialunanma V; Heather, Alison; Erickson, Jeffrey R

2018-05-01

Signalling mechanisms within and between cells of the vasculature enable function and maintain homeostasis. However, a number of these mechanisms also contribute to the pathophysiology of vascular disease states. The multifunctional signalling molecule calcium/calmodulin-dependent kinase II (CaMKII) has been shown to have critical functional effects in many tissue types. For example, CaMKII is known to have a dual role in cardiac physiology and pathology. The function of CaMKII within the vasculature is incompletely understood, but emerging evidence points to potential physiological and pathological roles. This review discusses the evidence for CaMKII signalling within the vasculature, with the aim to better understand both positive and potentially deleterious effects of CaMKII activation in vascular tissue. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Poroelastic mechanical effects of hemicelluloses on cellulosic hydrogels under compression.

PubMed

Lopez-Sanchez, Patricia; Cersosimo, Julie; Wang, Dongjie; Flanagan, Bernadine; Stokes, Jason R; Gidley, Michael J

2015-01-01

Hemicelluloses exhibit a range of interactions with cellulose, the mechanical consequences of which in plant cell walls are incompletely understood. We report the mechanical properties of cell wall analogues based on cellulose hydrogels to elucidate the contribution of xyloglucan or arabinoxylan as examples of two hemicelluloses displaying different interactions with cellulose. We subjected the hydrogels to mechanical pressures to emulate the compressive stresses experienced by cell walls in planta. Our results revealed that the presence of either hemicellulose increased the resistance to compression at fast strain rates. However, at slow strain rates, only xyloglucan increased composite strength. This behaviour could be explained considering the microstructure and the flow of water through the composites confirming their poroelastic nature. In contrast, small deformation oscillatory rheology showed that only xyloglucan decreased the elastic moduli. These results provide evidence for contrasting roles of different hemicelluloses in plant cell wall mechanics and man-made cellulose-based composite materials.

Opportunities in proteomics to understand hepatitis C and HIV coinfection.

PubMed

Meissner, Eric G; Suffredini, Anthony F; Kottilil, Shyamasundaran

2012-08-01

Antiretroviral therapy has significantly reduced morbidity and mortality associated with HIV infection. However, coinfection with HCV results in a more complicated disease course for both infections. HIV infection dramatically impacts the natural history of chronic liver disease due to HCV. Coinfected patients not on antiretroviral therapy for HIV develop liver fibrosis and cirrhosis at a faster rate, clear acute infection less commonly and respond to IFN-α-based therapy for chronic infection less often than HCV-monoinfected patients. The interaction between these two viruses, the immune system and the fibrotic machinery of the liver remains incompletely understood. In this review, we discuss recent advances in proteomics as applied to HCV and HIV and highlight issues in coinfection that are amenable to further discovery through proteomic approaches. We focus on clinical predictors of liver fibrosis and treatment outcome as these have the greatest potential clinical applicability.

Cigarette smoking and the pathogenesis of systemic lupus erythematosus.

PubMed

Speyer, Cameron B; Costenbader, Karen H

2018-06-01

Systemic lupus erythematosus (SLE) is a multi-system inflammatory autoimmune disease of incompletely understood etiology. It is thought that environmental exposures 'trigger' or accelerate the disease in genetically-predisposed individuals. Areas covered: Substantial epidemiological evidence exists to support the association between cigarette smoking and the risk of incident SLE. Recent evidence points to current smoking as the specific risk factor, with decreasing risk 5 years after smoking cessation, and the greatest risk for disease characterized by the presence of SLE-specific autoantibodies. Research has begun to search for possible explanations for the temporal nature of the relationship between current smoking and autoantibody positive-SLE. Here we review potential biologic mechanisms linking smoking and SLE risk, including effects upon T and B cells, inflammatory cytokines, oxidative stress, and the formation of short-lived DNA adducts. Expert commentary: The directions for future research in this field include studies of gene-environment interactions, epigenetics, metabolomics and putative biologic mechanisms.

Essential role for fibrillin-2 in zebrafish notochord and vascular morphogenesis.

PubMed

Gansner, John M; Madsen, Erik C; Mecham, Robert P; Gitlin, Jonathan D

2008-10-01

Recent studies demonstrate that lysyl oxidase cuproenzymes are critical for zebrafish notochord formation, but the molecular mechanisms of copper-dependent notochord morphogenesis are incompletely understood. We, therefore, conducted a forward genetic screen for zebrafish mutants that exhibit notochord sensitivity to lysyl oxidase inhibition, yielding a mutant with defects in notochord and vascular morphogenesis, puff daddygw1 (pfdgw1). Meiotic mapping and cloning reveal that the pfdgw1 phenotype results from disruption of the gene encoding the extracellular matrix protein fibrillin-2, and the spatiotemporal expression of fibrillin-2 is consistent with the pfdgw1 phenotype. Furthermore, each aspect of the pfdgw1 phenotype is recapitulated by morpholino knockdown of fibrillin-2. Taken together, the data reveal a genetic interaction between fibrillin-2 and the lysyl oxidases in notochord formation and demonstrate the importance of fibrillin-2 in specific early developmental processes in zebrafish. Copyright (c) 2008 Wiley-Liss, Inc.

Gender Dysphoria in Adults.

PubMed

Zucker, Kenneth J; Lawrence, Anne A; Kreukels, Baudewijntje P C

2016-01-01

Gender dysphoria (GD), a term that denotes persistent discomfort with one's biologic sex or assigned gender, replaced the diagnosis of gender identity disorder in the Diagnostic and Statistical Manual of Mental Disorders in 2013. Subtypes of GD in adults, defined by sexual orientation and age of onset, have been described; these display different developmental trajectories and prognoses. Prevalence studies conclude that fewer than 1 in 10,000 adult natal males and 1 in 30,000 adult natal females experience GD, but such estimates vary widely. GD in adults is associated with an elevated prevalence of comorbid psychopathology, especially mood disorders, anxiety disorders, and suicidality. Causal mechanisms in GD are incompletely understood, but genetic, neurodevelopmental, and psychosocial factors probably all contribute. Treatment of GD in adults, although largely standardized, is likely to evolve in response to the increasing diversity of persons seeking treatment, demands for greater client autonomy, and improved understanding of the benefits and limitations of current treatment modalities.

Metabolic Catastrophe in Mice Lacking Transferrin Receptor in Muscle.

PubMed

Barrientos, Tomasa; Laothamatas, Indira; Koves, Timothy R; Soderblom, Erik J; Bryan, Miles; Moseley, M Arthur; Muoio, Deborah M; Andrews, Nancy C

2015-11-01

Transferrin receptor (Tfr1) is ubiquitously expressed, but its roles in non-hematopoietic cells are incompletely understood. We used a tissue-specific conditional knockout strategy to ask whether skeletal muscle required Tfr1 for iron uptake. We found that iron assimilation via Tfr1 was critical for skeletal muscle metabolism, and that iron deficiency in muscle led to dramatic changes, not only in muscle, but also in adipose tissue and liver. Inactivation of Tfr1 incapacitated normal energy production in muscle, leading to growth arrest and a muted attempt to switch to fatty acid β oxidation, using up fat stores. Starvation signals stimulated gluconeogenesis in the liver, but amino acid substrates became limiting and hypoglycemia ensued. Surprisingly, the liver was also iron deficient, and production of the iron regulatory hormone hepcidin was depressed. Our observations reveal a complex interaction between iron homeostasis and metabolism that has implications for metabolic and iron disorders.

Region effects influence local tree species diversity.

PubMed

Ricklefs, Robert E; He, Fangliang

2016-01-19

Global patterns of biodiversity reflect both regional and local processes, but the relative importance of local ecological limits to species coexistence, as influenced by the physical environment, in contrast to regional processes including species production, dispersal, and extinction, is poorly understood. Failure to distinguish regional influences from local effects has been due, in part, to sampling limitations at small scales, environmental heterogeneity within local or regional samples, and incomplete geographic sampling of species. Here, we use a global dataset comprising 47 forest plots to demonstrate significant region effects on diversity, beyond the influence of local climate, which together explain more than 92% of the global variation in local forest tree species richness. Significant region effects imply that large-scale processes shaping the regional diversity of forest trees exert influence down to the local scale, where they interact with local processes to determine the number of coexisting species.

Depression, Stress, and Anhedonia: Toward a Synthesis and Integrated Model

PubMed Central

Pizzagalli, Diego A.

2014-01-01

Depression is a significant public health problem, but its etiology and pathophysiology remain poorly understood. Such incomplete understanding likely arises from the fact that depression encompasses a heterogeneous set of disorders. To overcome these limitations, renewed interest in intermediate phenotypes (endophenotypes) has resurfaced, and anhedonia has emerged as one of the most promising endophenotypes of depression. Here, a heuristic model is presented postulating that anhedonia arises from dysfunctional interactions between stress and brain reward systems. To this end, we review and integrate three bodies of independent literature investigating the role of (1) anhedonia, (2) dopamine, and (3) stress in depression. In a fourth section, we summarize animal data indicating that stress negatively affect mesocorticolimbic dopaminergic pathways critically implicated in incentive motivation and reinforcement learning. In the last section, we provide a synthesis of these four literatures, present initial evidence consistent with our model, and discuss directions for future research. PMID:24471371

Biological roles of cysteine proteinases in the pathogenesis of Trichomonas vaginalis

PubMed Central

Hernández, Hilda M.; Marcet, Ricardo; Sarracent, Jorge

2014-01-01

Human trichomonosis, infection with Trichomonas vaginalis, is the most common non-viral sexually transmitted disease in the world. The host-parasite interaction and pathophysiological processes of trichomonosis remain incompletely understood. This review focuses on the advancements reached in the area of the pathogenesis of T. vaginalis, especially in the role of the cysteine proteinases. It highlights various approaches made in this field and lists a group of trichomonad cysteine proteinases involved in diverse processes such as invasion of the mucous layer, cytoadherence, cytotoxicity, cytoskeleton disruption of red blood cells, hemolysis, and evasion of the host immune response. A better understanding of the biological roles of cysteine proteinases in the pathogenesis of this parasite could be used in the identification of new chemotherapeutic targets. An additional advantage could be the development of a vaccine in order to reduce transmission of T. vaginalis. PMID:25348828

The mitochondrial uniporter controls fight or flight heart rate increases.

PubMed

Wu, Yuejin; Rasmussen, Tyler P; Koval, Olha M; Joiner, Mei-Ling A; Hall, Duane D; Chen, Biyi; Luczak, Elizabeth D; Wang, Qiongling; Rokita, Adam G; Wehrens, Xander H T; Song, Long-Sheng; Anderson, Mark E

2015-01-20

Heart rate increases are a fundamental adaptation to physiological stress, while inappropriate heart rate increases are resistant to current therapies. However, the metabolic mechanisms driving heart rate acceleration in cardiac pacemaker cells remain incompletely understood. The mitochondrial calcium uniporter (MCU) facilitates calcium entry into the mitochondrial matrix to stimulate metabolism. We developed mice with myocardial MCU inhibition by transgenic expression of a dominant-negative (DN) MCU. Here, we show that DN-MCU mice had normal resting heart rates but were incapable of physiological fight or flight heart rate acceleration. We found that MCU function was essential for rapidly increasing mitochondrial calcium in pacemaker cells and that MCU-enhanced oxidative phoshorylation was required to accelerate reloading of an intracellular calcium compartment before each heartbeat. Our findings show that MCU is necessary for complete physiological heart rate acceleration and suggest that MCU inhibition could reduce inappropriate heart rate increases without affecting resting heart rate.

Zinc and Zinc Transporters: Novel Regulators of Ventricular Myocardial Development.

PubMed

Lin, Wen; Li, Deqiang

2018-06-01

Ventricular myocardial development is a well-orchestrated process involving different cardiac structures, multiple signal pathways, and myriad proteins. Dysregulation of this important developmental event can result in cardiomyopathies, such as left ventricle non-compaction, which affect the pediatric population and the adults. Human and mouse studies have shed light upon the etiology of some cardiomyopathy cases and highlighted the contribution of both genetic and environmental factors. However, the regulation of ventricular myocardial development remains incompletely understood. Zinc is an essential trace metal with structural, enzymatic, and signaling function. Perturbation of zinc homeostasis has resulted in developmental and physiological defects including cardiomyopathy. In this review, we summarize several mechanisms by which zinc and zinc transporters can impact the regulation of ventricular myocardial development. Based on our review, we propose that zinc deficiency and mutations of zinc transporters may underlie some cardiomyopathy cases especially those involving ventricular myocardial development defects.

Regulation of anoikis by Deleted in Breast Cancer-1 (DBC1) through NF-κB

PubMed Central

Park, Sun Hee; Riley, Philip; Frisch, Steven M

2013-01-01

Anoikis-resistance of tumor cells is critical for anchorage-independent growth and metastasis. The inflammatory-response transcription factor NF-κB contributes to anoikis-resistance and tumor progression through mechanisms that are understood incompletely. Deleted in Breast Cancer-1 protein (KIAA1967) is over-expressed in several tumor types, and correlates with a poorer prognosis in some cases. We report here that DBC1 suppressed anoikis in normal epithelial and breast cancer cell lines. DBC1 interacted with IKK-β, stimulating its kinase activity, promoting NF-κB transcriptional activity through the phosphorylation of relA serine-536 and enhancing the expression of the NF-κB target genes, c-FLIP and bcl-xl. Our results indicate that DBC1 is an important co-factor for the control of the IKK-β-NF-κB signaling pathway that regulates anoikis. PMID:23588592

New findings on venous thrombogenesis

PubMed Central

Byrnes, James R.; Wolberg, Alisa S.

2017-01-01

Summary Venous thrombosis (VT) is the third most common cause of cardiovascular death worldwide. Complications from VT and pulmonary embolism are the leading cause of lost disability-adjusted life years. Risks include genetic (e.g., non-O blood group, activated protein C resistance, hyperprothrombinemia) and acquired (e.g., age, surgery, cancer, pregnancy, immobilisation, female hormone use) factors. Pathophysiologic mechanisms that promote VT are incompletely understood, but involve abnormalities in blood coagulability, vessel function, and flow (so-called Virchow’s Triad). Epidemiologic studies of humans, animal models, and biochemical and biophysical investigations have revealed contributions from extrinsic, intrinsic, and common pathways of coagulation, endothelial cells, leukocytes, red blood cells, platelets, cell-derived microvesicles, stasis-induced changes in vascular cells, and blood rheology. Knowledge of these mechanisms may yield new therapeutic targets. Characterisation of mechanisms that mediate VT formation and stability, particularly in aging, are needed to advance understanding of VT. PMID:27878206

Enzymatic lipid oxidation by eosinophils propagates coagulation, hemostasis, and thrombotic disease

PubMed Central

Uderhardt, Stefan; Ackermann, Jochen A.; Fillep, Tobias; Hammond, Victoria J.; Willeit, Johann; Stark, Konstantin; Rossaint, Jan; Schubert, Irene; Mielenz, Dirk; Dietel, Barbara; Raaz-Schrauder, Dorette; Ay, Cihan; Thaler, Johannes; Heim, Christian; Collins, Peter W.; Schabbauer, Gernot; Mackman, Nigel; Voehringer, David; Nadler, Jerry L.; Lee, James J.; Massberg, Steffen; Rauh, Manfred; O’Donnell, Valerie B.

2017-01-01

Blood coagulation is essential for physiological hemostasis but simultaneously contributes to thrombotic disease. However, molecular and cellular events controlling initiation and propagation of coagulation are still incompletely understood. In this study, we demonstrate an unexpected role of eosinophils during plasmatic coagulation, hemostasis, and thrombosis. Using a large-scale epidemiological approach, we identified eosinophil cationic protein as an independent and predictive risk factor for thrombotic events in humans. Concurrent experiments showed that eosinophils contributed to intravascular thrombosis by exhibiting a strong endogenous thrombin-generation capacity that relied on the enzymatic generation and active provision of a procoagulant phospholipid surface enriched in 12/15-lipoxygenase–derived hydroxyeicosatetraenoic acid–phosphatidylethanolamines. Our findings reveal a previously unrecognized role of eosinophils and enzymatic lipid oxidation as regulatory elements that facilitate both hemostasis and thrombosis in response to vascular injury, thus identifying promising new targets for the treatment of thrombotic disease. PMID:28566277

Mitochondria localize to injured axons to support regeneration

PubMed Central

Han, Sung Min; Baig, Huma S.; Hammarlund, Marc

2016-01-01

SUMMARY Axon regeneration is essential to restore the nervous system after axon injury. However, the neuronal cell biology that underlies axon regeneration is incompletely understood. Here we use in vivo single-neuron analysis to investigate the relationship between nerve injury, mitochondrial localization, and axon regeneration. Mitochondria translocate into injured axons, so that average mitochondria density increases after injury. Moreover, single-neuron analysis reveals that axons that fail to increase mitochondria have poor regeneration. Experimental alterations to axonal mitochondrial distribution or mitochondrial respiratory chain function result in corresponding changes to regeneration outcomes. Axonal mitochondria are specifically required for growth cone migration, identifying a key energy challenge for injured neurons. Finally, mitochondrial localization to the axon after injury is regulated in part by dual-leucine zipper kinase-1 (DLK-1), a conserved regulator of axon regeneration. These data identify regulation of axonal mitochondria as a new cell biological mechanism that helps determine the regenerative response of injured neurons. PMID:28009276

CXCR4+ granulocytes reflect fungal cystic fibrosis lung disease.

PubMed

Carevic, Melanie; Singh, Anurag; Rieber, Nikolaus; Eickmeier, Olaf; Griese, Matthias; Hector, Andreas; Hartl, Dominik

2015-08-01

Cystic fibrosis airways are frequently colonised with fungi. However, the interaction of these fungi with immune cells and the clinical relevance in cystic fibrosis lung disease are incompletely understood.We characterised granulocytes in airway fluids and peripheral blood from cystic fibrosis patients with and without fungal colonisation, non-cystic fibrosis disease controls and healthy control subjects cross-sectionally and longitudinally and correlated these findings with lung function parameters.Cystic fibrosis patients with chronic fungal colonisation by Aspergillus fumigatus were characterised by an accumulation of a distinct granulocyte subset, expressing the HIV coreceptor CXCR4. Percentages of airway CXCR4(+) granulocytes correlated with lung disease severity in patients with cystic fibrosis.These studies demonstrate that chronic fungal colonisation with A. fumigatus in cystic fibrosis patients is associated with CXCR4(+) airway granulocytes, which may serve as a potential biomarker and therapeutic target in fungal cystic fibrosis lung disease. Copyright ©ERS 2015.

Metabolic Catastrophe in Mice Lacking Transferrin Receptor in Muscle

PubMed Central

Barrientos, Tomasa; Laothamatas, Indira; Koves, Timothy R.; Soderblom, Erik J.; Bryan, Miles; Moseley, M. Arthur; Muoio, Deborah M.; Andrews, Nancy C.

2015-01-01

Transferrin receptor (Tfr1) is ubiquitously expressed, but its roles in non-hematopoietic cells are incompletely understood. We used a tissue-specific conditional knockout strategy to ask whether skeletal muscle required Tfr1 for iron uptake. We found that iron assimilation via Tfr1 was critical for skeletal muscle metabolism, and that iron deficiency in muscle led to dramatic changes, not only in muscle, but also in adipose tissue and liver. Inactivation of Tfr1 incapacitated normal energy production in muscle, leading to growth arrest and a muted attempt to switch to fatty acid β oxidation, using up fat stores. Starvation signals stimulated gluconeogenesis in the liver, but amino acid substrates became limiting and hypoglycemia ensued. Surprisingly, the liver was also iron deficient, and production of the iron regulatory hormone hepcidin was depressed. Our observations reveal a complex interaction between iron homeostasis and metabolism that has implications for metabolic and iron disorders. PMID:26870796

Quantum space and quantum completeness

NASA Astrophysics Data System (ADS)

Jurić, Tajron

2018-05-01

Motivated by the question whether quantum gravity can "smear out" the classical singularity we analyze a certain quantum space and its quantum-mechanical completeness. Classical singularity is understood as a geodesic incompleteness, while quantum completeness requires a unique unitary time evolution for test fields propagating on an underlying background. Here the crucial point is that quantum completeness renders the Hamiltonian (or spatial part of the wave operator) to be essentially self-adjoint in order to generate a unique time evolution. We examine a model of quantum space which consists of a noncommutative BTZ black hole probed by a test scalar field. We show that the quantum gravity (noncommutative) effect is to enlarge the domain of BTZ parameters for which the relevant wave operator is essentially self-adjoint. This means that the corresponding quantum space is quantum complete for a larger range of BTZ parameters rendering the conclusion that in the quantum space one observes the effect of "smearing out" the singularity.

The Us3 Protein of Herpes Simplex Virus 1 Inhibits T Cell Signaling by Confining Linker for Activation of T Cells (LAT) Activation via TRAF6 Protein*

PubMed Central

Yang, Yin; Wu, Songfang; Wang, Yu; Pan, Shuang; Lan, Bei; Liu, Yaohui; Zhang, Liming; Leng, Qianli; Chen, Da; Zhang, Cuizhu; He, Bin; Cao, Youjia

2015-01-01

Herpes simplex virus 1 (HSV-1) is the most prevalent human virus and causes global morbidity because the virus is able to infect multiple cell types. Remarkably, HSV infection switches between lytic and latent cycles, where T cells play a critical role. However, the precise way of virus-host interactions is incompletely understood. Here we report that HSV-1 productively infected Jurkat T-cells and inhibited antigen-induced T cell receptor activation. We discovered that HSV-1-encoded Us3 protein interrupted TCR signaling and interleukin-2 production by inactivation of the linker for activation of T cells. This study unveils a mechanism by which HSV-1 intrudes into early events of TCR-mediated cell signaling and may provide novel insights into HSV infection, during which the virus escapes from host immune surveillance. PMID:25907557

Molecular and cellular mechanisms of pulmonary fibrosis

PubMed Central

2012-01-01

Pulmonary fibrosis is a chronic lung disease characterized by excessive accumulation of extracellular matrix (ECM) and remodeling of the lung architecture. Idiopathic pulmonary fibrosis is considered the most common and severe form of the disease, with a median survival of approximately three years and no proven effective therapy. Despite the fact that effective treatments are absent and the precise mechanisms that drive fibrosis in most patients remain incompletely understood, an extensive body of scientific literature regarding pulmonary fibrosis has accumulated over the past 35 years. In this review, we discuss three broad areas which have been explored that may be responsible for the combination of altered lung fibroblasts, loss of alveolar epithelial cells, and excessive accumulation of ECM: inflammation and immune mechanisms, oxidative stress and oxidative signaling, and procoagulant mechanisms. We discuss each of these processes separately to facilitate clarity, but certainly significant interplay will occur amongst these pathways in patients with this disease. PMID:22824096

Understanding the cellular basis and pathophysiology of Peyronie’s disease to optimize treatment for erectile dysfunction

PubMed Central

Alzubaidi, Raidh

2017-01-01

Erectile dysfunction (ED) is a common condition that significantly impacts a man’s physical and psychological well-being. ED is often associated with Peyronie’s disease (PD), which is an abnormal curvature of the penis. Delayed treatment of or surgical invention for PD often results in ED and therefore unsatisfied patients. The pathophysiology of PD is incompletely understood, but has been studied extensively and based on our current understanding of PD physiology, many medical treatment options have been proposed. In this paper, we will review what is known about the pathophysiology of PD and the medical treatment options that have been trialed as a result. More investigations in regards to the basic science of PD need to be carried out in order to elucidate the exact mechanisms of the fibrosis, and propose new, more successful treatment options which should be implemented prior to the onset of ED. PMID:28217450

On chirality of slime mould.

PubMed

Dimonte, Alice; Adamatzky, Andrew; Erokhin, Victor; Levin, Michael

2016-02-01

Left-right patterning and lateralised behaviour is an ubiquitous aspect of plants and animals. The mechanisms linking cellular chirality to the large-scale asymmetry of multicellular structures are incompletely understood, and it has been suggested that the chirality of living cells is hardwired in their cytoskeleton. We examined the question of biased asymmetry in a unique organism: the slime mould Physarum polycephalum, which is unicellular yet possesses macroscopic, complex structure and behaviour. In laboratory experiment using a T-shape, we found that Physarum turns right in more than 74% of trials. The results are in agreement with previously published studies on asymmetric movement of muscle cells, neutrophils, liver cells and growing neural filaments, and for the first time reveal the presence of consistently-biased laterality in the fungi kingdom. Exact mechanisms of the slime mould's direction preference remain unknown. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cp/Heph mutant mice have iron-induced neurodegeneration diminished by deferiprone

PubMed Central

Zhao, Liangliang; Hadziahmetovic, Majda; Wang, Chenguang; Xu, Xueying; Song, Ying; Jinnah, H.A.; Wodzinska, Jolanta; Iacovelli, Jared; Wolkow, Natalie; Krajacic, Predrag; Weissberger, Alyssa Cwanger; Connelly, John; Spino, Michael; Lee, Michael K.; Connor, James; Giasson, Benoit; Harris, Z. Leah; Dunaief, Joshua L.

2016-01-01

Brain iron accumulates in several neurodegenerative diseases and can cause oxidative damage, but mechanisms of brain iron homeostasis are incompletely understood. Patients with mutations in the cellular iron-exporting ferroxidase ceruloplasmin (Cp) have brain iron accumulation causing neurodegeneration. Here, we assessed the brains of mice with combined mutation of Cp and its homolog hephaestin. Compared to single mutants, brain iron accumulation was accelerated in double mutants in the cerebellum, substantia nigra, and hippocampus. Iron accumulated within glia, while neurons were iron deficient. There was loss of both neurons and glia. Mice developed ataxia and tremor, and most died by 9 months. Treatment with the oral iron chelator deferiprone diminished brain iron levels, protected against neuron loss, and extended lifespan. Ferroxidases play important, partially overlapping roles in brain iron homeostasis by facilitating iron export from glia, making iron available to neurons. PMID:26303407

Competing phases, phase separation, and coexistence in the extended one-dimensional bosonic Hubbard model

DOE PAGES

Batrouni, G. G.; Rousseau, V. G.; Scalettar, R. T.; ...

2014-11-17

Here, we study the phase diagram of the one-dimensional bosonic Hubbard model with contact (U) and near neighbor (V ) interactions focusing on the gapped Haldane insulating (HI) phase which is characterized by an exotic nonlocal order parameter. The parameter regime (U, V and μ) where this phase exists and how it competes with other phases such as the supersolid (SS) phase, is incompletely understood. We use the Stochastic Green Function quantum Monte Carlo algorithm as well as the density matrix renormalization group to map out the phase diagram. The HI exists only at = 1, the SS phase existsmore » for a very wide range of parameters (including commensurate fillings) and displays power law decay in the one body Green function were our main conclusions. Additionally, we show that at fixed integer density, the system exhibits phase separation in the (U, V ) plane.« less

Lethal Cardiomyopathy in Mice Lacking Transferrin Receptor in the Heart.

PubMed

Xu, Wenjing; Barrientos, Tomasa; Mao, Lan; Rockman, Howard A; Sauve, Anthony A; Andrews, Nancy C

2015-10-20

Both iron overload and iron deficiency have been associated with cardiomyopathy and heart failure, but cardiac iron utilization is incompletely understood. We hypothesized that the transferrin receptor (Tfr1) might play a role in cardiac iron uptake and used gene targeting to examine the role of Tfr1 in vivo. Surprisingly, we found that decreased iron, due to inactivation of Tfr1, was associated with severe cardiac consequences. Mice lacking Tfr1 in the heart died in the second week of life and had cardiomegaly, poor cardiac function, failure of mitochondrial respiration, and ineffective mitophagy. The phenotype could only be rescued by aggressive iron therapy, but it was ameliorated by administration of nicotinamide riboside, an NAD precursor. Our findings underscore the importance of both Tfr1 and iron in the heart, and may inform therapy for patients with heart failure. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Gamma-ray astronomy

NASA Technical Reports Server (NTRS)

Ramaty, R.; Lingenfelter, R. E.

1982-01-01

Cosmic gamma rays, the physical processes responsible for their production and the astrophysical sites from which they were seen are reported. The bulk of the observed gamma ray emission is in the photon energy range from about 0.1 MeV to 1 GeV, where observations are carried out above the atmosphere. There are also, however, gamma ray observations at higher energies obtained by detecting the Cerenkov light produced by the high energy photons in the atmosphere. Gamma ray emission was observed from sources as close as the Sun and the Moon and as distant as the quasar 3C273, as well as from various other galactic and extragalactic sites. The radiation processes also range from the well understood, e.g. energetic particle interactions with matter, to the still incompletely researched, such as radiation transfer in optically thick electron positron plasmas in intense neutron star magnetic fields.

The bioenergetics mechanisms and applications of sulfate-reducing bacteria in remediation of pollutants in drainage: A review.

PubMed

Li, Xin; Lan, Shi-Ming; Zhu, Zhong-Ping; Zhang, Chang; Zeng, Guang-Ming; Liu, Yun-Guo; Cao, Wei-Cheng; Song, Biao; Yang, Hong; Wang, Sheng-Fan; Wu, Shao-Hua

2018-04-20

Sulfate-reducing bacteria (SRB), a group of anaerobic prokaryotes, can use sulfur species as a terminal electron acceptor for the oxidation of organic compounds. They not only have significant ecological functions, but also play an important role in bioremediation of contaminated sites. Although numerous studies on metabolism and applications of SRB have been conducted, they still remain incompletely understood and even controversial. Fully understanding the metabolism of SRB paves the way for allowing the microorganisms to provide more beneficial services in bioremediation. Here we review progress in bioenergetics mechanisms and application of SRB including: (1) electron acceptors and donors for SRB; (2) pathway for sulfate reduction; (3) electron transfer in sulfate reduction; (4) application of SRB for economical and concomitant treatment of heavy metal, organic contaminants and sulfates. Moreover, current knowledge gaps and further research needs are identified. Copyright © 2018 Elsevier Inc. All rights reserved.

A dynamically coupled allosteric network underlies binding cooperativity in Src kinase

PubMed Central

Foda, Zachariah H.; Shan, Yibing; Kim, Eric T.; Shaw, David E.; Seeliger, Markus A.

2015-01-01

Protein tyrosine kinases are attractive drug targets because many human diseases are associated with the deregulation of kinase activity. However, how the catalytic kinase domain integrates different signals and switches from an active to an inactive conformation remains incompletely understood. Here we identify an allosteric network of dynamically coupled amino acids in Src kinase that connects regulatory sites to the ATP- and substrate-binding sites. Surprisingly, reactants (ATP and peptide substrates) bind with negative cooperativity to Src kinase while products (ADP and phosphopeptide) bind with positive cooperativity. We confirm the molecular details of the signal relay through the allosteric network by biochemical studies. Experiments on two additional protein tyrosine kinases indicate that the allosteric network may be largely conserved among these enzymes. Our work provides new insights into the regulation of protein tyrosine kinases and establishes a potential conduit by which resistance mutations to ATP-competitive kinase inhibitors can affect their activity. PMID:25600932

A review of brain circuitries involved in stuttering

PubMed Central

Craig-McQuaide, Anna; Akram, Harith; Zrinzo, Ludvic; Tripoliti, Elina

2014-01-01

Stuttering has been the subject of much research, nevertheless its etiology remains incompletely understood. This article presents a critical review of the literature on stuttering, with particular reference to the role of the basal ganglia (BG). Neuroimaging and lesion studies of developmental and acquired stuttering, as well as pharmacological and genetic studies are discussed. Evidence of structural and functional changes in the BG in those who stutter indicates that this motor speech disorder is due, at least in part, to abnormal BG cues for the initiation and termination of articulatory movements. Studies discussed provide evidence of a dysfunctional hyperdopaminergic state of the thalamocortical pathways underlying speech motor control in stuttering. Evidence that stuttering can improve, worsen or recur following deep brain stimulation for other indications is presented in order to emphasize the role of BG in stuttering. Further research is needed to fully elucidate the pathophysiology of this speech disorder, which is associated with significant social isolation. PMID:25452719

Kruppel-like factor 2 (KLF2) regulates proinflammatory activation of monocytes

PubMed Central

Das, Hiranmoy; Kumar, Ajay; Lin, Zhiyong; Patino, Willmar D.; Hwang, Paul M.; Feinberg, Mark W.; Majumder, Pradip K.; Jain, Mukesh K.

2006-01-01

The mechanisms regulating activation of monocytes remain incompletely understood. Herein we provide evidence that Kruppel-like factor 2 (KLF2) inhibits proinflammatory activation of monocytes. In vitro, KLF2 expression in monocytes is reduced by cytokine activation or differentiation. Consistent with this observation, KLF2 expression in circulating monocytes is reduced in patients with chronic inflammatory conditions such as coronary artery disease. Adenoviral overexpression of KLF2 inhibits the LPS-mediated induction of proinflammatory factors, cytokines, and chemokines and reduces phagocytosis. Conversely, short interfering RNA-mediated reduction in KLF2 increased inflammatory gene expression. Reconstitution of immunodeficient mice with KLF2-overexpressing monocytes significantly reduced carrageenan-induced acute paw edema formation. Mechanistically, KLF2 inhibits the transcriptional activity of both NF-κB and activator protein 1, in part by means of recruitment of transcriptional coactivator p300/CBP-associated factor. These observations identify KLF2 as a novel negative regulator of monocytic activation. PMID:16617118

Epidemiology of ovarian cancer.

PubMed

Permuth-Wey, Jennifer; Sellers, Thomas A

2009-01-01

Ovarian cancer represents the sixth most commonly diagnosed cancer among women in the world, and causes more deaths per year than any other cancer of the female reproductive system. Despite the high incidence and mortality rates, the etiology of this disease is poorly understood. Established risk factors for ovarian cancer include age and having a family history of the disease, while protective factors include increasing parity, oral contraceptive use, and oophorectomy. Lactation, incomplete pregnancies, and surgeries such as hysterectomy and tubal ligation may confer a weak protective effect against ovarian cancer. Infertility may contribute to ovarian cancer risk among nulliparous women. Other possible risk factors for ovarian cancer include postmenopausal hormone-replacement therapy and lifestyle factors such as cigarette smoking and alcohol consumption. Many of the causes of ovarian cancer are yet to be identified. Additional research is needed to better understand the etiology of this deadly disease.

Improved understanding of the pathophysiology of atrial fibrillation through the lens of discrete pathological pathways

PubMed Central

Balouch, Muhammad A.; Kolek, Matthew J.; Darbar, Dawood

2014-01-01

Atrial fibrillation (AF) is a common disorder with a complex and incompletely understood pathophysiology. Genetic approaches to understanding the pathophysiology of AF have led to the identification of several biological pathways important in the pathogenesis of the arrhythmia. These include pathways important for cardiac development, generation and propagation of atrial electrical impulses, and atrial remodeling and fibrosis. While common and rare genetic variants in these pathways are associated with increased susceptibility to AF, they differ substantially among patients with lone versus typical AF. Furthermore, how these pathways converge to a final common clinical phenotype of AF is unclear and might also vary among different patient populations. Here, we review the contemporary knowledge of AF pathogenesis and discuss how derangement in cardiac development, ion channel dysfunction, and promotion of atrial fibrosis may contribute to this common and important clinical disorder. PMID:25054116

Sulfur mustard skin lesions: A systematic review on pathomechanisms, treatment options and future research directions.

PubMed

Rose, Dorothee; Schmidt, Annette; Brandenburger, Matthias; Sturmheit, Tabea; Zille, Marietta; Boltze, Johannes

2018-09-01

Sulfur mustard (SM) is a chemical warfare, which has been used for one hundred years. However, its exact pathomechanisms are still incompletely understood and there is no specific therapy available so far. In this systematic review, studies published between January 2000 and July 2017 involving pathomechanisms and experimental treatments of SM-induced skin lesions were analyzed to summarize current knowledge on SM pathology, to provide an overview on novel treatment options, and to identify promising targets for future research to more effectively counter SM effects. We suggest that future studies should focus on (I) systemic effects of SM intoxication due to its distribution throughout the body, (II) removal of SM depots that continuously release active compound contributing to chronic skin damage, and (III) therapeutic options that counteract the pleiotropic effects of SM. Copyright © 2017 Elsevier B.V. All rights reserved.

Neural Basis of Reinforcement Learning and Decision Making

PubMed Central

Lee, Daeyeol; Seo, Hyojung; Jung, Min Whan

2012-01-01

Reinforcement learning is an adaptive process in which an animal utilizes its previous experience to improve the outcomes of future choices. Computational theories of reinforcement learning play a central role in the newly emerging areas of neuroeconomics and decision neuroscience. In this framework, actions are chosen according to their value functions, which describe how much future reward is expected from each action. Value functions can be adjusted not only through reward and penalty, but also by the animal’s knowledge of its current environment. Studies have revealed that a large proportion of the brain is involved in representing and updating value functions and using them to choose an action. However, how the nature of a behavioral task affects the neural mechanisms of reinforcement learning remains incompletely understood. Future studies should uncover the principles by which different computational elements of reinforcement learning are dynamically coordinated across the entire brain. PMID:22462543

Smallpox virus plaque phenotypes: genetic, geographical and case fatality relationships.

PubMed

Olson, Victoria A; Karem, Kevin L; Smith, Scott K; Hughes, Christine M; Damon, Inger K

2009-04-01

Smallpox (infection with Orthopoxvirus variola) remains a feared illness more than 25 years after its eradication. Historically, case-fatality rates (CFRs) varied between outbreaks (<1 to approximately 40 %), the reasons for which are incompletely understood. The extracellular enveloped virus (EEV) form of orthopoxvirus progeny is hypothesized to disseminate infection. Investigations with the closely related Orthopoxvirus vaccinia have associated increased comet formation (EEV production) with increased mouse mortality (pathogenicity). Other vaccinia virus genetic manipulations which affect EEV production inconsistently support this association. However, antisera against vaccinia virus envelope protect mice from lethal challenge, further supporting a critical role for EEV in pathogenicity. Here, we show that the increased comet formation phenotypes of a diverse collection of variola viruses associate with strain phylogeny and geographical origin, but not with increased outbreak-related CFRs; within clades, there may be an association of plaque size with CFR. The mechanisms for variola virus pathogenicity probably involves multiple host and pathogen factors.

Uncertainty, learning, and the optimal management of wildlife

USGS Publications Warehouse

Williams, B.K.

2001-01-01

Wildlife management is limited by uncontrolled and often unrecognized environmental variation, by limited capabilities to observe and control animal populations, and by a lack of understanding about the biological processes driving population dynamics. In this paper I describe a comprehensive framework for management that includes multiple models and likelihood values to account for structural uncertainty, along with stochastic factors to account for environmental variation, random sampling, and partial controllability. Adaptive optimization is developed in terms of the optimal control of incompletely understood populations, with the expected value of perfect information measuring the potential for improving control through learning. The framework for optimal adaptive control is generalized by including partial observability and non-adaptive, sample-based updating of model likelihoods. Passive adaptive management is derived as a special case of constrained adaptive optimization, representing a potentially efficient suboptimal alternative that nonetheless accounts for structural uncertainty.

Functional abdominal pain syndrome.

PubMed

Clouse, Ray E; Mayer, Emeran A; Aziz, Qasim; Drossman, Douglas A; Dumitrascu, Dan L; Mönnikes, Hubert; Naliboff, Bruce D

2006-04-01

Functional abdominal pain syndrome (FAPS) differs from the other functional bowel disorders; it is less common, symptoms largely are unrelated to food intake and defecation, and it has higher comorbidity with psychiatric disorders. The etiology and pathophysiology are incompletely understood. Because FAPS likely represents a heterogeneous group of disorders, peripheral neuropathic pain mechanisms, alterations in endogenous pain modulation systems, or both may be involved in any one patient. The diagnosis of FAPS is made on the basis of positive symptom criteria and a longstanding history of symptoms; in the absence of alarm symptoms, an extensive diagnostic evaluation is not required. Management is based on a therapeutic physician-patient relationship and empirical treatment algorithms using various classes of centrally acting drugs, including antidepressants and anticonvulsants. The choice, dose, and combination of drugs are influenced by psychiatric comorbidities. Psychological treatment options include psychotherapy, relaxation techniques, and hypnosis. Refractory FAPS patients may benefit from a multidisciplinary pain clinic approach.

Risk factors for community-acquired bacterial meningitis.

PubMed

Lundbo, Lene Fogt; Benfield, Thomas

2017-06-01

Bacterial meningitis is a significant burden of disease and mortality in all age groups worldwide despite the development of effective conjugated vaccines. The pathogenesis of bacterial meningitis is based on complex and incompletely understood host-pathogen interactions. Some of these are pathogen-specific, while some are shared between different bacteria. We searched the database PubMed to identify host risk factors for bacterial meningitis caused by the pathogens Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type b, because they are three most common causative bacteria beyond the neonatal period. We describe a number of risk factors; including socioeconomic factors, age, genetic variation of the host and underlying medical conditions associated with increased susceptibility to invasive bacterial infections in both children and adults. As conjugated vaccines are available for these infections, it is of utmost importance to identify high risk patients to be able to prevent invasive disease.

Inflammatory Mediators of Hepatic Steatosis

PubMed Central

Hijona, Elizabeth; Hijona, Lander; Arenas, Juan I.; Bujanda, Luis

2010-01-01

Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming a world-wide public health problem. NAFLD represents a spectrum of disease ranging from “simple steatosis”, which is considered relatively benign, to nonalcoholic steatohepatitis and to NAFLD-associated cirrhosis and end-stage liver disease. The etiology of NAFLD and its progression is complex and remains incompletely understood. The progression of the disease involves many factors. Apart from the two hits, the accumulation of TG and the development of fibrosis and necroinflammatory processes, exit numerous molecules associated with these two hits. Among them we can highlight the pro-inflammatory molecules and adiponectins. This review focuses on the growing evidence from both experimental and human studies suggesting a central role of cytokines in the pathogenesis of NAFLD. We review the role of cytokines as key regulators of insulin sensitivity and hepatic lipid overloading, liver injury and inflammation, and fibrosis with an emphasis on potential therapeutic implications. PMID:20300479

Idiopathic recurrent pericarditis as an immune-mediated disease: current insights into pathogenesis and emerging treatment options.

PubMed

Imazio, Massimo

2014-11-01

Idiopathic recurrent pericarditis affects 30-50% of patients with a previous attack of pericarditis. The etiopathogenesis is incompletely understood and most cases remain idiopathic with a presumed immune-mediated pathogenesis. The mainstay of therapy is aspirin or a nonsteroidal anti-inflammatory drug plus colchicine and the possible adjunct of a low-to-moderate dose of a corticosteroid in more difficult cases. Colchicine as an adjunct to anti-inflammatory therapy reduces by 50% the subsequent recurrent rate. For true refractory cases with failure of standard combination therapies, new and emerging options especially include human intravenous immunoglobulins and biological agents (i.e., anakinra). The outcome of idiopathic recurrent pericarditis is good with a negligible risk of developing constrictive pericarditis. Thus, it is important to reassure patients on their prognosis, explaining the nature of the disease and the likely course. Moreover, therapeutic choices should include less toxic agents and favor cheaper drugs whenever possible.

Increased sensitivity to apoptosis induced by methotrexate is mediated by Jun N-terminal kinase

PubMed Central

Spurlock, Charles F.; Aune, Zachary T.; Tossberg, John T.; Collins, Patrick L.; Aune, Jessica P.; Huston, Joseph W.; Crooke, Philip S.; Olsen, Nancy J.; Aune, Thomas M.

2011-01-01

Objective Low-dose methotrexate [MTX] is an effective therapy for rheumatoid arthritis yet its mechanism of action is incompletely understood. Here, we explored induction of apoptosis by MTX. Methods We employed flow cytometry to assess changes in levels of intracellular proteins, reactive oxygen species [ROS], and apoptosis.Quantitative polymerase chain reaction was usedtoassess changes in transcript levels of select target genes in response to MTX. Results MTX does not directly induce apoptosis but rather ‘primes’ cells for markedly increased sensitivity to apoptosis via either mitochondrial or death receptor pathways by a Jun N-terminal kinase [JNK]-dependent mechanism. Increased sensitivity to apoptosis is mediated, at least in part, by MTX-dependent production of reactive oxygen species, JNK activation and JNK-dependent induction of genes whose protein products promote apoptosis. Supplementation with tetrahydrobiopterin blocks these methotrexate-induced effects. Subjects with rheumatoid arthritis on low-dose MTX therapy express elevated levels of the JNK-target gene, JUN. Conclusions Our results support a model whereby methotrexate inhibits reduction of dihydrobiopterin to tetrahydrobiopterin resulting in increased production of ROS, increased JNK activity and increased sensitivity to apoptosis. The finding of increased JUN levels in subjects with RA taking low-dose MTX supports the notion that this pathway is activated by MTX, in vivo, and may contribute to efficacy of MTX in inflammatory disease. PMID:21618198

Effects of radiation type and delivery mode on a radioresistant eukaryote Cryptococcus neoformans

PubMed Central

Shuryak, Igor; Bryan, Ruth A.; Broitman, Jack; Marino, Stephen A.; Morgenstern, Alfred; Apostolidis, Christos; Dadachova, Ekaterina

2015-01-01

Introduction Most research on radioresistant fungi, particularly on human pathogens such as Cryptococcus neoformans, involves sparsely-ionizing radiation. Consequently, fungal responses to densely-ionizing radiation, which can be harnessed to treat life-threatening fungal infections, remain incompletely understood. Methods We addressed this issue by quantifying and comparing the effects of densely-ionizing α-particles (delivered either by external beam or by 213Bi-labeled monoclonal antibodies), and sparsely-ionizing 137Cs γ-rays, on Cryptococus neoformans. Results The best-fit linear-quadratic parameters for clonogenic survival were the following: α=0.24×10−2 Gy−1 for γ-rays and 1.07×10−2 Gy−1 for external-beam α-particles, and β=1.44×10−5 Gy−2 for both radiation types. Fungal cell killing by radiolabeled antibodies was consistent with predictions based on the α-particle dose to the cell nucleus and the linear-quadratic parameters for external-beam α-particles. The estimated RBE (for α-particles vs γ-rays) at low doses was 4.47 for the initial portion of the α-particle track, and 7.66 for the Bragg peak. Non-radiological antibody effects accounted for up to 23% of cell death. Conclusions These results quantify the degree of C. neoformans resistance to densely-ionizing radiations, and show how this resistance can be overcome with fungus-specific radiolabeled antibodies. PMID:25800676

Phenotypic modulation of smooth muscle cells during formation of neointimal thickenings following vascular injury.

PubMed

Thyberg, J

1998-07-01

Smooth muscle cells build up the media of mammalian arteries and constitute one of the principal cell types in atherosclerotic and restenotic lesions. Accordingly, they show a high degree of plasticity and are able to shift from a differentiated, contractile phenotype to a less differentiated, synthetic phenotype, and then back again. This modulation occurs as a response to vascular injury and includes a prominent structural reorganization with loss of myofilaments and formation of an extensive endoplasmic reticulum and a large Golgi complex. At the same time, the expression of cytoskeletal proteins and other gene products is altered. As a result, the cells lose their contractility and become able to migrate from the media to the intima, proliferate, and secrete extracellular matrix components, thereby contributing to the formation of intimal thickenings. The mechanisms behind this change in morphology and function of the smooth muscle cells are still incompletely understood. A crucial role has been ascribed to basement membrane proteins such as laminin and collagen type IV and adhesive proteins such as fibronectin. A significant role is also played by mitogenic proteins such as platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF). An improved knowledge of the regulation of smooth muscle differentiated properties represents an important part in the search for new methods of prevention and treatment of vascular disease.

Robust Long-Range Coordination of Spontaneous Neural Activity in Waking, Sleep and Anesthesia.

PubMed

Liu, Xiao; Yanagawa, Toru; Leopold, David A; Fujii, Naotaka; Duyn, Jeff H

2015-09-01

Although the emerging field of functional connectomics relies increasingly on the analysis of spontaneous fMRI signal covariation to infer the spatial fingerprint of the brain's large-scale functional networks, the nature of the underlying neuro-electrical activity remains incompletely understood. In part, this lack in understanding owes to the invasiveness of electrophysiological acquisition, the difficulty in their simultaneous recording over large cortical areas, and the absence of fully established methods for unbiased extraction of network information from these data. Here, we demonstrate a novel, data-driven approach to analyze spontaneous signal variations in electrocorticographic (ECoG) recordings from nearly entire hemispheres of macaque monkeys. Based on both broadband analysis and analysis of specific frequency bands, the ECoG signals were found to co-vary in patterns that resembled the fMRI networks reported in previous studies. The extracted patterns were robust against changes in consciousness associated with sleep and anesthesia, despite profound changes in intrinsic characteristics of the raw signals, including their spectral signatures. These results suggest that the spatial organization of large-scale brain networks results from neural activity with a broadband spectral feature and is a core aspect of the brain's physiology that does not depend on the state of consciousness. Published by Oxford University Press 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Intermedin protects against myocardial ischemia-reperfusion injury in diabetic rats

PubMed Central

2013-01-01

Background Diabetic patients, through incompletely understood mechanisms, endure exacerbated ischemic heart injury compared to non-diabetic patients. Intermedin (IMD) is a novel calcitonin gene-related peptide (CGRP) superfamily member with established cardiovascular protective effects. However, whether IMD protects against diabetic myocardial ischemia/reperfusion (MI/R) injury is unknown. Methods Diabetes was induced by streptozotocin in Sprague–Dawley rats. Animals were subjected to MI via left circumflex artery ligation for 30 minutes followed by 2 hours R. IMD was administered formally 10 minutes before R. Outcome measures included left ventricular function, oxidative stress, cellular death, infarct size, and inflammation. Results IMD levels were significantly decreased in diabetic rats compared to control animals. After MI/R, diabetic rats manifested elevated intermedin levels, both in plasma (64.95 ± 4.84 pmol/L, p < 0.05) and myocardial tissue (9.8 ± 0.60 pmol/L, p < 0.01) compared to pre-MI control values (43.62 ± 3.47 pmol/L and 4.4 ± 0.41). IMD administration to diabetic rats subjected to MI/R decreased oxidative stress product generation, apoptosis, infarct size, and inflammatory cytokine release (p < 0.05 or p < 0.01). Conclusions By reducing oxidative stress, inflammation, and apoptosis, IMD may represent a promising novel therapeutic target mitigating diabetic ischemic heart injury. PMID:23777472

Progesterone alters biliary flow dynamics.

PubMed Central

Tierney, S; Nakeeb, A; Wong, O; Lipsett, P A; Sostre, S; Pitt, H A; Lillemoe, K D

1999-01-01

OBJECTIVE: To test the hypothesis that progesterone alters sphincter of Oddi and gallbladder function and, therefore, bile flow dynamics. SUMMARY BACKGROUND DATA: Although the effects of progesterone on the biliary tract have been implicated in the increased incidence of gallstones among women, the specific effects of prolonged elevation of progesterone levels, such as occurs with contraceptive progesterone implants and during pregnancy, on the sphincter of Oddi and biliary flow dynamics are still incompletely understood. METHODS: Adult female prairie dogs were randomly assigned to receive subcutaneous implants containing either progesterone or inactive pellet matrix only. Hepatic bile partitioning and gallbladder emptying were determined 14 days later using 99mTc-Mebrofenin cholescintigraphy. RESULTS: Significantly less hepatic bile partitioned into the gallbladder in progesterone-treated than in control animals. The gallbladder ejection fraction was significantly reduced from 73+/-6% in controls to 59+/-3% in the progesterone-treated animals. The rate of gallbladder emptying was significantly reduced from 3.6+/-0.3%/minute to 2.9+/-0.1%/minute. CONCLUSIONS: Progesterone administered as subcutaneous implants alters partitioning of hepatic bile between gallbladder and small intestine and, therefore, gallbladder filling. Progesterone also significantly impairs gallbladder emptying in response to cholecystokinin. The effects of progesterone on the sphincter of Oddi and the gallbladder may contribute to the greater prevalence of gallstones and biliary motility disorders among women. Images Figure 1. Figure 2. Figure 3. Figure 4. PMID:10024101

Prevalence and Risk Factors of Lower Limb Amputation in Patients with End-Stage Renal Failure on Dialysis: A Systematic Review

PubMed Central

Vangaveti, Venkat N.

2016-01-01

Background. Renal dialysis has recently been recognised as a risk factor for lower limb amputation (LLA). However, exact rates and associated risk factors for the LLA are incompletely understood. Aim. Prevalence and risk factors of LLA in end-stage renal failure (ESRF) subjects on renal dialysis were investigated from the existing literature. Methods. Published data on the subject were derived from MEDLINE, PubMed, and Google Scholar search of English language literature from January 1, 1980, to July 31, 2015, using designated key words. Results. Seventy studies were identified out of which 6 full-text published studies were included in this systematic review of which 5 included patients on haemodialysis alone and one included patients on both haemodialysis and peritoneal dialysis. The reported findings on prevalence of amputation in the renal failure on dialysis cohort ranged from 1.7% to 13.4%. Five out of the six studies identified diabetes as the leading risk factor for amputation in subjects with ESRF on renal dialysis. Other risk factors identified were high haemoglobin A1c, elevated c-reactive protein, and low serum albumin. Conclusions. This review demonstrates high rate of LLA in ESRF patients receiving dialysis therapy. It has also identified diabetes and markers of inflammation as risk factors of amputation in ESRF subjects on dialysis. PMID:27529033

In Vivo Visualization of Bacterial Colonization, Antigen Expression, and Specific T-Cell Induction following Oral Administration of Live Recombinant Salmonella enterica Serovar Typhimurium

PubMed Central

Bumann, Dirk

2001-01-01

Live attenuated Salmonella strains that express a foreign antigen are promising oral vaccine candidates. Numerous genetic modifications have been empirically tested, but their effects on immunogenicity are difficult to interpret since important in vivo properties of recombinant Salmonella strains such as antigen expression and localization are incompletely characterized and the crucial early inductive events of an immune response to the foreign antigen are not fully understood. Here, methods were developed to directly localize and quantitate the in situ expression of an ovalbumin model antigen in recombinant Salmonella enterica serovar Typhimurium using two-color flow cytometry and confocal microscopy. In parallel, the in vivo activation, blast formation, and division of ovalbumin-specific CD4+ T cells were followed using a well-characterized transgenic T-cell receptor mouse model. This combined approach revealed a biphasic induction of ovalbumin-specific T cells in the Peyer's patches that followed the local ovalbumin expression of orally administered recombinant Salmonella cells in a dose- and time-dependent manner. Interestingly, intact Salmonella cells and cognate T cells seemed to remain in separate tissue compartments throughout induction, suggesting a transport of killed Salmonella cells from the colonized subepithelial dome area to the interfollicular inductive sites. The findings of this study will help to rationally optimize recombinant Salmonella strains as efficacious live antigen carriers for oral vaccination. PMID:11402006

A Multilevel Comprehensive Assessment of International Accreditation for Business Programmes-Based on AMBA Accreditation of GDUFS

ERIC Educational Resources Information Center

Jiang, Yong

2017-01-01

Traditional mathematical methods built around exactitude have limitations when applied to the processing of educational information, due to their uncertainty and imperfection. Alternative mathematical methods, such as grey system theory, have been widely applied in processing incomplete information systems and have proven effective in a number of…

Deep reticulation and incomplete lineage sorting obscure the diploid phylogeny of rain-lilies and allies (Amaryllidaceae tribe Hippeastreae)

USDA-ARS?s Scientific Manuscript database

Hybridization is currently considered to be a frequent and important force in plant evolution; NGS methods offer new possibilities for clade resolution and ambitious sampling of gene genealogies, yet difficulty remains in detecting deep reticulation events using currently available methods. We exami...

A random spatial sampling method in a rural developing nation

Treesearch

Michelle C. Kondo; Kent D.W. Bream; Frances K. Barg; Charles C. Branas

2014-01-01

Nonrandom sampling of populations in developing nations has limitations and can inaccurately estimate health phenomena, especially among hard-to-reach populations such as rural residents. However, random sampling of rural populations in developing nations can be challenged by incomplete enumeration of the base population. We describe a stratified random sampling method...

Effects of Missing Data Methods in SEM under Conditions of Incomplete and Nonnormal Data

ERIC Educational Resources Information Center

Li, Jian; Lomax, Richard G.

2017-01-01

Using Monte Carlo simulations, this research examined the performance of four missing data methods in SEM under different multivariate distributional conditions. The effects of four independent variables (sample size, missing proportion, distribution shape, and factor loading magnitude) were investigated on six outcome variables: convergence rate,…

Comparison of Implicit Schemes for the Incompressible Navier-Stokes Equations

NASA Technical Reports Server (NTRS)

Rogers, Stuart E.

1995-01-01

For a computational flow simulation tool to be useful in a design environment, it must be very robust and efficient. To develop such a tool for incompressible flow applications, a number of different implicit schemes are compared for several two-dimensional flow problems in the current study. The schemes include Point-Jacobi relaxation, Gauss-Seidel line relaxation, incomplete lower-upper decomposition, and the generalized minimum residual method preconditioned with each of the three other schemes. The efficiency of the schemes is measured in terms of the computing time required to obtain a steady-state solution for the laminar flow over a backward-facing step, the flow over a NACA 4412 airfoil, and the flow over a three-element airfoil using overset grids. The flow solver used in the study is the INS2D code that solves the incompressible Navier-Stokes equations using the method of artificial compressibility and upwind differencing of the convective terms. The results show that the generalized minimum residual method preconditioned with the incomplete lower-upper factorization outperforms all other methods by at least a factor of 2.

Why physician-assisted suicide perpetuates the idolatory of medicine.

PubMed

Cherry, Mark J

2003-01-01

Adequate response to physician-assisted suicide and euthanasia depends on fundamental philosophical and theological issues, including the character of an appropriate philosophically and theologically anchored anthropology, where the central element of traditional Christian anthropology is that humans are created to worship God. As I will argue, Christian morality and moral epistemology must be nested within and understood through this background Christian anthropology. As a result, I will argue that physician-assisted suicide and euthanasia can only be one-sidedly and inadequately appreciated through rational appeal to central values, such as "human dignity" and "self determination", or through "sola scriptura" biblical interpretation, or individual judgments of conscience. Adequately addressing physician-assisted suicide and euthanasia will depend on a more fundamental spiritual-therapeutic approach. This cluster of moral, epistemological, anthropological, and bioethical claims will be explored by drawing on the texts of St. Basil the Great, St. Maximos the Confessor, and St. Isaac the Syrian. Their reflections on medicine, the human good, and its relationship to worship, spiritual therapy, and God will be used as a basis to indicate a broader philosophical perspective, which will be needed to avoid a one-sided, incomplete approach to the challenges of physician-assisted suicide and euthanasia. Medical morality, I argue, is best understood within categories that transcend the right, the good, the just, and the virtuous; namely, the holy.

Pandemic influenza: certain uncertainties

PubMed Central

Morens, David M.; Taubenberger, Jeffery K.

2011-01-01

SUMMARY For at least five centuries, major epidemics and pandemics of influenza have occurred unexpectedly and at irregular intervals. Despite the modern notion that pandemic influenza is a distinct phenomenon obeying such constant (if incompletely understood) rules such as dramatic genetic change, cyclicity, “wave” patterning, virus replacement, and predictable epidemic behavior, much evidence suggests the opposite. Although there is much that we know about pandemic influenza, there appears to be much more that we do not know. Pandemics arise as a result of various genetic mechanisms, have no predictable patterns of mortality among different age groups, and vary greatly in how and when they arise and recur. Some are followed by new pandemics, whereas others fade gradually or abruptly into long-term endemicity. Human influenza pandemics have been caused by viruses that evolved singly or in co-circulation with other pandemic virus descendants and often have involved significant transmission between, or establishment of, viral reservoirs within other animal hosts. In recent decades, pandemic influenza has continued to produce numerous unanticipated events that expose fundamental gaps in scientific knowledge. Influenza pandemics appear to be not a single phenomenon but a heterogeneous collection of viral evolutionary events whose similarities are overshadowed by important differences, the determinants of which remain poorly understood. These uncertainties make it difficult to predict influenza pandemics and, therefore, to adequately plan to prevent them. PMID:21706672

Methodological congruence in phylogenomic analyses with morphological support for teiid lizards (Sauria: Teiidae).

PubMed

Tucker, Derek B; Colli, Guarino R; Giugliano, Lilian G; Hedges, S Blair; Hendry, Catriona R; Lemmon, Emily Moriarty; Lemmon, Alan R; Sites, Jack W; Pyron, R Alexander

2016-10-01

A well-known issue in phylogenetics is discordance among gene trees, species trees, morphology, and other data types. Gene-tree discordance is often caused by incomplete lineage sorting, lateral gene transfer, and gene duplication. Multispecies-coalescent methods can account for incomplete lineage sorting and are believed by many to be more accurate than concatenation. However, simulation studies and empirical data have demonstrated that concatenation and species tree methods often recover similar topologies. We use three popular methods of phylogenetic reconstruction (one concatenation, two species tree) to evaluate relationships within Teiidae. These lizards are distributed across the United States to Argentina and the West Indies, and their classification has been controversial due to incomplete sampling and the discordance among various character types (chromosomes, DNA, musculature, osteology, etc.) used to reconstruct phylogenetic relationships. Recent morphological and molecular analyses of the group resurrected three genera and created five new genera to resolve non-monophyly in three historically ill-defined genera: Ameiva, Cnemidophorus, and Tupinambis. Here, we assess the phylogenetic relationships of the Teiidae using "next-generation" anchored-phylogenomics sequencing. Our final alignment includes 316 loci (488,656bp DNA) for 244 individuals (56 species of teiids, representing all currently recognized genera) and all three methods (ExaML, MP-EST, and ASTRAL-II) recovered essentially identical topologies. Our results are basically in agreement with recent results from morphology and smaller molecular datasets, showing support for monophyly of the eight new genera. Interestingly, even with hundreds of loci, the relationships among some genera in Tupinambinae remain ambiguous (i.e. low nodal support for the position of Salvator and Dracaena). Copyright © 2016 Elsevier Inc. All rights reserved.

Coalescent-Based Analyses of Genomic Sequence Data Provide a Robust Resolution of Phylogenetic Relationships among Major Groups of Gibbons

PubMed Central

Shi, Cheng-Min; Yang, Ziheng

2018-01-01

Abstract The phylogenetic relationships among extant gibbon species remain unresolved despite numerous efforts using morphological, behavorial, and genetic data and the sequencing of whole genomes. A major challenge in reconstructing the gibbon phylogeny is the radiative speciation process, which resulted in extremely short internal branches in the species phylogeny and extensive incomplete lineage sorting with extensive gene-tree heterogeneity across the genome. Here, we analyze two genomic-scale data sets, with ∼10,000 putative noncoding and exonic loci, respectively, to estimate the species tree for the major groups of gibbons. We used the Bayesian full-likelihood method bpp under the multispecies coalescent model, which naturally accommodates incomplete lineage sorting and uncertainties in the gene trees. For comparison, we included three heuristic coalescent-based methods (mp-est, SVDQuartets, and astral) as well as concatenation. From both data sets, we infer the phylogeny for the four extant gibbon genera to be (Hylobates, (Nomascus, (Hoolock, Symphalangus))). We used simulation guided by the real data to evaluate the accuracy of the methods used. Astral, while not as efficient as bpp, performed well in estimation of the species tree even in presence of excessive incomplete lineage sorting. Concatenation, mp-est and SVDQuartets were unreliable when the species tree contains very short internal branches. Likelihood ratio test of gene flow suggests a small amount of migration from Hylobates moloch to H. pileatus, while cross-genera migration is absent or rare. Our results highlight the utility of coalescent-based methods in addressing challenging species tree problems characterized by short internal branches and rampant gene tree-species tree discordance. PMID:29087487

A Policy Representation Using Weighted Multiple Normal Distribution

NASA Astrophysics Data System (ADS)

Kimura, Hajime; Aramaki, Takeshi; Kobayashi, Shigenobu

In this paper, we challenge to solve a reinforcement learning problem for a 5-linked ring robot within a real-time so that the real-robot can stand up to the trial and error. On this robot, incomplete perception problems are caused from noisy sensors and cheap position-control motor systems. This incomplete perception also causes varying optimum actions with the progress of the learning. To cope with this problem, we adopt an actor-critic method, and we propose a new hierarchical policy representation scheme, that consists of discrete action selection on the top level and continuous action selection on the low level of the hierarchy. The proposed hierarchical scheme accelerates learning on continuous action space, and it can pursue the optimum actions varying with the progress of learning on our robotics problem. This paper compares and discusses several learning algorithms through simulations, and demonstrates the proposed method showing application for the real robot.

Some Families of the Incomplete H-Functions and the Incomplete \\overline H -Functions and Associated Integral Transforms and Operators of Fractional Calculus with Applications

NASA Astrophysics Data System (ADS)

Srivastava, H. M.; Saxena, R. K.; Parmar, R. K.

2018-01-01

Our present investigation is inspired by the recent interesting extensions (by Srivastava et al. [35]) of a pair of the Mellin-Barnes type contour integral representations of their incomplete generalized hypergeometric functions p γ q and p Γ q by means of the incomplete gamma functions γ( s, x) and Γ( s, x). Here, in this sequel, we introduce a family of the relatively more general incomplete H-functions γ p,q m,n ( z) and Γ p,q m,n ( z) as well as their such special cases as the incomplete Fox-Wright generalized hypergeometric functions p Ψ q (γ) [ z] and p Ψ q (Γ) [ z]. The main object of this paper is to study and investigate several interesting properties of these incomplete H-functions, including (for example) decomposition and reduction formulas, derivative formulas, various integral transforms, computational representations, and so on. We apply some substantially general Riemann-Liouville and Weyl type fractional integral operators to each of these incomplete H-functions. We indicate the easilyderivable extensions of the results presented here that hold for the corresponding incomplete \\overline H -functions as well. Potential applications of many of these incomplete special functions involving (for example) probability theory are also indicated.

Multiple imputation by chained equations for systematically and sporadically missing multilevel data.

PubMed

Resche-Rigon, Matthieu; White, Ian R

2018-06-01

In multilevel settings such as individual participant data meta-analysis, a variable is 'systematically missing' if it is wholly missing in some clusters and 'sporadically missing' if it is partly missing in some clusters. Previously proposed methods to impute incomplete multilevel data handle either systematically or sporadically missing data, but frequently both patterns are observed. We describe a new multiple imputation by chained equations (MICE) algorithm for multilevel data with arbitrary patterns of systematically and sporadically missing variables. The algorithm is described for multilevel normal data but can easily be extended for other variable types. We first propose two methods for imputing a single incomplete variable: an extension of an existing method and a new two-stage method which conveniently allows for heteroscedastic data. We then discuss the difficulties of imputing missing values in several variables in multilevel data using MICE, and show that even the simplest joint multilevel model implies conditional models which involve cluster means and heteroscedasticity. However, a simulation study finds that the proposed methods can be successfully combined in a multilevel MICE procedure, even when cluster means are not included in the imputation models.

Reproductive outcome after IVF following hysteroscopic division of incomplete uterine septum/arcuate uterine anomaly in women with primary infertility

PubMed Central

Abuzeid, M.; Ghourab, G.; Abuzeid, O.; Mitwally, M.; Ashraf, M.; Diamond, M.

2014-01-01

Objective: To determine reproductive outcome after in-vitro fertilization/embryo transfer (IVF-ET) in women with primary infertility following hysteroscopic septoplasty of incomplete uterine septum or arcuate uterine anomaly. Methods: This is a historical cohort study. The study group consisted of 156 consecutive patients who underwent a total of 221 cycles of IVF/ET following hysteroscopic septoplasty of an incomplete uterine septum or arcuate anomaly (Group 1). The control group included 196 consecutive patients with normal endometrial cavity on hysteroscopy who underwent a total of 369 cycles of IVF/ET (Group 2). The reproductive outcome after the first cycle of IVF-ET and the best reproductive outcome of all the cycles the patient underwent were calculated. In addition, we compared the reproductive outcome in the study group based on the type of the anomalies (septum versus arcuate). Results: In the first fresh cycle, following septoplasty, there were significantly higher clinical pregnancy and delivery rates in Group 1 (60.3% and 51.3% respectively) compared to Group 2 (38.8% and 33.2% respectively). However, there was no significant difference between the two groups in the clinical pregnancy (74.4% vs. 67.3%) or in the delivery (65.4% vs. 60.2%) rates per patient, respectively. There was no significant difference in the reproductive outcome after IVF-ET between patients who previously had arcuate uterine anomaly versus incomplete uterine septum. Conclusion: Reproductive outcome of IVF-ET after hysteroscopic correction of incomplete uterine septum/arcuate uterine anomaly in women with primary infertility is no different from women with normal uterine cavity. PMID:25593694

Retinal Wave Patterns Are Governed by Mutual Excitation among Starburst Amacrine Cells and Drive the Refinement and Maintenance of Visual Circuits

PubMed Central

Xu, Hong-Ping; Burbridge, Timothy J.; Ye, Meijun; Chen, Minggang; Ge, Xinxin; Zhou, Z. Jimmy

2016-01-01

Retinal waves are correlated bursts of spontaneous activity whose spatiotemporal patterns are critical for early activity-dependent circuit elaboration and refinement in the mammalian visual system. Three separate developmental wave epochs or stages have been described, but the mechanism(s) of pattern generation of each and their distinct roles in visual circuit development remain incompletely understood. We used neuroanatomical, in vitro and in vivo electrophysiological, and optical imaging techniques in genetically manipulated mice to examine the mechanisms of wave initiation and propagation and the role of wave patterns in visual circuit development. Through deletion of β2 subunits of nicotinic acetylcholine receptors (β2-nAChRs) selectively from starburst amacrine cells (SACs), we show that mutual excitation among SACs is critical for Stage II (cholinergic) retinal wave propagation, supporting models of wave initiation and pattern generation from within a single retinal cell type. We also demonstrate that β2-nAChRs in SACs, and normal wave patterns, are necessary for eye-specific segregation. Finally, we show that Stage III (glutamatergic) retinal waves are not themselves necessary for normal eye-specific segregation, but elimination of both Stage II and Stage III retinal waves dramatically disrupts eye-specific segregation. This suggests that persistent Stage II retinal waves can adequately compensate for Stage III retinal wave loss during the development and refinement of eye-specific segregation. These experiments confirm key features of the “recurrent network” model for retinal wave propagation and clarify the roles of Stage II and Stage III retinal wave patterns in visual circuit development. SIGNIFICANCE STATEMENT Spontaneous activity drives early mammalian circuit development, but the initiation and patterning of activity vary across development and among modalities. Cholinergic “retinal waves” are initiated in starburst amacrine cells and propagate to retinal ganglion cells and higher-order visual areas, but the mechanism responsible for creating their unique and critical activity pattern is incompletely understood. We demonstrate that cholinergic wave patterns are dictated by recurrent connectivity within starburst amacrine cells, and retinal ganglion cells act as “readouts” of patterned activity. We also show that eye-specific segregation occurs normally without glutamatergic waves, but elimination of both cholinergic and glutamatergic waves completely disrupts visual circuit development. These results suggest that each retinal wave pattern during development is optimized for concurrently refining multiple visual circuits. PMID:27030771

Estimating site occupancy rates for aquatic plants using spatial sub-sampling designs when detection probabilities are less than one

USGS Publications Warehouse

Nielson, Ryan M.; Gray, Brian R.; McDonald, Lyman L.; Heglund, Patricia J.

2011-01-01

Estimation of site occupancy rates when detection probabilities are <1 is well established in wildlife science. Data from multiple visits to a sample of sites are used to estimate detection probabilities and the proportion of sites occupied by focal species. In this article we describe how site occupancy methods can be applied to estimate occupancy rates of plants and other sessile organisms. We illustrate this approach and the pitfalls of ignoring incomplete detection using spatial data for 2 aquatic vascular plants collected under the Upper Mississippi River's Long Term Resource Monitoring Program (LTRMP). Site occupancy models considered include: a naïve model that ignores incomplete detection, a simple site occupancy model assuming a constant occupancy rate and a constant probability of detection across sites, several models that allow site occupancy rates and probabilities of detection to vary with habitat characteristics, and mixture models that allow for unexplained variation in detection probabilities. We used information theoretic methods to rank competing models and bootstrapping to evaluate the goodness-of-fit of the final models. Results of our analysis confirm that ignoring incomplete detection can result in biased estimates of occupancy rates. Estimates of site occupancy rates for 2 aquatic plant species were 19–36% higher compared to naive estimates that ignored probabilities of detection <1. Simulations indicate that final models have little bias when 50 or more sites are sampled, and little gains in precision could be expected for sample sizes >300. We recommend applying site occupancy methods for monitoring presence of aquatic species.

Technological Literacy for Students Aged 6-18: A New Method for Holistic Measuring of Knowledge, Capabilities, Critical Thinking and Decision-Making

ERIC Educational Resources Information Center

Avsec, Stanislav; Jamšek, Janez

2016-01-01

Technological literacy is identified as a vital achievement of technology- and engineering-intensive education. It guides the design of technology and technical components of educational systems and defines competitive employment in technological society. Existing methods for measuring technological literacy are incomplete or complicated,…

Impact of Violation of the Missing-at-Random Assumption on Full-Information Maximum Likelihood Method in Multidimensional Adaptive Testing

ERIC Educational Resources Information Center

Han, Kyung T.; Guo, Fanmin

2014-01-01

The full-information maximum likelihood (FIML) method makes it possible to estimate and analyze structural equation models (SEM) even when data are partially missing, enabling incomplete data to contribute to model estimation. The cornerstone of FIML is the missing-at-random (MAR) assumption. In (unidimensional) computerized adaptive testing…

Failsafe modes in incomplete minority game

NASA Astrophysics Data System (ADS)

Yao, Xiaobo; Wan, Shaolong; Chen, Wen

2009-09-01

We make a failsafe extension to the incomplete minority game model, give a brief analysis on how incompleteness will effect system efficiency. Simulations that limited incompleteness in strategies can improve the system efficiency. Among three failsafe modes, the “Back-to-Best” mode brings most significant improvement and keeps the system efficiency in a long range of incompleteness. A simple analytic formula has a trend which matches simulation results. The IMMG model is used to study the effect of distribution, and we find that there is one junction point in each series of curves, at which system efficiency is not influenced by the distribution of incompleteness. When pIbar > the concentration of incompleteness weakens the effect. On the other side of , concentration will be helpful. When pI is close to zero agents using incomplete strategies have on average better profits than those using standard strategies, and the “Back-to-Best” agents have a wider range of pI to win.

Dynamic Financial Constraints: Distinguishing Mechanism Design from Exogenously Incomplete Regimes*

PubMed Central

Karaivanov, Alexander; Townsend, Robert M.

2014-01-01

We formulate and solve a range of dynamic models of constrained credit/insurance that allow for moral hazard and limited commitment. We compare them to full insurance and exogenously incomplete financial regimes (autarky, saving only, borrowing and lending in a single asset). We develop computational methods based on mechanism design, linear programming, and maximum likelihood to estimate, compare, and statistically test these alternative dynamic models with financial/information constraints. Our methods can use both cross-sectional and panel data and allow for measurement error and unobserved heterogeneity. We estimate the models using data on Thai households running small businesses from two separate samples. We find that in the rural sample, the exogenously incomplete saving only and borrowing regimes provide the best fit using data on consumption, business assets, investment, and income. Family and other networks help consumption smoothing there, as in a moral hazard constrained regime. In contrast, in urban areas, we find mechanism design financial/information regimes that are decidedly less constrained, with the moral hazard model fitting best combined business and consumption data. We perform numerous robustness checks in both the Thai data and in Monte Carlo simulations and compare our maximum likelihood criterion with results from other metrics and data not used in the estimation. A prototypical counterfactual policy evaluation exercise using the estimation results is also featured. PMID:25246710

Mark-resight abundance estimation under incomplete identification of marked individuals

USGS Publications Warehouse

McClintock, Brett T.; Hill, Jason M.; Fritz, Lowell; Chumbley, Kathryn; Luxa, Katie; Diefenbach, Duane R.

2014-01-01

Often less expensive and less invasive than conventional mark–recapture, so-called 'mark-resight' methods are popular in the estimation of population abundance. These methods are most often applied when a subset of the population of interest is marked (naturally or artificially), and non-invasive sighting data can be simultaneously collected for both marked and unmarked individuals. However, it can often be difficult to identify marked individuals with certainty during resighting surveys, and incomplete identification of marked individuals is potentially a major source of bias in mark-resight abundance estimators. Previously proposed solutions are ad hoc and will tend to underperform unless marked individual identification rates are relatively high (>90%) or individual sighting heterogeneity is negligible.Based on a complete data likelihood, we present an approach that properly accounts for uncertainty in marked individual detection histories when incomplete identifications occur. The models allow for individual heterogeneity in detection, sampling with (e.g. Poisson) or without (e.g. Bernoulli) replacement, and an unknown number of marked individuals. Using a custom Markov chain Monte Carlo algorithm to facilitate Bayesian inference, we demonstrate these models using two example data sets and investigate their properties via simulation experiments.We estimate abundance for grassland sparrow populations in Pennsylvania, USA when sampling was conducted with replacement and the number of marked individuals was either known or unknown. To increase marked individual identification probabilities, extensive territory mapping was used to assign incomplete identifications to individuals based on location. Despite marked individual identification probabilities as low as 67% in the absence of this territorial mapping procedure, we generally found little return (or need) for this time-consuming investment when using our proposed approach. We also estimate rookery abundance from Alaskan Steller sea lion counts when sampling was conducted without replacement, the number of marked individuals was unknown, and individual heterogeneity was suspected as non-negligible.In terms of estimator performance, our simulation experiments and examples demonstrated advantages of our proposed approach over previous methods, particularly when marked individual identification probabilities are low and individual heterogeneity levels are high. Our methodology can also reduce field effort requirements for marked individual identification, thus, allowing potential investment into additional marking events or resighting surveys.

Orderings for conjugate gradient preconditionings

NASA Technical Reports Server (NTRS)

Ortega, James M.

1991-01-01

The effect of orderings on the rate of convergence of the conjugate gradient method with SSOR or incomplete Cholesky preconditioning is examined. Some results also are presented that help to explain why red/black ordering gives an inferior rate of convergence.

Tbx1 regulates oral epithelial adhesion and palatal development

PubMed Central

Funato, Noriko; Nakamura, Masataka; Richardson, James A.; Srivastava, Deepak; Yanagisawa, Hiromi

2012-01-01

Cleft palate, the most frequent congenital craniofacial birth defect, is a multifactorial condition induced by the interaction of genetic and environmental factors. In addition to complete cleft palate, a large number of human cases involve soft palate cleft and submucosal cleft palate. However, the etiology of these forms of cleft palate has not been well understood. T-box transcriptional factor (Tbx) family of transcriptional factors has distinct roles in a wide range of embryonic differentiation or response pathways. Here, we show that genetic disruption of Tbx1, a major candidate gene for the human congenital disorder 22q11.2 deletion syndrome (Velo-cardio-facial/DiGeorge syndrome), led to abnormal epithelial adhesion between the palate and mandible in mouse, resulting in various forms of cleft palate similar to human conditions. We found that hyperproliferative epithelium failed to undergo complete differentiation in Tbx1-null mice (Tbx1−/−). Inactivation of Tbx1 specifically in the keratinocyte lineage (Tbx1KCKO) resulted in an incomplete cleft palate confined to the anterior region of the palate. Interestingly, Tbx1 overexpression resulted in decreased cell growth and promoted cell-cycle arrest in MCF7 epithelial cells. These findings suggest that Tbx1 regulates the balance between proliferation and differentiation of keratinocytes and is essential for palatal fusion and oral mucosal differentiation. The impaired adhesion separation of the oral epithelium together with compromised palatal mesenchymal growth is an underlying cause for various forms of cleft palate phenotypes in Tbx1−/− mice. Our present study reveals new pathogenesis of incomplete and submucous cleft palate during mammalian palatogenesis. PMID:22371266

Dynamic Motor Compensations with Permanent, Focal Loss of Forelimb Force after Cervical Spinal Cord Injury

PubMed Central

López-Dolado, Elisa; Lucas-Osma, Ana M.

2013-01-01

Abstract Incomplete cervical lesion is the most common type of human spinal cord injury (SCI) and causes permanent paresis of arm muscles, a phenomenon still incompletely understood in physiopathological and neuroanatomical terms. We performed spinal cord hemisection in adult rats at the caudal part of the segment C6, just rostral to the bulk of triceps brachii motoneurons, and analyzed the forces and kinematics of locomotion up to 4 months postlesion to determine the nature of motor function loss and recovery. A dramatic (50%), immediate and permanent loss of extensor force occurred in the forelimb but not in the hind limb of the injured side, accompanied by elbow and wrist kinematic impairments and early adaptations of whole-body movements that initially compensated the balance but changed continuously over the follow-up period to allow effective locomotion. Overuse of both contralateral legs and ipsilateral hind leg was evidenced since 5 days postlesion. Ipsilateral foreleg deficits resulted mainly from interruption of axons that innervate the spinal cord segments caudal to the lesion, because chronic loss (about 35%) of synapses was detected at C7 while only 14% of triceps braquii motoneurons died, as assessed by synaptophysin immunohistochemistry and retrograde neural tracing, respectively. We also found a large pool of propriospinal neurons projecting from C2–C5 to C7 in normal rats, with topographical features similar to the propriospinal premotoneuronal system of cats and primates. Thus, concurrent axotomy at C6 of brain descending axons and cervical propriospinal axons likely hampered spontaneous recovery of the focal neurological impairments. PMID:23249275

Maintaining the continuity of HIV-care records for patients transferring care between centers: challenges, workloads, needs and risks.

PubMed

Gill, M John; Ody, Meagan; Lynch, Tarah; Jessiman-Perreault, Lynn; Krentz, Hartmut B

2016-08-01

With improved life expectancy, the medical records of HIV-infected patients are likely to be transferred repeatedly between HIV caregivers. The challenges, and risk for introducing medical error from incomplete record transfers are poorly understood. We measured number of requests for record transfer, the workload incurred, and explore, using genotypic antiretroviral resistance testing results (GART), the potential risk of incomplete records. Using retrospective database and chart review, we examined all patients followed at the Southern Alberta Clinic between 1 January 2004 and 1 January 2015, and determined how many patients transferred care into and out our program, the associated requests and the workload for record transfer. Using a complete record of all GART tests, the potential importance of absent historic records in current treatment decisions was analyzed. The annual churn rate was 22 ± 3.4%. We received requests for only 70% of patient records who had left our care. Median time for receipt of incoming medical records was 28 days; average clerical time for processing data was 2 hours/record. Of all GART results, 25% exhibited resistance. Of 111 patients with potentially misleading GART results (i.e., documented historical resistance not visible on more recent GART), 34 (30.6%) had moved in from elsewhere. Rigorous maintenance of the continuity of the HIV record is not universally practiced. Resources, costs and logistic challenges as well as a lack of appreciation of risks clearly shown by GART testing, may be relevant barriers. Addressing such issues is pressing as aging and transfers of care are increasingly common.

Aeromagnetic and aeromagnetic-based geologic maps of the Coastal Belt, Franciscan Complex, northern California

USGS Publications Warehouse

Langenheim, V.E.; Jachens, R.C.; McLaughlin, R.J.

2011-01-01

The Coastal belt of the Franciscan Complex represents a Late Cretaceous to Miocene accretionary prism and overlying slope deposits. Its equivalents may extend from the offshore outer borderland of southern California to north of the Mendocino Triple Junction under the Eel River Basin and in the offshore of Cascadia. The Coastal belt is exposed on land in northern California, yet its structure and stratigraphy are incompletely known because of discontinuous exposure, structural disruption, and lithologically non-distinctive clastic rocks. The intent of this report is to make available, in map form, aeromagnetic data covering the Coastal belt that provide a new dataset to aid in mapping, understanding, and interpreting the incompletely understood geology and structure in northern California.The newly merged aeromagnetic data over the Coastal belt of the Franciscan Complex reveal long, linear anomalies that indicate remarkably coherent structure within a terrane where mapping at the surface indicates complex deformation and that has been described as "broken formation" and, even locally as "mélange". The anomalies in the Coastal belt are primarily sourced by volcanic-rich graywackes and exotic blocks of basalt. Some anomalies along the contact of the Coastal belt with the Central belt are likely caused by local interleaving of components of the Coast Ranges ophiolite. These data can be used to map additional exotic blocks within the Coastal belt and to distinguish lithologically indistinct graywackes within the Coastal terrane. Using anomaly asymmetry allows projection of these "layers" into the subsurface. This analysis indicates predominant northeast dips consistent with tectonic interleaving of blocks within a subduction zone.

49 CFR 568.4 - Requirements for incomplete vehicle manufacturers.

Code of Federal Regulations, 2014 CFR

2014-10-01

... manufacturing operation on the incomplete vehicle. (3) Identification of the incomplete vehicle(s) to which the document applies. The identification shall be by vehicle identification number (VIN) or groups of VINs to... 49 Transportation 6 2014-10-01 2014-10-01 false Requirements for incomplete vehicle manufacturers...

49 CFR 568.4 - Requirements for incomplete vehicle manufacturers.

Code of Federal Regulations, 2011 CFR

2011-10-01

... manufacturing operation on the incomplete vehicle. (3) Identification of the incomplete vehicle(s) to which the document applies. The identification shall be by vehicle identification number (VIN) or groups of VINs to... 49 Transportation 6 2011-10-01 2011-10-01 false Requirements for incomplete vehicle manufacturers...

49 CFR 568.4 - Requirements for incomplete vehicle manufacturers.

Code of Federal Regulations, 2010 CFR

2010-10-01

... manufacturing operation on the incomplete vehicle. (3) Identification of the incomplete vehicle(s) to which the document applies. The identification shall be by vehicle identification number (VIN) or groups of VINs to... 49 Transportation 6 2010-10-01 2010-10-01 false Requirements for incomplete vehicle manufacturers...

49 CFR 529.4 - Requirements for incomplete automobile manufacturers.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 6 2012-10-01 2012-10-01 false Requirements for incomplete automobile... AUTOMOBILES § 529.4 Requirements for incomplete automobile manufacturers. (a) Except as provided in paragraph (c) of this section, §§ 529.5 and 529.6, each incomplete automobile manufacturer is considered, with...

49 CFR 529.4 - Requirements for incomplete automobile manufacturers.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 6 2010-10-01 2010-10-01 false Requirements for incomplete automobile... AUTOMOBILES § 529.4 Requirements for incomplete automobile manufacturers. (a) Except as provided in paragraph (c) of this section, §§ 529.5 and 529.6, each incomplete automobile manufacturer is considered, with...

49 CFR 529.4 - Requirements for incomplete automobile manufacturers.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 6 2014-10-01 2014-10-01 false Requirements for incomplete automobile... AUTOMOBILES § 529.4 Requirements for incomplete automobile manufacturers. (a) Except as provided in paragraph (c) of this section, §§ 529.5 and 529.6, each incomplete automobile manufacturer is considered, with...

49 CFR 529.4 - Requirements for incomplete automobile manufacturers.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 6 2013-10-01 2013-10-01 false Requirements for incomplete automobile... AUTOMOBILES § 529.4 Requirements for incomplete automobile manufacturers. (a) Except as provided in paragraph (c) of this section, §§ 529.5 and 529.6, each incomplete automobile manufacturer is considered, with...

49 CFR 529.4 - Requirements for incomplete automobile manufacturers.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 6 2011-10-01 2011-10-01 false Requirements for incomplete automobile... AUTOMOBILES § 529.4 Requirements for incomplete automobile manufacturers. (a) Except as provided in paragraph (c) of this section, §§ 529.5 and 529.6, each incomplete automobile manufacturer is considered, with...

Direct determination of one-dimensional interphase structures using normalized crystal truncation rod analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kawaguchi, Tomoya; Liu, Yihua; Reiter, Anthony

Here, a one-dimensional non-iterative direct method was employed for normalized crystal truncation rod analysis. The non-iterative approach, utilizing the Kramers–Kronig relation, avoids the ambiguities due to an improper initial model or incomplete convergence in the conventional iterative methods. The validity and limitations of the present method are demonstrated through both numerical simulations and experiments with Pt(111) in a 0.1 M CsF aqueous solution. The present method is compared with conventional iterative phase-retrieval methods.

Direct determination of one-dimensional interphase structures using normalized crystal truncation rod analysis

DOE PAGES

Kawaguchi, Tomoya; Liu, Yihua; Reiter, Anthony; ...

2018-04-20

Here, a one-dimensional non-iterative direct method was employed for normalized crystal truncation rod analysis. The non-iterative approach, utilizing the Kramers–Kronig relation, avoids the ambiguities due to an improper initial model or incomplete convergence in the conventional iterative methods. The validity and limitations of the present method are demonstrated through both numerical simulations and experiments with Pt(111) in a 0.1 M CsF aqueous solution. The present method is compared with conventional iterative phase-retrieval methods.

Statistical aspects of point count sampling

USGS Publications Warehouse

Barker, R.J.; Sauer, J.R.; Ralph, C.J.; Sauer, J.R.; Droege, S.

1995-01-01

The dominant feature of point counts is that they do not census birds, but instead provide incomplete counts of individuals present within a survey plot. Considering a simple model for point count sampling, we demon-strate that use of these incomplete counts can bias estimators and testing procedures, leading to inappropriate conclusions. A large portion of the variability in point counts is caused by the incomplete counting, and this within-count variation can be confounded with ecologically meaningful varia-tion. We recommend caution in the analysis of estimates obtained from point counts. Using; our model, we also consider optimal allocation of sampling effort. The critical step in the optimization process is in determining the goals of the study and methods that will be used to meet these goals. By explicitly defining the constraints on sampling and by estimating the relationship between precision and bias of estimators and time spent counting, we can predict the optimal time at a point for each of several monitoring goals. In general, time spent at a point will differ depending on the goals of the study.

Novel Approach to Classify Plants Based on Metabolite-Content Similarity.

PubMed

Liu, Kang; Abdullah, Azian Azamimi; Huang, Ming; Nishioka, Takaaki; Altaf-Ul-Amin, Md; Kanaya, Shigehiko

2017-01-01

Secondary metabolites are bioactive substances with diverse chemical structures. Depending on the ecological environment within which they are living, higher plants use different combinations of secondary metabolites for adaptation (e.g., defense against attacks by herbivores or pathogenic microbes). This suggests that the similarity in metabolite content is applicable to assess phylogenic similarity of higher plants. However, such a chemical taxonomic approach has limitations of incomplete metabolomics data. We propose an approach for successfully classifying 216 plants based on their known incomplete metabolite content. Structurally similar metabolites have been clustered using the network clustering algorithm DPClus. Plants have been represented as binary vectors, implying relations with structurally similar metabolite groups, and classified using Ward's method of hierarchical clustering. Despite incomplete data, the resulting plant clusters are consistent with the known evolutional relations of plants. This finding reveals the significance of metabolite content as a taxonomic marker. We also discuss the predictive power of metabolite content in exploring nutritional and medicinal properties in plants. As a byproduct of our analysis, we could predict some currently unknown species-metabolite relations.

Novel Approach to Classify Plants Based on Metabolite-Content Similarity

PubMed Central

Abdullah, Azian Azamimi; Huang, Ming; Nishioka, Takaaki

2017-01-01

Secondary metabolites are bioactive substances with diverse chemical structures. Depending on the ecological environment within which they are living, higher plants use different combinations of secondary metabolites for adaptation (e.g., defense against attacks by herbivores or pathogenic microbes). This suggests that the similarity in metabolite content is applicable to assess phylogenic similarity of higher plants. However, such a chemical taxonomic approach has limitations of incomplete metabolomics data. We propose an approach for successfully classifying 216 plants based on their known incomplete metabolite content. Structurally similar metabolites have been clustered using the network clustering algorithm DPClus. Plants have been represented as binary vectors, implying relations with structurally similar metabolite groups, and classified using Ward's method of hierarchical clustering. Despite incomplete data, the resulting plant clusters are consistent with the known evolutional relations of plants. This finding reveals the significance of metabolite content as a taxonomic marker. We also discuss the predictive power of metabolite content in exploring nutritional and medicinal properties in plants. As a byproduct of our analysis, we could predict some currently unknown species-metabolite relations. PMID:28164123

CURRENT METHODS AND RESEARCH STRATEGIES FOR MODELING ATMOSPHERIC MERCURY

EPA Science Inventory

The atmospheric pathway of the global mercury cycle is known to be the primary source of mercury contamination to most threatened aquatic ecosystems. Current efforts toward numerical modeling of atmospheric mercury are hindered by an incomplete understanding of emissions, atmosp...

[Historia magistra vitae: on the methods of historical demography].

PubMed

Botev, N

1992-01-01

Indirect estimation techniques are applied to data for Bulgaria from 1891 to 1958 to assess trends in population dynamics. An interdisciplinary approach is suggested for the study of countries where data are often incomplete. (SUMMARY IN ENG AND RUS)

A functional-dependencies-based Bayesian networks learning method and its application in a mobile commerce system.

PubMed

Liao, Stephen Shaoyi; Wang, Huai Qing; Li, Qiu Dan; Liu, Wei Yi

2006-06-01

This paper presents a new method for learning Bayesian networks from functional dependencies (FD) and third normal form (3NF) tables in relational databases. The method sets up a linkage between the theory of relational databases and probabilistic reasoning models, which is interesting and useful especially when data are incomplete and inaccurate. The effectiveness and practicability of the proposed method is demonstrated by its implementation in a mobile commerce system.

Multi-color incomplete Cholesky conjugate gradient methods for vector computers. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Poole, E. L.

1986-01-01

In this research, we are concerned with the solution on vector computers of linear systems of equations, Ax = b, where A is a larger, sparse symmetric positive definite matrix. We solve the system using an iterative method, the incomplete Cholesky conjugate gradient method (ICCG). We apply a multi-color strategy to obtain p-color matrices for which a block-oriented ICCG method is implemented on the CYBER 205. (A p-colored matrix is a matrix which can be partitioned into a pXp block matrix where the diagonal blocks are diagonal matrices). This algorithm, which is based on a no-fill strategy, achieves O(N/p) length vector operations in both the decomposition of A and in the forward and back solves necessary at each iteration of the method. We discuss the natural ordering of the unknowns as an ordering that minimizes the number of diagonals in the matrix and define multi-color orderings in terms of disjoint sets of the unknowns. We give necessary and sufficient conditions to determine which multi-color orderings of the unknowns correpond to p-color matrices. A performance model is given which is used both to predict execution time for ICCG methods and also to compare an ICCG method to conjugate gradient without preconditioning or another ICCG method. Results are given from runs on the CYBER 205 at NASA's Langley Research Center for four model problems.

Postmodeling Sensitivity Analysis to Detect the Effect of Missing Data Mechanisms

ERIC Educational Resources Information Center

Jamshidian, Mortaza; Mata, Matthew

2008-01-01

Incomplete or missing data is a common problem in almost all areas of empirical research. It is well known that simple and ad hoc methods such as complete case analysis or mean imputation can lead to biased and/or inefficient estimates. The method of maximum likelihood works well; however, when the missing data mechanism is not one of missing…

Mapping of Bird Distributions from Point Count Surveys

Treesearch

John R. Sauer; Grey W. Pendleton; Sandra Orsillo

1995-01-01

Maps generated from bird survey data are used for a variety of scientific purposes, but little is known about their bias and precision. We review methods for preparing maps from point count data and appropriate sampling methods for maps based on point counts. Maps based on point counts can be affected by bias associated with incomplete counts, primarily due to changes...

Efficient network disintegration under incomplete information: the comic effect of link prediction

NASA Astrophysics Data System (ADS)

Tan, Suo-Yi; Wu, Jun; Lü, Linyuan; Li, Meng-Jun; Lu, Xin

2016-03-01

The study of network disintegration has attracted much attention due to its wide applications, including suppressing the epidemic spreading, destabilizing terrorist network, preventing financial contagion, controlling the rumor diffusion and perturbing cancer networks. The crux of this matter is to find the critical nodes whose removal will lead to network collapse. This paper studies the disintegration of networks with incomplete link information. An effective method is proposed to find the critical nodes by the assistance of link prediction techniques. Extensive experiments in both synthetic and real networks suggest that, by using link prediction method to recover partial missing links in advance, the method can largely improve the network disintegration performance. Besides, to our surprise, we find that when the size of missing information is relatively small, our method even outperforms than the results based on complete information. We refer to this phenomenon as the “comic effect” of link prediction, which means that the network is reshaped through the addition of some links that identified by link prediction algorithms, and the reshaped network is like an exaggerated but characteristic comic of the original one, where the important parts are emphasized.

Efficient network disintegration under incomplete information: the comic effect of link prediction.

PubMed

Tan, Suo-Yi; Wu, Jun; Lü, Linyuan; Li, Meng-Jun; Lu, Xin

2016-03-10

The study of network disintegration has attracted much attention due to its wide applications, including suppressing the epidemic spreading, destabilizing terrorist network, preventing financial contagion, controlling the rumor diffusion and perturbing cancer networks. The crux of this matter is to find the critical nodes whose removal will lead to network collapse. This paper studies the disintegration of networks with incomplete link information. An effective method is proposed to find the critical nodes by the assistance of link prediction techniques. Extensive experiments in both synthetic and real networks suggest that, by using link prediction method to recover partial missing links in advance, the method can largely improve the network disintegration performance. Besides, to our surprise, we find that when the size of missing information is relatively small, our method even outperforms than the results based on complete information. We refer to this phenomenon as the "comic effect" of link prediction, which means that the network is reshaped through the addition of some links that identified by link prediction algorithms, and the reshaped network is like an exaggerated but characteristic comic of the original one, where the important parts are emphasized.

Efficient network disintegration under incomplete information: the comic effect of link prediction

PubMed Central

Tan, Suo-Yi; Wu, Jun; Lü, Linyuan; Li, Meng-Jun; Lu, Xin

2016-01-01

The study of network disintegration has attracted much attention due to its wide applications, including suppressing the epidemic spreading, destabilizing terrorist network, preventing financial contagion, controlling the rumor diffusion and perturbing cancer networks. The crux of this matter is to find the critical nodes whose removal will lead to network collapse. This paper studies the disintegration of networks with incomplete link information. An effective method is proposed to find the critical nodes by the assistance of link prediction techniques. Extensive experiments in both synthetic and real networks suggest that, by using link prediction method to recover partial missing links in advance, the method can largely improve the network disintegration performance. Besides, to our surprise, we find that when the size of missing information is relatively small, our method even outperforms than the results based on complete information. We refer to this phenomenon as the “comic effect” of link prediction, which means that the network is reshaped through the addition of some links that identified by link prediction algorithms, and the reshaped network is like an exaggerated but characteristic comic of the original one, where the important parts are emphasized. PMID:26960247

Results from a study using misoprostol for management of incomplete abortion in Vietnamese hospitals: implications for task shifting.

PubMed

Ngoc, Nguyen Thi Nhu; Shochet, Tara; Blum, Jennifer; Hai, Pham Thanh; Dung, Duong Lan; Nhan, Tran Thanh; Winikoff, Beverly

2013-05-22

Complications following spontaneous or induced abortion are a major cause of maternal morbidity. To manage these complications, post-abortion care (PAC) services should be readily available and easy to access. Standard PAC treatment includes surgical interventions that are highly effective but require surgical providers and medical centers that have the necessary space and equipment. Misoprostol has been shown to be an effective alternative to surgical evacuation and can be offered by lower level clinicians. This study sought to assess whether 400 mcg sublingual misoprostol could effectively evacuate the uterus after incomplete abortion and to confirm its applicability for use at lower level settings. All women presenting with incomplete abortion at one of three hospitals in Vietnam were enrolled. Providers were not asked to record if the abortion was spontaneous or induced. It is likely that all were spontaneous given the legal status and easy access to abortion services in Vietnam. Participants were given 400 mcg sublingual misoprostol and instructed to hold the pills under their tongue for 30 minutes and then swallow any remaining fragments. They were then asked to return one week later to confirm their clinical status. Study clinicians were instructed to confirm a complete expulsion clinically. All women were asked to complete a questionnaire regarding satisfaction with the treatment. Three hundred and two women were enrolled between September 2009 and May 2010. Almost all participants (96.3%) had successful completions using a single dose of 400 mcg misoprostol. The majority of women (87.2%) found the side effects to be tolerable or easily tolerable. Most women (84.3%) were satisfied or very satisfied with the treatment they received; only one was dissatisfied (0.3%). Nine out of ten women would select this method again and recommend it to a friend (91.0% and 90.0%, respectively). This study confirms that 400 mcg sublingual misoprostol effectively evacuates the uterus for most women experiencing incomplete abortion. The high levels of satisfaction and side effect tolerability also attest to the ease of use of this method. From these data and given the international consensus around the effectiveness of misoprostol for incomplete abortion care, it seems timely that use of the drug for this indication be widely expanded both throughout Vietnam and wherever access to abortion care is limited. ClinicalTrials.gov, NCT00670761.

Development of Bio-Oil Commodity Fuel as a Refinery Feedstock from High Impact Algae Biomass

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kastner, James; Mani, Sudhagar; Das, K. C.

A two-stage hydrothermal liquefaction (HTL) process was developed to 1) reduce nitrogen levels in algal oil, 2) generate a nitrogen rich stream with limited inhibitors for recycle and algae cultivation, and 3) improve downstream catalytic hydrodenitrogenation and hydrodeoxygenation of the algal oil to refinery intermediates. In the first stage, low temperature HTL was conducted at 125, 175, and 225°C at holding times ranging from 1 to 30 min (time at reaction temperature). A consortium of three algal strains, namely Chlorella sorokiniana, Chlorella minutissima, and Scenedesmus bijuga were used to grow and harvest biomass in a raceway system – this consortiummore » is called the UGA Raceway strain throughout the report. Subsequent analysis of the final harvested product indicated that only two strains predominated in the final harvest - Chlorella sorokiniana and Scenedesmus bijuga. Two additional strains representing a high protein (Spirulina platensis) and high lipid algae (Nannochloropsis) strains were also used in this study. These strains were purchased from suppliers. S. platensis biomass was provided by Earthrise Nutritionals LLC (Calipatria, CA) in dry powder form with defined properties, and was stored in airtight packages at 4°C prior to use. A Nannochloropsis paste from Reed Mariculture was purchased and used in the two-stage HTL/HDO experiments. The solids and liquids from this low temperature HTL pretreatment step were separated and analyzed, leading to the following conclusions. Overall, these results indicate that low temperature HTL (200-250°C) at short residence times (5-15 min) can be used to lyse algae cells and remove/separate protein and nitrogen before subsequent higher temperature HTL (for lipid and other polymer hydrolysis) and HDO. The significant reduction in nitrogen when coupled with low protein/high lipid algae cultivation methods at scale could significantly improve downstream catalytic HDO results. However, significant barriers and knowledge gaps exist that must be overcome and understood. The ability of the separated protein/nitrogen rich aqueous stream to support algae cultivation needs to be verified (and the kinetics of growth measured). The kinetics of algae hydrothermal liquefaction on a mechanistic basis needs to be measured and understood. A better understanding of Maillard reactions during algae HTL is needed. And the impact of Maillard reaction products and incompletely hydrolyzed cell wall components on catalyst deactivation during HDO needs to be understood. Finally, an inexpensive HDO process and associated catalyst capable of converting the algal oil to hydrocarbons needs to be developed.« less

Microcosmic mechanisms for protein incomplete release and stability of various amphiphilic mPEG-PLA microspheres.

PubMed

Wei, Yi; Wang, Yu Xia; Wang, Wei; Ho, Sa V; Qi, Feng; Ma, Guang Hui; Su, Zhi Guo

2012-10-02

The microcosmic mechanisms of protein (recombinant human growth hormone, rhGH) incomplete release and stability from amphiphilic poly(monomethoxypolyethylene glycol-co-D,L-lactide) (mPEG-PLA, PELA) microspheres were investigated. PELA with different hydrophilicities (PELA-1, PELA-2, and PELA-3) based on various ratios of mPEG to PLA were employed to prepare microspheres exhibiting a narrow size distribution using a combined double emulsion and premix membrane emulsification method. The morphology, rhGH encapsulation efficiency, in vitro release profile, and rhGH stability of PELA microspheres during the release were characterized and compared in detail. It was found that increasing amounts of PLA enhanced the encapsulation efficiency of PELA microspheres but reduced both the release rate of rhGH and its stability. Contact angle, atomic force microscope (AFM), and quartz crystal microbalance with dissipation (QCM-D) techniques were first combined to elucidate the microcosmic mechanism of incomplete release by measuring the hydrophilicity of the PELA film and its interaction with rhGH. In addition, the pH change within the microsphere microenvironment was monitored by confocal laser scanning microscopy (CLSM) employing a pH-sensitive dye, which clarified the stability of rhGH during the release. These results suggested that PELA hydrophilicity played an important role in rhGH incomplete release and stability. Thus, the selection of suitable hydrophilic polymers with adequate PEG lengths is critical in the preparation of optimum protein drug sustained release systems. This present work is a first report elucidating the microcosmic mechanisms responsible for rhGH stability and its interaction with the microspheres. Importantly, this research demonstrated the application of promising new experimental methods in investigating the interaction between biomaterials and biomacromolecules, thus opening up a range of exciting potential applications in the biomedical field including drug delivery and tissue regeneration.

How Global Education Is Understood and to What Extent It Is Implemented in One Educator Preparation Program

ERIC Educational Resources Information Center

Amewu-Sirleaf, Lydia Valentina

2015-01-01

This mixed method study investigated the overarching question "how global education is understood and implemented in an educator preparation program in a Colorado university". The sub-questions used to answer the research question are: (1) How is global education/perspective understood and implemented by the faculty; (2) How do students…

Algebraic Methods to Design Signals

DTIC Science & Technology

2015-08-27

sequence pairs with optimal correlation values. 5. K.T. Arasu, Pradeep Bansal , Cody Watson, Partially balanced incomplete block designs with two...IEEE Transactions Information Theory, Volume: 58, Issue: 11, Nov 2012, Page(s): 6968 – 6978 5. K.T. Arasu, Pradeep Bansal , Cody Watson, Partially

SOLID-FUEL HOUSEHOLD COOK STOVES: CHARACTERIZATION OF PERFORMANCE AND EMISSIONS

EPA Science Inventory

Previous studies have shown that some fuel-efficient solid-fuel cook stoves have had worse pollutant emissions of PICs (products of incomplete combustion) than traditional cooking methods. Better stoves have been developed to reduce emissions, but test results have not previously...

Transcriptome assembly and digital gene expression atlas of the rainbow trout

USDA-ARS?s Scientific Manuscript database

Background: Transcriptome analysis is a preferred method for gene discovery, marker development and gene expression profiling in non-model organisms. Previously, we sequenced a transcriptome reference using Sanger-based and 454-pyrosequencing, however, a transcriptome assembly is still incomplete an...

Developmental psycholinguistics teaches us that we need multi-method, not single-method, approaches to the study of linguistic representation.

PubMed

Rowland, Caroline F; Monaghan, Padraic

2017-01-01

In developmental psycholinguistics, we have, for many years, been generating and testing theories that propose both descriptions of adult representations and explanations of how those representations develop. We have learnt that restricting ourselves to any one methodology yields only incomplete data about the nature of linguistic representations. We argue that we need a multi-method approach to the study of representation.

Timing of silicone stent removal in patients with post-tuberculosis bronchial stenosis

PubMed Central

Eom, Jung Seop; Kim, Hojoong; Park, Hye Yun; Jeon, Kyeongman; Um, Sang-Won; Koh, Won-Jung; Suh, Gee Young; Chung, Man Pyo; Kwon, O. Jung

2013-01-01

CONTEXT: In patients with post-tuberculosis bronchial stenosis (PTBS), the severity of bronchial stenosis affects the restenosis rate after the silicone stent is removed. In PTBS patients with incomplete bronchial obstruction, who had a favorable prognosis, the timing of stent removal to ensure airway patency is not clear. AIMS: We evaluated the time for silicone stent removal in patients with incomplete PTBS. SETTINGS AND DESIGN: A retrospective study examined PTBS patients who underwent stenting and removal of a silicone stent. METHODS: Incomplete bronchial stenosis was defined as PTBS other than total bronchial obstruction, which had a luminal opening at the stenotic segment on bronchoscopic intervention. The duration of stenting was defined as the interval from stent insertion to removal. The study included 44 PTBS patients and the patients were grouped at intervals of 6 months according to the duration of stenting. RESULTS: Patients stented for more than 12 months had a significantly lower restenosis rate than those stented for less than 12 months (4% vs. 35%, P = 0.009). Multiple logistic regression revealed an association between stenting for more than 12 months and a low restenosis rate (odds ratio 12.095; 95% confidence interval 1.097-133.377). Moreover, no restenosis was observed in PTBS patients when the stent was placed more than 14 months previously. CONCLUSIONS: In patients with incomplete PTBS, stent placement for longer than 12 months reduced restenosis after stent removal. PMID:24250736

Computing multiple aggregation levels and contextual features for road facilities recognition using mobile laser scanning data

NASA Astrophysics Data System (ADS)

Yang, Bisheng; Dong, Zhen; Liu, Yuan; Liang, Fuxun; Wang, Yongjun

2017-04-01

In recent years, updating the inventory of road infrastructures based on field work is labor intensive, time consuming, and costly. Fortunately, vehicle-based mobile laser scanning (MLS) systems provide an efficient solution to rapidly capture three-dimensional (3D) point clouds of road environments with high flexibility and precision. However, robust recognition of road facilities from huge volumes of 3D point clouds is still a challenging issue because of complicated and incomplete structures, occlusions and varied point densities. Most existing methods utilize point or object based features to recognize object candidates, and can only extract limited types of objects with a relatively low recognition rate, especially for incomplete and small objects. To overcome these drawbacks, this paper proposes a semantic labeling framework by combing multiple aggregation levels (point-segment-object) of features and contextual features to recognize road facilities, such as road surfaces, road boundaries, buildings, guardrails, street lamps, traffic signs, roadside-trees, power lines, and cars, for highway infrastructure inventory. The proposed method first identifies ground and non-ground points, and extracts road surfaces facilities from ground points. Non-ground points are segmented into individual candidate objects based on the proposed multi-rule region growing method. Then, the multiple aggregation levels of features and the contextual features (relative positions, relative directions, and spatial patterns) associated with each candidate object are calculated and fed into a SVM classifier to label the corresponding candidate object. The recognition performance of combining multiple aggregation levels and contextual features was compared with single level (point, segment, or object) based features using large-scale highway scene point clouds. Comparative studies demonstrated that the proposed semantic labeling framework significantly improves road facilities recognition precision (90.6%) and recall (91.2%), particularly for incomplete and small objects.

Recovery of Technetium Adsorbed on Charcoal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Engelmann, Mark D.; Metz, Lori A.; Ballou, Nathan E.

2006-05-01

Two methods capable of near complete recovery of technetium adsorbed on charcoal are presented. The first involves liquid extraction of the technetium from the charcoal by hot 4M nitric acid. An average recovery of 98% (n=3) is obtained after three rounds of extraction. The second method involves dry ashing with air in a quartz combustion tube at 400-450 C. This method yields an average recovery of 96% (n=5). Other thermal methods were attempted, but resulted in reduced recovery and incomplete material balance

Probability density function learning by unsupervised neurons.

PubMed

Fiori, S

2001-10-01

In a recent work, we introduced the concept of pseudo-polynomial adaptive activation function neuron (FAN) and presented an unsupervised information-theoretic learning theory for such structure. The learning model is based on entropy optimization and provides a way of learning probability distributions from incomplete data. The aim of the present paper is to illustrate some theoretical features of the FAN neuron, to extend its learning theory to asymmetrical density function approximation, and to provide an analytical and numerical comparison with other known density function estimation methods, with special emphasis to the universal approximation ability. The paper also provides a survey of PDF learning from incomplete data, as well as results of several experiments performed on real-world problems and signals.

Six reasons why thermospheric measurements and models disagree

NASA Technical Reports Server (NTRS)

Moe, Kenneth

1987-01-01

The differences between thermospheric measurements and models are discussed. Sometimes the model is in error and at other times the measurements are, but it also is possible for both to be correct, yet have the comparison result in an apparent disagreement. These reasons are collected for disagreement, and, whenever possible, methods of reducing or eliminating them are suggested. The six causes of disagreement discussed are: actual errors caused by the limited knowledge of gas-surface interactions and by in-track winds; limitations of the thermospheric general circulation models due to incomplete knowledge of the energy sources and sinks as well as incompleteness of the parameterization which must be employed; and limitations imposed on the empirical models by the conceptual framework and the transient waves.

The Incomplete Conditional Stellar Mass Function: Unveiling the Stellar Mass Functions of Galaxies at 0.1 < Z < 0.8 from BOSS Observations

NASA Astrophysics Data System (ADS)

Guo, Hong; Yang, Xiaohu; Lu, Yi

2018-05-01

We propose a novel method to constrain the missing fraction of galaxies using galaxy clustering measurements in the galaxy conditional stellar mass function (CSMF) framework, which is applicable to surveys that suffer significantly from sample selection effects. The clustering measurements, which are not sensitive to the random sampling (missing fraction) of galaxies, are widely used to constrain the stellar–halo mass relation (SHMR). By incorporating a missing fraction (incompleteness) component into the CSMF model (ICSMF), we use the incomplete stellar mass function and galaxy clustering to simultaneously constrain the missing fractions and the SHMRs. Tests based on mock galaxy catalogs with a few typical missing fraction models show that this method can accurately recover the missing fraction and the galaxy SHMR, hence providing us with reliable measurements of the galaxy stellar mass functions. We then apply it to the Baryon Oscillation Spectroscopic Survey (BOSS) over the redshift range of 0.1 < z < 0.8 for galaxies of M * > 1011 M ⊙. We find that the sample completeness for BOSS is over 80% at z < 0.6 but decreases at higher redshifts to about 30%. After taking these completeness factors into account, we provide accurate measurements of the stellar mass functions for galaxies with {10}11 {M}ȯ < {M}* < {10}12 {M}ȯ , as well as the SHMRs, over the redshift range 0.1 < z < 0.8 in this largest galaxy redshift survey.

Kisspeptin modulates sexual and emotional brain processing in humans

PubMed Central

Comninos, Alexander N.; Wall, Matthew B.; Demetriou, Lysia; Shah, Amar J.; Clarke, Sophie A.; Narayanaswamy, Shakunthala; Nesbitt, Alexander; Izzi-Engbeaya, Chioma; Prague, Julia K.; Abbara, Ali; Ratnasabapathy, Risheka; Salem, Victoria; Nijher, Gurjinder M.; Jayasena, Channa N.; Tanner, Mark; Bassett, Paul; Mehta, Amrish; Rabiner, Eugenii A.; Hönigsperger, Christoph; Silva, Meire Ribeiro; Brandtzaeg, Ole Kristian; Wilson, Steven Ray; Brown, Rachel C.; Thomas, Sarah A.; Bloom, Stephen R.; Dhillo, Waljit S.

2017-01-01

BACKGROUND. Sex, emotion, and reproduction are fundamental and tightly entwined aspects of human behavior. At a population level in humans, both the desire for sexual stimulation and the desire to bond with a partner are important precursors to reproduction. However, the relationships between these processes are incompletely understood. The limbic brain system has key roles in sexual and emotional behaviors, and is a likely candidate system for the integration of behavior with the hormonal reproductive axis. We investigated the effects of kisspeptin, a recently identified key reproductive hormone, on limbic brain activity and behavior. METHODS. Using a combination of functional neuroimaging and hormonal and psychometric analyses, we compared the effects of kisspeptin versus vehicle administration in 29 healthy heterosexual young men. RESULTS. We demonstrated that kisspeptin administration enhanced limbic brain activity specifically in response to sexual and couple-bonding stimuli. Furthermore, kisspeptin’s enhancement of limbic brain structures correlated with psychometric measures of reward, drive, mood, and sexual aversion, providing functional significance. In addition, kisspeptin administration attenuated negative mood. CONCLUSIONS. Collectively, our data provide evidence of an undescribed role for kisspeptin in integrating sexual and emotional brain processing with reproduction in humans. These results have important implications for our understanding of reproductive biology and are highly relevant to the current pharmacological development of kisspeptin as a potential therapeutic agent for patients with common disorders of reproductive function. FUNDING. National Institute for Health Research (NIHR), Wellcome Trust (Ref 080268), and the Medical Research Council (MRC). PMID:28112678

A pilot study of herbal medicine use in a Midwest Latino population

PubMed Central

Kiefer, David; Bradbury, E. Jane; Tellez-Girón, Patricia

2014-01-01

Background Herbal medicine use is common in the United States, especially in immigrant populations. This plant use is incompletely understood, with significant gaps in the literature for people living in the Midwest, about the plant species used, and about how home herbal medicine use interacts with allopathic medicine. Methods This pilot project used a qualitative research approach (interviews and focus groups, convenience sampling) to explore this topic for Latin America immigrants living in Madison, Wisconsin. Results Eight interviews and focus groups consisting of 42 people yielded 199 minutes of audio recordings and the mention of 57 medicinal plants. These plants were obtained from gardens, relatives and friends (abroad and local), mail order, and ten local retail establishments. Retail sites sold fresh plants, dried plants, spices, foods, and packaged products, ranging from 20 to over 150 plant products per site. A preponderance of plants, especially in Latino-focused stores, was food that also served a medicinal purpose. Participants mentioned 35 distinct health and disease categories for which herbal medicines were used, and sometimes, but not always, discussed plant use with their health care provider. When compared with likely Latin binomial taxonomic names, clinically-relevant confusions with the use of common plant names were also identified. Conclusions Overall, the findings presented illustrate the complexities surrounding herbal medicine use, and create a case for future work to involve other demographics, and focus on botanical identification, the quantification of disclosure rates, and the development of educational interventions for physicians and patients. PMID:24908901

Comparison of synovial fluid, urine, and serum ion levels in metal-on-metal total hip arthroplasty at a minimum follow-up of 18 years.

PubMed

Lass, Richard; Grübl, Alexander; Kolb, Alexander; Stelzeneder, David; Pilger, Alexander; Kubista, Bernd; Giurea, Alexander; Windhager, Reinhard

2014-09-01

Diagnosis of adverse reactions to metal debris in metal-on-metal hip arthroplasty is a multifactorial process. Systemic ion levels are just one factor in the evaluation and should not be relied upon solely to determine the need for revision surgery. Furthermore, the correlation between cobalt or chromium serum, urine, or synovial fluid levels and adverse local tissue reactions is still incompletely understood. The hypothesis was that elevated serum and urine metal-ion concentrations are associated with elevated local metal-ion concentrations in primary total hip arthroplasties (THA) and with failure of metal-on-metal articulations in the long-term. In our present study, we evaluated these concentrations in 105 cementless THA with metal-on-metal articulating surfaces with small head diameter at a minimum of 18 years postoperatively. Spearman correlation showed a high correlation between the joint fluid aspirate concentration of cobalt and chromium with the serum cobalt (r = 0.81) and chromium level (r = 0.77) in patients with the THA as the only source of metal-ions. In these patients serum metal-ion analysis is a valuable method for screening. In patients with more than one source of metal or renal insufficiency additional investigations, like joint aspirations are an important tool for evaluation of wear and adverse tissue reactions in metal-on-metal THA. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Relationships Between Problem-Gambling Severity and Psychopathology as Moderated by Income.

PubMed

Sanacora, Rachel L; Whiting, Seth W; Pilver, Corey E; Hoff, Rani A; Potenza, Marc N

2016-09-01

Background and aims Problem and pathological gambling have been associated with elevated rates of both Axis-I and Axis-II psychiatric disorders. Although both problem gambling and psychiatric disorders have been reported as being more prevalent among lower income vs. middle/higher income groups, how income might moderate the relationship between problem-gambling severity and psychopathology is incompletely understood. To examine the associations between problem-gambling severity and psychopathology in lower income and middle/higher income groups. Methods Data from the first wave of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) (n = 43,093) were analyzed in adjusted logistic regression models to investigate the relationships between problem-gambling severity and psychiatric disorders within and across income groups. Results Greater problem-gambling severity was associated with increased odds of multiple psychiatric disorders for both lower income and middle/higher income groups. Income moderated the association between problem/pathological gambling and alcohol abuse/dependence, with a stronger association seen among middle/higher income respondents than among lower income respondents. Discussion and conclusions The findings that problem-gambling severity is related to psychopathology across income groups suggest a need for public health initiatives across social strata to reduce the impact that problem/pathological gambling may have in relation to psychopathology. Middle/higher income populations, perhaps owing to the availability of more "disposable income," may be at greater risk for co-occurring gambling and alcohol-use psychopathology and may benefit preferentially from interventions targeting both gambling and alcohol use.

Economics In Optical Design, Analysis, And Production

NASA Astrophysics Data System (ADS)

Willey, Ronald R.

1983-10-01

There are indications that we are entering an era wherein economics will play an increasing role in the optical design and production process. Economics has always been a factor in the competition between commercial ventures in the product arena. Now, we may begin to see competition between different technologies for the scarce resources of the society, including money. A proper design approach begins with a thorough examination and refinement of the requirements from the top down. The interrelationships of the various components must be properly understood and balanced. The specifications must be clear, complete, and realistic. Improper or incomplete system design can cause an extensive waste of resources. The detail optical design to meet the performance requirements has sometimes been the only part of the process that the designer has considered his own responsibility. The final optimization should also consider economic related factors: the cost of tolerances, the available tools test plates, materials, and test equipment. In the preliminary design stage, he should have decided which alignment and test methods are most appropriate to the system. The distribution of tolerances in an optical/mechanical system is a frequently neglected opportunity to reduce cost. We have reported previously on our work in this area, and expand further on it in the context of this paper. The designer now has an opportunity to generate better designs at a lower cost that are more economical to produce. The watchword for the 1980's may become the one found in the assembly automation industry: "more, better, for less".

Computational and Biochemical Docking of the Irreversible Cocaine Analog RTI 82 Directly Demonstrates Ligand Positioning in the Dopamine Transporter Central Substrate-binding Site*

PubMed Central

Dahal, Rejwi Acharya; Pramod, Akula Bala; Sharma, Babita; Krout, Danielle; Foster, James D.; Cha, Joo Hwan; Cao, Jianjing; Newman, Amy Hauck; Lever, John R.; Vaughan, Roxanne A.; Henry, L. Keith

2014-01-01

The dopamine transporter (DAT) functions as a key regulator of dopaminergic neurotransmission via re-uptake of synaptic dopamine (DA). Cocaine binding to DAT blocks this activity and elevates extracellular DA, leading to psychomotor stimulation and addiction, but the mechanisms by which cocaine interacts with DAT and inhibits transport remain incompletely understood. Here, we addressed these questions using computational and biochemical methodologies to localize the binding and adduction sites of the photoactivatable irreversible cocaine analog 3β-(p-chlorophenyl)tropane-2β-carboxylic acid, 4′-azido-3′-iodophenylethyl ester ([125I]RTI 82). Comparative modeling and small molecule docking indicated that the tropane pharmacophore of RTI 82 was positioned in the central DA active site with an orientation that juxtaposed the aryliodoazide group for cross-linking to rat DAT Phe-319. This prediction was verified by focused methionine substitution of residues flanking this site followed by cyanogen bromide mapping of the [125I]RTI 82-labeled mutants and by the substituted cysteine accessibility method protection analyses. These findings provide positive functional evidence linking tropane pharmacophore interaction with the core substrate-binding site and support a competitive mechanism for transport inhibition. This synergistic application of computational and biochemical methodologies overcomes many uncertainties inherent in other approaches and furnishes a schematic framework for elucidating the ligand-protein interactions of other classes of DA transport inhibitors. PMID:25179220

Attentional selection in visual perception, memory and action: a quest for cross-domain integration

PubMed Central

Schneider, Werner X.; Einhäuser, Wolfgang; Horstmann, Gernot

2013-01-01

For decades, the cognitive and neural sciences have benefitted greatly from a separation of mind and brain into distinct functional domains. The tremendous success of this approach notwithstanding, it is self-evident that such a view is incomplete. Goal-directed behaviour of an organism requires the joint functioning of perception, memory and sensorimotor control. A prime candidate for achieving integration across these functional domains are attentional processes. Consequently, this Theme Issue brings together studies of attentional selection from many fields, both experimental and theoretical, that are united in their quest to find overreaching integrative principles of attention between perception, memory and action. In all domains, attention is understood as combination of competition and priority control (‘bias’), with the task as a decisive driving factor to ensure coherent goal-directed behaviour and cognition. Using vision as the predominant model system for attentional selection, many studies of this Theme Issue focus special emphasis on eye movements as a selection process that is both a fundamental action and serves a key function in perception. The Theme Issue spans a wide range of methods, from measuring human behaviour in the real word to recordings of single neurons in the non-human primate brain. We firmly believe that combining such a breadth in approaches is necessary not only for attentional selection, but also to take the next decisive step in all of the cognitive and neural sciences: to understand cognition and behaviour beyond isolated domains. PMID:24018715

Safe clinical practice for patients hospitalised in a suicidal crisis: a study protocol for a qualitative case study

PubMed Central

Berg, Siv Hilde; Rørtveit, Kristine; Walby, Fredrik A; Aase, Karina

2017-01-01

Introduction Suicide prevention in psychiatric care is arguably complex and incompletely understood as a patient safety issue. A resilient healthcare approach provides perspectives through which to understand this complexity by understanding everyday clinical practice. By including suicidal patients and healthcare professionals as sources of knowledge, a deeper understanding of what constitutes safe clinical practice can be achieved. Methods This planned study aims to adopt the perspective of resilient healthcare to provide a deeper understanding of safe clinical practice for suicidal patients in psychiatric inpatient care. It will describe the experienced components and conditions of safe clinical practice and the experienced practice of patient safety. The study will apply a descriptive case study approach consisting of qualitative semistructured interviews and focus groups. The data sources are hospitalised patients in a suicidal crisis and healthcare professionals in clinical practice. Ethics and dissemination This study was approved by the Regional Ethics Committee (2016/34). The results will be disseminated through scientific articles, a PhD dissertation, and national and international conferences. These findings can generate knowledge to be integrated into the practice of safety for suicidal inpatients in Norway and to improve the feasibility of patient safety measures. Theoretical generalisations can be drawn regarding safe clinical practice by taking into account the experiences of patients and healthcare professionals. Thus, this study can inform the conceptual development of safe clinical practice for suicidal patients. PMID:28132001

Tensor decomposition-based and principal-component-analysis-based unsupervised feature extraction applied to the gene expression and methylation profiles in the brains of social insects with multiple castes.

PubMed

Taguchi, Y-H

2018-05-08

Even though coexistence of multiple phenotypes sharing the same genomic background is interesting, it remains incompletely understood. Epigenomic profiles may represent key factors, with unknown contributions to the development of multiple phenotypes, and social-insect castes are a good model for elucidation of the underlying mechanisms. Nonetheless, previous studies have failed to identify genes associated with aberrant gene expression and methylation profiles because of the lack of suitable methodology that can address this problem properly. A recently proposed principal component analysis (PCA)-based and tensor decomposition (TD)-based unsupervised feature extraction (FE) can solve this problem because these two approaches can deal with gene expression and methylation profiles even when a small number of samples is available. PCA-based and TD-based unsupervised FE methods were applied to the analysis of gene expression and methylation profiles in the brains of two social insects, Polistes canadensis and Dinoponera quadriceps. Genes associated with differential expression and methylation between castes were identified, and analysis of enrichment of Gene Ontology terms confirmed reliability of the obtained sets of genes from the biological standpoint. Biologically relevant genes, shown to be associated with significant differential gene expression and methylation between castes, were identified here for the first time. The identification of these genes may help understand the mechanisms underlying epigenetic control of development of multiple phenotypes under the same genomic conditions.

Research in computer science

NASA Technical Reports Server (NTRS)

Ortega, J. M.

1986-01-01

Various graduate research activities in the field of computer science are reported. Among the topics discussed are: (1) failure probabilities in multi-version software; (2) Gaussian Elimination on parallel computers; (3) three dimensional Poisson solvers on parallel/vector computers; (4) automated task decomposition for multiple robot arms; (5) multi-color incomplete cholesky conjugate gradient methods on the Cyber 205; and (6) parallel implementation of iterative methods for solving linear equations.

The roles of nearest neighbor methods in imputing missing data in forest inventory and monitoring databases

Treesearch

Bianca N. I. Eskelson; Hailemariam Temesgen; Valerie Lemay; Tara M. Barrett; Nicholas L. Crookston; Andrew T. Hudak

2009-01-01

Almost universally, forest inventory and monitoring databases are incomplete, ranging from missing data for only a few records and a few variables, common for small land areas, to missing data for many observations and many variables, common for large land areas. For a wide variety of applications, nearest neighbor (NN) imputation methods have been developed to fill in...

Biochar production method and composition therefrom

DOEpatents

Lee, James W; Buchanan, III, Archibald C; Evans, Barbara R; Kidder, Michelle K

2014-04-29

The invention is directed to a method for producing an oxygenated biochar material possessing a cation-exchanging property, wherein a biochar source is reacted with one or more oxygenating compounds in such a manner that the biochar source homogeneously acquires oxygen-containing cation-exchanging groups in an incomplete combustion process. The invention is also directed to oxygenated biochar compositions and soil formulations containing the oxygenated biochar material.

Biochar production method and composition therefrom

DOEpatents

Lee, James W.; Buchanan, III, Archibald C.; Evans, Barbara R.; Kidder, Michelle K.

2013-03-19

The invention is directed to a method for producing an oxygenated biochar material possessing a cation-exchanging property, wherein a biochar source is reacted with one or more oxygenating compounds in such a manner that the biochar source homogeneously acquires oxygen-containing cation-exchanging groups in an incomplete combustion process. The invention is also directed to oxygenated biochar compositions and soil formulations containing the oxygenated biochar material.

Influence of incomplete fusion on complete fusion at energies above the Coulomb barrier

NASA Astrophysics Data System (ADS)

Shuaib, Mohd; Sharma, Vijay R.; Yadav, Abhishek; Sharma, Manoj Kumar; Singh, Pushpendra P.; Singh, Devendra P.; Kumar, R.; Singh, R. P.; Muralithar, S.; Singh, B. P.; Prasad, R.

2017-10-01

In the present work, excitation functions of several reaction residues in the system 19F+169Tm, populated via the complete and incomplete fusion processes, have been measured using off-line γ-ray spectroscopy. The analysis of excitation functions has been done within the framework of statistical model code pace4. The excitation functions of residues populated via xn and pxn channels are found to be in good agreement with those estimated by the theoretical model code, which confirms the production of these residues solely via complete fusion process. However, a significant enhancement has been observed in the cross-sections of residues involving α-emitting channels as compared to the theoretical predictions. The observed enhancement in the cross-sections has been attributed to the incomplete fusion processes. In order to have a better insight into the onset and strength of incomplete fusion, the incomplete fusion strength function has been deduced. At present, there is no theoretical model available which can satisfactorily explain the incomplete fusion reaction data at energies ≈4-6 MeV/nucleon. In the present work, the influence of incomplete fusion on complete fusion in the 19F+169Tm system has also been studied. The measured cross-section data may be important for the development of reactor technology as well. It has been found that the incomplete fusion strength function strongly depends on the α-Q value of the projectile, which is found to be in good agreement with the existing literature data. The analysis strongly supports the projectile-dependent mass-asymmetry systematics. In order to study the influence of Coulomb effect ({Z}{{P}}{Z}{{T}}) on incomplete fusion, the deduced strength function for the present work is compared with the nearby projectile-target combinations. The incomplete fusion strength function is found to increase linearly with {Z}{{P}}{Z}{{T}}, indicating a strong influence of Coulomb effect in the incomplete fusion reactions.

Do we really need a large number of particles to simulate bimolecular reactive transport with random walk methods? A kernel density estimation approach

NASA Astrophysics Data System (ADS)

Rahbaralam, Maryam; Fernàndez-Garcia, Daniel; Sanchez-Vila, Xavier

2015-12-01

Random walk particle tracking methods are a computationally efficient family of methods to solve reactive transport problems. While the number of particles in most realistic applications is in the order of 106-109, the number of reactive molecules even in diluted systems might be in the order of fractions of the Avogadro number. Thus, each particle actually represents a group of potentially reactive molecules. The use of a low number of particles may result not only in loss of accuracy, but also may lead to an improper reproduction of the mixing process, limited by diffusion. Recent works have used this effect as a proxy to model incomplete mixing in porous media. In this work, we propose using a Kernel Density Estimation (KDE) of the concentrations that allows getting the expected results for a well-mixed solution with a limited number of particles. The idea consists of treating each particle as a sample drawn from the pool of molecules that it represents; this way, the actual location of a tracked particle is seen as a sample drawn from the density function of the location of molecules represented by that given particle, rigorously represented by a kernel density function. The probability of reaction can be obtained by combining the kernels associated to two potentially reactive particles. We demonstrate that the observed deviation in the reaction vs time curves in numerical experiments reported in the literature could be attributed to the statistical method used to reconstruct concentrations (fixed particle support) from discrete particle distributions, and not to the occurrence of true incomplete mixing. We further explore the evolution of the kernel size with time, linking it to the diffusion process. Our results show that KDEs are powerful tools to improve computational efficiency and robustness in reactive transport simulations, and indicates that incomplete mixing in diluted systems should be modeled based on alternative mechanistic models and not on a limited number of particles.

Retention Among North American HIV–infected Persons in Clinical Care, 2000–2008

PubMed Central

Rebeiro, Peter; Althoff, Keri N.; Buchacz, Kate; Gill, M. John; Horberg, Michael; Krentz, Hartmut; Moore, Richard; Sterling, Timothy R.; Brooks, John T.; Gebo, Kelly A.; Hogg, Robert; Klein, Marina; Martin, Jeffrey; Mugavero, Michael; Rourke, Sean; Silverberg, Michael J.; Thorne, Jennifer; Gange, Stephen J.

2013-01-01

Background Retention in care is key to improving HIV outcomes. Our goal was to describe “churn” in patterns of entry, exit, and retention in HIV care in the US and Canada. Methods Adults contributing ≥1 CD4 count or HIV-1 RNA (HIV-lab) from 2000–2008 in North American Cohort Collaboration on Research and Design (NA-ACCORD) clinical cohorts were included. Incomplete retention was defined as lack of 2 HIV-labs (≥90 days apart) within 12 months, summarized by calendar year. We used beta-binomial regression models to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) of factors associated with incomplete retention. Results Among 61,438 participants, 15,360 (25%) with incomplete retention significantly differed in univariate analyses (p<0.001) from 46,078 (75%) consistently retained by age, race/ethnicity, HIV risk, CD4, ART use, and country of care (US vs. Canada). From 2000–2004, females (OR=0.82, CI:0.70–0.95), older individuals (OR=0.78, CI:0.74–0.83 per 10 years), and ART users (OR= 0.61, CI:0.54–0.68 vs all others) were less likely to have incomplete retention, while black individuals (OR=1.31, CI:1.16–1.49, vs. white), those with injection drug use (IDU) HIV risk (OR=1.68, CI:1.49–1.89, vs. non-IDU) and those in care longer (OR=1.09, CI:1.07–1.11 per year) were more likely to have incomplete retention. Results from 2005–2008 were similar. Discussion From 2000 to 2008, 75% of the NA-ACCORD population was consistently retained in care with 25% experiencing some change in status, or churn. In addition to the programmatic and policy implications, our findings identify patient groups who may benefit from focused retention efforts. PMID:23242158

Clinical Review of Antidiabetic Drugs: Implications for Type 2 Diabetes Mellitus Management

PubMed Central

Chaudhury, Arun; Duvoor, Chitharanjan; Reddy Dendi, Vijaya Sena; Kraleti, Shashank; Chada, Aditya; Ravilla, Rahul; Marco, Asween; Shekhawat, Nawal Singh; Montales, Maria Theresa; Kuriakose, Kevin; Sasapu, Appalanaidu; Beebe, Alexandria; Patil, Naveen; Musham, Chaitanya K.; Lohani, Govinda Prasad; Mirza, Wasique

2017-01-01

Type 2 diabetes mellitus (T2DM) is a global pandemic, as evident from the global cartographic picture of diabetes by the International Diabetes Federation (http://www.diabetesatlas.org/). Diabetes mellitus is a chronic, progressive, incompletely understood metabolic condition chiefly characterized by hyperglycemia. Impaired insulin secretion, resistance to tissue actions of insulin, or a combination of both are thought to be the commonest reasons contributing to the pathophysiology of T2DM, a spectrum of disease originally arising from tissue insulin resistance and gradually progressing to a state characterized by complete loss of secretory activity of the beta cells of the pancreas. T2DM is a major contributor to the very large rise in the rate of non-communicable diseases affecting developed as well as developing nations. In this mini review, we endeavor to outline the current management principles, including the spectrum of medications that are currently used for pharmacologic management, for lowering the elevated blood glucose in T2DM. PMID:28167928

Obsessive-compulsive disorder and its related disorders: a reappraisal of obsessive-compulsive spectrum concepts.

PubMed

Murphy, Dennis L; Timpano, Kiara R; Wheaton, Michael G; Greenberg, Benjamin D; Miguel, Euripedes C

2010-01-01

Obsessive-compulsive disorder (OCD) is a clinical syndrome whose hallmarks are excessive, anxiety-evoking thoughts and compulsive behaviors that are generally recognized as unreasonable, but which cause significant distress and impairment. When these are the exclusive symptoms, they constitute uncomplicated OCD. OCD may also occur in the context of other neuropsychiatric disorders, most commonly other anxiety and mood disorders. The question remains as to whether these combinations of disorders should be regarded as independent, cooccurring disorders or as different manifestations of an incompletely understood constellation of OCD spectrum disorders with a common etiology. Additional considerations are given here to two potential etiology-based subgroups: (i) an environmentally based group in which OCD occurs following apparent causal events such as streptococcal infections, brain injury, or atypical neuroleptic treatment; and (ii) a genomically based group in which OCD is related to chromosomal anomalies or specific genes. Considering the status of current research, the concept of OCD and OCD-related spectrum conditions seems fluid in 2010, and in need of ongoing reappraisal.

Oxidant/Antioxidant Imbalance in Alzheimer's Disease: Therapeutic and Diagnostic Prospects

PubMed Central

2018-01-01

Alzheimer's disease (AD) is the most common cause of dementia and a great socioeconomic burden in the aging society. Compelling evidence demonstrates that molecular change characteristics for AD, such as oxidative stress and amyloid β (Aβ) oligomerization, precede by decades the onset of clinical dementia and that the disease represents a biological and clinical continuum of stages, from asymptomatic to severely impaired. Nevertheless, the sequence of the early molecular alterations and the interplay between them are incompletely understood. This review presents current knowledge about the oxidative stress-induced impairments and compromised oxidative stress defense mechanisms in AD brain and the cross-talk between various pathophysiological insults, with the focus on excessive reactive oxygen species (ROS) generation and Aβ overproduction at the early stages of the disease. Prospects for AD therapies targeting oxidant/antioxidant imbalance are being discussed, as well as for the development of novel oxidative stress-related, blood-based biomarkers for early, noninvasive AD diagnostics. PMID:29636850

Amyloidosis in a Captive Zebra Finch (Taeniopygia guttata) Research Colony

PubMed Central

Shientag, Lisa J; Garlick, David S; Galati, Erin

2016-01-01

Five birds in a captive zebra finch research colony were diagnosed with systemic amyloidosis within a 7-mo period by means of postmortem Congo red staining and green birefringence under polarized light. The liver was the most frequently and usually the most seriously affected organ, followed by the spleen and then the kidney. All 5 birds had been clinically affected with various inflammatory, infectious, and neoplastic conditions associated with amyloid A (AA) amyloidosis in humans and animals. Immunohistochemistry using antisera against duck AA protein revealed that tissues from 2 of the 5 birds were positive for the presence of AA protein and systemic inflammation-associated amyloidosis. Although the development of AA amyloidosis has been associated with chronic inflammation, trauma, and various infectious and neoplastic diseases as well as possible genetic predispositions and stresses linked to overcrowding, the root causes for individual cases of AA amyloidosis are incompletely understood. As far as we know, this report is the first description of AA amyloidosis in captive, research zebra finches. PMID:27298248

Salicylate, diflunisal and their metabolites inhibit CBP/p300 and exhibit anticancer activity.

PubMed

Shirakawa, Kotaro; Wang, Lan; Man, Na; Maksimoska, Jasna; Sorum, Alexander W; Lim, Hyung W; Lee, Intelly S; Shimazu, Tadahiro; Newman, John C; Schröder, Sebastian; Ott, Melanie; Marmorstein, Ronen; Meier, Jordan; Nimer, Stephen; Verdin, Eric

2016-05-31

Salicylate and acetylsalicylic acid are potent and widely used anti-inflammatory drugs. They are thought to exert their therapeutic effects through multiple mechanisms, including the inhibition of cyclo-oxygenases, modulation of NF-κB activity, and direct activation of AMPK. However, the full spectrum of their activities is incompletely understood. Here we show that salicylate specifically inhibits CBP and p300 lysine acetyltransferase activity in vitro by direct competition with acetyl-Coenzyme A at the catalytic site. We used a chemical structure-similarity search to identify another anti-inflammatory drug, diflunisal, that inhibits p300 more potently than salicylate. At concentrations attainable in human plasma after oral administration, both salicylate and diflunisal blocked the acetylation of lysine residues on histone and non-histone proteins in cells. Finally, we found that diflunisal suppressed the growth of p300-dependent leukemia cell lines expressing AML1-ETO fusion protein in vitro and in vivo. These results highlight a novel epigenetic regulatory mechanism of action for salicylate and derivative drugs.

Silk Self-Assembly Mechanisms and Control-From Thermodynamics to Kinetics

PubMed Central

Lu, Qiang; Zhu, Hesun; Zhang, Cencen; Zhang, Feng; Zhang, Bing; Kaplan, David L.

2012-01-01

Silkworms and spiders generate fibres that exhibit high strength and extensibility. The underlying mechanisms involved in processing silk proteins into fiber form remain incompletely understood, resulting in the failure to fully recapitulate the remarkable properties of native fibers in vitro from regenerated silk solutions. In the present study, the extensibility and high strength of regenerated silks were achieved by mimicking the natural spinning process. Conformational transitions inside micelles, followed by aggregation of micelles and their stabilization as they relate to the metastable structure of silk are described. Subsequently, the mechanisms to control the formation of nanofibrous structures were elucidated. The results clarify that the self-assembly of silk in aqueous solution is a thermodynamically driven process where kinetics also play a key role. Four key factors, molecular mobility, charge, hydrophilic interactions and concentration underlie the process. Adjusting these factors can balance nanostructure and conformational composition, and be used to achieve silk-based materials with properties comparable to native fibers. These mechanisms suggest new directions to design silk-based multifunctional materials. PMID:22320432

Structural basis of the 9-fold symmetry of centrioles.

PubMed

Kitagawa, Daiju; Vakonakis, Ioannis; Olieric, Natacha; Hilbert, Manuel; Keller, Debora; Olieric, Vincent; Bortfeld, Miriam; Erat, Michèle C; Flückiger, Isabelle; Gönczy, Pierre; Steinmetz, Michel O

2011-02-04

The centriole, and the related basal body, is an ancient organelle characterized by a universal 9-fold radial symmetry and is critical for generating cilia, flagella, and centrosomes. The mechanisms directing centriole formation are incompletely understood and represent a fundamental open question in biology. Here, we demonstrate that the centriolar protein SAS-6 forms rod-shaped homodimers that interact through their N-terminal domains to form oligomers. We establish that such oligomerization is essential for centriole formation in C. elegans and human cells. We further generate a structural model of the related protein Bld12p from C. reinhardtii, in which nine homodimers assemble into a ring from which nine coiled-coil rods radiate outward. Moreover, we demonstrate that recombinant Bld12p self-assembles into structures akin to the central hub of the cartwheel, which serves as a scaffold for centriole formation. Overall, our findings establish a structural basis for the universal 9-fold symmetry of centrioles. Copyright © 2011 Elsevier Inc. All rights reserved.

Gentle reenergization of electrons in merging galaxy clusters

PubMed Central

de Gasperin, Francesco; Intema, Huib T.; Shimwell, Timothy W.; Brunetti, Gianfranco; Brüggen, Marcus; Enßlin, Torsten A.; van Weeren, Reinout J.; Bonafede, Annalisa; Röttgering, Huub J. A.

2017-01-01

Galaxy clusters are the most massive constituents of the large-scale structure of the universe. Although the hot thermal gas that pervades galaxy clusters is relatively well understood through observations with x-ray satellites, our understanding of the nonthermal part of the intracluster medium (ICM) remains incomplete. With Low-Frequency Array (LOFAR) and Giant Metrewave Radio Telescope (GMRT) observations, we have identified a phenomenon that can be unveiled only at extremely low radio frequencies and offers new insights into the nonthermal component. We propose that the interplay between radio-emitting plasma and the perturbed intracluster medium can gently reenergize relativistic particles initially injected by active galactic nuclei. Sources powered through this mechanism can maintain electrons at higher energies than radiative aging would allow. If this mechanism is common for aged plasma, a population of mildly relativistic electrons can be accumulated inside galaxy clusters providing the seed population for merger-induced reacceleration mechanisms on larger scales such as turbulence and shock waves. PMID:28983512

Ultrasound screening of periarticular soft tissue abnormality around metal-on-metal bearings.

PubMed

Nishii, Takashi; Sakai, Takashi; Takao, Masaki; Yoshikawa, Hideki; Sugano, Nobuhiko

2012-06-01

Although metal hypersensitivity or pseudotumors are concerns for metal-on-metal (MoM) bearings, detailed pathologies of patterns, severity, and incidence of periprosthetic soft tissue lesions are incompletely understood. We examined the potential of ultrasound for screening of periarticular soft tissue lesions around MoM bearings. Ultrasound examinations were conducted in 88 hips (79 patients) with MoM hip resurfacings or MoM total hip arthroplasties with a large femoral head. Four qualitative ultrasound patterns were shown, including normal pattern in 69 hips, joint-expansion pattern in 11 hips, cystic pattern in 5 hips, and mass pattern in 3 hips. Hips with the latter 3 abnormal patterns showed significantly higher frequency of clinical symptoms, without significant differences of sex, duration of implantation, head sizes, and cup abduction/anteversion angles, compared with hips with normal pattern. Ultrasound examination provides sensitive screening of soft tissue reactions around MoM bearings and may be useful in monitoring progression and defining treatment for periarticular soft tissue abnormalities. Copyright © 2012 Elsevier Inc. All rights reserved.

Interferon lambda: opportunities, risks, and uncertainties in the fight against HCV.

PubMed

Laidlaw, Stephen M; Dustin, Lynn B

2014-01-01

Innate immunity is key to the fight against the daily onslaught from viruses that our bodies are subjected to. Essential to this response are the interferons (IFNs) that prime our cells to block viral pathogens. Recent evidence suggests that the Type III (λ) IFNs are intimately associated with the immune response to hepatitis C virus (HCV) infection. Genome-wide association studies have identified polymorphisms within the IFN-λ gene locus that correlate with response to IFNα-based antiviral therapy and with spontaneous clearance of HCV infection. The mechanisms for these correlations are incompletely understood. Restricted expression of the IFN-λ receptor, and the ability of IFN-λ to induce IFN-stimulated genes in HCV-infected cells, suggest potential roles for IFN-λ in HCV therapy even in this era of directly acting antivirals. This review summarizes our current understanding of the IFN-λ family and the role of λ IFNs in the natural history of HCV infection.

Observation, Inference, and Imagination: Elements of Edgar Allan Poe's Philosophy of Science

NASA Astrophysics Data System (ADS)

Gelfert, Axel

2014-03-01

Edgar Allan Poe's standing as a literary figure, who drew on (and sometimes dabbled in) the scientific debates of his time, makes him an intriguing character for any exploration of the historical interrelationship between science, literature and philosophy. His sprawling `prose-poem' Eureka (1848), in particular, has sometimes been scrutinized for anticipations of later scientific developments. By contrast, the present paper argues that it should be understood as a contribution to the raging debates about scientific methodology at the time. This methodological interest, which is echoed in Poe's `tales of ratiocination', gives rise to a proposed new mode of—broadly abductive—inference, which Poe attributes to the hybrid figure of the `poet-mathematician'. Without creative imagination and intuition, Science would necessarily remain incomplete, even by its own standards. This concern with imaginative (abductive) inference ties in nicely with his coherentism, which grants pride of place to the twin virtues of Simplicity and Consistency, which must constrain imagination lest it degenerate into mere fancy.

Lipids and ions traverse the membrane by the same physical pathway in the nhTMEM16 scramblase

PubMed Central

Jiang, Tao; Yu, Kuai

2017-01-01

From bacteria to mammals, different phospholipid species are segregated between the inner and outer leaflets of the plasma membrane by ATP-dependent lipid transporters. Disruption of this asymmetry by ATP-independent phospholipid scrambling is important in cellular signaling, but its mechanism remains incompletely understood. Using MD simulations coupled with experimental assays, we show that the surface hydrophilic transmembrane cavity exposed to the lipid bilayer on the fungal scramblase nhTMEM16 serves as the pathway for both lipid translocation and ion conduction across the membrane. Ca2+ binding stimulates its open conformation by altering the structure of transmembrane helices that line the cavity. We have identified key amino acids necessary for phospholipid scrambling and validated the idea that ions permeate TMEM16 Cl- channels via a structurally homologous pathway by showing that mutation of two residues in the pore region of the TMEM16A Ca2+-activated Cl- channel convert it into a robust scramblase. PMID:28917060

Alteration of the RANKL/RANK/OPG System in Periprosthetic Osteolysis with Septic Loosening.

PubMed

Wang, Long; Dai, Zixun; Xie, Jie; Liao, Hao; Lv, Cheng; Hu, Yihe

2016-02-01

The pathogenesis of periprosthetic osteolysis with septic loosening remains incompletely understood. The purpose of this study was to investigate whether expression of the RANKL/RANK/OPG system is altered in septic interface membranes (SIMs). Seventeen cases with a SIM, 26 cases with an aseptic interface membrane (AIM), and 12 cases with a normal synovium (NS) were assessed. Scanning and transmission electron microscopy (SEM and TEM, respectively) were used to observe the microscopic morphology of three tissue conditions. Differences in RANKL, RANK, and OPG expression at the mRNA level were assessed by real-time quantitative PCR, and differences at the protein level were assessed by immunohistochemical staining and Western blotting. SEM showed wear debris widely distributed on the AIM surface, and TEM showed Bacillus activity in the SIM. RANKL expression and the RANKL/OPG ratio were significantly increased in SIMs. Imbalance in the RANKL/RANK/OPG system is related to periprosthetic osteolysis with septic loosening but is not the only possible pathogenic mechanism.

Scientific Evidence of Rice By-Products for Cancer Prevention: Chemopreventive Properties of Waste Products from Rice Milling on Carcinogenesis In Vitro and In Vivo

PubMed Central

Tan, Bee Ling

2017-01-01

Cancer is a significant global health concern affecting men and women worldwide. Although current chemopreventive drugs could inhibit the growth of cancer cells, they exert many adverse side effects. Dietary factor plays a crucial role in the management of cancers and has drawn the attention of researchers to be used as an option to combat this disease. Both in vitro and in vivo studies showed that rice and its by-products display encouraging results in the prevention of this disease. The mechanism of anticancer effect is suggested partly through potentiation of bioactive compounds like vitamin E, phytic acid, γ-aminobutyric acid (GABA), γ-oryzanol, and phenolics. Nevertheless, the bioactivity of rice and its by-products is still incompletely understood. In this review, we present the findings from a preclinical study both in in vitro and in animal experiments on the promising role of rice by-products with focus on cancer prevention. PMID:28210630

SAS-1 Is a C2 Domain Protein Critical for Centriole Integrity in C. elegans

PubMed Central

Delattre, Marie; Balestra, Fernando R.; Blanchoud, Simon; Finger, Susanne; Knott, Graham; Müller-Reichert, Thomas; Gönczy, Pierre

2014-01-01

Centrioles are microtubule-based organelles important for the formation of cilia, flagella and centrosomes. Despite progress in understanding the underlying assembly mechanisms, how centriole integrity is ensured is incompletely understood, including in sperm cells, where such integrity is particularly critical. We identified C. elegans sas-1 in a genetic screen as a locus required for bipolar spindle assembly in the early embryo. Our analysis reveals that sperm-derived sas-1 mutant centrioles lose their integrity shortly after fertilization, and that a related defect occurs when maternal sas-1 function is lacking. We establish that sas-1 encodes a C2 domain containing protein that localizes to centrioles in C. elegans, and which can bind and stabilize microtubules when expressed in human cells. Moreover, we uncover that SAS-1 is related to C2CD3, a protein required for complete centriole formation in human cells and affected in a type of oral-facial-digital (OFD) syndrome. PMID:25412110

HIV-1 gp120 Upregulates Brain-Derived Neurotrophic Factor (BDNF) Expression in BV2 Cells via the Wnt/β-Catenin Signaling Pathway.

PubMed

Wang, Yongdi; Liao, Jinxu; Tang, Shao-Jun; Shu, Jianhong; Zhang, Wenping

2017-06-01

HIV-1 gp120 plays a critical role in the pathogenesis of HIV-associated pain, but the underlying molecular mechanisms are incompletely understood. This study aims to determine the effect and possible mechanism of HIV-1 gp120 on BDNF expression in BV2 cells (a murine-derived microglial cell line). We observed that gp120 (10 ng/ml) activated BV2 cells in cultures and upregulated proBDNF/mBDNF. Furthermore, gp120-treated BV2 also accumulated Wnt3a and β-catenin, suggesting the activation of the Wnt/β-catenin pathway. We demonstrated that activation of the pathway by Wnt3a upregulated BDNF expression. In contrast, inhibition of the Wnt/β-catenin pathway by either DKK1 or IWR-1 attenuated BDNF upregulation induced by gp120 or Wnt3a. These findings collectively suggest that gp120 stimulates BDNF expression in BV2 cells via the Wnt/β-catenin signaling pathway.

A review of the immunomodulatory role of dietary tryptophan in livestock and poultry.

PubMed

Bai, Miaomiao; Liu, Hongnan; Xu, Kang; Oso, Abimbola Oladele; Wu, Xin; Liu, Gang; Tossou, Myrlene Carine B; Al-Dhabi, Naif Abdullah; Duraipandiyan, Veeramuthu; Xi, Qianyun; Yin, Yinlong

2017-01-01

Tryptophan, a nutritionally essential amino acid, is active in the regulation of immune responses in animals. The products of tryptophan metabolism, such as indoleamine 2,3-dioxygenase, kynurenine, quinolinic acid, and melatonin, may improve immunity in an organism and induce anti-inflammatory responses. The immune tolerance processes mediated by tryptophan metabolites are not well understood. Recent studies have reported that the enzymes that break down tryptophan through the kynurenine metabolic pathway are found in numerous cell types, including immunocytes. Moreover, some tryptophan metabolites have been shown to play a role in the inhibition of T lymphocyte proliferation, elevation of immunoglobulin levels in the blood, and promotion of antigen-presenting organization in tissues. This review summarizes the effects and mechanisms of tryptophan and metabolites in immune functions in livestock and poultry. It also highlights the areas in which our understanding of the role(s) of tryptophan is incomplete and suggests possible future research that might prove of benefit to livestock and poultry producers.

Neurons for hunger and thirst transmit a negative-valence teaching signal

PubMed Central

Gong, Rong; Magnus, Christopher J.; Yu, Yang; Sternson, Scott M.

2015-01-01

Homeostasis is a biological principle for regulation of essential physiological parameters within a set range. Behavioural responses due to deviation from homeostasis are critical for survival, but motivational processes engaged by physiological need states are incompletely understood. We examined motivational characteristics and dynamics of two separate neuron populations that regulate energy and fluid homeostasis by using cell type-specific activity manipulations in mice. We found that starvation-sensitive AGRP neurons exhibit properties consistent with a negative-valence teaching signal. Mice avoided activation of AGRP neurons, indicating that AGRP neuron activity has negative valence. AGRP neuron inhibition conditioned preference for flavours and places. Correspondingly, deep-brain calcium imaging revealed that AGRP neuron activity rapidly reduced in response to food-related cues. Complementary experiments activating thirst-promoting neurons also conditioned avoidance. Therefore, these need-sensing neurons condition preference for environmental cues associated with nutrient or water ingestion, which is learned through reduction of negative-valence signals during restoration of homeostasis. PMID:25915020

Rules of engagement: incomplete and complete pronoun resolution.

PubMed

Love, Jessica; McKoon, Gail

2011-07-01

Research on shallow processing suggests that readers sometimes encode only a superficial representation of a text and fail to make use of all available information. Greene, McKoon, and Ratcliff (1992) extended this work to pronouns, finding evidence that readers sometimes fail to automatically identify referents even when these are unambiguous. In this paper we revisit those findings. In 11 recognition probe, priming, and self-report experiments, we manipulated Greene et al.'s stories to discover under what circumstances a pronoun's referent is automatically understood. We lengthened the stories from 4 to 8 lines. This simple manipulation led to automatic and correct resolution, which we attribute to readers' increased engagement with the stories. We found evidence of resolution even when the additional text did not mention the pronoun's referent. In addition, our results suggest that the pronoun temporarily boosts the referent's accessibility, an advantage that disappears by the end of the next sentence. Finally, we present evidence from memory experiments that supports complete pronoun resolution for the longer but not the shorter stories.

Dendritic cells and macrophages in the kidney: a spectrum of good and evil

PubMed Central

Rogers, NM; Ferenbach, DA; Isenberg, JS; Thomson, AW; Hughes, J

2015-01-01

Renal dendritic cells (DC) and macrophages (Mac) represent a constitutive, extensive and contiguous network of innate immune cells that provide sentinel and immune intelligence function. They induce and regulate inflammatory responses to freely-filtered antigenic material and protect the kidney from infection. Tissue–resident or infiltrating DC and Mac are key to the initiation and propagation of renal disease, as well as essential contributors to subsequent tissue regeneration regardless of its etiology and pathogenesis. Their identification, functional and phenotypic distinction, interplay and relationship with effector and regulatory adaptive immune cells is complex and incompletely understood. This review discusses both the common and distinct characteristics of these cells, as well as recent key advances in the field that have identified renal-specific functions of DC and Mac that enable these important, phagocytic, antigen-presenting, cells to mediate or mitigate intrinsic kidney disease. We also identify priority areas for further investigation and prospects for translational and therapeutic application of acquired knowledge. PMID:25266210

Redox-dependent substrate-cofactor interactions in the Michaelis-complex of a flavin-dependent oxidoreductase

NASA Astrophysics Data System (ADS)

Werther, Tobias; Wahlefeld, Stefan; Salewski, Johannes; Kuhlmann, Uwe; Zebger, Ingo; Hildebrandt, Peter; Dobbek, Holger

2017-07-01

How an enzyme activates its substrate for turnover is fundamental for catalysis but incompletely understood on a structural level. With redox enzymes one typically analyses structures of enzyme-substrate complexes in the unreactive oxidation state of the cofactor, assuming that the interaction between enzyme and substrate is independent of the cofactors oxidation state. Here, we investigate the Michaelis complex of the flavoenzyme xenobiotic reductase A with the reactive reduced cofactor bound to its substrates by X-ray crystallography and resonance Raman spectroscopy and compare it to the non-reactive oxidized Michaelis complex mimics. We find that substrates bind in different orientations to the oxidized and reduced flavin, in both cases flattening its structure. But only authentic Michaelis complexes display an unexpected rich vibrational band pattern uncovering a strong donor-acceptor complex between reduced flavin and substrate. This interaction likely activates the catalytic ground state of the reduced flavin, accelerating the reaction within a compressed cofactor-substrate complex.

Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline

DOE PAGES

Leal, Stephanie L.; Landau, Susan M.; Bell, Rachel K.; ...

2017-02-08

The amyloid hypothesis suggests that beta-amyloid (Aβ) deposition leads to alterations in neural function and ultimately to cognitive decline in Alzheimer’s disease. However, factors that underlie Aβ deposition are incompletely understood. One proposed model suggests that synaptic activity leads to increased Aβ deposition. More specifically, hyperactivity in the hippocampus may be detrimental and could be one factor that drives Aβ deposition. To test this model, we examined the relationship between hippocampal activity during a memory task using fMRI and subsequent longitudinal change in Aβ using PIB-PET imaging in cognitively normal older adults. We found that greater hippocampal activation at baselinemore » was associated with increased Aβ accumulation. Furthermore, increasing Aβ accumulation mediated the influence of hippocampal activation on declining memory performance, demonstrating a crucial role of Aβ in linking hippocampal activation and memory. These findings support a model linking increased hippocampal activation to subsequent Aβ deposition and cognitive decline.« less

Ketamine: 50 Years of Modulating the Mind

PubMed Central

Li, Linda; Vlisides, Phillip E.

2016-01-01

Ketamine was introduced into clinical practice in the 1960s and continues to be both clinically useful and scientifically fascinating. With considerably diverse molecular targets and neurophysiological properties, ketamine’s effects on the central nervous system remain incompletely understood. Investigators have leveraged the unique characteristics of ketamine to explore the invariant, fundamental mechanisms of anesthetic action. Emerging evidence indicates that ketamine-mediated anesthesia may occur via disruption of corticocortical information transfer in a frontal-to-parietal (“top down”) distribution. This proposed mechanism of general anesthesia has since been demonstrated with anesthetics in other pharmacological classes as well. Ketamine remains invaluable to the fields of anesthesiology and critical care medicine, in large part due to its ability to maintain cardiorespiratory stability while providing effective sedation and analgesia. Furthermore, there may be an emerging role for ketamine in treatment of refractory depression and Post-Traumatic Stress Disorder. In this article, we review the history of ketamine, its pharmacology, putative mechanisms of action and current clinical applications. PMID:27965560

Insights into GATA-1 Mediated Gene Activation versus Repression via Genome-wide Chromatin Occupancy Analysis

PubMed Central

Yu, Ming; Riva, Laura; Xie, Huafeng; Schindler, Yocheved; Moran, Tyler B.; Cheng, Yong; Yu, Duonan; Hardison, Ross; Weiss, Mitchell J; Orkin, Stuart H.; Bernstein, Bradley E.; Fraenkel, Ernest; Cantor, Alan B.

2009-01-01

Summary The transcription factor GATA-1 is required for terminal erythroid maturation and functions as an activator or repressor depending on gene context. Yet its in vivo site selectivity and ability to distinguish between activated versus repressed genes remain incompletely understood. In this study, we performed GATA-1 ChIP-seq in erythroid cells and compared it to GATA-1 induced gene expression changes. Bound and differentially expressed genes contain a greater number of GATA binding motifs, a higher frequency of palindromic GATA sites, and closer occupancy to the transcriptional start site versus non-differentially expressed genes. Moreover, we show that the transcription factor Zbtb7a occupies GATA-1 bound regions of some direct GATA-1 target genes, that the presence of SCL/TAL1 helps distinguish transcriptional activation versus repression, and that Polycomb Repressive Complex 2 (PRC2) is involved in epigenetic silencing of a subset of GATA-1 repressed genes. These data provide insights into GATA-1 mediated gene regulation in vivo. PMID:19941827

Real-time tracking of cell cycle progression during CD8+ effector and memory T-cell differentiation

PubMed Central

Kinjyo, Ichiko; Qin, Jim; Tan, Sioh-Yang; Wellard, Cameron J.; Mrass, Paulus; Ritchie, William; Doi, Atsushi; Cavanagh, Lois L.; Tomura, Michio; Sakaue-Sawano, Asako; Kanagawa, Osami; Miyawaki, Atsushi; Hodgkin, Philip D.; Weninger, Wolfgang

2015-01-01

The precise pathways of memory T-cell differentiation are incompletely understood. Here we exploit transgenic mice expressing fluorescent cell cycle indicators to longitudinally track the division dynamics of individual CD8+ T cells. During influenza virus infection in vivo, naive T cells enter a CD62Lintermediate state of fast proliferation, which continues for at least nine generations. At the peak of the anti-viral immune response, a subpopulation of these cells markedly reduces their cycling speed and acquires a CD62Lhi central memory cell phenotype. Construction of T-cell family division trees in vitro reveals two patterns of proliferation dynamics. While cells initially divide rapidly with moderate stochastic variations of cycling times after each generation, a slow-cycling subpopulation displaying a CD62Lhi memory phenotype appears after eight divisions. Phenotype and cell cycle duration are inherited by the progeny of slow cyclers. We propose that memory precursors cell-intrinsically modulate their proliferative activity to diversify differentiation pathways. PMID:25709008

Inferring multi-scale neural mechanisms with brain network modelling

PubMed Central

Schirner, Michael; McIntosh, Anthony Randal; Jirsa, Viktor; Deco, Gustavo

2018-01-01

The neurophysiological processes underlying non-invasive brain activity measurements are incompletely understood. Here, we developed a connectome-based brain network model that integrates individual structural and functional data with neural population dynamics to support multi-scale neurophysiological inference. Simulated populations were linked by structural connectivity and, as a novelty, driven by electroencephalography (EEG) source activity. Simulations not only predicted subjects' individual resting-state functional magnetic resonance imaging (fMRI) time series and spatial network topologies over 20 minutes of activity, but more importantly, they also revealed precise neurophysiological mechanisms that underlie and link six empirical observations from different scales and modalities: (1) resting-state fMRI oscillations, (2) functional connectivity networks, (3) excitation-inhibition balance, (4, 5) inverse relationships between α-rhythms, spike-firing and fMRI on short and long time scales, and (6) fMRI power-law scaling. These findings underscore the potential of this new modelling framework for general inference and integration of neurophysiological knowledge to complement empirical studies. PMID:29308767

Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leal, Stephanie L.; Landau, Susan M.; Bell, Rachel K.

The amyloid hypothesis suggests that beta-amyloid (Aβ) deposition leads to alterations in neural function and ultimately to cognitive decline in Alzheimer’s disease. However, factors that underlie Aβ deposition are incompletely understood. One proposed model suggests that synaptic activity leads to increased Aβ deposition. More specifically, hyperactivity in the hippocampus may be detrimental and could be one factor that drives Aβ deposition. To test this model, we examined the relationship between hippocampal activity during a memory task using fMRI and subsequent longitudinal change in Aβ using PIB-PET imaging in cognitively normal older adults. We found that greater hippocampal activation at baselinemore » was associated with increased Aβ accumulation. Furthermore, increasing Aβ accumulation mediated the influence of hippocampal activation on declining memory performance, demonstrating a crucial role of Aβ in linking hippocampal activation and memory. These findings support a model linking increased hippocampal activation to subsequent Aβ deposition and cognitive decline.« less

Pathological implications of cell cycle re-entry in Alzheimer disease.

PubMed

Bonda, David J; Lee, Hyun-pil; Kudo, Wataru; Zhu, Xiongwei; Smith, Mark A; Lee, Hyoung-gon

2010-06-29

The complex neurodegeneration underlying Alzheimer disease (AD), although incompletely understood, is characterised by an aberrant re-entry into the cell cycle in neurons. Pathological evidence, in the form of cell cycle markers and regulatory proteins, suggests that cell cycle re-entry is an early event in AD, which precedes the formation of amyloid-beta plaques and neurofibrillary tangles (NFTs). Although the exact mechanisms that induce and mediate these cell cycle events in AD are not clear, significant advances have been made in further understanding the pathological role of cell cycle re-entry in AD. Importantly, recent studies indicate that cell cycle re-entry is not a consequence, but rather a cause, of neurodegeneration, suggesting that targeting of cell cycle re-entry may provide an opportunity for therapeutic intervention. Moreover, multiple inducers of cell cycle re-entry and their interactions in AD have been proposed. Here, we review the most recent advances in understanding the pathological implications of cell cycle re-entry in AD.

Azithromycin-induced rash in a patient of infectious mononucleosis - a case report with review of literature.

PubMed

Banerjee, Indranil; Mondal, Somnath; Sen, Sukanta; Tripathi, Santanu Kumar; Banerjee, Gautam

2014-08-01

Antibiotic induced skin rash in setting of infectious mononucleosis is often encountered in clinical practice. However, macrolides like azithromycin are considered relatively safe and till date only two cases of azithromycin induced rash in setting of infectious mononucleosis have been reported. The following report illustrates the case of a 23-year-old man suffering from infectious mononucleosis who exhibited a generalized cutaneous rash following treatment with azithromycin. Using the Naranjo ADR probability scale, this case of acute onset rash following azithromycin administration was found to be in 'probable' category. The mechanism of antibiotic-induced rash in patients suffering from infectious mononucleosis is incompletely understood. It has been suggested that the rash could result from virus mediated immunomodulation or due to altered drug metabolism. The report calls for cautious use of antibiotics in the setting of suspected viral infections like infectious mononucleosis as injudicious use might increase the risk of deleterious skin reactions and increase the cost of healthcare.

Opposing effects of cancer-type-specific SPOP mutants on BET protein degradation and sensitivity to BET inhibitors.

PubMed

Janouskova, Hana; El Tekle, Geniver; Bellini, Elisa; Udeshi, Namrata D; Rinaldi, Anna; Ulbricht, Anna; Bernasocchi, Tiziano; Civenni, Gianluca; Losa, Marco; Svinkina, Tanya; Bielski, Craig M; Kryukov, Gregory V; Cascione, Luciano; Napoli, Sara; Enchev, Radoslav I; Mutch, David G; Carney, Michael E; Berchuck, Andrew; Winterhoff, Boris J N; Broaddus, Russell R; Schraml, Peter; Moch, Holger; Bertoni, Francesco; Catapano, Carlo V; Peter, Matthias; Carr, Steven A; Garraway, Levi A; Wild, Peter J; Theurillat, Jean-Philippe P

2017-09-01

It is generally assumed that recurrent mutations within a given cancer driver gene elicit similar drug responses. Cancer genome studies have identified recurrent but divergent missense mutations affecting the substrate-recognition domain of the ubiquitin ligase adaptor SPOP in endometrial and prostate cancers. The therapeutic implications of these mutations remain incompletely understood. Here we analyzed changes in the ubiquitin landscape induced by endometrial cancer-associated SPOP mutations and identified BRD2, BRD3 and BRD4 proteins (BETs) as SPOP-CUL3 substrates that are preferentially degraded by endometrial cancer-associated SPOP mutants. The resulting reduction of BET protein levels sensitized cancer cells to BET inhibitors. Conversely, prostate cancer-specific SPOP mutations resulted in impaired degradation of BETs, promoting their resistance to pharmacologic inhibition. These results uncover an oncogenomics paradox, whereby mutations mapping to the same domain evoke opposing drug susceptibilities. Specifically, we provide a molecular rationale for the use of BET inhibitors to treat patients with endometrial but not prostate cancer who harbor SPOP mutations.

Real-time tracking of cell cycle progression during CD8+ effector and memory T-cell differentiation.

PubMed

Kinjyo, Ichiko; Qin, Jim; Tan, Sioh-Yang; Wellard, Cameron J; Mrass, Paulus; Ritchie, William; Doi, Atsushi; Cavanagh, Lois L; Tomura, Michio; Sakaue-Sawano, Asako; Kanagawa, Osami; Miyawaki, Atsushi; Hodgkin, Philip D; Weninger, Wolfgang

2015-02-24

The precise pathways of memory T-cell differentiation are incompletely understood. Here we exploit transgenic mice expressing fluorescent cell cycle indicators to longitudinally track the division dynamics of individual CD8(+) T cells. During influenza virus infection in vivo, naive T cells enter a CD62L(intermediate) state of fast proliferation, which continues for at least nine generations. At the peak of the anti-viral immune response, a subpopulation of these cells markedly reduces their cycling speed and acquires a CD62L(hi) central memory cell phenotype. Construction of T-cell family division trees in vitro reveals two patterns of proliferation dynamics. While cells initially divide rapidly with moderate stochastic variations of cycling times after each generation, a slow-cycling subpopulation displaying a CD62L(hi) memory phenotype appears after eight divisions. Phenotype and cell cycle duration are inherited by the progeny of slow cyclers. We propose that memory precursors cell-intrinsically modulate their proliferative activity to diversify differentiation pathways.

ALK1 Signaling Inhibits Angiogenesis by Cooperating with the Notch Pathway

PubMed Central

Larrivée, Bruno; Prahst, Claudia; Gordon, Emma; del Toro, Raquel; Mathivet, Thomas; Duarte, Antonio; Simons, Michael; Eichmann, Anne

2014-01-01

SUMMARY Activin receptor-like kinase 1 (ALK1) is an endothelial-specific member of the TGF-β/BMP receptor family that is inactivated in patients with hereditary hemorrhagic telangiectasia (HHT). How ALK1 signaling regulates angiogenesis remains incompletely understood. Here we show that ALK1 inhibits angiogenesis by cooperating with the Notch pathway. Blocking Alk1 signaling during postnatal development in mice leads to retinal hypervascularization and the appearance of arteriovenous malformations (AVMs). Combined blockade of Alk1 and Notch signaling further exacerbates hypervascularization, whereas activation of Alk1 by its high-affinity ligand BMP9 rescues hypersprouting induced by Notch inhibition. Mechanistically, ALK1-dependent SMAD signaling synergizes with activated Notch in stalk cells to induce expression of the Notch targets HEY1 and HEY2, thereby repressing VEGF signaling, tip cell formation, and endothelial sprouting. Taken together, these results uncover a direct link between ALK1 and Notch signaling during vascular morpho-genesis that may be relevant to the pathogenesis of HHT vascular lesions. PMID:22421041

Redox-dependent substrate-cofactor interactions in the Michaelis-complex of a flavin-dependent oxidoreductase

PubMed Central

Werther, Tobias; Wahlefeld, Stefan; Salewski, Johannes; Kuhlmann, Uwe; Zebger, Ingo; Hildebrandt, Peter; Dobbek, Holger

2017-01-01

How an enzyme activates its substrate for turnover is fundamental for catalysis but incompletely understood on a structural level. With redox enzymes one typically analyses structures of enzyme–substrate complexes in the unreactive oxidation state of the cofactor, assuming that the interaction between enzyme and substrate is independent of the cofactors oxidation state. Here, we investigate the Michaelis complex of the flavoenzyme xenobiotic reductase A with the reactive reduced cofactor bound to its substrates by X-ray crystallography and resonance Raman spectroscopy and compare it to the non-reactive oxidized Michaelis complex mimics. We find that substrates bind in different orientations to the oxidized and reduced flavin, in both cases flattening its structure. But only authentic Michaelis complexes display an unexpected rich vibrational band pattern uncovering a strong donor–acceptor complex between reduced flavin and substrate. This interaction likely activates the catalytic ground state of the reduced flavin, accelerating the reaction within a compressed cofactor–substrate complex.

The molecular basis of herpes simplex virus latency

PubMed Central

Nicoll, Michael P; Proença, João T; Efstathiou, Stacey

2012-01-01

Herpes simplex virus type 1 is a neurotropic herpesvirus that establishes latency within sensory neurones. Following primary infection, the virus replicates productively within mucosal epithelial cells and enters sensory neurones via nerve termini. The virus is then transported to neuronal cell bodies where latency can be established. Periodically, the virus can reactivate to resume its normal lytic cycle gene expression programme and result in the generation of new virus progeny that are transported axonally back to the periphery. The ability to establish lifelong latency within the host and to periodically reactivate to facilitate dissemination is central to the survival strategy of this virus. Although incompletely understood, this review will focus on the mechanisms involved in the regulation of latency that centre on the functions of the virus-encoded latency-associated transcripts (LATs), epigenetic regulation of the latent virus genome and the molecular events that precipitate reactivation. This review considers current knowledge and hypotheses relating to the mechanisms involved in the establishment, maintenance and reactivation herpes simplex virus latency. PMID:22150699

Rfx6 Directs Islet Formation and Insulin Production in Mice and Humans

PubMed Central

Smith, Stuart B.; Qu, Hui-Qi; Taleb, Nadine; Kishimoto, Nina; Scheel, David W.; Lu, Yang; Patch, Ann-Marie; Grabs, Rosemary; Wang, Juehu; Lynn, Francis C.; Miyatsuka, Takeshi; Mitchell, John; Seerke, Rina; Désir, Julie; Eijnden, Serge Vanden; Abramowicz, Marc; Kacet, Nadine; Weill, Jacques; Renard, Marie-Éve; Gentile, Mattia; Hansen, Inger; Dewar, Ken; Hattersley, Andrew T.; Wang, Rennian; Wilson, Maria E.; Johnson, Jeffrey D.; Polychronakos, Constantin; German, Michael S.

2009-01-01

Insulin from the β-cells of the pancreatic islets of Langerhans controls energy homeostasis in vertebrates, and its deficiency causes diabetes mellitus. During embryonic development, the transcription factor Neurogenin3 initiates the differentiation of the β-cells and other islet cell types from pancreatic endoderm, but the genetic program that subsequently completes this differentiation remains incompletely understood. Here we show that the transcription factor Rfx6 directs islet cell differentiation downstream of Neurogenin3. Mice lacking Rfx6 failed to generate any of the normal islet cell types except for pancreatic-polypeptide-producing cells. In human infants with a similar autosomal recessive syndrome of neonatal diabetes, genetic mapping and subsequent sequencing identified mutations in the human RFX6 gene. These studies demonstrate a unique position for Rfx6 in the hierarchy of factors that coordinate pancreatic islet development in both mice and humans. Rfx6 could prove useful in efforts to generate β-cells for patients with diabetes. PMID:20148032

DOE Office of Scientific and Technical Information (OSTI.GOV)

Du, Lanying; Kao, Richard Y.; Zhou, Yusen

The spike (S) protein of SARS coronavirus (SARS-CoV) has been known to recognize and bind to host receptors, whose conformational changes then facilitate fusion between the viral envelope and host cell membrane, leading to viral entry into target cells. However, other functions of SARS-CoV S protein such as proteolytic cleavage and its implications to viral infection are incompletely understood. In this study, we demonstrated that the infection of SARS-CoV and a pseudovirus bearing the S protein of SARS-CoV was inhibited by a protease inhibitor Ben-HCl. Also, the protease Factor Xa, a target of Ben-HCl abundantly expressed in infected cells, wasmore » able to cleave the recombinant and pseudoviral S protein into S1 and S2 subunits, and the cleavage was inhibited by Ben-HCl. Furthermore, this cleavage correlated with the infectivity of the pseudovirus. Taken together, our study suggests a plausible mechanism by which SARS-CoV cleaves its S protein to facilitate viral infection.« less