Chapter 13: Recent Advances on the Genomics of Litter- and Soil-Inhabiting Agaricomycetes

Treesearch

Phil Kersten; Dan Cullen

2013-01-01

Woody biomass makes up the major portion of terrestrial carbon, and forest ecosystems contain enormous reservoirs of lignocellulose belowground, in dead trees, and litter. Decomposition of this recalcitrant material and mobilization of nutrients are essential for forest health [reviewed by Boddy and Watkinson (1995)]. Although mechanisms are incompletely understood,...

The Class I HDAC Inhibitor RGFP963 Enhances Consolidation of Cued Fear Extinction

ERIC Educational Resources Information Center

Bowers, Mallory E.; Xia, Bing; Carreiro, Samantha; Ressler, Kerry J.

2015-01-01

Evidence indicates that broad, nonspecific histone deacetylase (HDAC) inhibition enhances learning and memory, however, the contribution of the various HDACs to specific forms of learning is incompletely understood. Here, we show that the Class I HDAC inhibitor, RGFP963, enhances consolidation of cued fear extinction. However, RGFP966, a strong…

The role of reduced oxygen in the developmental physiology of growth and metamorphosis initiation in Drosophila

USDA-ARS?s Scientific Manuscript database

Rearing oxygen level is known to affect final body size in a variety of insects, but the physiological mechanisms by which oxygen affects size are incompletely understood. In Manduca and Drosophila, the larval size at which metamorphosis is initiated largely determines adult size, and metamorphosis ...

Dynamic variation in sapwood specific conductivity in six woody species.

Treesearch

J.C. Domec; F.C. Meinzer; B.L. Gartner; J. Housset

2007-01-01

Relationships between pressure gradients and flow rates in the xylem are incompletely understood because steady-state conductivity coefficients are inadequate for predicting and interpreting flow under the non-steady-state conditions more prevalent in intact trees. The goal of this study was to determine the magnitude of deviation of trunk sapwood specific conductivity...

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...

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

Abnormal center-periphery gradient in spatial attention in simultanagnosia.

PubMed

Balslev, Daniela; Odoj, Bartholomaeus; Rennig, Johannes; Karnath, Hans-Otto

2014-12-01

Patients suffering from simultanagnosia cannot perceive more than one object at a time. The underlying mechanism is incompletely understood. One hypothesis is that simultanagnosia reflects "tunnel vision," a constricted attention window around gaze, which precludes the grouping of individual objects. Although this idea has a long history in neuropsychology, the question whether the patients indeed have an abnormal attention gradient around the gaze has so far not been addressed. Here we tested this hypothesis in two simultanagnosia patients with bilateral parieto-occipital lesions and two control groups, with and without brain damage. We assessed the participants' ability to discriminate letters presented briefly at fixation with and without a peripheral distractor or in the visual periphery, with or without a foveal distractor. A constricted span of attention around gaze would predict an increased susceptibility to foveated versus peripheral distractors. Contrary to this prediction and unlike both control groups, the patients' ability to discriminate the target decreased more in the presence of peripheral compared with foveated distractors. Thus, the attentional spotlight in simultanagnosia does not fall on foveated objects as previously assumed, but rather abnormally highlights the periphery. Furthermore, we found the same center-periphery gradient in the patients' ability to recognize multiple objects. They detected multiple, but not single objects more accurately in the periphery than at fixation. These results suggest that an abnormal allocation of attention around the gaze can disrupt the grouping of individual objects into an integrated visual scene.

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 ...

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.

Index markers of chronic fatigue syndrome with dysfunction of TCA and urea cycles

PubMed Central

Yamano, Emi; Sugimoto, Masahiro; Hirayama, Akiyoshi; Kume, Satoshi; Yamato, Masanori; Jin, Guanghua; Tajima, Seiki; Goda, Nobuhito; Iwai, Kazuhiro; Fukuda, Sanae; Yamaguti, Kouzi; Kuratsune, Hirohiko; Soga, Tomoyoshi; Watanabe, Yasuyoshi; Kataoka, Yosky

2016-01-01

Chronic fatigue syndrome (CFS) is a persistent and unexplained pathological state characterized by exertional and severely debilitating fatigue, with/without infectious or neuropsychiatric symptoms, lasting at least 6 consecutive months. Its pathogenesis remains incompletely understood. Here, we performed comprehensive metabolomic analyses of 133 plasma samples obtained from CFS patients and healthy controls to establish an objective diagnosis of CFS. CFS patients exhibited significant differences in intermediate metabolite concentrations in the tricarboxylic acid (TCA) and urea cycles. The combination of ornithine/citrulline and pyruvate/isocitrate ratios discriminated CFS patients from healthy controls, yielding area under the receiver operating characteristic curve values of 0.801 (95% confidential interval [CI]: 0.711–0.890, P < 0.0001) and 0.750 (95% CI: 0.584–0.916, P = 0.0069) for training (n = 93) and validation (n = 40) datasets, respectively. These findings provide compelling evidence that a clinical diagnostic tool could be developed for CFS based on the ratios of metabolites in plasma. PMID:27725700

Heat-transfer dynamics during cryogen spray cooling of substrate at different initial temperatures.

PubMed

Jia, Wangcun; Aguilar, Guillermo; Wang, Guo-Xiang; Nelson, J Stuart

2004-12-07

Cryogen spray cooling (CSC) is used to minimize the risk of epidermal damage during laser dermatologic therapy. However, the dominant mechanisms of heat transfer during the transient cooling process are incompletely understood. The objective of this study is to elucidate the physics of CSC by measuring the effect of initial substrate temperature (T0) on cooling dynamics. Cryogen was delivered by a straight-tube nozzle onto a skin phantom. A fast-response thermocouple was used to record the phantom temperature changes before, during and after the cryogen spray. Surface heat fluxes (q") and heat-transfer coefficients (h) were computed using an inverse heat conduction algorithm. The maximum surface heat flux (q"max) was observed to increase with T0. The surface temperature corresponding to q"max also increased with T0 but the latter has no significant effect on h. It is concluded that heat transfer between the cryogen spray and skin phantom remains in the nucleate boiling region even if T0 is 80 degrees C.

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.

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.

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.

Incomplete gastric metaplasia in children with insulin-dependent diabetes mellitus and celiac disease. An ultrastructural study

PubMed Central

Bertini, Marina; Sbarbati, Andrea; Valletta, Enrico; Pinelli, Leonardo; Tatò, Luciano

2001-01-01

Background The association of insulin-dependent diabetes mellitus (IDDM) and celiac disease (CD) has been widely reported in children but the relationship between the two conditions is incompletely understood. Moreover, specific studies on intestinal biopsies of patients with the association of the two diseases are still lacking. Methods We studied the ultrastructure of the duodenal mucosa in 12 patients with both IDDM and CD. Results All patients had either total or partial atrophy of duodenal mucosa. In seven subjects, an accumulation of electrondense granules in the apical cytoplasm of groups of enterocytes was found. In four of them, a double population of granules existed (mean diameter: 400-800 nm and 100-200 nm respectively) showing a biphasic pattern. In the other three patients, only smaller granules (100- 200 nm) were found in the enterocytes. Conclusions The present work suggests that patients with IDDM/CD may represent a subgroup in the context of the CD population. Intestinal biopsies of such individuals often show accumulation of electrondense granules in the apical cytoplasm of enterocytes that can be interpreted as incomplete gastric metaplasia. PMID:11466133

Binding and segmentation via a neural mass model trained with Hebbian and anti-Hebbian mechanisms.

PubMed

Cona, Filippo; Zavaglia, Melissa; Ursino, Mauro

2012-04-01

Synchronization of neural activity in the gamma band, modulated by a slower theta rhythm, is assumed to play a significant role in binding and segmentation of multiple objects. In the present work, a recent neural mass model of a single cortical column is used to analyze the synaptic mechanisms which can warrant synchronization and desynchronization of cortical columns, during an autoassociation memory task. The model considers two distinct layers communicating via feedforward connections. The first layer receives the external input and works as an autoassociative network in the theta band, to recover a previously memorized object from incomplete information. The second realizes segmentation of different objects in the gamma band. To this end, units within both layers are connected with synapses trained on the basis of previous experience to store objects. The main model assumptions are: (i) recovery of incomplete objects is realized by excitatory synapses from pyramidal to pyramidal neurons in the same object; (ii) binding in the gamma range is realized by excitatory synapses from pyramidal neurons to fast inhibitory interneurons in the same object. These synapses (both at points i and ii) have a few ms dynamics and are trained with a Hebbian mechanism. (iii) Segmentation is realized with faster AMPA synapses, with rise times smaller than 1 ms, trained with an anti-Hebbian mechanism. Results show that the model, with the previous assumptions, can correctly reconstruct and segment three simultaneous objects, starting from incomplete knowledge. Segmentation of more objects is possible but requires an increased ratio between the theta and gamma periods.

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

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.

Sensitivity and Specificity of Hypnosis Effects on Gastric Myoelectrical Activity

PubMed Central

Enck, Paul; Weimer, Katja; Muth, Eric R.; Zipfel, Stephan; Martens, Ute

2013-01-01

Objectives The effects of hypnosis on physiological (gastrointestinal) functions are incompletely understood, and it is unknown whether they are hypnosis-specific and gut-specific, or simply unspecific effects of relaxation. Design Sixty-two healthy female volunteers were randomly assigned to either a single session of hypnotic suggestion of ingesting an appetizing meal and an unappetizing meal, or to relax and concentrate on having an appetizing or unappetizing meal, while the electrogastrogram (EGG) was recorded. At the end of the session, participants drank water until they felt full, in order to detect EGG-signal changes after ingestion of a true gastric load. During both conditions participants reported their subjective well-being, hunger and disgust at several time points. Results Imagining eating food induced subjective feelings of hunger and disgust as well as changes in the EGG similar to, but more pronounced than those seen with a real gastric water load during both hypnosis and relaxation conditions. These effects were more pronounced when imagining an appetizing meal than with an unappetizing meal. There was no significant difference between the hypnosis and relaxation conditions. Conclusion Imagination with and without hypnosis exhibits similar changes in subjective and objective measures in response to imagining an appetizing and an unappetizing food, indicating high sensitivity but low specificity. PMID:24358287

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...

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

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

Modulation of hand aperture during reaching in persons with incomplete cervical spinal cord injury.

PubMed

Stahl, Victoria A; Hayes, Heather B; Buetefisch, Cathrin M; Wolf, Steven L; Trumbower, Randy D

2015-03-01

The intact neuromotor system prepares for object grasp by first opening the hand to an aperture that is scaled according to object size and then closing the hand around the object. After cervical spinal cord injury (SCI), hand function is significantly impaired, but the degree to which object-specific hand aperture scaling is affected remains unknown. Here, we hypothesized that persons with incomplete cervical SCI have a reduced maximum hand opening capacity but exhibit novel neuromuscular coordination strategies that permit object-specific hand aperture scaling during reaching. To test this hypothesis, we measured hand kinematics and surface electromyography from seven muscles of the hand and wrist during attempts at maximum hand opening as well as reaching for four balls of different diameters. Our results showed that persons with SCI exhibited significantly reduced maximum hand aperture compared to able-bodied (AB) controls. However, persons with SCI preserved the ability to scale peak hand aperture with ball size during reaching. Persons with SCI also used distinct muscle coordination patterns that included increased co-activity of flexors and extensors at the wrist and hand compared to AB controls. These results suggest that motor planning for aperture modulation is preserved even though execution is limited by constraints on hand opening capacity and altered muscle co-activity. Thus, persons with incomplete cervical SCI may benefit from rehabilitation aimed at increasing hand opening capacity and reducing flexor-extensor co-activity at the wrist and hand.

Modulation of hand aperture during reaching in persons with incomplete cervical spinal cord injury

PubMed Central

Stahl, Victoria; Hayes, Heather B; Buetefisch, Cathrin; Wolf, Steven L; Trumbower, Randy D

2014-01-01

The intact neuromotor system prepares for object grasp by first opening the hand to an aperture that is scaled according to object size and then closing the hand around the object. After cervical spinal cord injury (SCI), hand function is significantly impaired, but the degree to which object-specific hand aperture scaling is affected remains unknown. Here we hypothesized that persons with incomplete cervical SCI have a reduced maximum hand opening capacity but exhibit novel neuromuscular coordination strategies that permit object-specific hand aperture scaling during reaching. To test this hypothesis, we measured hand kinematics and surface electromyography (EMG) from seven muscles of the hand and wrist during attempts at maximum hand opening as well as reaching for four balls of different diameters. Our results showed that persons with SCI exhibited significantly reduced maximum hand aperture compared to able-bodied (AB) controls. However, persons with SCI preserved the ability to scale peak hand aperture with ball size during reaching. Persons with SCI also used distinct muscle coordination patterns that included increased co-activity of flexors and extensors at the wrist and hand compared to AB controls. These results suggest that motor planning for aperture modulation is preserved even though execution is limited by constraints on hand opening capacity and altered muscle co-activity. Thus, persons with incomplete cervical SCI may benefit from rehabilitation aimed at increasing hand opening capacity and reducing flexor-extensor co-activity at the wrist and hand. PMID:25511164

Barriers to Specialty Care and Specialty Referral Completion in the Community Health Center Setting

PubMed Central

Zuckerman, Katharine E.; Perrin, James M.; Hobrecker, Karin; Donelan, Karen

2013-01-01

Objective To assess the frequency of barriers to specialty care and to assess which barriers are associated with an incomplete specialty referral (not attending a specialty visit when referred by a primary care provider) among children seen in community health centers. Study design Two months after their child’s specialty referral, 341 parents completed telephone surveys assessing whether a specialty visit was completed and whether they experienced any of 10 barriers to care. Family/community barriers included difficulty leaving work, obtaining childcare, obtaining transportation, and inadequate insurance. Health care system barriers included getting appointments quickly, understanding doctors and nurses, communicating with doctors’ offices, locating offices, accessing interpreters, and inconvenient office hours. We calculated barrier frequency and total barriers experienced. Using logistic regression, we assessed which barriers were associated with incomplete referral, and whether experiencing ≥4 barriers was associated with incomplete referral. Results A total of 22.9% of families experienced incomplete referral. 42.0% of families encountered 1 or more barriers. The most frequent barriers were difficulty leaving work, obtaining childcare, and obtaining transportation. On multivariate analysis, difficulty getting appointments quickly, difficulty finding doctors’ offices, and inconvenient office hours were associated with incomplete referral. Families experiencing ≥4 barriers were more likely than those experiencing ≤3 barriers to have incomplete referral. Conclusion Barriers to specialty care were common and associated with incomplete referral. Families experiencing many barriers had greater risk of incomplete referral. Improving family/community factors may increase satisfaction with specialty care; however, improving health system factors may be the best way to reduce incomplete referrals. PMID:22929162

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.

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.

Fast-adapting mechanoreceptors are important for force control in precision grip but not for sensorimotor memory.

PubMed

Park, Susanna B; Davare, Marco; Falla, Marika; Kennedy, William R; Selim, Mona M; Wendelschafer-Crabb, Gwen; Koltzenburg, Martin

2016-06-01

Sensory feedback from cutaneous mechanoreceptors in the fingertips is important in effective object manipulation, allowing appropriate scaling of grip and load forces during precision grip. However, the role of mechanoreceptor subtypes in these tasks remains incompletely understood. To address this issue, psychophysical tasks that may specifically assess function of type I fast-adapting (FAI) and slowly adapting (SAI) mechanoreceptors were used with object manipulation experiments to examine the regulation of grip force control in an experimental model of graded reduction in tactile sensitivity (healthy volunteers wearing 2 layers of latex gloves). With gloves, tactile sensitivity decreased significantly from 1.9 ± 0.4 to 12.3 ± 2.2 μm in the Bumps task assessing function of FAI afferents but not in a grating orientation task assessing SAI afferents (1.6 ± 0.1 to 1.8 ± 0.2 mm). Six axis force/torque sensors measured peak grip (PGF) and load (PLF) forces generated by the fingertips during a grip-lift task. With gloves there was a significant increase of PGF (14 ± 6%), PLF (17 ± 5%), and grip and load force rates (26 ± 8%, 20 ± 8%). A variable-weight series task was used to examine sensorimotor memory. There was a 20% increase in PGF when the lift of a light object was preceded by a heavy relative to a light object. This relationship was not significantly altered when lifting with gloves, suggesting that the addition of gloves did not change sensorimotor memory effects. We conclude that FAI fibers may be important for the online force scaling but not for the buildup of a sensorimotor memory. Copyright © 2016 the American Physiological Society.

Is Grammar Instruction Beneficial for Heritage Language Learners? Dative Case Marking in Spanish

ERIC Educational Resources Information Center

Montrul, Silvina; Bowles, Melissa

2010-01-01

Spanish heritage speakers have been shown to have incomplete knowledge of dative case marking with both animate direct objects (also known as differential object marking (DOM) or "a-personal") and dative experiencers with "gustar"-psych verbs in oral and written modes (Montrul, 2004; Montrul & Bowles, in press). In general, Spanish objects that…

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

Intracapsular implant rupture: MR findings of incomplete shell collapse.

PubMed

Soo, M S; Kornguth, P J; Walsh, R; Elenberger, C; Georgiade, G S; DeLong, D; Spritzer, C E

1997-01-01

The objective of this study was to determine the frequency and significance of the MR findings of incomplete shell collapse for detecting implant rupture in a series of surgically removed breast prostheses. MR images of 86 breast implants in 44 patients were studied retrospectively and correlated with surgical findings at explantation. MR findings included (a) complete shell collapse (linguine sign), 21 implants; (b) incomplete shell collapse (subcapsular line sign, teardrop sign, and keyhole sign), 33 implants; (c) radial folds, 31 implants; and (d) normal, 1 implant. The subcapsular line sign was seen in 26 implants, the teardrop sign was seen in 27 implants, and the keyhole sign was seen in 23 implants. At surgery, 48 implants were found to be ruptured and 38 were intact. The MR findings of ruptured implants showed signs of incomplete collapse in 52% (n = 25), linguine sign in 44% (n = 21), and radial folds in 4% (n = 2). The linguine sign perfectly predicted implant rupture, but sensitivity was low. Findings of incomplete shell collapse improved sensitivity and negative predictive values, and the subcapsular line sign produced a significant incremental increase in predictive ability. MRI signs of incomplete shell collapse were more common than the linguine sign in ruptured implants and are significant contributors to the high sensitivity and negative predictive values of MRI for evaluating implant integrity.

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.

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.

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.

Mechanisms and management of functional abdominal pain.

PubMed

Farmer, Adam D; Aziz, Qasim

2014-09-01

Functional abdominal pain syndrome is characterised by frequent or continuous abdominal pain associated with a degree of loss of daily activity. It has a reported population prevalence of between 0.5% and 1.7%, with a female preponderance. The pathophysiology of functional abdominal pain is incompletely understood although it has been postulated that peripheral sensitisation of visceral afferents, central sensitisation of the spinal dorsal horn and aberrancies within descending modulatory systems may have an important role. The management of patients with functional abdominal pain requires a tailored multidisciplinary approach in a supportive and empathetic environment in order to develop an effective therapeutic relationship. Patient education directed towards an explanation of the pathophysiology of functional abdominal pain is in our opinion a prerequisite step and provides the rationale for the introduction of interventions. Interventions can usefully be categorised into general measures, pharmacotherapy, psychological interventions and 'step-up' treatments. Pharmacotherapeutic/step-up options include tricyclic antidepressants, serotonin noradrenergic reuptake inhibitors and the gabapentinoids. Psychological treatments include cognitive behavioural therapy and hypnotherapy. However, the objective evidence base for these interventions is largely derived from other chronic pain syndrome, and further research is warranted in adult patients with functional abdominal pain. © The Royal Society of Medicine.

Holographic interferometry of transparent media with reflection from imbedded test objects

NASA Technical Reports Server (NTRS)

Prikryl, I.; Vest, C. M.

1981-01-01

In applying holographic interferometry, opaque objects blocking a portion of the optical beam used to form the interferogram give rise to incomplete data for standard computer tomography algorithms. An experimental technique for circumventing the problem of data blocked by opaque objects is presented. The missing data are completed by forming an interferogram using light backscattered from the opaque object, which is assumed to be diffuse. The problem of fringe localization is considered.

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.

Development of Three-Dimensional Object Completion in Infancy

ERIC Educational Resources Information Center

Soska, Kasey C.; Johnson, Scott P.

2008-01-01

Three-dimensional (3D) object completion was investigated by habituating 4- and 6-month-old infants (n = 24 total) with a computer-generated wedge stimulus that pivoted 15[degrees], providing only a limited view. Two displays, rotating 360[degrees], were then shown: a complete, solid volume and an incomplete, hollow form composed only of the sides…

Group prioritisation with unknown expert weights in incomplete linguistic context

NASA Astrophysics Data System (ADS)

Cheng, Dong; Cheng, Faxin; Zhou, Zhili; Wang, Juan

2017-09-01

In this paper, we study a group prioritisation problem in situations when the expert weights are completely unknown and their judgement preferences are linguistic and incomplete. Starting from the theory of relative entropy (RE) and multiplicative consistency, an optimisation model is provided for deriving an individual priority vector without estimating the missing value(s) of an incomplete linguistic preference relation. In order to address the unknown expert weights in the group aggregating process, we define two new kinds of expert weight indicators based on RE: proximity entropy weight and similarity entropy weight. Furthermore, a dynamic-adjusting algorithm (DAA) is proposed to obtain an objective expert weight vector and capture the dynamic properties involved in it. Unlike the extant literature of group prioritisation, the proposed RE approach does not require pre-allocation of expert weights and can solve incomplete preference relations. An interesting finding is that once all the experts express their preference relations, the final expert weight vector derived from the DAA is fixed irrespective of the initial settings of expert weights. Finally, an application example is conducted to validate the effectiveness and robustness of the RE approach.

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

Jester, Sebastian; Schneider, Donald P.; Richards, Gordon T.

The author investigates the extent to which the Palomar-Green (PG) Bright Quasar Survey (BQS) is complete and representative of the general quasar population by comparing with imaging and spectroscopy from the Sloan Digital Sky Survey. A comparison of SDSS and PG photometry of both stars and quasars reveals the need to apply a color and magnitude recalibration to the PG data. Using the SDSS photometric catalog, they define the PG's parent sample of objects that are not main-sequence stars and simulate the selection of objects from this parent sample using the PG photometric criteria and errors. This simulation shows thatmore » the effective U-B cut in the PG survey is U-B < -0.71, implying a color-related incompleteness. As the color distribution of bright quasars peaks near U-B = -0.7 and the 2-{sigma} error in U-B is comparable to the full width of the color distribution of quasars, the color incompleteness of the BQS is approximately 50% and essentially random with respect to U-B color for z < 0.5. There is however, a bias against bright quasars at 0.5 < z < 1, which is induced by the color-redshift relation of quasars (although quasars at z > 0.5 are inherently rare in bright surveys in any case). They find no evidence for any other systematic incompleteness when comparing the distributions in color, redshift, and FIRST radio properties of the BQS and a BQS-like subsample of the SDSS quasar sample. However, the application of a bright magnitude limit biases the BQS toward the inclusion of objects which are blue in g-i, in particular compared to the full range of g-i colors found among the i-band limited SDSS quasars, and even at i-band magnitudes comparable to those of the BQS objects.« less

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

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.

Interferometric tomography of continuous fields with incomplete projections

NASA Technical Reports Server (NTRS)

Cha, Soyoung S.; Sun, Hogwei

1988-01-01

Interferometric tomography in the presence of an opaque object is investigated. The developed iterative algorithm does not need to augment the missing information. It is based on the successive reconstruction of the difference field, the difference between the object field to be reconstructed and its estimate, only in the difined region. The application of the algorithm results in stable convergence.

Distributed topology control algorithm for multihop wireless netoworks

NASA Technical Reports Server (NTRS)

Borbash, S. A.; Jennings, E. H.

2002-01-01

We present a network initialization algorithmfor wireless networks with distributed intelligence. Each node (agent) has only local, incomplete knowledge and it must make local decisions to meet a predefined global objective. Our objective is to use power control to establish a topology based onthe relative neighborhood graph which has good overall performance in terms of power usage, low interference, and reliability.

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

Microcavitation as a Neuronal Damage Mechanism in Blast Traumatic Brain Injury

NASA Astrophysics Data System (ADS)

Franck, Christian; Estrada, Jonathan

2015-11-01

Blast traumatic brain injury (bTBI) is a leading cause of injury in the armed forces. Diffuse axonal injury, the hallmark feature of blunt TBI, has been investigated in direct mechanical loading conditions. However, recent evidence suggests inertial cavitation as a possible bTBI mechanism, particularly in the case of exposure to blasts. Cavitation damage to free surfaces has been well-studied, but bubble interactions within confined 3D environments, in particular their stress and strain signatures are not well understood. The structural damage due to cavitation in living tissues - particularly at the cellular level - are incompletely understood, in part due to the rapid bubble formation and deformation strain rates of up to ~ 105-106 s-1. This project aims to characterize material damage in 2D and 3D cell culture environments by utilizing a novel high-speed red-blue diffraction assisted image correlation method at speeds of up to 106 frames per second. We gratefully acknowledge funding from the Office of Naval Research (POC: Dr. Tim Bentley).

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.

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

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

When Machines Think: Radiology's Next Frontier.

PubMed

Dreyer, Keith J; Geis, J Raymond

2017-12-01

Artificial intelligence (AI), machine learning, and deep learning are terms now seen frequently, all of which refer to computer algorithms that change as they are exposed to more data. Many of these algorithms are surprisingly good at recognizing objects in images. The combination of large amounts of machine-consumable digital data, increased and cheaper computing power, and increasingly sophisticated statistical models combine to enable machines to find patterns in data in ways that are not only cost-effective but also potentially beyond humans' abilities. Building an AI algorithm can be surprisingly easy. Understanding the associated data structures and statistics, on the other hand, is often difficult and obscure. Converting the algorithm into a sophisticated product that works consistently in broad, general clinical use is complex and incompletely understood. To show how these AI products reduce costs and improve outcomes will require clinical translation and industrial-grade integration into routine workflow. Radiology has the chance to leverage AI to become a center of intelligently aggregated, quantitative, diagnostic information. Centaur radiologists, formed as a synergy of human plus computer, will provide interpretations using data extracted from images by humans and image-analysis computer algorithms, as well as the electronic health record, genomics, and other disparate sources. These interpretations will form the foundation of precision health care, or care customized to an individual patient. © RSNA, 2017.

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.

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.

Enrichment of cardiac differentiation of mouse embryonic stem cells by optimizing the hanging drop method.

PubMed

Chen, Ming; Lin, Yong-Qing; Xie, Shuang-Lun; Wu, Hong-Fu; Wang, Jing-Feng

2011-04-01

Hanging drop (HD) culture is used to induce differentiation of embryonic stem cells (ESCs) into other cell types including cardiomyocytes. However, the factors affecting cardiac differentiation of ESCs with this method remain incompletely understood. We have investigated the effects of the starting number of ESCs in embryoid bodies (EBs) and the time of EB adherence to gelatin-coated plates on cardiac differentiation: cardiac differentiation was increased in the EBs by a larger number of ESCs and was decreased by plating EBs at day 4 or earlier. These two factors can thus be optimized to enrich the cardiac differentiation in ESCs using the HD method.

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.

Predictors of incompletion of immunization among children residing in the slums of Kathmandu valley, Nepal: a case-control study.

PubMed

Shrestha, Sumina; Shrestha, Monika; Wagle, Rajendra Raj; Bhandari, Gita

2016-09-13

Immunization is one of the most effective health interventions averting an estimated 2-3 million deaths every year. In Nepal, as in most low-income countries, infants are immunized with standard WHO recommended vaccines. However, 16.4 % of children did not receive complete immunization by 12 months of age in Nepal in 2011. Studies from different parts of the world showed that incomplete immunization is even higher in slums. The objective of this study was to identify the predictors of incompletion of immunization among children aged 12-23 months living in the slums of Kathmandu Valley, Nepal. The unmatched case-control study was conducted in 22 randomly selected slums of Kathmandu Valley. The sampling frame was first identified by complete enumeration of entire households of the study area from which 59 incompletely immunized children as cases and 177 completely immunized children as controls were chosen randomly in 1:3 ratio. Data were collected from the primary caretakers of the children. Backward logistic regression with 95 % confidence interval and adjusted odds ratio (AOR) were applied to assess the factors independently associated with incomplete immunization. Twenty-six percent of the children were incompletely vaccinated. The coverage of BCG vaccine was 95.0 % while it was 80.5 % for measles vaccine. The significant predictors of incomplete immunization were the home delivery of a child, the family residing on rent, a primary caretaker with poor knowledge about the schedule of vaccination and negative perception towards vaccinating a sick child, conflicting priorities, and development of abscess following immunization. Reduction of abscess formation rate can be a potential way to improve immunization rates. Community health volunteers should increase their follow-up on children born at home and those living in rent. Health institutions and volunteers should be influential in creating awareness about immunization, its schedule, and post-vaccination side effects.

A Prospective Phase 2 Multicenter Study for the Efficacy of Radiation Therapy Following Incomplete Transarterial Chemoembolization in Unresectable Hepatocellular Carcinoma

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

Choi, Chihwan; Koom, Woong Sub; Kim, Tae Hyun

2014-12-01

Purpose: The purpose of this study was to investigate the efficacy and toxicity of radiation therapy (RT) following incomplete transarterial chemoembolization (TACE) in unresectable hepatocellular carcinoma (HCC). Methods and Materials: The study was designed as a prospective phase 2 multicenter trial. Patients with unresectable HCC, who had viable tumor after TACE of no more than 3 courses, were eligible. Three-dimensional conformal RT (3D-CRT) was added for HCC treatment with incomplete uptake of iodized oil, and the interval from TACE to RT was 4 to 6 weeks. The primary endpoint of this study was the tumor response after RT following incomplete TACEmore » in unresectable HCC. Secondary endpoints were patterns of failure, progression-free survival (PFS), time to tumor progression (TTP), overall survival (OS) rates at 2 years, and treatment-associated toxicity. Survival was calculated from the start of RT. Results: Between August 2008 and December 2010, 31 patients were enrolled. RT was delivered at a median dose of 54 Gy (range, 46-59.4 Gy) at 1.8 to 2 Gy per fraction. A best objective in-field response rate was achieved in 83.9% of patients, with complete response (CR) in 22.6% of patients and partial response in 61.3% of patients within 12 weeks post-RT. A best objective overall response rate was achieved in 64.5% of patients with CR in 19.4% of patients and PR in 45.1% of patients. The 2-year in-field PFS, PFS, TTP, and OS rates were 45.2%, 29.0%, 36.6%, and 61.3%, respectively. The Barcelona Clinic liver cancer stage was a significant independent prognostic factor for PFS (P=.023). Classic radiation-induced liver disease was not observed. There were no treatment-related deaths or hepatic failure. Conclusions: Early 3D-CRT following incomplete TACE is a safe and practical treatment option for patients with unresectable HCC.« less

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

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

Review of the genus Tenuipalpus (Acari: Tenuipalpidae)

USDA-ARS?s Scientific Manuscript database

Tenuipalpus Donnadieu is the most speciose genus of the family Tenuipalpidae, with over 300 described species. The descriptions of many of these species are incomplete, and lack important information necessary for accurate species identification. The objective of this study was to re-describe specie...

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

Coil occlusion of residual shunts after surgical closure of patent ductus arteriosus.

PubMed

Fujii, Yoko; Keene, Bruce W; Mathews, Kyle G; Atkins, Clarke E; Defrancesco, Teresa C; Hardie, Elizabeth M; Wakao, Yoshito

2006-12-01

OBJECTIVE; To describe use of coil embolization to occlude residual flow through a patent ductus arteriosus (PDA) after incomplete surgical ligation. Clinical study. Dogs (n=4) with continuous murmur after surgical ligation of PDA. After PDA ligation, residual ductal flow through the PDA was visible on color-flow Doppler examination and left ventricular end-diastolic diameter remained increased. Coil embolization by an arterial approach was performed to achieve complete occlusion of the PDA. Embolization coils were delivered without complications and hemodynamically successful occlusion was achieved. Doppler-visible flow resolved in 2 dogs within 3 months after embolization. Left ventricular end-diastolic diameter indexed to body weight decreased in all dogs. Transcatheter coil embolization appears to be a safe and minimally invasive procedure for complete occlusion of residual PDA flow after incomplete surgical ligation. Transcatheter coil embolization should be considered for correction of hemodynamically significant residual shunts in dogs that have incomplete PDA occlusion after open surgical ligation.

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.

Amodal completion of moving objects by pigeons.

PubMed

Nagasaka, Yasuo; Wasserman, Edward A

2008-01-01

In a series of four experiments, we explored whether pigeons complete partially occluded moving shapes. Four pigeons were trained to discriminate between a complete moving shape and an incomplete moving shape in a two-alternative forced-choice task. In testing, the birds were presented with a partially occluded moving shape. In experiment 1, none of the pigeons appeared to complete the testing stimulus; instead, they appeared to perceive the testing stimulus as incomplete fragments. However, in experiments 2, 3, and 4, three of the birds appeared to complete the partially occluded moving shapes. These rare positive results suggest that motion may facilitate amodal completion by pigeons, perhaps by enhancing the figure - ground segregation process.

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

Effect of compensatory growth on Palmer amaranth response to glyphosate.

USDA-ARS?s Scientific Manuscript database

Incomplete weed control can occur after herbicide applications. Death of one or many shoot meristems could remove apical dominance, leading to compensatory growth from once dormant lateral buds. Palmer amaranth (PA) dieback and regrowth in response to POST herbicides has been observed. The objective...

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].

SERUM THYROTROPIN CONCENTRATIONS ARE NOT PREDICTIVE OF AGGRESSIVE BREAST CANCER BIOLOGY IN EUTHYROID INDIVIDUALS

PubMed Central

Villa, Natalie M.; Li, Ning; Yeh, Michael W.; Hurvitz, Sara A.; Dawson, Nicole A.; Leung, Angela M.

2015-01-01

Objective The potential influence of hypothyroidism on breast cancer remains incompletely understood. The objective of this study was to investigate the relationship between serum thyrotropin [thyroid-stimulating hormone (TSH)] concentration and markers of aggressive breast cancer biology, as defined by receptor expression profile, tumor grade, and American Joint Committee on Cancer (AJCC) stage characteristics. Methods This was a retrospective cohort study of patients from 2002–2014. All breast cancer patients who had complete receptor (estrogen receptor, ER; progesterone receptor, PR; and Her2/neu) and pre-diagnosis serum TSH data (n=437) were included. All patients had one of six receptor profiles: ER+ PR+ Her2/neu −, ER+ PR− Her2/neu−, ER+ PR+ Her2/neu+, ER+ PRHer2/ neu+, ER− PR− Her2/neu+, ER− PR− Her2/neu−. Log-transformed serum TSH concentrations were analyzed using multinomial and logistic regressions for a potential relationship with markers of breast cancer aggressiveness. Results Increasing serum TSH concentration was associated with a lower probability of having the receptor expression profile ER+ PR+ Her2/neu+ compared to patients with the ER+ PR+ Her2/neu− profile (OR=0.52, p=0.0045). No significant associations between other receptor expression profiles and serum TSH concentration were found. All time-weighted and unweighted median serum TSH concentrations were within normal limits. No significant associations between serum TSH concentration and tumor grade, overall AJCC stage, or tumor size (T), lymph node positivity (N), or presence of metastasis (M) were observed. Conclusions Serum TSH was not associated with markers of breast cancer aggressiveness in our cohort. PMID:26121443

Effects of buprenorphine in the adrenal, thyroid, and cytokine intra-operative responses in a rat model (Rattus norvegicus): a preliminary study

PubMed Central

Félix, Nuno M; Leal, Rodolfo O; Goy-Thollot, I; Walton, Ronald S; Gil, Solange A; Mateus, Luísa M; Matos, Ana S; Niza, Maria M R E

2017-01-01

Objective(s): Buprenorphine is a common analgesic in experimental research, due to effectiveness and having few side-effects, including a limited influence in the immune and endocrine systems. However, how buprenorphine affects cytokine levels and the adrenal and thyroid response during general anesthesia and surgery is incompletely understood. This study aimed to assess whether buprenorphine modulated significantly those responses in rats submitted to general anesthesia, mechanical ventilation, and surgical insertion of intravascular catheters. Materials and Methods: Animals were anesthetized with isoflurane, mechanically ventilated, and surgically instrumented for carotid artery and the femoral vein catheter placement. The test group (n=16), received buprenorphine subcutaneously before surgery, whereas the control group (n=16) received normal saline. Blood sampling to determine plasma levels of adrenocorticotropic hormone (ACTH), corticosterone (CS), total thyroxine (TT4), total triiodothyronine (TT3), thyroid-stimulating hormone (TSH), TNF-α, IL6, IL10, TNF-α, IL6, and IL10 mRNA was performed at 10 min after completion of all surgical procedures and at 90, 150, 240, and 300 min thereafter, with the animals still anesthetized and with mechanical ventilation. Results: Buprenorphine-treated animals had higher levels of ACTH, CS, and TT4 at several time points (P<0.05) and TSH and TT3 at all-time points (P<0.05). They also had increased IL10, TNF-α, and IL10 mRNA levels. Conclusion: In this model, buprenorphine significantly modulated the intra-operative cytokine and endocrine response to anesthesia, mechanical ventilation, and surgical placement of intravascular catheters. The mechanism and significance of these findings remain undetermined. Researchers should be aware of these effects when considering the use of buprenorphine for analgesic purposes. PMID:28804607

Manifestation of Incompleteness in Obsessive-Compulsive Disorder (OCD) as Reduced Functionality and Extended Activity beyond Task Completion

PubMed Central

Zor, Rama; Szechtman, Henry; Hermesh, Haggai; Fineberg, Naomi A.; Eilam, David

2011-01-01

Background This study focused on hypotheses regarding the source of incompleteness in obsessive-compulsive disorder (OCD). For this, we had to document the behavioral manifestation of incompleteness in compulsive rituals, predicting that an exaggerated focus on acts that are appropriate for the task will support the hypothesis on heightened responsibility/perfectionism. In contrast, activity past the expected terminal act for the motor task would support the “stop signal deficiency” hypothesis. Methodology and Principal Findings We employed video-telemetry to analyze 39 motor OCD rituals and compared each with a similar task performed by a non-OCD individual, in order to objectively and explicitly determine the functional end of the activity. We found that 75% of OCD rituals comprised a “tail,” which is a section that follows the functional end of the task that the patients ascribed to their activity. The other 25% tailless rituals comprised a relatively high number and higher rate of repetition of non-functional acts. Thus, in rituals with tail, incompleteness was manifested by the mere presence of the tail whereas in tailless rituals, incompleteness was manifested by the reduced functionality of the task due to an inflated execution and repetition of non-functional acts. Conclusions The prevalence of activity after the functional end (“tail”) and the elevated non-functionality in OCD motor rituals support the “lack of stop signal” theories as the underlying mechanism in OCD. Furthermore, the presence and content of the tail might have a therapeutic potential in cognitive-behavior therapy. PMID:21966460

The consequences of hospital autonomization in Colombia: a transaction cost economics analysis.

PubMed

Castano, Ramon; Mills, Anne

2013-03-01

Granting autonomy to public hospitals in developing countries has been common over recent decades, and implies a shift from hierarchical to contract-based relationships with health authorities. Theory on transactions costs in contractual relationships suggests they stem from relationship-specific investments and contract incompleteness. Transaction cost economics argues that the parties involved in exchanges seek to reduce transaction costs. The objective of this research was to analyse the relationships observed between purchasers and the 22 public hospitals of the city of Bogota, Colombia, in order to understand the role of relationship-specific investments and contract incompleteness as sources of transaction costs, through a largely qualitative study. We found that contract-based relationships showed relevant transaction costs associated mainly with contract incompleteness, not with relationship-specific investments. Regarding relationships between insurers and local hospitals for primary care services, compulsory contracting regulations locked-in the parties to the contracts. For high-complexity services (e.g. inpatient care), no restrictions applied and relationships suggested transaction-cost minimizing behaviour. Contract incompleteness was found to be a source of transaction costs on its own. We conclude that transaction costs seemed to play a key role in contract-based relationships, and contract incompleteness by itself appeared to be a source of transaction costs. The same findings are likely in other contexts because of difficulties in defining, observing and verifying the contracted products and the underlying information asymmetries. The role of compulsory contracting might be context-specific, although it is likely to emerge in other settings due to the safety-net role of public hospitals.

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

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

When champions meet: Rethinking the Bohr-Einstein debate

NASA Astrophysics Data System (ADS)

Landsman, N. P.

Einstein's philosophy of physics (as clarified by Fine, Howard, and Held) was predicated on his Trennungsprinzip, a combination of separability and locality, without which he believed objectification, and thereby "physical thought" and "physical laws', to be impossible. Bohr's philosophy (as elucidated by Hooker, Scheibe, Folse, Howard, Held, and others), on the other hand, was grounded in a seemingly different doctrine about the possibility of objective knowledge, namely the necessity of classical concepts. In fact, it follows from Raggio's Theorem in algebraic quantum theory that-within an appropriate class of physical theories-suitable mathematical translations of the doctrines of Bohr and Einstein are equivalent. Thus-upon our specific formalization-quantum mechanics accommodates Einstein's Trennungsprinzip if and only if it is interpreted à la Bohr through classical physics. Unfortunately, the protagonists themselves failed to discuss their differences in this constructive way, since their debate was dominated by Einstein's ingenious but ultimately flawed attempts to establish the "incompleteness" of quantum mechanics. This aspect of their debate may still be understood and appreciated, however, as reflecting a much deeper and insurmountable disagreement between Bohr and Einstein about the knowability of Nature. Using the theological controversy on the knowability of God as a analogy, we can say that Einstein was a Spinozist, whereas Bohr could be said to be on the side of Maimonides. Thus Einstein's off-the-cuff characterization of Bohr as a 'Talmudic philosopher' was spot-on.

The Small GTPase Rif Is Dispensable for Platelet Filopodia Generation in Mice

PubMed Central

Goggs, Robert; Savage, Joshua S.; Mellor, Harry; Poole, Alastair W.

2013-01-01

Background Formation of filopodia and other shape change events are vital for platelet hemostatic function. The mechanisms regulating filopodia formation by platelets are incompletely understood however. In particular the small GTPase responsible for initiating filopodia formation by platelets remains elusive. The canonical pathway involving Cdc42 is not essential for filopodia formation in mouse platelets. The small GTPase Rif (RhoF) provides an alternative route to filopodia generation in other cell types and is expressed in both human and mouse platelets. Hypothesis/Objective We hypothesized that Rif might be responsible for generating filopodia by platelets and generated a novel knockout mouse model to investigate the functional role of Rif in platelets. Methodology/Principal Findings Constitutive RhoF−/− mice are viable and have normal platelet, leukocyte and erythrocyte counts and indices. RhoF−/− platelets form filopodia and spread normally on various agonist surfaces in static conditions and under arterial shear. In addition, RhoF−/− platelets have normal actin dynamics, are able to activate and aggregate normally and secrete from alpha and dense granules in response to collagen related peptide and thrombin stimulation. Conclusions The small GTPase Rif does not appear to be critical for platelet function in mice. Functional overlap between Rif and other small GTPases may be responsible for the non-essential role of Rif in platelets. PMID:23359340

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

Making drug policy together: reflections on evidence, engagement and participation.

PubMed

Roberts, Marcus

2014-09-01

This commentary considers the relationship between evidence, engagement and participation in drug policy governance. It argues that the use of various forms of evidence (for example, statistical data and service user narratives) is critical for meaningful stakeholder engagement and public participation in drug policy, as well as effective policy design and implementation. The respective roles of these different kinds of evidence in consultation processes need to be better understood. It discusses the limits of evidence, which it suggests is rarely conclusive or decisive for drug policy. This is partly because of the incompleteness of most research agendas and the lack of consensus among researchers, but also because issues in drug policy are inherently contestable, involving considerations that lie outside the competency of drug policy specialist as such. In particular, this is because they involve normative and evaluative issues that are properly political (for example, about the relative weight to be accorded to different kinds of harm and benefit). It concludes by supporting calls for a more nuanced understanding of the relationship between evidence, engagement and politics than is implicit in the term 'evidence based policy'. It also argues that we should view the inherent contestability of drug policy not as something that can or should be resolved by 'objective' evidence, but as a source of vitality and creativity in policy development and evaluation. Copyright © 2014 Elsevier B.V. All rights reserved.

Anti-food allergic activity of sulfated polysaccharide from gracilaria lemaneiformis is dependent on immunosuppression and inhibition of p38 mapk

USDA-ARS?s Scientific Manuscript database

Polysaccharides from marine sources offer diverse therapeutic functions due to their multifarious biological nature. Polysaccharide from Gracilaria lemaneiformis possesses various bioactive functions, but its anti-allergic activity remains incompletely defined. Objective: This study aimed to extract...

THP-1 macrophage lipid accumulation unaffected by fatty acid double bond geometric or positional configuration

USDA-ARS?s Scientific Manuscript database

Dietary fatty acid type alters atherosclerotic lesion progression and macrophage lipid accumulation. Incompletely elucidated are the mechanisms by which fatty acids differing in double-bond geometric or positional configuration alter arterial lipid accumulation. The objective of this study was to ev...

Examining the Factors That Facilitate Athletic Training Faculty Socialization into Higher Education

ERIC Educational Resources Information Center

Mazerolle, Stephanie M.; Barrett, Jessica L.; Nottingham, Sara

2016-01-01

Context: Doctoral education is the mechanism whereby athletic trainers can develop an awareness of their future roles and responsibilities in higher education. Evidence suggests that doctoral education may provide an incomplete understanding of these roles and responsibilities, warranting further investigation. Objective: To gain a better…

Reconstructing missing daily precipitation data using regression trees and artificial neural networks

USDA-ARS?s Scientific Manuscript database

Incomplete meteorological data has been a problem in environmental modeling studies. The objective of this work was to develop a technique to reconstruct missing daily precipitation data in the central part of Chesapeake Bay Watershed using regression trees (RT) and artificial neural networks (ANN)....

Basic Statistical Concepts and Methods for Earth Scientists

USGS Publications Warehouse

Olea, Ricardo A.

2008-01-01

INTRODUCTION Statistics is the science of collecting, analyzing, interpreting, modeling, and displaying masses of numerical data primarily for the characterization and understanding of incompletely known systems. Over the years, these objectives have lead to a fair amount of analytical work to achieve, substantiate, and guide descriptions and inferences.

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.

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

Cost-Effectiveness of Blood Donation Screening for Trypanosoma cruzi in Mexico.

PubMed

Sánchez-González, Gilberto; Figueroa-Lara, Alejandro; Elizondo-Cano, Miguel; Wilson, Leslie; Novelo-Garza, Barbara; Valiente-Banuet, Leopoldo; Ramsey, Janine M

2016-03-01

An estimated 2 million inhabitants are infected with Chagas disease in Mexico, with highest prevalence coinciding with highest demographic density in the southern half of the country. After vector-borne transmission, Trypanosoma cruzi is principally transmitted to humans via blood transfusion. Despite initiation of serological screening of blood donations or donors for T. cruzi since 1990 in most Latin American countries, Mexico only finally included mandatory serological screening nationwide in official Norms in 2012. Most recent regulatory changes and segmented blood services in Mexico may affect compliance of mandatory screening guidelines. The objective of this study was to calculate the incremental cost-effectiveness ratio for total compliance of current guidelines from both Mexican primary healthcare and regular salaried worker health service institutions: the Secretary of Health and the Mexican Institute for Social Security. We developed a bi-modular model to analyze compliance using a decision tree for the most common screening algorithms for each health institution, and a Markov transition model for the natural history of illness and care. The incremental cost effectiveness ratio based on life-years gained is US$ 383 for the Secretary of Health, while the cost for an additional life-year gained is US$ 463 for the Social Security Institute. The results of the present study suggest that due to incomplete compliance of Mexico's national legislation during 2013 and 2014, the MoH has failed to confirm 15,162 T. cruzi infections, has not prevented 2,347 avoidable infections, and has lost 333,483 life-years. Although there is a vast difference in T. cruzi prevalence between Bolivia and Mexico, Bolivia established mandatory blood screening for T.cruzi in 1996 and until 2002 detected and discarded 11,489 T. cruzi -infected blood units and prevented 2,879 potential infections with their transfusion blood screening program. In the first two years of Mexico's mandated program, the two primary institutions failed to prevent due to incomplete compliance more potential infections than those gained from the first five years of Bolivia's program. Full regulatory compliance should be clearly understood as mandatory for the sake of blood security, and its monitoring and analysis in Mexico should be part of the health authority's responsibility.

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

Surgical management of vertical root fractures for posterior teeth: report of four cases.

PubMed

Floratos, Spyros G; Kratchman, Samuel I

2012-04-01

The objective of this article was to present a surgical treatment option for teeth with incomplete vertical root fracture in maxillary and mandibular posterior teeth. Four cases are presented in which 1 endodontically treated maxillary or mandibular molar had an incomplete vertical root fracture involving 1 of the roots. The tooth underwent a flap elevation procedure to visualize the pattern of bone loss and assess the extent of root fracture. The fracture line was eliminated by resecting the root in a beveled manner, after which root-end preparation and root-end filling were performed by using mineral trioxide aggregate. The osteotomy was covered with an absorbable collagen membrane. Cases were followed up for 8-24 months after surgery. The procedure was shown to be predictable and successful in this series. Root length was preserved, and tooth extraction was avoided. The microsurgical treatment option for multirooted teeth with incomplete vertical root fracture resulted in long-term clinical success. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

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.

[Prospects in getting accordance between chemical analytic control means and medical technical requirements to safety system concerning chemical weapons destruction].

PubMed

Rembovskiĭ, V R; Mogilenkova, L A; Savel'eva, E I

2005-01-01

The major unit monitoring chemical weapons destruction objects is a system of chemical analyticcontrol over the technologic process procedures and possibility of environment and workplace pollution withtoxicchemicals and their destruction products. At the same time, physical and chemical control means meet sanitary and hygienic requirements incompletely. To provide efficient control, internationally recognized approaches should be adapted to features of Russian system monitoring pollution of chemical weapons destruction objects with toxic chemicals.

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

Subject and Object Expression in Spanish Heritage Speakers: A Case of Morphosyntactic Convergence

ERIC Educational Resources Information Center

Montrul, Silvina

2004-01-01

Many simultaneous bilinguals exhibit loss or incomplete acquisition of their heritage language under conditions of exposure and use of the majority language (Silva-Corvalan, 1994, 2003; Polinsky, 1997; Toribio, 2001; Montrul, 2002). Recent work within discourse-functional (Silva-Corvalan 1994) and generative perspectives (Sorace, 2000; Montrul;…

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

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

Upfront chemotherapy and subsequent resection for molecularly defined gliomas.

PubMed

Sasaki, Hikaru; Hirose, Yuichi; Yazaki, Takahito; Kitamura, Yohei; Katayama, Makoto; Kimura, Tokuhiro; Fujiwara, Hirokazu; Toda, Masahiro; Ohira, Takayuki; Yoshida, Kazunari

2015-08-01

Functional preservation is critical in glioma surgery, and the extent of resection influences survival outcome. Neoadjuvant chemotherapy is a promising option because of its potential to facilitate tumor shrinkage and maximum tumor resection. The object of this study was to assess the utility of the neoadjuvant strategy in a prospective series of gliomas with favorable molecular status. Twenty-six consecutive cases of diffuse gliomas of WHO grade II or III with either 1p19q codeletion or MGMT methylation were treated with upfront chemotherapy following maximal safe removal. In cases of incomplete initial surgery, second-look resection was intended after tumor volume decrease by chemotherapy. Among 22 evaluable cases, chemotherapy led to a median change in the sum of the product of perpendicular diameters of -35 %, and 14 out of the 22 cases (64 %) showed objective response. Second-look resection after tumor volume decrease was performed in 12 out of 19 cases of incomplete initial surgery (GTR/STR 9, removal of residual methionine PET uptake 3). The median progression-free survival among the 22 patients with grade II tumors was 57 months, with some cases showing durable progression-free survival after second-look resection. MIB-1 indices of the second-look resected tumors were lower than those of the initial tumors, and the methylation status of the MGMT gene was unchanged. Neoadjuvant chemotherapy based on molecular guidance often produces significant volume decrease of incompletely resected gliomas. Radical second-look resection is an optional advantage of upfront chemotherapy for chemosensitive gliomas compared with initial radiotherapy.

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

A New Moving Object Detection Method Based on Frame-difference and Background Subtraction

NASA Astrophysics Data System (ADS)

Guo, Jiajia; Wang, Junping; Bai, Ruixue; Zhang, Yao; Li, Yong

2017-09-01

Although many methods of moving object detection have been proposed, moving object extraction is still the core in video surveillance. However, with the complex scene in real world, false detection, missed detection and deficiencies resulting from cavities inside the body still exist. In order to solve the problem of incomplete detection for moving objects, a new moving object detection method combined an improved frame-difference and Gaussian mixture background subtraction is proposed in this paper. To make the moving object detection more complete and accurate, the image repair and morphological processing techniques which are spatial compensations are applied in the proposed method. Experimental results show that our method can effectively eliminate ghosts and noise and fill the cavities of the moving object. Compared to other four moving object detection methods which are GMM, VIBE, frame-difference and a literature's method, the proposed method improve the efficiency and accuracy of the detection.

The Spatial Distribution of Attention within and across Objects

ERIC Educational Resources Information Center

Hollingworth, Andrew; Maxcey-Richard, Ashleigh M.; Vecera, Shaun P.

2012-01-01

Attention operates to select both spatial locations and perceptual objects. However, the specific mechanism by which attention is oriented to objects is not well understood. We examined the means by which object structure constrains the distribution of spatial attention (i.e., a "grouped array"). Using a modified version of the Egly et…

The Use of Educational Objects

ERIC Educational Resources Information Center

Stearns, Clio

2016-01-01

This conceptual paper looks at the Winnicottian notion of object use as it relates to education. Object use is understood as the process of attaching to but then attempting to destroy the educator in an effort to create new knowledge and relationships. The paper argues for educational object use as a way of understanding and normalising resistance…

Research in computer science

NASA Technical Reports Server (NTRS)

Ortega, J. M.

1984-01-01

The research efforts of University of Virginia students under a NASA sponsored program are summarized and the status of the program is reported. The research includes: testing method evaluations for N version programming; a representation scheme for modeling three dimensional objects; fault tolerant protocols for real time local area networks; performance investigation of Cyber network; XFEM implementation; and vectorizing incomplete Cholesky conjugate gradients.

VizieR Online Data Catalog: Catalog of Suspected Nearby Young Stars (Riedel+, 2017)

NASA Astrophysics Data System (ADS)

Riedel, A. R.; Blunt, S. C.; Lambrides, E. L.; Rice, E. L.; Cruz, K. L.; Faherty, J. K.

2018-04-01

LocAting Constituent mEmbers In Nearby Groups (LACEwING) is a frequentist observation space kinematic moving group identification code. Using the spatial and kinematic information available about a target object (α, δ, Dist, μα, μδ, and γ), it determines the probability that the object is a member of each of the known nearby young moving groups (NYMGs). As with other moving group identification codes, LACEwING is capable of estimating memberships for stars with incomplete kinematic and spatial information. (2 data files).

Factors Related to Incomplete Treatment of Breast Cancer in Kumasi, Ghana

PubMed Central

Obrist, Mark; Osei-Bonsu, Ernest; Ahwah, Baffour; Watanabe-Galloway, Shinobu; Merajver, Sofia D.; Schmid, Kendra; Soliman, Amr S.

2014-01-01

Purpose The burden of cancer in Africa is an enlarging public health challenge. Breast cancer in Ghana is the second most common cancer among Ghanaian women and the proportion of diagnosed patients who complete prescribed treatment is estimated to be very limited, thereby potentially adding to lower survival and poor quality of life after diagnosis. The objective of this study was to identify the patient and system factors related to incomplete treatment of breast cancer among patients. Methods This study was conducted at the Komfo Anokye Teaching Hospital in Kumasi, Ghana. We interviewed 117 breast cancer patients and next of kin of breast cancer patients diagnosed from 2008 to 2010. Results Islamic religion, seeking treatment with traditional healers, and lack of awareness about national health insurance coverage of breast cancer treatment were predictors of incomplete treatment. Conclusions The results of this study support that Ghanaian women with diagnosed breast cancer have multiple addressable and modifiable patient factors that may deter them from completing the prescribed treatment. The results highlight the need for developing and testing specific interventions about the importance of completing treatment with a special focus on addressing religious, cultural, and system navigation barriers in developing countries. PMID:25282667

Effect of Robotic-Assisted Gait Training in Patients With Incomplete Spinal Cord Injury

PubMed Central

Shin, Ji Cheol; Kim, Ji Yong; Park, Han Kyul

2014-01-01

Objective To determine the effect of robotic-assisted gait training (RAGT) compared to conventional overground training. Methods Sixty patients with motor incomplete spinal cord injury (SCI) were included in a prospective, randomized clinical trial by comparing RAGT to conventional overground training. The RAGT group received RAGT three sessions per week at duration of 40 minutes with regular physiotherapy in 4 weeks. The conventional group underwent regular physiotherapy twice a day, 5 times a week. Main outcomes were lower extremity motor score of American Spinal Injury Association impairment scale (LEMS), ambulatory motor index (AMI), Spinal Cord Independence Measure III mobility section (SCIM3-M), and walking index for spinal cord injury version II (WISCI-II) scale. Results At the end of rehabilitation, both groups showed significant improvement in LEMS, AMI, SCIM3-M, and WISCI-II. Based on WISCI-II, statistically significant improvement was observed in the RAGT group. For the remaining variables, no difference was found. Conclusion RAGT combined with conventional physiotherapy could yield more improvement in ambulatory function than conventional therapy alone. RAGT should be considered as one additional tool to provide neuromuscular reeducation in patient with incomplete SCI. PMID:25566469

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

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

Brady, Robert T.; Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin; Advanced Materials and BioEngineering Research Centre

Bone formation requires the recruitment, proliferation and osteogenic differentiation of mesenchymal progenitors. A potent stimulus driving this process is mechanical loading, yet the signalling mechanisms underpinning this are incompletely understood. The objective of this study was to investigate the role of the mechanically-stimulated osteocyte and osteoblast secretome in coordinating progenitor contributions to bone formation. Initially osteocytes (MLO-Y4) and osteoblasts (MC3T3) were mechanically stimulated for 24hrs and secreted factors within the conditioned media were collected and used to evaluate mesenchymal stem cell (MSC) and osteoblast recruitment, proliferation and osteogenesis. Paracrine factors secreted by mechanically stimulated osteocytes significantly enhanced MSC migration, proliferationmore » and osteogenesis and furthermore significantly increased osteoblast migration and proliferation when compared to factors secreted by statically cultured osteocytes. Secondly, paracrine factors secreted by mechanically stimulated osteoblasts significantly enhanced MSC migration but surprisingly, in contrast to the osteocyte secretome, inhibited MSC proliferation when compared to factors secreted by statically cultured osteoblasts. A similar trend was observed in osteoblasts. This study provides new information on mechanically driven signalling mechanisms in bone and highlights a contrasting secretome between cells at different stages in the bone lineage, furthering our understanding of loading-induced bone formation and indirect biophysical regulation of osteoprogenitors. - Highlights: • Physically stimulated osteocytes secrete factors that regulate osteoprogenitors. • These factors enhance recruitment, proliferation and osteogenic differentiation. • Physically stimulated osteoblasts secrete factors that also regulate progenitors. • These factors enhance recruitment but inhibit proliferation of osteoprogenitors. • This study highlights a contrasting secretome between osteocytes and osteoblasts.« less

Initiation of follicular atresia: gene networks during early atresia in pig ovaries.

PubMed

Zhang, Jinbi; Liu, Yang; Yao, Wang; Li, Qifa; Liu, Hong-Lin; Pan, Zengxiang

2018-05-09

In mammals, more than 99% of ovarian follicles undergo a degenerative process known as atresia. The molecular events involve in atresia initiation remain incompletely understood. The objective of this study was to analyze differential gene expression profiles of medium antral ovarian follicles during early atresia in pig. The transcriptome evaluation was performed on cDNA microarrays using healthy and early atretic follicle samples and was validated by quantitative PCR. Annotation analysis applying current database (sus scrofa 11.1) revealed 450 significantly differential expressed genes between healthy and early atretic follicles. Among them, 142 were significantly up-regulated in early atretic with respect to healthy group and 308 were down-regulated. Similar expression trends were observed between microarray data and qRT-PCR confirmation, which indicated the reliability of the microarray analysis. Further analysis of the differential expressed genes revealed the most significantly affected biological functions during early atresia including blood vessel development, regulation of DNA-templated transcription in response to stress and negative regulation of cell adhesion. The pathway and interaction analysis suggested that atresia initiation associates with 1) a crosstalk of cell apoptosis, autophagy, and ferroptosis rather than change of typical apoptosis markers, 2) dramatic shift of steroidogenic enzymes, 3) deficient glutathione metabolism, and 4) vascular degeneration. The novel gene candidates and pathways identified in the current study will lead to a comprehensive view of the molecular regulation of ovarian follicular atresia and a new understanding of atresia initiation.

At seeming safe concentrations, synergistic effects of PM2.5 and formaldehyde co-exposure induces Alzheimer-like changes in mouse brain.

PubMed

Liu, Xudong; Zhang, Yuchao; Luo, Chen; Kang, Jun; Li, Jinquan; Wang, Kun; Ma, Ping; Yang, Xu

2017-11-17

Alzheimer's disease (AD) is a serious, common, global disease, yet its etiology and pathogenesis are incompletely understood. Air pollution is a multi-pollutants co-exposure system, which may affect brain. The indoor environment is where exposure to both air particulate matter (<2.5 μm in diameter) (PM 2.5 ) and formaldehyde (FA) can occur simultaneously. Whether exposure to such a multi-pollutant (PM 2.5 plus FA) mixture contributes to the development of AD, and whether there is a difference between exposure to PM 2.5 or FA alone needs to be investigated. To determine the objective, C57BL/6J mice were exposed daily to PM 2.5 (0.193 mg/Kg/day), FA (0.155 mg/Kg/day) or multi-pullutants (0.193 mg/Kg/day PM 2.5 plus 0.155 mg/Kg/day FA) for one week. AD-like changes and upstream events were investigated after exposure. The results showed that exposure to PM 2.5 or FA alone in this study had little or no adverse effects on the mouse brain. However, some AD-like pathologies were detected after multi-pullutants co-exposure. This work suggested PM 2.5 plus FA co-exposure has more potential to induce AD-like pathologies than exposure alone. Oxidative stress and inflammation may be involved into the toxic mechanisms. Synergistic effects of co-exposure may induce the hygienic or safety standards of each pollutant not safe.

Border collie comprehends object names as verbal referents.

PubMed

Pilley, John W; Reid, Alliston K

2011-02-01

Four experiments investigated the ability of a border collie (Chaser) to acquire receptive language skills. Experiment 1 demonstrated that Chaser learned and retained, over a 3-year period of intensive training, the proper-noun names of 1022 objects. Experiment 2 presented random pair-wise combinations of three commands and three names, and demonstrated that she understood the separate meanings of proper-noun names and commands. Chaser understood that names refer to objects, independent of the behavior directed toward those objects. Experiment 3 demonstrated Chaser's ability to learn three common nouns--words that represent categories. Chaser demonstrated one-to-many (common noun) and many-to-one (multiple-name) name-object mappings. Experiment 4 demonstrated Chaser's ability to learn words by inferential reasoning by exclusion--inferring the name of an object based on its novelty among familiar objects that already had names. Together, these studies indicate that Chaser acquired referential understanding of nouns, an ability normally attributed to children, which included: (a) awareness that words may refer to objects, (b) awareness of verbal cues that map words upon the object referent, and (c) awareness that names may refer to unique objects or categories of objects, independent of the behaviors directed toward those objects. Copyright © 2010 Elsevier B.V. All rights reserved.

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.

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.

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.

Exploring Undergraduate Students' Mental Models of the Environment: Are They Related to Environmental Affect and Behavior?

ERIC Educational Resources Information Center

Liu, Shu-Chiu; Lin, Huann-shyang

2015-01-01

A draw-and-explain task and questionnaire were used to explore Taiwanese undergraduate students' mental models of the environment and whether and how they relate to their environmental affect and behavioral commitment. We found that students generally held incomplete mental models of the environment, focusing on objects rather than on processes or…

Self-reports of induced abortion: an empathetic setting can improve the quality of data.

PubMed Central

Rasch, V; Muhammad, H; Urassa, E; Bergström, S

2000-01-01

OBJECTIVES: This study estimated the proportion of incomplete abortions that are induced in hospital-based settings in Tanzania. METHODS: A cross-sectional questionnaire study was conducted in 2 phases at 3 hospitals in Tanzania. Phase 1 included 302 patients with a diagnosis of incomplete abortion, and phase 2 included 823 such patients. RESULTS: In phase 1, in which cases were classified by clinical criteria and information from the patient, 3.9% to 16.1% of the cases were classified as induced abortion. In phase 2, in which the structured interview was changed to an empathetic dialogue and previously used clinical criteria were omitted, 30.9% to 60.0% of the cases were classified as induced abortion. CONCLUSIONS: An empathetic dialogue improves the quality of data collected among women with induced abortion. PMID:10897196

Introduction: Reengaging with instruments.

PubMed

Taub, Liba

2011-12-01

Over the past twenty years or so, historians of science have become increasingly sensitized to issues involved in studying and interpreting scientific and medical instruments. The contributors to this Focus section are historians of science who have worked closely with museum objects and collections, specifically instruments used in scientific and medical contexts. Such close engagement by historians of science is somewhat rare, provoking distinctive questions as to how we define and understand instruments, opening up issues regarding the value of broken or incomplete objects, and raising concerns about which scientific and medical artifacts are displayed and interpreted in museums and in what manner. It is hoped that these essays point historians of science in new directions for reengaging with scientific objects and collections.

Detecting Edges in Images by Use of Fuzzy Reasoning

NASA Technical Reports Server (NTRS)

Dominguez, Jesus A.; Klinko, Steve

2003-01-01

A method of processing digital image data to detect edges includes the use of fuzzy reasoning. The method is completely adaptive and does not require any advance knowledge of an image. During initial processing of image data at a low level of abstraction, the nature of the data is indeterminate. Fuzzy reasoning is used in the present method because it affords an ability to construct useful abstractions from approximate, incomplete, and otherwise imperfect sets of data. Humans are able to make some sense of even unfamiliar objects that have imperfect high-level representations. It appears that to perceive unfamiliar objects or to perceive familiar objects in imperfect images, humans apply heuristic algorithms to understand the images

Tomography by iterative convolution - Empirical study and application to interferometry

NASA Technical Reports Server (NTRS)

Vest, C. M.; Prikryl, I.

1984-01-01

An algorithm for computer tomography has been developed that is applicable to reconstruction from data having incomplete projections because an opaque object blocks some of the probing radiation as it passes through the object field. The algorithm is based on iteration between the object domain and the projection (Radon transform) domain. Reconstructions are computed during each iteration by the well-known convolution method. Although it is demonstrated that this algorithm does not converge, an empirically justified criterion for terminating the iteration when the most accurate estimate has been computed is presented. The algorithm has been studied by using it to reconstruct several different object fields with several different opaque regions. It also has been used to reconstruct aerodynamic density fields from interferometric data recorded in wind tunnel tests.

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.

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.

The Teaching and Learning of Diffusion and Osmosis: What Can We Learn from Analysis of Classroom Practices? A Case Study

ERIC Educational Resources Information Center

Hasni, Abdelkrim; Roy, Patrick; Dumais, Nancy

2016-01-01

The objective of this study is to describe the way in which two important biological phenomena, namely diffusion and osmosis, are addressed in the classroom. The study builds on extensive research conducted over the past twenty years showing that students' appropriation of these two phenomena remains partial and incomplete. To understand some of…

New Directions in the Digital Signal Processing of Image Data.

DTIC Science & Technology

1987-05-01

and identify by block number) FIELD GROUP SUB-GROUP Object detection and idLntification 12 01 restoration of photon noise limited imagery 15 04 image...from incomplete information, restoration of blurred images in additive and multiplicative noise , motion analysis with fast hierarchical algorithms...different resolutions. As is well known, the solution to the matched filter problem under additive white noise conditions is the correlation receiver

Cost-Effectiveness of Blood Donation Screening for Trypanosoma cruzi in Mexico

PubMed Central

Sánchez-González, Gilberto; Figueroa-Lara, Alejandro; Elizondo-Cano, Miguel; Wilson, Leslie; Novelo-Garza, Barbara; Valiente-Banuet, Leopoldo; Ramsey, Janine M.

2016-01-01

An estimated 2 million inhabitants are infected with Chagas disease in Mexico, with highest prevalence coinciding with highest demographic density in the southern half of the country. After vector-borne transmission, Trypanosoma cruzi is principally transmitted to humans via blood transfusion. Despite initiation of serological screening of blood donations or donors for T. cruzi since 1990 in most Latin American countries, Mexico only finally included mandatory serological screening nationwide in official Norms in 2012. Most recent regulatory changes and segmented blood services in Mexico may affect compliance of mandatory screening guidelines. The objective of this study was to calculate the incremental cost-effectiveness ratio for total compliance of current guidelines from both Mexican primary healthcare and regular salaried worker health service institutions: the Secretary of Health and the Mexican Institute for Social Security. We developed a bi-modular model to analyze compliance using a decision tree for the most common screening algorithms for each health institution, and a Markov transition model for the natural history of illness and care. The incremental cost effectiveness ratio based on life-years gained is US$ 383 for the Secretary of Health, while the cost for an additional life-year gained is US$ 463 for the Social Security Institute. The results of the present study suggest that due to incomplete compliance of Mexico’s national legislation during 2013 and 2014, the MoH has failed to confirm 15,162 T. cruzi infections, has not prevented 2,347 avoidable infections, and has lost 333,483 life-years. Although there is a vast difference in T. cruzi prevalence between Bolivia and Mexico, Bolivia established mandatory blood screening for T.cruzi in 1996 and until 2002 detected and discarded 11,489 T. cruzi -infected blood units and prevented 2,879 potential infections with their transfusion blood screening program. In the first two years of Mexico’s mandated program, the two primary institutions failed to prevent due to incomplete compliance more potential infections than those gained from the first five years of Bolivia’s program. Full regulatory compliance should be clearly understood as mandatory for the sake of blood security, and its monitoring and analysis in Mexico should be part of the health authority’s responsibility. PMID:27002523

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.

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.

Maternal autonomy and child health care utilization in India: results from the National Family Health Survey.

PubMed

Malhotra, Chetna; Malhotra, Rahul; Østbye, Truls; Subramanian, S V

2014-07-01

The objective of this study was to examine the association of maternal autonomy with preventive and curative child health care utilization in India. Data from the National Family Health Survey 2005-2006 were used to ascertain association of maternal autonomy (in 3 dimensions: decision making, access to financial resources, freedom of movement) with child's primary immunization status (indicative of preventive health care use) and treatment seeking for child's acute respiratory infection (indicative of curative health care use). Low maternal freedom of movement was associated with higher odds of incomplete primary immunization of the child and for not seeking treatment for the child's acute respiratory infection. Low maternal financial access was associated with increased odds for incomplete primary immunization of the child. The findings show that improvement in autonomy of Indian mothers, especially their freedom of movement, may help improve utilization of health care for their children. © 2012 APJPH.

Limited Plasticity of Prismatic Visuomotor Adaptation

PubMed Central

Wischhusen, Sven; Fahle, Manfred

2017-01-01

Movements toward an object displaced optically through prisms adapt quickly, a striking example for the plasticity of neuronal visuomotor programs. We investigated the degree and time course of this system’s plasticity. Participants performed goal-directed throwing or pointing movements with terminal feedback before, during, and after wearing prism goggles shifting the visual world laterally either to the right or to the left. Prism adaptation was incomplete even after 240 throwing movements, still deviating significantly laterally by on average of 0.8° (CI = 0.20°) at the end of the adaptation period. The remaining lateral deviation was significant for pointing movements only with left shifting prisms. In both tasks, removal of the prisms led to an aftereffect which disappeared in the course of further training. This incomplete prism adaptation may be caused by movement variability combined with an adaptive neuronal control system exhibiting a finite capacity for evaluating movement errors. PMID:28473909

Discordance of conflict of interest self-disclosure and the Centers of Medicare and Medicaid Services.

PubMed

Cherla, Deepa V; Olavarria, Oscar A; Holihan, Julie L; Viso, Cristina Perez; Hannon, Craig; Kao, Lillian S; Ko, Tien C; Liang, Mike K

2017-10-01

The Open Payments Database (OPD) discloses financial transactions between manufacturers and physicians. The concordance of OPD versus self-reported conflicts of interest (COI) is unknown. Our objectives were to compare (1) industry and self-disclosed COI in clinical literature, (2) payments within each disclosure level, and (3) industry- and self-disclosed COI and payments by specialty. This was an observational study. PubMed was searched for clinical studies accepted for publication from January 2014 to June 2016. Author and OPD-disclosed COIs were compared. Articles and authors were divided into full disclosure, incomplete industry disclosure, incomplete self-disclosure, and no COI. Primary outcome (differences in reported COI per article) was assessed using McNemar's test. Payment differences were compared using Kruskal-Wallis test. OPD- and self-disclosed COI differed (65.0% discordance rate by article, P < 0.001). Percentages of authors within each disclosure category differed between specialties (P < 0.001). Hematology articles exhibited the highest discordance rate (79.0%) and received the highest median payment for incomplete self-disclosure ($30,812). Significant discordance exists between self- and OPD-reported COI. Additional research is needed to determine reasons for these differences. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

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

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

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

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

The neuropsychology of the Klüver-Bucy syndrome in children.

PubMed

Lippe, S; Gonin-Flambois, C; Jambaqué, I

2013-01-01

The Klüver-Bucy syndrome (KBS) is characterized by a number of peculiar behavioral symptoms. The syndrome was first observed in 1939 by Heinrich Klüver and Paul Bucy in the rhesus monkey following removal of the greater portion of the monkey's temporal lobes and rhinencephalon. The animal showed (a) visual agnosia (inability to recognize objects without general loss of visual discrimination), (b) excessive oral tendency (oral exploration of objects), (c) hypermetamorphosis (excessive visual attentiveness), (d) placidity with loss of normal fear and anger responses, (e) altered sexual behavior manifesting mainly as marked and indiscriminate hypersexuality, and (f) changes in eating behavior. In humans, KBS can be complete or incomplete. It occurs as a consequence of neurological disorders that essentially cause destruction or dysfunction of bilateral mesial temporal lobe structures (i.e., Pick disease, Alzheimer disease, cerebral trauma, cerebrovascular accidents, temporal lobe epilepsy, herpetic encephalopathy, heat stroke). As for epilepsy, complete and incomplete KBS are well documented in temporal lobe epilepsy, temporal lobectomy, and partial status epilepticus. KBS can occur at any age. Children seem to show similar symptoms to adults, although some differences in the manifestations of symptoms may be related to the fact that children have not yet learned certain behaviors. Copyright © 2013 Elsevier B.V. All rights reserved.

Lipid Partitioning, Incomplete Fatty Acid Oxidation, and Insulin Signal Transduction in Primary Human Muscle Cells: Effects of Severe Obesity, Fatty Acid Incubation, and Fatty Acid Translocase/CD36 Overexpression

PubMed Central

Bell, Jill A.; Reed, Melissa A.; Consitt, Leslie A.; Martin, Ola J.; Haynie, Kimberly R.; Hulver, Matthew W.; Muoio, Deborah M.; Dohm, G. Lynis

2010-01-01

Context: Intracellular lipid partitioning toward storage and the incomplete oxidation of fatty acids (FA) have been linked to insulin resistance. Objective: To gain insight into how intracellular lipid metabolism is related to insulin signal transduction, we examined the effects of severe obesity, excess FA, and overexpression of the FA transporter, FA translocase (FAT)/CD36, in primary human skeletal myocytes. Design, Setting, and Patients: Insulin signal transduction, FA oxidation, and metabolism were measured in skeletal muscle cells harvested from lean and severely obese women. To emulate the obesity phenotype in our cell culture system, we incubated cells from lean individuals with excess FA or overexpressed FAT/CD36 using recombinant adenoviral technology. Results: Complete oxidation of FA was significantly reduced, whereas total lipid accumulation, FA esterification into lipid intermediates, and incomplete oxidation were up-regulated in the muscle cells of severely obese subjects. Insulin signal transduction was reduced in the muscle cells from severely obese subjects compared to lean controls. Incubation of muscle cells from lean subjects with lipids reduced insulin signal transduction and increased lipid storage and incomplete FA oxidation. CD36 overexpression increased FA transport capacity, but did not impair complete FA oxidation and insulin signal transduction in muscle cells from lean subjects. Conclusions: Cultured myocytes from severely obese women express perturbations in FA metabolism and insulin signaling reminiscent of those observed in vivo. The obesity phenotype can be recapitulated in muscle cells from lean subjects via exposure to excess lipid, but not by overexpressing the FAT/CD36 FA transporter. PMID:20427507

Value of water-soluble contrast (meglumine amidotrizoate) in the diagnosis and management of small bowel obstruction.

PubMed

Al Salamah, Saleh Moh'd Al; Fahim, Fraz; Mirza, Shaukat Mahmood

2006-07-01

The object of the present study was to determine the effectiveness of a water-soluble contrast follow-through study for differentiating complete from incomplete small bowel obstruction (SBO) and for predicting the need for surgery. This prospective study was conducted at Riyadh Medical Complex, Saudi Arabia and spanned 2 years. All adult patients admitted with SBO were included, except those with obstructed hernias, peritonitis, or postabdominal irradiation. The initial resuscitation meglumine amidotrizoate (Gastrografin) follow-though was performed and was considered positive for complete obstruction if the contrast failed to reach the colon as shown on the 24-hour film. Patients were operated on only if they developed signs of strangulation or failed to improve within 48 hours. Our study group consisted of 73 patients, 48 (65.7%) of whom were male. The mean age was 35.70+/-12.65 years. In 60 (82.2%) patients, contrast reached the ascending colon within 24 hours, giving a definitive diagnosis of incomplete obstruction; among these 60 cases, 49 (81.7%) resolved on conservative management. The other 13 (17.8%) patients were diagnosed as having a complete obstruction; 4 (30.8%) of them were treated conservatively, and 9 (69.2%) underwent surgery. Therefore the sensitivity, specificity, positive predictive value, and negative predictive value for meglumine amidotrizoate follow-through as an indicator for operative treatment of SBO were 45.0, 92.5, 81.7, and 69.2, respectively. The P value using Fisher's exact test was 0.0006. We can confidently diagnose complete and incomplete SBO and differentiate one from the other. This accurate diagnosis indicates a high chance of success with conservative management for incomplete obstruction but does not always correlate with the need for surgical intervention.

CT colonography after incomplete optical colonoscopy

PubMed Central

Theis, Jake; Kim, David H.; Lubner, Meghan G.; del Rio, Alejandro Muñoz; Pickhardt, Perry J.

2017-01-01

Purpose To objectively compare the volume, density, and distribution of luminal fluid for same-day oral-contrast-enhanced CTC following incomplete optical colonoscopy (OC) versus deferred CTC on a separate day utilizing a dedicated CTC bowel preparation. Methods HIPAA-compliant, IRB-approved retrospective study compared 103 same-day CTC studies after incomplete OC (utilizing 30 ml oral diatrizoate) against 151 CTC examinations performed on a separate day after failed OC using a dedicated CTC bowel preparation (oral magnesium citrate/dilute barium/diatrizoate the evening before). A subgroup of 15 patients who had both same-day CTC and separate-day routine CTC was also identified and underwent separate analysis. CTC exams were analyzed for opacified fluid distribution within the GI tract, as well as density and volume. Data was analyzed utilizing Kruskal-Wallis and Wilcoxon Signed Rank tests. Results Opacified luminal fluid extended to the rectum in 56% (58/103) of same-day CTC versus 100% (151/151) of deferred separate-day CTC (p<0.0001). For same-day CTC, contrast failed to reach the colon in 11% (11/103) and failed to reach the left colon in 26% (27/103). Volumetric colonic fluid segmentation for fluid analysis (successful in 80 same-day and 147 separate-day cases) showed significantly more fluid in the same-day cohort (mean, 227 ml vs. 166 ml; p<0.0001); the actual difference is underestimated due to excluded cases. Mean colonic fluid attenuation was significantly lower in the same-day cohort (545 HU vs. 735 HU; p<0.0001). Similar findings were identified in the smaller cohort with direct intra-patient CTC comparison. Conclusions Dedicated CTC bowel preparation on a separate day following incomplete OC results in a much higher quality examination compared with same-day CTC. PMID:26830606

A randomized trial of functional electrical stimulation for walking in incomplete spinal cord injury: Effects on walking competency

PubMed Central

Kapadia, Naaz; Masani, Kei; Catharine Craven, B.; Giangregorio, Lora M.; Hitzig, Sander L.; Richards, Kieva; Popovic, Milos R.

2014-01-01

Background Multi-channel surface functional electrical stimulation (FES) for walking has been used to improve voluntary walking and balance in individuals with spinal cord injury (SCI). Objective To investigate short- and long-term benefits of 16 weeks of thrice-weekly FES-assisted walking program, while ambulating on a body weight support treadmill and harness system, versus a non-FES exercise program, on improvements in gait and balance in individuals with chronic incomplete traumatic SCI, in a randomized controlled trial design. Methods Individuals with traumatic and chronic (≥18 months) motor incomplete SCI (level C2 to T12, American Spinal Cord Injury Association Impairment Scale C or D) were recruited from an outpatient SCI rehabilitation hospital, and randomized to FES-assisted walking therapy (intervention group) or aerobic and resistance training program (control group). Outcomes were assessed at baseline, and after 4, 6, and 12 months. Gait, balance, spasticity, and functional measures were collected. Results Spinal cord independence measure (SCIM) mobility sub-score improved over time in the intervention group compared with the control group (baseline/12 months: 17.27/21.33 vs. 19.09/17.36, respectively). On all other outcome measures the intervention and control groups had similar improvements. Irrespective of group allocation walking speed, endurance, and balance during ambulation all improved upon completion of therapy, and majority of participants retained these gains at long-term follow-ups. Conclusions Task-oriented training improves walking ability in individuals with incomplete SCI, even in the chronic stage. Further randomized controlled trials, involving a large number of participants are needed, to verify if FES-assisted treadmill training is superior to aerobic and strength training. PMID:25229735

Incomplete adherence among treatment-experienced adults on antiretroviral therapy in Tanzania, Uganda and Zambia

PubMed Central

Denison, Julie A.; Koole, Olivier; Tsui, Sharon; Menten, Joris; Torpey, Kwasi; van Praag, Eric; Mukadi, Ya Diul; Colebunders, Robert; Auld, Andrew F.; Agolory, Simon; Kaplan, Jonathan E.; Mulenga, Modest; Kwesigabo, Gideon P.; Wabwire-Mangen, Fred; Bangsberg, David R.

2016-01-01

Objectives To characterize antiretroviral therapy (ART) adherence across different programmes and examine the relationship between individual and programme characteristics and incomplete adherence among ART clients in sub-Saharan Africa. Design A cross-sectional study. Methods Systematically selected ART clients (≥18 years; on ART ≥6 months) attending 18 facilities in three countries (250 clients/facility) were interviewed. Client self-reports (3-day, 30-day, Case Index ≥48 consecutive hours of missed ART), healthcare provider estimates and the pharmacy medication possession ratio (MPR) were used to estimate ART adherence. Participants from two facilities per country underwent HIV RNA testing. Optimal adherence measures were selected on the basis of degree of association with concurrent HIV RNA dichotomized at less than or greater/equal to 1000 copies/ml. Multivariate regression analysis, adjusted for site-level clustering, assessed associations between incomplete adherence and individual and programme factors. Results A total of 4489 participants were included, of whom 1498 underwent HIV RNA testing. Nonadherence ranged from 3.2% missing at least 48 consecutive hours to 40.1% having an MPR of less than 90%. The percentage with HIV RNA at least 1000 copies/ml ranged from 7.2 to 17.2% across study sites (mean = 9.9%). Having at least 48 consecutive hours of missed ART was the adherence measure most strongly related to virologic failure. Factors significantly related to incomplete adherence included visiting a traditional healer, screening positive for alcohol abuse, experiencing more HIV symptoms, having an ART regimen without nevirapine and greater levels of internalized stigma. Conclusion Results support more in-depth investigations of the role of traditional healers, and the development of interventions to address alcohol abuse and internalized stigma among treatment-experienced adult ART patients. PMID:25686684

A comparative study of two protocols for treadmill walking exercise testing in ambulating subjects with incomplete spinal cord injury.

PubMed

Lundgaard, E; Wouda, M F; Strøm, V

2017-10-01

This is a comparative study of two exercise testing protocols. The objective of this study was to compare maximal oxygen uptake (VO 2 max) and achieved criteria for maximal exercise testing between the Sunnaas Protocol-a newly designed treadmill exercise test protocol-and the Modified Bruce Protocol in persons with incomplete spinal cord injury (SCI). This study was conducted in Sunnaas Rehabilitation Hospital, Norway. Twenty persons (19 men) with incomplete SCI (AIS D) capable of ambulating without assistive devices performed two treadmill walking exercise tests (Sunnaas Protocol and Modified Bruce Protocol) until exhaustion 1-3 days apart. The key differences between the protocols are the smaller increments in speed and shorter duration on each workload in the Sunnaas Protocol. Cardiovascular responses were measured continuously throughout both tests. The subjects exhibited statistically significantly higher VO 2 max when using the Sunnaas Protocol (37.1±9.9 vs 35.4±9.8 ml kg -1  min -1 , P=0.01), with a mean between-test difference of 1.8 ml kg -1  min -1 (95% confidence interval: 0.49-3.16). There was no significant difference in mean maximal heart rate (HR max). Nineteen (95%) subjects achieved at least three of the four criteria for maximal oxygen uptake using the Sunnaas Protocol. Thirteen (65%) subjects achieved at least three of the criteria using a Modified Bruce protocol. The small differences in both VO 2 max and achieved criteria in favor of the Sunnaas Protocol suggest that it could be a useful alternative treadmill exercise test protocol for ambulating persons with incomplete SCI.

A history of obesity leaves an inflammatory fingerprint in liver and adipose tissue

PubMed Central

Fischer, I P; Irmler, M; Meyer, C W; Sachs, S J; Neff, F; Hrabě de Angelis, M; Beckers, J; Tschöp, M H; Hofmann, S M; Ussar, S

2018-01-01

Background/Objectives: Dieting is a popular yet often ineffective way to lower body weight, as the majority of people regain most of their pre-dieting weights in a relatively short time. The underlying molecular mechanisms driving weight regain and the increased risk for metabolic disease are still incompletely understood. Here we investigate the molecular alterations inherited from a history of obesity. Methods: In our model, male high-fat diet (HFD)-fed obese C57BL/6J mice were switched to a low caloric chow diet, resulting in a decline of body weight to that of lean mice. We measured body composition, as well as metrics of glucose, insulin and lipid homeostasis. This was accompanied by histological and gene expression analysis of adipose tissue and liver to assess adipose tissue inflammation and hepatosteatosis. Moreover, acute hypothalamic response to (re-) exposure to HFD was assessed by qPCR. Results & Conclusions: Within 7 weeks after diet switch, most obesity-associated phenotypes, such as body mass, glucose intolerance and blood metabolite levels were reversed. However, hepatic inflammation, hepatic steatosis as well as hypertrophy and inflammation of perigonadal, but not subcutaneous, adipocytes persisted in formerly obese mice. Transcriptional profiling of liver and perigonadal fat revealed an upregulation of pathways associated with immune function and cellularity. Thus, we show that weight reduction leaves signs of inflammation in liver and perigonadal fat, indicating that persisting proinflammatory signals in liver and adipose tissue could contribute to an increased risk of formerly obese subjects to develop the metabolic syndrome upon recurring weight gain. PMID:28901330

PCBs-high-fat diet interactions as mediators of gut microbiota dysbiosis and abdominal fat accumulation in female mice.

PubMed

Chi, Yulang; Lin, Yi; Zhu, Huimin; Huang, Qiansheng; Ye, Guozhu; Dong, Sijun

2018-04-16

Polychlorinated biphenyls (PCBs), one type of lipophilic pollutant, are ubiquitous in daily life. PCBs exposure has been implicated in the alterations of gut microbial community which is profoundly associated with diverse metabolic disorders, including obesity. High-fat diet (H) is a dietary pattern characterized by a high percentage of fat. According to the theory that similarities can be easily solvable in each other, PCBs and H exposures are inevitably and objectively coexistent in a real living environment, prompting great concerns about their individual and combined effects on hosts. However, the effects of PCBs-H interactions on gut microbiota and obesity are still incompletely understood. In the present study, the effects of PCBs and/or H on the gut microbiota alteration and obesity risk in mice were examined and the interactions between PCBs and H were investigated. Obtained results showed that PCBs and/or H exposure induced prominent variations in the gut microbiota composition and diversity. Exposure to PCBs also resulted in higher body fat percentage, greater size of abdominal subcutaneous adipocytes and increased expression of proinflammatory cytokines including TNF-α, iNOS and IL-6. Such PCBs-induced changes could be further enhanced upon the co-exposure of H, implying that obese individuals may be vulnerable to PCBs exposure. Taken together, the present study is helpful for a better understanding of the gut microbiota variation influenced by PCBs and/or H exposure, and furthermore, provides a novel insight into the mechanism of PCBs-H interactions on host adiposity. Copyright © 2018 Elsevier Ltd. All rights reserved.

The prevalence of chest compression leaning during in-hospital cardiopulmonary resuscitation

PubMed Central

Fried, David A.; Leary, Marion; Smith, Douglas A.; Sutton, Robert M.; Niles, Dana; Herzberg, Daniel L.; Becker, Lance B.; Abella, Benjamin S.

2011-01-01

Objective Successful resuscitation from cardiac arrest requires the delivery of high-quality chest compressions, encompassing parameters such as adequate rate, depth, and full recoil between compressions. The lack of compression recoil (“leaning” or “incomplete recoil”) has been shown to adversely affect hemodynamics in experimental arrest models, but the prevalence of leaning during actual resuscitation is poorly understood. We hypothesized that leaning varies across resuscitation events, possibly due to rescuer and/or patient characteristics and may worsen over time from rescuer fatigue during continuous chest compressions. Methods This was an observational clinical cohort study at one academic medical center. Data were collected from adult in-hospital and Emergency Department arrest events using monitor/defibrillators that record chest compression characteristics and provide real-time feedback. Results We analyzed 112,569 chest compressions from 108 arrest episodes from 5/2007 to 2/2009. Leaning was present in 98/108 (91%) cases; 12% of all compressions exhibited leaning. Leaning varied widely across cases: 41/108 (38%) of arrest episodes exhibited <5% leaning yet 20/108 (19%) demonstrated >20% compression leaning. When evaluating blocks of continuous compressions (>120 sec), only 4/33 (12%) had an increase in leaning over time and 29/33 (88%) showed a decrease (p<0.001). Conclusions Chest compression leaning was common during resuscitation care and exhibited a wide distribution, with most leaning within a subset of resuscitations. Leaning decreased over time during continuous chest compression blocks, suggesting that either leaning may not be a function of rescuer fatiguing, or that it may have been mitigated by automated feedback provided during resuscitation episodes. PMID:21482010

Suicide risk among prisoners in French Guiana: prevalence and predictive factors.

PubMed

Ayhan, Gülen; Arnal, Romain; Basurko, Célia; About, Vincent; Pastre, Agathe; Pinganaud, Eric; Sins, Dominique; Jehel, Louis; Falissard, Bruno; Nacher, Mathieu

2017-05-02

Suicide rates in prison are high and their risk factors are incompletely understood. The objective of the present study is to measure the risk of suicide and its predictors in the only prison of multicultural French Guiana. All new prisoners arriving between September 2013 and December 2014 were included. The Mini International Neuropsychiatric Interview (MINI) was used and socio-demographic data was collected. In order to identify the predictors of suicide risk multivariate logistic regression was used. Of the 707 prisoners included 13.2% had a suicidal risk, 14.0% of whom had a high risk, 15.1% a moderate risk and 41.9% a low risk. Predictive factors were depression (OR 7.44, 95% CI: 3.50-15.87), dysthymia (OR 4.22, 95% CI: 1.34-13.36), panic disorder (OR 3.47, 95% CI: 1.33-8.99), general anxiety disorder (GAD) (OR 2.19, 95% CI: 1.13-4.22), men having been abused during childhood (OR 21.01, 95%, CI: 3.26-135.48), having been sentenced for sexual assault (OR 7.12, 95% CI: 1.98-25.99) and smoking (OR 2.93, 95%, CI 1.30-6.63). The suicide risk was lower than in mainland France, possibly reflecting the differences in the social stigma attached to incarceration because of migrant populations and the importance and trivialization of drug trafficking among detainees. However, there were no differences between nationalities. The results reemphasize the importance of promptly identifying and treating psychiatric disorders, which were the main suicide risk factors.

Mixed species biofilms of Fusobacterium necrophorum and Porphyromonas levii impair the oxidative response of bovine neutrophils in vitro.

PubMed

Lockhart, Joey S; Buret, Andre G; Ceri, Howard; Storey, Douglas G; Anderson, Stefanie J; Morck, Douglas W

2017-10-01

Biofilms composed of anaerobic bacteria can result in persistent infections and chronic inflammation. Host immune cells have difficulties clearing biofilm-related infections and this can result in tissue damage. Neutrophils are a vital component of the innate immune system and help clear biofilms. The comparative neutrophilic response to biofilms versus planktonic bacteria remains incompletely understood, particularly in the context of mixed infections. The objective of this study was to generate mixed species anaerobic bacterial biofilms composed of two opportunistic pathogens, Fusobacterium necrophorum and Porphyromonas levii, and evaluate neutrophil responses to extracellular fractions from both biofilms and planktonic cell co-cultures of the same bacteria. Purified bovine neutrophils exposed to culture supernatants from mixed species planktonic bacteria showed elevated oxidative activity compared to neutrophils exposed to biofilms composed of the same bacteria. Bacterial lipopolysaccharide plays a significant role in the stimulation of neutrophils; biofilms produced substantially more lipopolysaccharide than planktonic bacteria under these experimental conditions. Removal of lipopolysaccharide significantly reduced neutrophil oxidative response to culture supernatants of planktonic bacteria. Oxidative responses to LPS-removed biofilm supernatants and LPS-removed planktonic cell supernatants were similar. The limited neutrophil response to biofilm bacteria observed in this study supports the reduced ability of the innate immune system to eradicate biofilm-associated infections. Lipopolysaccharide is likely important in neutrophil response; however, the presence of other extracellular, immune modifying molecules in the bacterial media also appears to be important in altering neutrophil function. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of dog ownership and genotype on immune development and atopy in infancy.

PubMed

Gern, James E; Reardon, Claudia L; Hoffjan, Sabine; Nicolae, Dan; Li, Zhanhai; Roberg, Kathy A; Neaville, William A; Carlson-Dakes, Kirstin; Adler, Kiva; Hamilton, Rebekah; Anderson, Elizabeth; Gilbertson-White, Stephanie; Tisler, Christopher; Dasilva, Douglas; Anklam, Kelly; Mikus, Lance D; Rosenthal, Louis A; Ober, Carole; Gangnon, Ronald; Lemanske, Robert F

2004-02-01

Exposure to furred pets might confer protection against the development of allergic sensitization through a mechanism that is incompletely understood. The objective of this study was to determine the effects of pet exposure and genotype on immunologic development and the incidence of atopic markers and diseases in the first year of life. Pet exposure in the home was compared with cytokine secretion patterns (mitogen-stimulated mononuclear cells at birth and age 1 year) and indicators of atopy (allergen-specific and total IgE, eosinophilia, food allergy, atopic dermatitis) in 285 infants. Interactions with genotype at the CD14 locus were also evaluated in the data analyses. Exposure to dogs was associated with reduced allergen sensitization (19% vs 33%, P =.020) and atopic dermatitis (30% vs 51%, P <.001). The risk for atopic dermatitis was further influenced by genotype at the CD14 locus (P =.006), even after adjusting for exposure to dogs (P =.003). Furthermore, infants with the genotype -159TT were less likely to develop atopic dermatitis if they were exposed to a dog (5% vs 43%, P =.04). Last, dog exposure was associated with increased IL-10 (117 vs 79 pg/mL, P =.002) and IL-13 (280 vs 226 pg/mL, P =.013) responses at age 1 year. Having a dog in infancy is associated with higher IL-10 and IL-13 cytokine secretion profiles and reduced allergic sensitization and atopic dermatitis. These findings suggest that postnatal exposure to dogs can influence immune development in a genotype-specific fashion and thereby attenuate the development of atopy in at-risk children.

Molecular epidemiology of an outbreak of clinical mastitis in sheep caused by Mannheimia haemolytica.

PubMed

Omaleki, Lida; Browning, Glenn F; Allen, Joanne L; Markham, Philip F; Barber, Stuart R

2016-08-15

The aetiology and epidemiology of outbreaks of clinical mastitis in sheep under extensive pastoral conditions are incompletely understood. The objective of this study was to conduct a detailed investigation of a clinical mastitis outbreak that affected more than 10% of 230 at-risk ewes on a sheep and grain producing property in south east Australia during drought conditions in 2009. Milk samples were collected aseptically from all affected ewes and plated on sheep blood agar for bacterial identification. M. haemolytica was isolated from 80% of the samples that yielded cultivable microorganisms and thus was the main microorganism responsible for the outbreak. Analysis of the restriction endonuclease cleavage patterns of the isolates using pulsed field gel electrophoresis revealed some evidence of clonality, suggesting the possibility of horizontal transmission, but there was also considerable diversity between the clusters of closely related isolates. Multilocus sequence typing of the M. haemolytica isolates revealed most of the isolates belonged to ST1 with no association between the PFGE and MLST fingerprints of the isolates. Resistance to neomycin, streptomycin and sulphafurazole was detected in some of the isolates, but they were all susceptible to penicillin, ampicillin, ceftiofur, amoxycillin/clavulanic acid, ciprofloxacin, tetracycline, erythromycin and trimethoprim. This is the first published record of a comparison of the strains of M. haemolytica involved in a clinical mastitis outbreak in sheep and demonstrates the importance of this pathogen in sheep production systems, particularly during adverse climatic conditions and increased stocking rate. Copyright © 2016 Elsevier B.V. All rights reserved.

Ammonia-induced brain swelling and neurotoxicity in an organotypic slice model

PubMed Central

Back, Adam; Tupper, Kelsey Y.; Bai, Tao; Chiranand, Paulpoj; Goldenberg, Fernando D.; Frank, Jeffrey I.; Brorson, James R.

2013-01-01

Objectives Acute liver failure produces cerebral dysfunction and edema, mediated in part by elevated ammonia concentrations, often leading to coma and death. The pathophysiology of cerebral edema in acute liver failure is incompletely understood. In vitro models of the cerebral effects of acute liver failure have predominately consisted of dissociated astrocyte cultures or acute brain slices. We describe a stable long-term culture model incorporating both neural and glial elements in a three-dimensional tissue structure offering significant advantages to the study of astrocytic-neuronal interactions in the pathophysiology of cerebral edema and dysfunction in acute liver failure. Methods We utilized chronic organotypic slice cultures from mouse forebrain, applying ammonium acetate in iso-osmolar fashion for 72 hours. Imaging of slice thickness to assess for tissue swelling was accomplished in living slices with optical coherence tomography, and confocal microscopy of fluorescence immunochemical and histochemical staining served to assess astrocyte and neuronal numbers, morphology, and volume in the fixed brain slices. Results Ammonia exposure at 1–10 mM produced swelling of immunochemically-identified astrocytes, and at 10 mM resulted in macroscopic tissue swelling, with slice thickness increasing by about 30%. Astrocytes were unchanged in number. In contrast, 10 mM ammonia treatment severely disrupted neuronal morphology and reduced neuronal survival at 72 hours by one-half. Discussion Elevated ammonia produces astrocytic swelling, tissue swelling, and neuronal toxicity in cerebral tissues. Ammonia-treated organotypic brain slice cultures provide an in vitro model of cerebral effects of conditions relevant to acute liver failure, applicable to pathophysiological investigations. PMID:22196764

Performance Analysis: Work Control Events Identified January - August 2010

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

De Grange, C E; Freeman, J W; Kerr, C E

2011-01-14

This performance analysis evaluated 24 events that occurred at LLNL from January through August 2010. The analysis identified areas of potential work control process and/or implementation weaknesses and several common underlying causes. Human performance improvement and safety culture factors were part of the causal analysis of each event and were analyzed. The collective significance of all events in 2010, as measured by the occurrence reporting significance category and by the proportion of events that have been reported to the DOE ORPS under the ''management concerns'' reporting criteria, does not appear to have increased in 2010. The frequency of reporting inmore » each of the significance categories has not changed in 2010 compared to the previous four years. There is no change indicating a trend in the significance category and there has been no increase in the proportion of occurrences reported in the higher significance category. Also, the frequency of events, 42 events reported through August 2010, is not greater than in previous years and is below the average of 63 occurrences per year at LLNL since 2006. Over the previous four years, an average of 43% of the LLNL's reported occurrences have been reported as either ''management concerns'' or ''near misses.'' In 2010, 29% of the occurrences have been reported as ''management concerns'' or ''near misses.'' This rate indicates that LLNL is now reporting fewer ''management concern'' and ''near miss'' occurrences compared to the previous four years. From 2008 to the present, LLNL senior management has undertaken a series of initiatives to strengthen the work planning and control system with the primary objective to improve worker safety. In 2008, the LLNL Deputy Director established the Work Control Integrated Project Team to develop the core requirements and graded elements of an institutional work planning and control system. By the end of that year this system was documented and implementation had begun. In 2009, training of the workforce began and as of the time of this report more than 50% of authorized Integration Work Sheets (IWS) use the activity-based planning process. In 2010, LSO independently reviewed the work planning and control process and confirmed to the Laboratory that the Integrated Safety Management (ISM) System was implemented. LLNL conducted a cross-directorate management self-assessment of work planning and control and is developing actions to respond to the issues identified. Ongoing efforts to strengthen the work planning and control process and to improve the quality of LLNL work packages are in progress: completion of remaining actions in response to the 2009 DOE Office of Health, Safety, and Security (HSS) evaluation of LLNL's ISM System; scheduling more than 14 work planning and control self-assessments in FY11; continuing to align subcontractor work control with the Institutional work planning and control system; and continuing to maintain the electronic IWS application. The 24 events included in this analysis were caused by errors in the first four of the five ISMS functions. The most frequent cause was errors in analyzing the hazards (Function 2). The second most frequent cause was errors occurring when defining the work (Function 1), followed by errors during the performance of work (Function 4). Interestingly, very few errors in developing controls (Function 3) resulted in events. This leads one to conclude that if improvements are made to defining the scope of work and analyzing the potential hazards, LLNL may reduce the frequency or severity of events. Analysis of the 24 events resulted in the identification of ten common causes. Some events had multiple causes, resulting in the mention of 39 causes being identified for the 24 events. The most frequent cause was workers, supervisors, or experts believing they understood the work and the hazards but their understanding was incomplete. The second most frequent cause was unclear, incomplete or confusing documents directing the work. Together, these two causes were mentioned 17 times and contributed to 13 of the events. All of the events with the cause of ''workers, supervisors, or experts believing they understood the work and the hazards but their understanding was incomplete'' had this error in the first two ISMS functions: define the work and analyze the hazard. This means that these causes result in the scope of work being ill-defined or the hazard(s) improperly analyzed. Incomplete implementation of these functional steps leads to the hazards not being controlled. The causes are then manifested in events when the work is conducted. The process to operate safely relies on accurately defining the scope of work. This review has identified a number of examples of latent organizational weakness in the execution of work control processes.« less

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.

Taking Another Look: Sensuous, Consistent Form.

ERIC Educational Resources Information Center

Townley, Mary Ross

1983-01-01

There is a natural progression from making single objects to creating sculpture. By modeling the forms of objects like funnels and light bulbs, students become aware of the quality of curves and the edges of angles. Sculptural form in architecture can be understood as consistency in the forms. (CS)

Is MBO Appropriate in the Academic Setting?

ERIC Educational Resources Information Center

Lasher, Harry J.

1978-01-01

A model for implementing a Management by Objectives (MBO) system in the academic environment is presented and potential problems are explored. Some of the pitfalls discussed include: organizational climate, clarity of objectives, assumption that MBO concepts are readily understood, instant success syndrome, and economic reward myopia. (JMD)

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…

Student Use of Physics to Make Sense of Incomplete but Functional VPython Programs in a Lab Setting

NASA Astrophysics Data System (ADS)

Weatherford, Shawn A.

2011-12-01

Computational activities in Matter & Interactions, an introductory calculus-based physics course, have the instructional goal of providing students with the experience of applying the same set of a small number of fundamental principles to model a wide range of physical systems. However there are significant instructional challenges for students to build computer programs under limited time constraints, especially for students who are unfamiliar with programming languages and concepts. Prior attempts at designing effective computational activities were successful at having students ultimately build working VPython programs under the tutelage of experienced teaching assistants in a studio lab setting. A pilot study revealed that students who completed these computational activities had significant difficultly repeating the exact same tasks and further, had difficulty predicting the animation that would be produced by the example program after interpreting the program code. This study explores the interpretation and prediction tasks as part of an instructional sequence where students are asked to read and comprehend a functional, but incomplete program. Rather than asking students to begin their computational tasks with modifying program code, we explicitly ask students to interpret an existing program that is missing key lines of code. The missing lines of code correspond to the algebraic form of fundamental physics principles or the calculation of forces which would exist between analogous physical objects in the natural world. Students are then asked to draw a prediction of what they would see in the simulation produced by the VPython program and ultimately run the program to evaluate the students' prediction. This study specifically looks at how the participants use physics while interpreting the program code and creating a whiteboard prediction. This study also examines how students evaluate their understanding of the program and modification goals at the beginning of the modification task. While working in groups over the course of a semester, study participants were recorded while they completed three activities using these incomplete programs. Analysis of the video data showed that study participants had little difficulty interpreting physics quantities, generating a prediction, or determining how to modify the incomplete program. Participants did not base their prediction solely from the information from the incomplete program. When participants tried to predict the motion of the objects in the simulation, many turned to their knowledge of how the system would evolve if it represented an analogous real-world physical system. For example, participants attributed the real-world behavior of springs to helix objects even though the program did not include calculations for the spring to exert a force when stretched. Participants rarely interpreted lines of code in the computational loop during the first computational activity, but this changed during latter computational activities with most participants using their physics knowledge to interpret the computational loop. Computational activities in the Matter & Interactions curriculum were revised in light of these findings to include an instructional sequence of tasks to build a comprehension of the example program. The modified activities also ask students to create an additional whiteboard prediction for the time-evolution of the real-world phenomena which the example program will eventually model. This thesis shows how comprehension tasks identified by Palinscar and Brown (1984) as effective in improving reading comprehension are also effective in helping students apply their physics knowledge to interpret a computer program which attempts to model a real-world phenomena and identify errors in their understanding of the use, or omission, of fundamental physics principles in a computational model.

Barriers to Healthier Eating in a Disadvantaged Community

ERIC Educational Resources Information Center

O'Neill, Martin; Rebane, Deanne; Lester, Carolyn

2004-01-01

Objective: The research objective was to identify how healthy eating was understood in a disadvantaged community and how barriers to healthy eating might be overcome. Design: Participatory action research. Setting: Communities in Gurnos, Merthyr Tydfil, one of the most deprived areas in the UK. Method: Trainees on a participative methods course…

Using Digital Learning Objects to Introduce Students to the Nature of Models and the Nature of Matter

ERIC Educational Resources Information Center

Gustafson, Brenda; Mahaffy, Peter; Martin, Brian

2011-01-01

This article reports a subset of findings from a larger study centered on designing a series of six digital learning objects to help Grade 5 (age 10-12) students begin to consider the nature of models (understood as the physical or mental representation of objects, phenomena, or processes), the particle nature of matter, and the behavior of…

Pelvic floor muscle training in spinal cord injury and its impact on neurogenic detrusor over-activity and incontinence.

PubMed

Vásquez, N; Knight, S L; Susser, J; Gall, A; Ellaway, P H; Craggs, M D

2015-12-01

Two case studies. To determine whether 6 weeks of regular pelvic floor muscle training (PFMT) can improve the strength and endurance of voluntary contractions in incomplete spinal cord injury and reduce neurogenic detrusor over-activity (NDO) and incontinence. The London Spinal Cord Injury Centre, Stanmore, London, UK. A 6-week programme of PFMT was conducted in two male subjects with stable supra-sacral motor incomplete (AIS C and D) spinal cord injuries. Clinical evaluations before and after training comprised measures of strength and endurance of voluntary pelvic floor contractions both objectively by anal canal-pressure measurements and subjectively using the modified Oxford grading system. NDO was determined by standard urodynamic tests of bladder function and incontinence measured by the International Consultation on Incontinence Questionnaire-Urology. Both subjects improved the strength and endurance of their pelvic floor muscle contractions by over 100% at the end of training. After training, Subject 1 (AIS D) was able to reduce bladder pressure during over-activity almost completely by voluntarily contracting the pelvic floor muscles. Subject 2 (AIS C) achieved a lesser reduction overall after training. Continence improved only in subject 1. These case studies provide evidence that a 6-week programme of PFMT may have a beneficial effect on promoting voluntary control of NDO and reduce incontinence in selected cases with a motor incomplete spinal cord lesion.

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.

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

Dentate Gyrus Is Necessary for Disambiguating Similar Object-Place Representations

ERIC Educational Resources Information Center

Lee, Inah; Solivan, Frances

2010-01-01

Objects are often remembered with their locations, which is an important aspect of event memory. Despite the well-known involvement of the hippocampus in event memory, detailed intrahippocampal mechanisms are poorly understood. In particular, no experimental evidence has been provided in support of the role of the dentate gyrus (DG) in…

Modeling Lolium perenne L. roots in the presence of empirical black holes

USDA-ARS?s Scientific Manuscript database

Plant root models are designed for understanding structural or functional aspects of root systems. When a process is not thoroughly understood, a black box object is used. However, when a process exists but empirical data do not indicate its existence, you have a black hole. The object of this re...

Attention to Attributes and Objects in Working Memory

PubMed Central

Cowan, Nelson; Blume, Christopher L.; Saults, J. Scott

2013-01-01

It has been debated on the basis of change-detection procedures whether visual working memory is limited by the number of objects, task-relevant attributes within those objects, or bindings between attributes. This debate, however, has been hampered by several limitations, including the use of conditions that vary between studies and the absence of appropriate mathematical models to estimate the number of items in working memory in different stimulus conditions. We re-examined working memory limits in two experiments with a wide array of conditions involving color and shape attributes, relying on a set of new models to fit various stimulus situations. In Experiment 2, a new procedure allowed identical retrieval conditions across different conditions of attention at encoding. The results show that multiple attributes compete for attention, but that retaining the binding between attributes is accomplished only by retaining the attributes themselves. We propose a theoretical account in which a fixed object capacity limit contains within it the possibility of the incomplete retention of object attributes, depending on the direction of attention. PMID:22905929

Delamination measurement of a laminates composite panel due to hole punching based on the focus variation technique

NASA Astrophysics Data System (ADS)

Abdullah, A. B.; Zain, M. S. M.; Abdullah, M. S.; Samad, Z.

2017-07-01

Structural materials, such as composite panels, must be assembled, and such panels are typically constructed via the insertion of a fastener through a drilled hole. The main problem encountered in drilling is delamination, which affects assembly strength. The cost of drilling is also high because of the severe wear on drill bits. The main goal of this research is to develop a new punching method as an alternative to drilling during hole preparation. In this study, the main objective is to investigate the effect of different puncher profiles on the quality of holes punched into carbon fiber reinforcement polymer (CFRP) composite panels. Six types of puncher profiles were fabricated with minimum die clearance (1%), and two quality aspects, namely, incomplete shearing and delamination factor, were measured. The conical puncher incurred the least defects in terms of delamination and yielded an acceptable amount of incomplete shearing in comparison with the other punchers.

Science friction: data, metadata, and collaboration.

PubMed

Edwards, Paul N; Mayernik, Matthew S; Batcheller, Archer L; Bowker, Geoffrey C; Borgman, Christine L

2011-10-01

When scientists from two or more disciplines work together on related problems, they often face what we call 'science friction'. As science becomes more data-driven, collaborative, and interdisciplinary, demand increases for interoperability among data, tools, and services. Metadata--usually viewed simply as 'data about data', describing objects such as books, journal articles, or datasets--serve key roles in interoperability. Yet we find that metadata may be a source of friction between scientific collaborators, impeding data sharing. We propose an alternative view of metadata, focusing on its role in an ephemeral process of scientific communication, rather than as an enduring outcome or product. We report examples of highly useful, yet ad hoc, incomplete, loosely structured, and mutable, descriptions of data found in our ethnographic studies of several large projects in the environmental sciences. Based on this evidence, we argue that while metadata products can be powerful resources, usually they must be supplemented with metadata processes. Metadata-as-process suggests the very large role of the ad hoc, the incomplete, and the unfinished in everyday scientific work.

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.

Problem of two-level hierarchical minimax program control the final state of regional social and economic system with incomplete information

NASA Astrophysics Data System (ADS)

Shorikov, A. F.

2016-12-01

In this article we consider a discrete-time dynamical system consisting of a set a controllable objects (region and forming it municipalities). The dynamics each of these is described by the corresponding linear or nonlinear discrete-time recurrent vector relations and its control system consist from two levels: basic level (control level I) that is dominating level and auxiliary level (control level II) that is subordinate level. Both levels have different criterions of functioning and united by information and control connections which defined in advance. In this article we study the problem of optimization of guaranteed result for program control by the final state of regional social and economic system in the presence of risks vectors. For this problem we propose a mathematical model in the form of two-level hierarchical minimax program control problem of the final states of this system with incomplete information and the general scheme for its solving.

Acupuncture and vitamin B12 injection for Bell’s palsy: no high-quality evidence exists

PubMed Central

Wang, Li-li; Guan, Ling; Hao, Peng-liang; Du, Jin-long; Zhang, Meng-xue

2015-01-01

OBJECTIVE: To assess the efficacy of acupuncture combined with vitamin B12 acupoint injection versus acupuncture alone to reduce incomplete recovery in patients with Bell’s palsy. DATA RETRIEVAL: A computer-based online retrieval of Medline, Web of Science, CNKI, CBM databases until April 2014 was performed for relevant trials, using the key words “Bell’s palsy or idiopathic facial palsy or facial palsy” and “acupuncture or vitamin B12 or methylcobalamin”. STUDY SELECTION: All randomized controlled trials that compared acupuncture with acupuncture combined with vitamin B12 in patients with Bell’s palsy were included in the meta-analysis. The initial treatment lasted for at least 4 weeks. The outcomes of incomplete facial recovery were monitored. The scoring index varied and the definition of healing was consistent. The combined effect size was calculated by using relative risk (RR) with 95% confidence interval (CI) using the fixed effect model of Review Manager. MAIN OUTCOME MEASURES: Incomplete recovery rates were chosen as the primary outcome. RESULTS: Five studies involving 344 patients were included in the final analysis. Results showed that the incomplete recovery rate of Bell’s palsy patients was 44.50% in the acupuncture combined with vitamin B12 group but 62.57% in the acupuncture alone group. The major acupoints were Taiyang (EX-HN5), Jiache (ST6), Dicang (ST4) and Sibai (ST2). The combined effect size showed that acupuncture combined with vitamin B12 was better than acupuncture alone for the treatment of Bell’s palsy (RR = 0.71, 95%CI: 0.58–0.87; P = 0.001), this result held true when 8 patients lost to follow up in one study were included into the analyses (RR = 0.70, 95%CI: 0.58–0.86; P = 0.0005). In the subgroup analyses, the therapeutic effect in patients of the electroacupuncture subgroup was better than in the non-electroacupuncture subgroup (P = 0.024). There was no significant difference in the incomplete recovery rate by subgroup analysis on drug types and treatment period. Most of the included studies were moderate or low quality, and bias existed. CONCLUSION: In patients with Bell’s palsy, acupuncture combined with vitamin B12 can reduce the risk of incomplete recovery compared with acupuncture alone in our meta-analysis. Because of study bias and methodological limitations, this conclusion is uncertain and the clinical application of acupuncture combined with vitamin B12 requires further exploration. PMID:26109959

Mobile User Objective System (MUOS) Multi-Service Operational Test and Evaluation-2 Report (with Classified Annex)

DTIC Science & Technology

2016-06-01

an effective system monitoring and display capability. The SOM, C-SSE, and resource managers access MUOS via a web portal called the MUOS Planning...and Provisioning Application (PlanProvApp). This web portal is their window into MUOS and is designed to provide them with a shared understanding of...including page loading errors, partially loaded web pages, incomplete reports, and inaccurate reports. For example, MUOS reported that there were

A "taxonomic affidavit": Why it is needed?

PubMed

Por, Francis Dov

2007-06-01

Imprecise and faulty taxonomic identification of the biological objects of many ecological and experimental studies renders these studies irreproducible. Incomplete identification to the species level and excessive use of vernacular species names are additional problems. Good science must be able to be falsified. I recommend that publications and granting agencies use and mention the names of the zoologists or botanists who identified the species. Voucher specimens should be marked and deposited in scientific museums for future checking.

The differing magnitude distributions of the two Jupiter Trojan color populations

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

Wong, Ian; Brown, Michael E.; Emery, Joshua P., E-mail: iwong@caltech.edu

The Jupiter Trojans are a significant population of minor bodies in the middle solar system that have garnered substantial interest in recent years. Several spectroscopic studies of these objects have revealed notable bimodalities with respect to near-infrared spectra, infrared albedo, and color, which suggest the existence of two distinct groups among the Trojan population. In this paper, we analyze the magnitude distributions of these two groups, which we refer to as the red and less red color populations. By compiling spectral and photometric data from several previous works, we show that the observed bimodalities are self-consistent and categorize 221 ofmore » the 842 Trojans with absolute magnitudes in the range H<12.3 into the two color populations. We demonstrate that the magnitude distributions of the two color populations are distinct to a high confidence level (>95%) and fit them individually to a broken power law, with special attention given to evaluating and correcting for incompleteness in the Trojan catalog as well as incompleteness in our categorization of objects. A comparison of the best-fit curves shows that the faint-end power-law slopes are markedly different for the two color populations, which indicates that the red and less red Trojans likely formed in different locations. We propose a few hypotheses for the origin and evolution of the Trojan population based on the analyzed data.« less

Urodynamic findings in women with pelvic organ prolapse and obstructive voiding symptoms.

PubMed

Dain, Lena; Auslander, Ron; Rosen, Talma; Segev, Yakir; Goldschmidt, Eyal; Abramov, Yoram

2010-11-01

To determine whether obstructive voiding symptoms in women with advanced pelvic organ prolapse (POP) were associated with objective bladder outflow tract obstruction. We reviewed preoperative data from patients with advanced POP who underwent surgical correction at the Department of Obstetrics and Gynecology, Carmel Medical Center, Haifa, Israel, between December 1, 2005, and November 30, 2007. Obstructive voiding symptoms were recorded from Pelvic Floor Distress Inventory-20 questionnaires. Of the 81 women aged 44-80 years who were included in the study, 40 (49.4%) reported incomplete bladder emptying preoperatively. There was no significant difference between these women and asymptomatic women in terms of demographic and clinical parameters such as age, parity, and stage of prolapse. Furthermore, there was no significant difference with regard to postvoid residual bladder volume (52.8 ± 65.8 vs 41.6 ± 41.2 mL), maximal (23.8 ± 11 vs 21.9 ± 9.6 mL/second) and average (10.3 ± 6.2 vs 9.3 ± 4 mL/second) urinary flow velocities, prevalence of increased postvoid residual volume (10.0% vs 4.8%), or obstructive urinary flow (17.5% vs 7.3%). Almost half of all women with advanced POP experienced incomplete bladder emptying; however, this symptom did not correlate with objective urodynamic bladder outflow tract obstruction. Copyright © 2010 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

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.

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

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.

Universal Robotic Gripper Based on the Jamming of Granular Material

DTIC Science & Technology

2010-11-02

gas inside, can be turned into rigid molds for lifting the object. However, the mechanism for this transfor- mation was not understood and no data...are actuated passively by contact with the surface of the object to be gripped and are locked in place by a single active element, a pump that...interlocking between gripper and object surfaces, static friction from normal stresses at contact, and an additional suction effect , if the gripper

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.

Education and Coronary Heart Disease Risk: Potential Mechanisms Such as Literacy, Perceived Constraints, and Depressive Symptoms

ERIC Educational Resources Information Center

Loucks, Eric B.; Gilman, Stephen E.; Howe, Chanelle J.; Kawachi, Ichiro; Kubzansky, Laura D.; Rudd, Rima E.; Martin, Laurie T.; Nandi, Arijit; Wilhelm, Aude; Buka, Stephen L.

2015-01-01

Objective: Education is inversely associated with coronary heart disease (CHD) risk; however the mechanisms are poorly understood. The study objectives were to evaluate the extent to which rarely measured factors (literacy, time preference, sense of control) and more commonly measured factors (income, depressive symptomatology, body mass index) in…

The Semological Structure of the English Verbs of Motion.

ERIC Educational Resources Information Center

Ikegami, Yoshihiko

Verbs of motion are understood in this paper as those verbs which refer to changes in locus. This definition is meant to exclude those cases in which only part of an object is moved, while the object as a whole remains in the same place ("swell,""expand,""stretch"). A discussion of this definition (Chapter 1) is…

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...

Hierarchical extraction of urban objects from mobile laser scanning data

NASA Astrophysics Data System (ADS)

Yang, Bisheng; Dong, Zhen; Zhao, Gang; Dai, Wenxia

2015-01-01

Point clouds collected in urban scenes contain a huge number of points (e.g., billions), numerous objects with significant size variability, complex and incomplete structures, and variable point densities, raising great challenges for the automated extraction of urban objects in the field of photogrammetry, computer vision, and robotics. This paper addresses these challenges by proposing an automated method to extract urban objects robustly and efficiently. The proposed method generates multi-scale supervoxels from 3D point clouds using the point attributes (e.g., colors, intensities) and spatial distances between points, and then segments the supervoxels rather than individual points by combining graph based segmentation with multiple cues (e.g., principal direction, colors) of the supervoxels. The proposed method defines a set of rules for merging segments into meaningful units according to types of urban objects and forms the semantic knowledge of urban objects for the classification of objects. Finally, the proposed method extracts and classifies urban objects in a hierarchical order ranked by the saliency of the segments. Experiments show that the proposed method is efficient and robust for extracting buildings, streetlamps, trees, telegraph poles, traffic signs, cars, and enclosures from mobile laser scanning (MLS) point clouds, with an overall accuracy of 92.3%.

A Novel Quantitative Computed Tomographic Analysis Suggests How Sirolimus Stabilizes Progressive Air Trapping in Lymphangioleiomyomatosis

PubMed Central

Kokosi, Maria; Lo, Pechin; Kim, Hyun J.; Ravenel, James G.; Meyer, Cristopher; Goldin, Jonathan; Lee, Hye-Seung; Strange, Charlie; McCormack, Francis X.

2016-01-01

Rationale: The Multicenter International Lymphangioleiomyomatosis Efficacy and Safety of Sirolimus (MILES) trial demonstrated that sirolimus stabilized lung function and improved measures of functional performance and quality of life in patients with lymphangioleiomyomatosis. The physiologic mechanisms of these beneficial actions of sirolimus are incompletely understood. Objectives: To prospectively determine the longitudinal computed tomographic lung imaging correlates of lung function change in MILES patients treated with placebo or sirolimus. Methods: We determined the baseline to 12-month change in computed tomographic image–derived lung volumes and the volume of the lung occupied by cysts in the 31 MILES participants (17 in sirolimus group, 14 in placebo group) with baseline and 12-month scans. Measurements and Main Results: There was a trend toward an increase in median expiratory cyst volume percentage in the placebo group and a reduction in the sirolimus group (+2.68% vs. +0.97%, respectively; P = 0.10). The computed tomographic image–derived residual volume and the ratio of residual volume to total lung capacity increased more in the placebo group than in the sirolimus group (+214.4 ml vs. +2.9 ml [P = 0.054] and +0.05 ml vs. −0.01 ml [P = 0.0498], respectively). A Markov transition chain analysis of respiratory cycle cyst volume changes revealed greater dynamic variation in the sirolimus group than in the placebo group at the 12-month time point. Conclusions: Collectively, these data suggest that sirolimus attenuates progressive gas trapping in lymphangioleiomyomatosis, consistent with a beneficial effect of the drug on airflow obstruction. We speculate that a reduction in lymphangioleiomyomatosis cell burden around small airways and cyst walls alleviates progressive airflow limitation and facilitates cyst emptying. PMID:26799509

Tunnel Propagation Following Defibrillation with ICD Shocks: Hidden Postshock Activations in the Left Ventricular Wall Underlie Isoelectric Window

PubMed Central

Constantino, Jason; Long, Yun; Ashihara, Takashi; Trayanova, Natalia A.

2010-01-01

Background Following near-defibrillation threshold (DFT) shocks from an ICD, the first postshock activation that leads to defibrillation failure arises focally after an isolelectric window (IW). The mechanisms underlying the IW remain incompletely understood. Objective The goal of this study was to provide mechanistic insight into the origins of postshock activations and IW following ICD shocks, and to link shock outcome to the preshock state of the ventricles. We hypothesized that the non-uniform ICD field results in the formation of an intramural excitable area (tunnel) only in the LV free wall, through which both pre-existing and new shock-induced wavefronts propagate during the IW. Methods Simulations were conducted using a realistic 3-D model of defibrillation in the rabbit ventricles. Biphasic ICD shocks of varying strengths were delivered to 27 different fibrillatory states. Results Following near-DFT shocks, regardless of preshock state, the main postshock excitable area was always located within LV free wall, creating an intramural tunnel. Either preexisting fibrillatory or shock-induced wavefronts propagated during the IW (duration of up to 74ms) in this tunnel and emerged as breakthroughs on LV epicardium. Preshock activity within the LV played a significant role in shock outcome: large number of preshock filaments resulted in an IW associated with tunnel propagation of preexisting rather than shock-induced wavefronts. Furthermore, shocks were more likely to succeed if LV excitable area was smaller. Conclusions The LV intramural excitable area is the primary reason for near-DFT failure. Any intervention that decreases the extent of this area will improve the likelihood of defibrillation success. PMID:20348028

African-American women's Upward Economic Mobility and Small for Gestational Age Births: A Population-Based Study.

PubMed

Collins, James W; Mariani, Allison; Rankin, Kristin

2018-03-01

Background The relationship between African-American women's upward economic mobility and small for gestational age (weight for gestational < 10th percentile, SGA) rates is incompletely understood. Objective To ascertain the extent to which African-American women's upward economic mobility from early-life impoverishment is coupled with reduced SGA rates. Methods Stratified and multilevel logistic regression analyses were completed on the Illinois transgenerational dataset of African-American infants (1989-1991) and their Chicago-born mothers (1956-1976) with linked U.S. census income information. Results Impoverished-born (defined as lowest quartile of neighborhood income distribution) African-American women (n = 4891) who remained impoverished by the time of delivery had a SGA rate of 19.7%. Individuals who achieved low (n = 5827), modest (n = 2254), or high (n = 732) upward economic mobility by adulthood had lower SGA rates of 17.2, 14.8, and 13.7%, respectively; RR = 0.9 (0.8-0.9), 0.8 (0.7-0.8), and 0.7 (0.6-0.8), respectively. In adjusted (controlling for traditional individual-level risk factors) multilevel regression models, there was a decreasing linear trend in SGA rates with increasing levels of upward economic mobility; the adjusted RR of SGA birth for impoverished-born African-American women who experienced low, modest, of high (compared to no) upward mobility equaled 0.95 (0.91, 0.99), 0.90 (0.83, 0.98), and 0.86 (0.75, 0.98), respectively, p < 0.05. Conclusions African-American women's upward economic mobility from early-life residence in poor urban communities is associated with lower SGA rates independent of adulthood risk status.

Peanut oral immunotherapy results in increased antigen-induced regulatory T-cell function and hypomethylation of forkhead box protein 3 (FOXP3).

PubMed

Syed, Aleena; Garcia, Marco A; Lyu, Shu-Chen; Bucayu, Robert; Kohli, Arunima; Ishida, Satoru; Berglund, Jelena P; Tsai, Mindy; Maecker, Holden; O'Riordan, Gerri; Galli, Stephen J; Nadeau, Kari C

2014-02-01

The mechanisms contributing to clinical immune tolerance remain incompletely understood. This study provides evidence for specific immune mechanisms that are associated with a model of operationally defined clinical tolerance. Our overall objective was to study laboratory changes associated with clinical immune tolerance in antigen-induced T cells, basophils, and antibodies in subjects undergoing oral immunotherapy (OIT) for peanut allergy. In a phase 1 single-site study, we studied participants (n = 23) undergoing peanut OIT and compared them with age-matched allergic control subjects (n = 20) undergoing standard of care (abstaining from peanut) for 24 months. Participants were operationally defined as clinically immune tolerant (IT) if they had no detectable allergic reactions to a peanut oral food challenge after 3 months of therapy withdrawal (IT, n = 7), whereas those who had an allergic reaction were categorized as nontolerant (NT; n = 13). Antibody and basophil activation measurements did not statistically differentiate between NT versus IT participants. However, T-cell function and demethylation of forkhead box protein 3 (FOXP3) CpG sites in antigen-induced regulatory T cells were significantly different between IT versus NT participants. When IT participants were withdrawn from peanut therapy for an additional 3 months (total of 6 months), only 3 participants remained classified as IT participants, and 4 participants regained sensitivity along with increased methylation of FOXP3 CpG sites in antigen-induced regulatory T cells. In summary, modifications at the DNA level of antigen-induced T-cell subsets might be predictive of a state of operationally defined clinical immune tolerance during peanut OIT. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

The Effect of Treating Institution on Outcomes in Head and Neck Cancer

PubMed Central

Lassig, Amy Anne D.; Joseph, Anne M.; Lindgren, Bruce R.; Fernandes, Patricia; Cooper, Sarah; Schotzko, Chelsea; Khariwala, Samir; Reynolds, Margaret; Yueh, Bevan

2017-01-01

Objective Factors leading patients with head and neck cancer (HNCA) to seek radiation or chemoradiation in an academic center versus the community are incompletely understood, as are the effects of site of treatment on treatment completion and survival. Study Design Historical cohort study. Setting Tertiary academic center, community practices. Methods A historical cohort study was completed of patients with mucosal HNCA identified by International Classification of Disease, Ninth Revision (ICD-9) codes receiving consultation at the authors’ institution from 2003 to 2008. Patients who received primary and adjuvant radiation at an academic center or in the community were included. The authors compared treatment completion rates and performed univariate and multivariate analyses of treatment outcomes. Results Of 388 patients, 210 completed treatment at an academic center and 145 at a community center (33 excluded, location unknown). Patients with HNCA undergoing radiation at an academic site had more advanced disease (P = .024) and were more likely to receive concurrent chemotherapy. Academic hospitals had a higher percentage of noncurrent smokers, higher median income, and higher percentage of oropharyngeal tumors. There was no significant difference in the rate of planned treatment completion between community and academic centers (93.7% vs 94.7%, P > .81) or rate of treatment breaks (22.4% vs 28.4%, P > .28). On Kaplan-Meier analysis, the 5-year survival rate was 53.2% (95% confidence interval [CI], 45.3%–61.1%) for academic centers and 32.8% (95% CI, 22.0%–43.6%) for community hospitals (P <.001). Conclusion In this cohort, although treatment completion and treatment breaks were similar between academic and community centers, survival rates were higher in patients treated in an academic setting. PMID:22875780

Vorticity is a marker of diastolic ventricular interdependency in pulmonary hypertension

PubMed Central

Browning, James; Schroeder, Joyce D.; Shandas, Robin; Kheyfets, Vitaly O.; Buckner, J. Kern; Hunter, Kendall S.; Hertzberg, Jean R.; Fenster, Brett E.

2016-01-01

Abstract Our objective was to determine whether left ventricular (LV) vorticity (ω), the local spinning motion of a fluid element, correlated with markers of ventricular interdependency in pulmonary hypertension (PH). Maladaptive ventricular interdependency is associated with interventricular septal shift, impaired LV performance, and poor outcomes in PH patients, yet the pathophysiologic mechanisms underlying fluid-structure interactions in ventricular interdependency are incompletely understood. Because conformational changes in chamber geometry affect blood flow formations and dynamics, LV ω may be a marker of LV-RV (right ventricular) interactions in PH. Echocardiography was performed for 13 PH patients and 10 controls for assessment of interdependency markers, including eccentricity index (EI), and biventricular diastolic dysfunction, including mitral valve (MV) and tricuspid valve (TV) early and late velocities (E and A, respectively) as well as MV septal and lateral early tissue Doppler velocities (e′). Same-day 4-dimensional cardiac magnetic resonance was performed for LV E (early)-wave ω measurement. LV E-wave ω was significantly decreased in PH patients (P = 0.008) and correlated with diastolic EI (Rho = −0.53, P = 0.009) as well as with markers of LV diastolic dysfunction, including MV E(Rho = 0.53, P = 0.011), E/A (Rho = 0.56, P = 0.007), septal e′ (Rho = 0.63, P = 0.001), and lateral e′ (Rho = 0.57, P = 0.007). Furthermore, LV E-wave ω was associated with indices of RV diastolic dysfunction, including TV e′ (Rho = 0.52, P = 0.012) and TV E/A (Rho = 0.53, P = 0.009). LV E-wave ω is decreased in PH and correlated with multiple echocardiographic markers of ventricular interdependency. LV ω may be a novel marker for fluid-tissue biomechanical interactions in LV-RV interdependency. PMID:27162613

S-nitrosation of β-catenin and p120 catenin: a novel regulatory mechanism in endothelial hyperpermeability

PubMed Central

Marín, N.; Zamorano, P.; Carrasco, R.; Mujica, P.; González, FG.; Quezada, C.; Meininger, CJ.; Boric, MP.; Durán, WN.; Sánchez, FA.

2014-01-01

Rationale Endothelial adherens junction proteins constitute an important element in the control of microvascular permeability. Platelet-activating factor (PAF) increases permeability to macromolecules via translocation of eNOS to cytosol and stimulation of eNOS-derived NO signaling cascade. The mechanisms by which NO signaling regulates permeability at adherens junctions are still incompletely understood. Objective We explored the hypothesis that PAF stimulates hyperpermeability via S-nitrosation (SNO) of adherens junction proteins. Methods and Results We measured PAF-stimulated S-nitrosation of β-catenin and p120-catenin (p120) in three cell lines: ECV-eNOSGFP, EAhy926 (derived from human umbilical vein) and CVEC (derived from bovine heart endothelium) and in the mouse cremaster muscle in vivo. SNO correlated with diminished abundance of β-catenin and p120 at the adherens junction and with hyperpermeability. TNF-α increased NO production and caused similar increase in S-nitrosation as PAF. To ascertain the importance of eNOS subcellular location in this process, we used ECV-304 cells transfected with cytosolic eNOS (GFPeNOSG2A) and plasma membrane eNOS (GFPeNOSCAAX). PAF induced S-nitrosation of β-catenin and p120 and significantly diminished association between these proteins in cells with cytosolic eNOS but not in cells wherein eNOS is anchored to the cell membrane. Inhibitors of NO production and of S-nitrosation blocked PAF-induced S-nitrosation and hyperpermeability whereas inhibition of the cGMP pathway had no effect. Mass spectrometry analysis of purified p120 identified cysteine 579 as the main S-nitrosated residue in the region that putatively interacts with VE-cadherin. Conclusions Our results demonstrate that agonist-induced SNO contributes to junctional membrane protein changes that enhance endothelial permeability. PMID:22777005

Satisfaction With Communication In Primary Care For Spanish-Speaking And English-Speaking Parents

PubMed Central

Flower, Kori B.; Skinner, Asheley C.; Yin, H. Shonna; Rothman, Russell L.; Sanders, Lee M.; Delamater, Alan; Perrin, Eliana M.

2017-01-01

Background and Objective Effective communication with primary care physicians is important yet incompletely understood for Spanish-speaking parents. We predicted lower satisfaction among Spanish-speaking compared with English-speaking Latino and non-Latino parents. Methods Cross-sectional analysis at 2-month well visits within the Greenlight study at 4 pediatric resident clinics. Parents reported satisfaction with 14 physician communication items using the validated Communication Assessment Tool (CAT). High satisfaction was defined as “excellent” on each CAT item. Mean estimations compared satisfaction for communication items among Spanish and English-speaking Latinos and non-Latinos. We used generalized linear regression modeling, adjusted for parent age, education, income, and clinic site. Among Spanish-speaking parents, we compared visits conducted in Spanish with and without an interpreter, and in English. Results Compared with English-speaking Latino (N=127) and non-Latino parents (N=432), fewer Spanish-speaking parents (N=303) reported satisfaction with 14 communication items. No significant differences were found between English-speaking Latinos and non-Latinos. Greatest differences were found in: greeting that made the parent comfortable (59.4% of Spanish-speaking Latinos endorsing “Excellent” vs. 77.5% English-speaking Latinos, p<0.01) and discussing follow-up (62.5% of Spanish-speaking Latinos vs. 79.8% English-speaking Latinos, p<0.01). After adjusting for parent age, education, income, and study site, Spanish-speaking Latinos were still less likely to report high satisfaction with these communication items. Satisfaction was not different among Spanish-speaking parents when the physician spoke Spanish versus used an interpreter. Conclusions Satisfaction with physician communication was associated with language, but not ethnicity. Spanish-speaking parents less frequently report satisfaction with communication, and innovative solutions to enhance communication quality are needed. PMID:28104488

Antipsychotic-Induced Changes in Blood Levels of Leptin in Schizophrenia: A Meta-Analysis

PubMed Central

Potvin, Stéphane; Zhornitsky, Simon; Stip, Emmanuel

2015-01-01

Objectives: Weight gain is a major side effect of antipsychotics (APs), which contributes to poor treatment adherence and significant morbidity. The mechanisms involved in AP-induced weight gain are incompletely understood. Recently, it has been proposed that changes in leptin, an cadipocyte-derived hormone exerting anorexigenic effects, may be involved in AP-induced weight gain. Thus far, studies on leptin changes during AP treatment have produced inconsistent results, prompting our group to perform a meta-analysis. Method: A search of the literature was performed using PubMed and Embase. Studies were included only if reporting peripheral levels of leptin before and after AP treatment in schizophrenia. Effect size estimates were calculated with Hedges g and were aggregated using a random effects model as results were heterogeneous (P < 0.10). Meta-regression analyses were performed using study length and changes in body mass index (BMI) as moderator variables. Results: Twenty-eight studies were retrieved, including 39 comparisons. A moderate and positive effect size was observed across studies. Olanzapine, clozapine, and quetiapine produced moderate leptin elevations, whereas haloperidol and risperidone were associated with small (nonsignificant) leptin changes. Across studies, BMI changes were significantly associated with increases in leptin levels. There was no effect of sex on AP-induced changes in leptin. Conclusions: A physiological role of leptin in AP-induced weight gain is supported because the most significant leptin increases were observed with APs inducing the most weight gain and because of the observed association between leptin increases and BMI changes. The overall increase in leptin levels suggests that leptin acts as a negative feedback signal in the event of fat increase. PMID:25886677

Prevalence, awareness, treatment and control of hypertension in a self-selected sub-Saharan African urban population: a cross-sectional study

PubMed Central

Dzudie, Anastase; Kengne, André Pascal; Muna, Walinjom F T; Ba, Hamadou; Menanga, Alain; Kouam Kouam, Charles; Abah, Joseph; Monkam, Yves; Biholong, Christian; Mintom, Pierre; Kamdem, Félicité; Djomou, Armel; Ndjebet, Jules; Wambo, Cyrille; Luma, Henry; Ngu, Kathleen Blackett; Kingue, Samuel

2012-01-01

Objectives Hypertension has been established as a major public health problem in Africa, but its specific contributions to disease burden are still incompletely understood. We report the prevalence and determinants of hypertension, detection, treatment and control rates among adults in major cities in Cameroon. Design Cross-sectional study. Settings Community-based multicentre study in major cities in Cameroon. Participants Participants were self-selected urban dwellers from the Center, Littoral, North-West and West Regions, who attended on 17 May 2011 a screening campaign advertised through mass media. Primary and secondary outcomes measures Hypertension defined as systolic (and/or diastolic) blood pressure (BP)≥ 140 (90) mm Hg, or ongoing BP-lowering medications. Results In all, 2120 participants (1003 women) were included. Among them, 1007 (prevalence rate 47.5%) had hypertension, including 319 (awareness rate 31.7%) who were aware of their status. The prevalence of hypertension increased with age overall and by sex and region. Among aware hypertensive participants, 191 (treatment rate 59.9%) were on regular BP-lowering medication, and among those treated, 47 (controlled rate 24.6%) were at target BP levels (ie, systolic (and diastolic) BP<140 (90) mm Hg). In multivariable logistic regression analysis, male gender, advanced age, parental history of hypertension, diabetes mellitus, elevated waist and elevated body mass index (BMI) were the significant predictors of hypertension. Likewise, male gender, high BMI and physical inactivity were associated with poor control. Conclusions High prevalence of hypertension with low awareness, treatment and control were found in this urban population; these findings are significant and alarming with consideration to the various improvements in the access to healthcare and the continuing efforts to educate communities over the last few decades. PMID:22923629

Severe menopausal symptoms are widespread among survivors of breast cancer treatment regardless of time since diagnosis.

PubMed

Mortimer, Joanne; Behrendt, Carolyn E

2013-09-01

The intensity and persistence of treatment-related symptoms among breast cancer survivors is incompletely understood. The objective of the study was to estimate prevalence of severe symptoms well after initial treatment for breast cancer, to test whether symptom intensity diminishes with time or varies by treatment received. This was a cross-sectional survey of female survivors of stage I-III invasive breast cancer, seen for routine follow-up a year or more after diagnosis. Data was derived from three validated questionnaires indicating physical and emotional domains. Symptoms rated in the top two levels of four- or five-item Likert scales were "severe." Associations with symptom intensity were tested using multivariate linear regression. Survey response was 68.5% (50/73). Respondents were age 55.4 (±9.1) years, median 2.2 (1.0-13.1) years since diagnosis; 64% were receiving endocrine therapy. Severe levels of hot flashes (42% of respondents), weight gain (32%), low libido (32%), and joint pain (30%) were common; (36%) of respondents rated sleep "fairly poor" or "very bad;" 30% were fatigued at least half the day. For 34%, health typically limited vigorous activities "a lot." Most (84%) respondents were experiencing at least one severe symptom. Symptom intensity did not vary with time since diagnosis. Of seven symptoms, three (hot flashes, weight gain, low libido) were more intense when systemic treatment had included endocrine therapy. Time in past month feeling down, nervous, or worn out increased with intensity of physical symptoms. Given their severity, persistence, and association with emotional burden, treatment-related symptoms among breast cancer survivors (BCS) merit greater attention toward clinical management, patient education, and longitudinal study.

ANTICONVULSANT AND ANTIEPILEPTIC ACTIONS OF 2-DEOXY-DGLUCOSE IN EPILEPSY MODELS

PubMed Central

Stafstrom, Carl E.; Ockuly, Jeffrey C.; Murphree, Lauren; Valley, Matthew T.; Roopra, Avtar; Sutula, Thomas P.

2009-01-01

Objective Conventional anticonvulsants reduce neuronal excitability through effects on ion channels and synaptic function. Anticonvulsant mechanisms of the ketogenic diet remain incompletely understood. Since carbohydrates are restricted in patients on the ketogenic diet, we evaluated the effects of limiting carbohydrate availability by reducing glycolysis using the glycolytic inhibitor 2-deoxy-D-glucose (2DG) in experimental models of seizures and epilepsy. Methods Acute anticonvulsant actions of 2DG were assessed in vitro in rat hippocampal slices perfused with 7.5mM [K+]o, 4-aminopyridine (4-AP), or bicuculline and in vivo against seizures evoked by 6 Hz stimulation in mice, audiogenic stimulation in Fring’s mice, and maximal electroshock and subcutaneous Metrazol in rats. Chronic antiepileptic effects of 2DG were evaluated in rats kindled from olfactory bulb or perforant path. Results 2DG (10mM) reduced interictal epileptiform bursts induced by high [K+]o, 4-AP and bicuculline, and electrographic seizures induced by high [K+]o in CA3 of hippocampus. 2DG reduced seizures evoked by 6 Hz stimulation in mice (ED50 = 79.7 mg/kg) and audiogenic stimulation in Fring’s mice (ED50 = 206.4 mg/kg). 2DG exerted chronic antiepileptic action by increasing afterdischarge thresholds in perforant path (but not olfactory bulb) kindling and caused a 2-fold slowing in progression of kindled seizures at both stimulation sites. 2DG did not protect against maximal electroshock or Metrazol seizures. Interpretation The glycolytic inhibitor 2DG exerts acute anticonvulsant and chronic antiepileptic actions and has a novel pattern of effectiveness in preclinical screening models. These results identify metabolic regulation as a potential therapeutic target for seizure suppression and modification of epileptogenesis. PMID:19399874

Physiological response to submaximal isometric contractions of the paravertebral muscles

NASA Technical Reports Server (NTRS)

Jensen, B. R.; Jorgensen, K.; Hargens, A. R.; Nielsen, P. K.; Nicolaisen, T.

1999-01-01

STUDY DESIGN: Brief (30-second) isometric trunk extensions at 5%, 20%, 40%, 60%, and 80% of maximal voluntary contraction (MVC) and 3 minutes of prolonged trunk extension (20% MVC) in erect position were studied in nine healthy male subjects. OBJECTIVES: To investigate the intercorrelation between intramuscular pressure and tissue oxygenation of the paravertebral muscles during submaximal isometric contractions and further, to evaluate paravertebral electromyogram and intramuscular pressure as indicators of force development. SUMMARY OF BACKGROUND DATA: Local physiologic responses to muscle contraction are incompletely understood. METHODS: Relative oxygenation was monitored with noninvasive near-infrared spectroscopy, intramuscular pressure was measured with a transducer-tipped catheter, and surface electromyogram was monitored at three recording sites. RESULTS: The root mean square amplitudes of the paravertebral electromyogram (L4, left and right; T12, right) and intramuscular pressure measured in the lumbar multifidus muscle at L4 increased with greater force development in a curvilinear manner. A significant decrease in the oxygenation of the lumbar paravertebral muscle in response to muscle contraction was found at an initial contraction level of 20% MVC. This corresponded to a paravertebral intramuscular pressure of 30-40 mm Hg. However, during prolonged trunk extension, no further decrease in tissue oxygenation was found compared with the tissue oxygenation level at the end of the brief contractions, indicating that homeostatic adjustments (mean blood pressure and heart rate) over time were sufficient to maintain paravertebral muscle oxygen levels. CONCLUSION: At a threshold intramuscular pressure of 30-40 mm Hg during muscle contraction, oxygenation in the paravertebral muscles is significantly reduced. The effect of further increase in intramuscular pressure on tissue oxygenation over time may be compensated for by an increase in blood pressure and heart rate. Surface electromyogram amplitudes and intramuscular pressure can be used as indicators of paravertebral muscle force.

Ventilatory control sensitivity in patients with obstructive sleep apnea is sleep stage dependent.

PubMed

Landry, Shane A; Andara, Christopher; Terrill, Philip I; Joosten, Simon A; Leong, Paul; Mann, Dwayne L; Sands, Scott A; Hamilton, Garun S; Edwards, Bradley A

2018-05-01

The severity of obstructive sleep apnea (OSA) is known to vary according to sleep stage; however, the pathophysiology responsible for this robust observation is incompletely understood. The objective of the present work was to examine how ventilatory control system sensitivity (i.e. loop gain) varies during sleep in patients with OSA. Loop gain was estimated using signals collected from standard diagnostic polysomnographic recordings performed in 44 patients with OSA. Loop gain measurements associated with nonrapid eye movement (NREM) stage 2 (N2), stage 3 (N3), and REM sleep were calculated and compared. The sleep period was also split into three equal duration tertiles to investigate how loop gain changes over the course of sleep. Loop gain was significantly lower (i.e. ventilatory control more stable) in REM (Mean ± SEM: 0.51 ± 0.04) compared with N2 sleep (0.63 ± 0.04; p = 0.001). Differences in loop gain between REM and N3 (p = 0.095), and N2 and N3 (p = 0.247) sleep were not significant. Furthermore, N2 loop gain was significantly lower in the first third (0.57 ± 0.03) of the sleep period compared with later second (0.64 ± 0.03, p = 0.012) and third (0.64 ± 0.03, p = 0.015) tertiles. REM loop gain also tended to increase across the night; however, this trend was not statistically significant [F(2, 12) = 3.49, p = 0.09]. These data suggest that loop gain varies between REM and NREM sleep and modestly increases over the course of sleep. Lower loop gain in REM is unlikely to contribute to the worsened OSA severity typically observed in REM sleep, but may explain the reduced propensity for central sleep apnea in this sleep stage.

Content validity of the Benign Prostatic Hyperplasia Impact Index (BII); a measure of how urinary trouble and problems associated with BPH may impact the patient.

PubMed

Kingery, L; Martin, M L; Naegeli, A N; Khan, S; Viktrup, L

2012-09-01

The objective of this qualitative interview study was to assess the content validity of the Benign Prostatic Hyperplasia Impact Index (BII) in a sample of men with signs and symptoms of Benign Prostatic Obstruction believed to be caused by benign prostatic hyperplasia (BPH lower urinary tract symptoms/BPH-LUTS) using concept elicitation (CE) and cognitive interviewing (CI) methods. Fifty men with BPH-LUTS participated in the study; 27 completed CE interviews and 23 completed cognitive interviews. Patient's average age was 69 years with a mean duration of BPH-LUTS of 6.5 years. IPSS scores ranged from 8 to 33 (higher scores indicating greater symptom severity). Overall, the most frequent symptoms (prevalence of ≥ 75%) reported spontaneously or after further explanation were awakening from sleep, increased daytime voiding (frequency), urgent desire to void (urgency), slow stream, and feeling of incomplete bladder emptying. Symptoms primarily recognized in response to follow up probe questions with a prevalence of ≥ 40% included terminal dribble, splitting of urinary stream, intermittent stream, straining and post-micturition dribble. Especially bothersome [> 5 on the numerical rating scale (NRS) of 0-10] and frequent symptoms included urgency and awakening at night to void. Discomfort or pain while urinating and post-micturition dribble were equally bothersome though less frequent. Five BPH symptom-related impact themes were identified: coping, daily responsibilities, emotion, lifestyle and relationships, and sleep. The BII was found to be easily understood, does capture clinically relevant BPH impacts related to urinary trouble and problems, and does capture most of the important symptom-related impacts as described by participants in this study. © 2012 Blackwell Publishing Ltd.

Functional Targets of the Monogenic Diabetes Transcription Factors HNF-1α and HNF-4α Are Highly Conserved Between Mice and Humans

PubMed Central

Boj, Sylvia F.; Servitja, Joan Marc; Martin, David; Rios, Martin; Talianidis, Iannis; Guigo, Roderic; Ferrer, Jorge

2009-01-01

OBJECTIVE The evolutionary conservation of transcriptional mechanisms has been widely exploited to understand human biology and disease. Recent findings, however, unexpectedly showed that the transcriptional regulators hepatocyte nuclear factor (HNF)-1α and -4α rarely bind to the same genes in mice and humans, leading to the proposal that tissue-specific transcriptional regulation has undergone extensive divergence in the two species. Such observations have major implications for the use of mouse models to understand HNF-1α– and HNF-4α–deficient diabetes. However, the significance of studies that assess binding without considering regulatory function is poorly understood. RESEARCH DESIGN AND METHODS We compared previously reported mouse and human HNF-1α and HNF-4α binding studies with independent binding experiments. We also integrated binding studies with mouse and human loss-of-function gene expression datasets. RESULTS First, we confirmed the existence of species-specific HNF-1α and -4α binding, yet observed incomplete detection of binding in the different datasets, causing an underestimation of binding conservation. Second, only a minor fraction of HNF-1α– and HNF-4α–bound genes were downregulated in the absence of these regulators. This subset of functional targets did not show evidence for evolutionary divergence of binding or binding sequence motifs. Finally, we observed differences between conserved and species-specific binding properties. For example, conserved binding was more frequently located near transcriptional start sites and was more likely to involve multiple binding events in the same gene. CONCLUSIONS Despite evolutionary changes in binding, essential direct transcriptional functions of HNF-1α and -4α are largely conserved between mice and humans. PMID:19188435

ANGPT2 Genetic Variant Is Associated with Trauma-associated Acute Lung Injury and Altered Plasma Angiopoietin-2 Isoform Ratio

PubMed Central

Meyer, Nuala J.; Li, Mingyao; Feng, Rui; Bradfield, Jonathan; Gallop, Robert; Bellamy, Scarlett; Fuchs, Barry D.; Lanken, Paul N.; Albelda, Steven M.; Rushefski, Melanie; Aplenc, Richard; Abramova, Helen; Atochina-Vasserman, Elena N.; Beers, Michael F.; Calfee, Carolyn S.; Cohen, Mitchell J.; Pittet, Jean-Francois; Christiani, David C.; O'Keefe, Grant E.; Ware, Lorraine B.; May, Addison K.; Wurfel, Mark M.; Hakonarson, Hakon; Christie, Jason D.

2011-01-01

Rationale: Acute lung injury (ALI) acts as a complex genetic trait, yet its genetic risk factors remain incompletely understood. Large-scale genotyping has not previously been reported for ALI. Objectives: To identify ALI risk variants after major trauma using a large-scale candidate gene approach. Methods: We performed a two-stage genetic association study. We derived findings in an African American cohort (n = 222) using a cardiopulmonary disease–centric 50K single nucleotide polymorphism (SNP) array. Genotype and haplotype distributions were compared between subjects with ALI and without ALI, with adjustment for clinical factors. Top performing SNPs (P < 10−4) were tested in a multicenter European American trauma-associated ALI case-control population (n = 600 ALI; n = 2,266 population-based control subjects) for replication. The ALI-associated genomic region was sequenced, analyzed for in silico prediction of function, and plasma was assayed by ELISA and immunoblot. Measurements and Main Results: Five SNPs demonstrated a significant association with ALI after adjustment for covariates in Stage I. Two SNPs in ANGPT2 (rs1868554 and rs2442598) replicated their significant association with ALI in Stage II. rs1868554 was robust to multiple comparison correction: odds ratio 1.22 (1.06–1.40), P = 0.0047. Resequencing identified predicted novel splice sites in linkage disequilibrium with rs1868554, and immunoblots showed higher proportion of variant angiopoietin-2 (ANG2) isoform associated with rs1868554T (0.81 vs. 0.48; P = 0.038). Conclusions: An ANGPT2 region is associated with both ALI and variation in plasma angiopoietin-2 isoforms. Characterization of the variant isoform and its genetic regulation may yield important insights about ALI pathogenesis and susceptibility. PMID:21257790

Somatic Symptoms Evoked by Exam Stress in University Students: The Role of Alexithymia, Neuroticism, Anxiety and Depression

PubMed Central

Zunhammer, Matthias; Eberle, Hanna; Eichhammer, Peter; Busch, Volker

2013-01-01

Objective The etiology of somatization is incompletely understood, but could be elucidated by models of psychosocial stress. Academic exam stress has effectively been applied as a naturalistic stress model, however its effect on somatization symptoms according to ICD-10 and DSM-IV criteria has not been reported so far. Baseline associations between somatization and personality traits, such as alexithymia, have been studied exhaustively. Nevertheless, it is largely unknown if personality traits have an explanatory value for stress induced somatization. Methods This longitudinal, quasi-experimental study assessed the effects of university exams on somatization — and the reversal of effects after an exam-free period. Repeated-observations were obtained within 150 students, measuring symptom intensity before, during and after an exam period, according to the Screening for Somatoform Symptoms 7-day (SOMS-7d). Additionally, self-reports on health status were used to differentiate between medically explained and medically unexplained symptoms. Alexithymia, neuroticism, trait-anxiety and baseline depression were surveyed using the Toronto-Alexithymia Scale (TAS-20), the Big-Five Personality Interview (NEO-FFI), the State Trait Anxiety Inventory (STAI) and Beck’s Depression Inventory (BDI-II). These traits were competitively tested for their ability to explain somatization increases under exam stress. Results Somatization significantly increased across a wide range of symptoms under exam stress, while health reports pointed towards a reduction in acute infections and injuries. Neuroticism, alexithymia, trait anxiety and depression explained variance in somatization at baseline, but only neuroticism was associated with symptom increases under exam stress. Conclusion Exam stress is an effective psychosocial stress model inducing somatization. A comprehensive quantitative description of bodily symptoms under exam stress is supplied. The results do not support the stress-alexithymia hypothesis, but favor neuroticism as a personality trait of importance for somatization. PMID:24367700

Determination of lumbosacral transitional vertebrae in kidney urinary bladder x-ray films in the Saudi population

PubMed Central

Khashoggi, Khalid G.; Hafiz, Rawan M.; Bock, Yasmin M.; Kaki, Abdullah M.

2017-01-01

Objectives: To investigated the rate of occurrence of lumbosacral transitional vertebrae (LSTV), spinal variant, in kidney urinary bladder (KUB) plain radiographs in a Saudi population. Methods: Between January 2012 to January 2015, KUB plain films obtained from patients at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, were reviewed, and the presence or absence of LSTV was documented and classified as incomplete or complete. Patients who had evidence of spinal surgery that would obscure the view were excluded. Results: A total of 2078 patients underwent KUB examinations during the study period; LSTV anomalies were detected in 158 of these. Sacralization was present in 153 (96.8%) of this cohort, while lumbarization was present in 5 (3.2%). A total of 136 (86.1%) of the sacralized segments were of the incomplete type, whereas 17 (10.7%) were complete. Of the lumbarized vertebrae, 3 (1.8%) were incomplete, and 2 (1.2%) were complete. The most frequent type in men was type Ib (28.5%) for sacralized segments, and type IIb for lumbarized segments (0.6%). In women, type Ia was the most common form of sacralized segments (11.3%) and type IIb was the most common form of lumbarized segments (2.8%). Conclusion: The prevalence of LSTV in Saudi patients is 7.6%, with a higher incidence of sacralization than lumbarization. Further studies with larger sample sizes and longer follow-up time are needed to demonstrate the clinical significance thereof. PMID:28762430

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

Angiographic and epidemiological characteristics associated with aneurysm remnants after microsurgical clipping

PubMed Central

Dellaretti, Marcos; da Silva Martins, Warley Carvalho; Dourado, Jules Carlos; Faglioni, Wilson; Quadros, Ricardo Souza; de Souza Moraes, Vítor Vieira; de Souza Filho, Carlos Batista Alves

2017-01-01

Background: Despite new techniques for the treatment of cerebral aneurysms, the percentage of aneurysm remnants after surgical intervention seems to be relatively constant. The objective of this study was to assess angiographic and epidemiological features associated with aneurysm remnants after microsurgical clipping. Methods: This study was conducted from February 2009 to August 2012 on a series of 90 patients with 105 aneurysms referred to the Santa Casa of Belo Horizonte who were surgically treated and angiographically controlled. Results: Surgical clipping was considered incomplete in 13.3% of the aneurysms. The mean age of cases with an aneurysm remnant was 57.5 years, whereas the mean age without aneurysm remnant was 49.7 years (P = 0.02). Aneurysm remnants were detected more frequently on the internal carotid artery, nevertheless, no statistically significant differences were verified when comparing the locations. Aneurysm size in the preoperative angiography verified that the mean size of aneurysms operated was 6.56 mm, such that in cases showing a postoperative remnant, the mean size was 9.7 mm and in cases with complete clipping it was 6.08 mm (P = 0.02). Postoperative angiography showed that, in cases with residual aneurysm, the number of clips used was higher – a mean of 1.8 for complete clipping and 3.1 for incomplete clipping (P < 0.001). Conclusions: Aneurysm size and patient age showed significant correlations with residual intracranial aneurysm. The mean number of clips used was higher in cases with incomplete occlusion. PMID:28904825

[Strangulation marks in homicides caused by choking ? On an irritant blood stain picture].

PubMed

Metter, D

1988-01-01

Three homicides and one attempted homicide by choking in which apparent signs of throttling were present on the skin of the neck are described. The victims wore slender necklaces which were pressed against the skin by the hands of the perpetrator, causing transverse hematomas and cutaneous abrasions. The following criterious are typical for simulated signs of throttling: similarity to objects on the neck, incomplete course around the neck, absence of coarctation of the soft tissues, no lesions of subcutaneous structures.

Adaptive management: Chapter 1

USGS Publications Warehouse

Allen, Craig R.; Garmestani, Ahjond S.; Allen, Craig R.; Garmestani, Ahjond S.

2015-01-01

Adaptive management is an approach to natural resource management that emphasizes learning through management where knowledge is incomplete, and when, despite inherent uncertainty, managers and policymakers must act. Unlike a traditional trial and error approach, adaptive management has explicit structure, including a careful elucidation of goals, identification of alternative management objectives and hypotheses of causation, and procedures for the collection of data followed by evaluation and reiteration. The process is iterative, and serves to reduce uncertainty, build knowledge and improve management over time in a goal-oriented and structured process.

Adaptive management

USGS Publications Warehouse

Allen, Craig R.; Garmestani, Ahjond S.

2015-01-01

Adaptive management is an approach to natural resource management that emphasizes learning through management where knowledge is incomplete, and when, despite inherent uncertainty, managers and policymakers must act. Unlike a traditional trial and error approach, adaptive management has explicit structure, including a careful elucidation of goals, identification of alternative management objectives and hypotheses of causation, and procedures for the collection of data followed by evaluation and reiteration. The process is iterative, and serves to reduce uncertainty, build knowledge and improve management over time in a goal-oriented and structured process.

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

Evaluation and Management of Dyslipidemia in Patients with HIV Infection

PubMed Central

Green, Michael L

2002-01-01

OBJECTIVE Persons with HIV infection develop metabolic abnormalities related to their antiretroviral therapy and HIV infection itself. The objective of this study was to summarize the emerging evidence for the incidence, etiology, health risks, and treatment of dyslipidemias in HIV disease. DESIGN Systematic review of original research with quantitative synthesis. MAIN RESULTS Dyslipidemia is common in persons with HIV infection on highly active antiretroviral therapy (HAART), but methodologic differences between studies preclude precise estimates of prevalence and incidence. The typical pattern includes elevated total cholesterol, low-density lipoprotein cholesterol, and triglycerides, which may be markedly elevated. The dyslipidemia may be associated with lipodystrophy, insulin resistance, and, rarely, frank diabetes mellitus. Exposure to protease inhibitors (PIs) is associated with this entire range of metabolic abnormalities. PI-naïve patients on nucleoside reverse transcriptase inhibitors (NRTIs) may develop lipodystrophy, insulin resistance, hypercholesterolemia, and possibly modest elevations in triglycerides but not severe hypertriglyceridemia, which appears to be linked to PIs alone. Most studies have not found an association between CD4 lymphocyte count or HIV viral load and lipid abnormalities. The pathogenesis is incompletely understood and appears to be multifactorial. There are insufficient data to definitively support an increased coronary heart disease risk in patients with HIV-related dyslipidemia. However, some of the same metabolic abnormalities remain firmly established risk factors in other populations. Patients on HAART with severe hypertriglyceridemia may develop pancreatitis or other manifestations of the chylomicronemia syndrome. Some of the metabolic derangements (particularly hypertriglyceridemia) may improve upon replacing a PI with a non-nucleoside reverse transcriptase inhibitor. The limited experience suggests that fibrates, pravastatin, and atorvastatin can safely treat lipid abnormalities in HIV-infected patients. CONCLUSIONS Patients with HIV infection on HAART should be screened for lipid disorders, given their incidence, potential for morbidity, and possible long-term cardiovascular risk. Treatment decisions are complex and must include assessments of cardiac risk, HIV infection status, reversibility of the dyslipidemia, and the effectiveness and toxicities of lipid-lowering medications. The multiple potential drug interactions with antiretroviral or other HIV-related medications should be considered in lipid-lowering drug selection and monitoring. PMID:12390557

A Review of Auditory Prediction and Its Potential Role in Tinnitus Perception.

PubMed

Durai, Mithila; O'Keeffe, Mary G; Searchfield, Grant D

2018-06-01

The precise mechanisms underlying tinnitus perception and distress are still not fully understood. A recent proposition is that auditory prediction errors and related memory representations may play a role in driving tinnitus perception. It is of interest to further explore this. To obtain a comprehensive narrative synthesis of current research in relation to auditory prediction and its potential role in tinnitus perception and severity. A narrative review methodological framework was followed. The key words Prediction Auditory, Memory Prediction Auditory, Tinnitus AND Memory, Tinnitus AND Prediction in Article Title, Abstract, and Keywords were extensively searched on four databases: PubMed, Scopus, SpringerLink, and PsychINFO. All study types were selected from 2000-2016 (end of 2016) and had the following exclusion criteria applied: minimum age of participants <18, nonhuman participants, and article not available in English. Reference lists of articles were reviewed to identify any further relevant studies. Articles were short listed based on title relevance. After reading the abstracts and with consensus made between coauthors, a total of 114 studies were selected for charting data. The hierarchical predictive coding model based on the Bayesian brain hypothesis, attentional modulation and top-down feedback serves as the fundamental framework in current literature for how auditory prediction may occur. Predictions are integral to speech and music processing, as well as in sequential processing and identification of auditory objects during auditory streaming. Although deviant responses are observable from middle latency time ranges, the mismatch negativity (MMN) waveform is the most commonly studied electrophysiological index of auditory irregularity detection. However, limitations may apply when interpreting findings because of the debatable origin of the MMN and its restricted ability to model real-life, more complex auditory phenomenon. Cortical oscillatory band activity may act as neurophysiological substrates for auditory prediction. Tinnitus has been modeled as an auditory object which may demonstrate incomplete processing during auditory scene analysis resulting in tinnitus salience and therefore difficulty in habituation. Within the electrophysiological domain, there is currently mixed evidence regarding oscillatory band changes in tinnitus. There are theoretical proposals for a relationship between prediction error and tinnitus but few published empirical studies. American Academy of Audiology.

Seizures in Children with Severe Traumatic Brain Injury

PubMed Central

Bennett, Kimberly Statler; DeWitt, Peter E.; Harlaar, Nicole; Bennett, Tellen D.

2016-01-01

Objective Traumatic brain injury (TBI) causes substantial morbidity and mortality in children. Post-traumatic seizures (PTS) may worsen outcomes after TBI. PTS risk factors are incompletely understood. Our objective was to clarify PTS risk factors in a large cohort of children with severe TBI. Design Retrospective cohort study of a probabilistically linked dataset from the National Trauma Data Bank (NTDB) and the Pediatric Health Information Systems (PHIS) database, 2007–2010 Setting 29 U.S. children’s hospitals Patients 2,122 children (age < 18 years old at admission) with linked NTDB and PHIS records, severe (Emergency Department [ED] Glasgow Coma Scale [GCS] < 8) TBI, hospital length of stay > 24 hours, and non-missing disposition Interventions None Measurements and Main Results The outcome was PTS, identified using validated ICD-9-CM diagnosis codes. Pre-specified candidate predictors of PTS included age, injury mechanism, ED GCS, intracranial hemorrhage type, hypoxia, hypotension, and cardiac arrest. PTS were diagnosed in 25.2% of children with severe TBI. In those without abuse/assault or subdural hemorrhage (SDH), the PTS rate varied between 36.6% in those < 2 years old and 16.4% in those 14–17 years old. Age, abusive mechanism, and subdural hemorrhage (SDH) are each significant predictors of PTS. The risk of PTS has a complex relationship with these predictors. The estimated odds of PTS decrease with advancing age, OR = 0.929 (0.905, 0.954) per additional year of age with no abuse/assault and no SDH; OR = 0.820 (0.730, 0.922) per additional year of age when abuse and SDH are present. An infant with accidental TBI and SDH has approximately the same estimated probability of PTS as an abused infant without SDH, 47% (95% CI: 39%, 55%) versus 50% (95% CI: 41%, 58%), P = 0.69. The triad of young age, injury by abuse/assault, and SDH confers the greatest estimated probability for PTS, 60% (95% CI: 53%, 66%). Conclusions PTS risk in children with severe TBI is greatest with a triad of younger age, injury by abuse/assault, and SDH. However, PTS is common even in the absence of these factors. PMID:27654815

Fasting Serum Taurine-Conjugated Bile Acids Are Elevated in Type 2 Diabetes and Do Not Change With Intensification of Insulin

PubMed Central

Wewalka, Marlene; Patti, Mary-Elizabeth; Barbato, Corinne; Houten, Sander M.

2014-01-01

Context: Bile acids (BAs) are newly recognized signaling molecules in glucose and energy homeostasis. Differences in BA profiles with type 2 diabetes mellitus (T2D) remain incompletely understood. Objective: The objective of the study was to assess serum BA composition in impaired glucose-tolerant, T2D, and normal glucose-tolerant persons and to monitor the effects of improving glycemia on serum BA composition in T2D patients. Design and Setting: This was a cross-sectional cohort study in a general population (cohort 1) and nonrandomized intervention (cohort 2). Patients and Interventions: Ninety-nine volunteers underwent oral glucose tolerance testing, and 12 persons with T2D and hyperglycemia underwent 8 weeks of intensification of treatment. Main Outcome Measures: Serum free BA and respective taurine and glycine conjugates were measured by HPLC tandem mass spectrometry. Results: Oral glucose tolerance testing identified 62 normal-, 25 impaired glucose-tolerant, and 12 T2D persons. Concentrations of total taurine-conjugated BA were higher in T2D and intermediate in impaired- compared with normal glucose-tolerant persons (P = .009). Univariate regression revealed a positive association between total taurine-BA and fasting glucose (R = 0.37, P < .001), postload glucose (R = 0.31, P < .002), hemoglobin A1c (R = 0.26, P < .001), fasting insulin (R = 0.21, P = .03), and homeostatic model assessment-estimated insulin resistance (R = 0.26, P = .01) and an inverse association with oral disposition index (R = −0.36, P < .001). Insulin-mediated glycemic improvement in T2D patients did not change fasting serum total BA or BA composition. Conclusion: Fasting taurine-conjugated BA concentrations are higher in T2D and intermediate in impaired compared with normal glucose-tolerant persons and are associated with fasting and postload glucose. Serum BAs are not altered in T2D in response to improved glycemia. Further study may elucidate whether this pattern of taurine-BA conjugation can be targeted to provide novel therapeutic approaches to treat T2D. PMID:24432996

Minimax terminal approach problem in two-level hierarchical nonlinear discrete-time dynamical system

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

Shorikov, A. F., E-mail: afshorikov@mail.ru

We consider a discrete–time dynamical system consisting of three controllable objects. The motions of all objects are given by the corresponding vector nonlinear or linear discrete–time recurrent vector relations, and control system for its has two levels: basic (first or I level) that is dominating and subordinate level (second or II level) and both have different criterions of functioning and united a priori by determined informational and control connections defined in advance. For the dynamical system in question, we propose a mathematical formalization in the form of solving a multistep problem of two-level hierarchical minimax program control over the terminalmore » approach process with incomplete information and give a general scheme for its solving.« less

Heat flow in variable polarity plasma arc welds

NASA Technical Reports Server (NTRS)

Abdelmessih, Amanie N.

1992-01-01

The space shuttle external tank and the space station Freedom are fabricated by the variable polarity plasma arc (VPPA) welding. Heat sink effects (taper) are observed when there are irregularities in the work-piece configuration especially if these irregularities are close to the weld bead. These heat sinks affect the geometry of the weld bead, and in extreme cases they could cause defects such as incomplete fusion. Also, different fixtures seem to have varying heat sink effects. The objective of the previous, present, and consecutive research studies is to investigate the effect of irregularities in the work-piece configuration and fixture differences on the weld bead geometry with the ultimate objective to compensate automatically for the heat sink effects and achieve a perfect weld.

Research on comprehensive decision-making of PV power station connecting system

NASA Astrophysics Data System (ADS)

Zhou, Erxiong; Xin, Chaoshan; Ma, Botao; Cheng, Kai

2018-04-01

In allusion to the incomplete indexes system and not making decision on the subjectivity and objectivity of PV power station connecting system, based on the combination of improved Analytic Hierarchy Process (AHP), Criteria Importance Through Intercriteria Correlation (CRITIC) as well as grey correlation degree analysis (GCDA) is comprehensively proposed to select the appropriate system connecting scheme of PV power station. Firstly, indexes of PV power station connecting system are divided the recursion order hierarchy and calculated subjective weight by the improved AHP. Then, CRITIC is adopted to determine the objective weight of each index through the comparison intensity and conflict between indexes. The last the improved GCDA is applied to screen the optimal scheme, so as to, from the subjective and objective angle, select the connecting system. Comprehensive decision of Xinjiang PV power station is conducted and reasonable analysis results are attained. The research results might provide scientific basis for investment decision.

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.

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.

A telepresence robot system realized by embedded object concept

NASA Astrophysics Data System (ADS)

Vallius, Tero; Röning, Juha

2006-10-01

This paper presents the Embedded Object Concept (EOC) and a telepresence robot system which is a test case for the EOC. The EOC utilizes common object-oriented methods used in software by applying them to combined Lego-like software-hardware entities. These entities represent objects in object-oriented design methods, and they are the building blocks of embedded systems. The goal of the EOC is to make the designing embedded systems faster and easier. This concept enables people without comprehensive knowledge in electronics design to create new embedded systems, and for experts it shortens the design time of new embedded systems. We present the current status of a telepresence robot created with second-generation Atomi-objects, which is the name for our implementation of the embedded objects. The telepresence robot is a relatively complex test case for the EOC. The robot has been constructed using incremental device development, which is made possible by the architecture of the EOC. The robot contains video and audio exchange capability and a controlling system for driving with two wheels. The robot is built in two versions, the first consisting of a PC device and Atomi-objects, and the second consisting of only Atomi-objects. The robot is currently incomplete, but most of it has been successfully tested.

Commognitive analysis of undergraduate mathematics students' first encounter with the subgroup test

NASA Astrophysics Data System (ADS)

Ioannou, Marios

2018-06-01

This study analyses learning aspects of undergraduate mathematics students' first encounter with the subgroup test, using the commognitive theoretical framework. It focuses on students' difficulties as these are related to the object-level and metalevel mathematical learning in group theory, and, when possible, highlights any commognitive conflicts. In the data analysis, one can identify three types of difficulties, relevant to object-level learning: namely regarding the frequently observed confusion between groups and sets, the object-level rules of visual mediators, and the object-level rules of contextual notions, such as permutations, exponentials, sets and matrices. In addition, data analysis suggests two types of difficulties, relevant to metalevel learning. The first refers to the actual proof that the three conditions of subgroup test hold, and the second is related to syntactic inaccuracies, incomplete argumentation and problematic use of visual mediators. Finally, this study suggests that there are clear links between object-level and metalevel learning, mainly due to the fact that objectification of the various relevant mathematical notions influences the endorsement of the governing metarules.

Iterative Region-of-Interest Reconstruction from Limited Data Using Prior Information

NASA Astrophysics Data System (ADS)

Vogelgesang, Jonas; Schorr, Christian

2017-12-01

In practice, computed tomography and computed laminography applications suffer from incomplete data. In particular, when inspecting large objects with extremely different diameters in longitudinal and transversal directions or when high resolution reconstructions are desired, the physical conditions of the scanning system lead to restricted data and truncated projections, also known as the interior or region-of-interest (ROI) problem. To recover the searched-for density function of the inspected object, we derive a semi-discrete model of the ROI problem that inherently allows the incorporation of geometrical prior information in an abstract Hilbert space setting for bounded linear operators. Assuming that the attenuation inside the object is approximately constant, as for fibre reinforced plastics parts or homogeneous objects where one is interested in locating defects like cracks or porosities, we apply the semi-discrete Landweber-Kaczmarz method to recover the inner structure of the object inside the ROI from the measured data resulting in a semi-discrete iteration method. Finally, numerical experiments for three-dimensional tomographic applications with both an inherent restricted source and ROI problem are provided to verify the proposed method for the ROI reconstruction.

Understanding the Milky Way Halo through Large Surveys

NASA Astrophysics Data System (ADS)

Koposov, Sergey

This thesis presents an extensive study of stellar substructure in the outskirts of the Milky Way(MW), combining data mining of SDSS with theoretical modeling. Such substructure, either bound star clusters and satellite galaxies, or tidally disrupted objects forming stellar streams are powerful diagnostics of the Milky Way's dynamics and formation history. I have developed an algorithmic technique of searching for stellar overdensities in the MW halo, based on SDSS catalogs. This led to the discovery of unusual ultra-faint ~ (1000Lsun) globular clusters with very compact sizes and relaxation times << t_Hubble. The detailed analysis of a known stellar stream (GD-1), allowed me to make the first 6-D phase space map for such an object along 60 degrees on the sky. By modeling the stream's orbit I could place strong constraints on the Galactic potential, e.g. Vcirc(R0)= 224+/-13 km/s. The application of the algorithmic search for stellar overdensities to the SDSS dataset and to mock datasets allowed me to quantify SDSS's severe radial incompleteness in its search for ultra-faint dwarf galaxies and to determine the luminosity function of MW satellites down to luminosities of M_V ~ -3. I used the semi-analytical model in order to compare the CDM model predictions for the MW satellite population with the observations; this comparison has shown that the recently increased census of MW satellites, better understanding of the radial incompleteness and the suppression of star formation after the reionization can fully solve the "Missing satellite problem".

Influence of cryogenic treatment on microstructure and mechanical properties of high strength AISI D2 tool steel =

NASA Astrophysics Data System (ADS)

Ghasemi Nanesa, Hadi

Cryogenic treatment, known as treating materials at sub-zero temperatures, has been added to conventional heat treatment cycle of high alloyed steels where martensitic transformation is incomplete after quenching to room temperature. Incomplete martensitic transformation occurs due to the effect of high content of alloying elements on pushing down martensite start and finish temperatures to very low values, specifically, on tool steels. In spite of obtaining significant improvements in mechanical and wear properties after cryogenic treatment, there is no cohesive picture about what exactly modifies the microstructure of tool steels during cryogenic treatment and therefore divergent opinions on the influence of process parameters are still reported. For example, the suggested time length for cryogenic treatment starts from few seconds to several days indicating the lack of understanding about micromechanisms responsible for microstructural evolution while holding at cryogenic temperatures. In this regard, the main objective of this project is to develop a better understanding on the fundamental micromechanisms operating during cryogenic treatment. To attain this objective, the following milestones are pursued. - To study the conventional cryogenic treatment and finding challenges. - To identify and characterize the optimum starting microstructure before cryogenic treatment. - To determine the important processing parameters those control the evolution of microstructure and hardness. - To investigate the interaction between carbide precipitation and martensitic transformation in the AISI D2 steel. - To propose an optimal cryogenic treatment for AISI D2 steel.

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.

[Several mechanisms of visual gnosis disorders in local brain lesions].

PubMed

Meerson, Ia A

1981-01-01

The object of the studies were peculiarities of recognizing visual images by patients with local cerebral lesions under conditions of incomplete sets of the image features, disjunction of the latter, distortion of their spatial arrangement, and unusual spatial orientation of the image as a whole. It was found that elimination of even one essential feature sharply hampered the recognition of the image both by healthy individuals (control), and patients with extraoccipital lesions, whereas elimination of several nonessential features only slowed down the process. In distinction from this the difficulties of the recognition of incomplete images by patients with occipital lesions were directly proportional to the number of the eliminated features irrespective of the latters' significance, i.e. these patients were unable to evaluate the hierarchy of the features. The recognition process in these patients were followed the way of scanning individual features. The reaccumulation and summation. The recognition of the fragmental, spatially distorted and unusually oriented images was found to be affected selectively in patients with parietal lobe affections. The patients with occipital lesions recognized such images practically as good as the ordinary ones.

Cross-linguistic evidence for memory storage costs in filler-gap dependencies with wh-adjuncts

PubMed Central

Stepanov, Arthur; Stateva, Penka

2015-01-01

This study investigates processing of interrogative filler-gap dependencies in which the filler integration site or gap is not directly subcategorized by the verb. This is the case when the wh-filler is a structural adjunct such as how or when rather than subject or object. Two self-paced reading experiments in English and Slovenian provide converging cross-linguistic evidence that wh-adjuncts elicit a kind of memory storage cost similar to that previously shown in the literature for wh-arguments. Experiment 1 investigates the storage costs elicited by the adjunct when in Slovenian, and Experiment 2 the storage costs elicited by how quickly and why in English. The results support the class of theories of storage costs based on the metric in terms of incomplete phrase structure rules or incomplete syntactic head predictions. We also demonstrate that the endpoint of the storage cost for a wh-adjunct filler provides valuable processing evidence for its base structural position, the identification of which remains a rather murky issue in current grammatical research. PMID:26388806

New Structural Patterns in Moribund Grammar: Case Marking in Heritage German

PubMed Central

Yager, Lisa; Hellmold, Nora; Joo, Hyoun-A; Putnam, Michael T.; Rossi, Eleonora; Stafford, Catherine; Salmons, Joseph

2015-01-01

Research treats divergences between monolingual and heritage grammars in terms of performance—‘L1 attrition,’ e.g., lexical retrieval—or competence—‘incomplete acquisition’, e.g., lack of overt tense markers (e.g., Polinsky, 1995; Sorace, 2004; Montrul, 2008; Schmid, 2010). One classic difference between monolingual and Heritage German is reduction in morphological case in the latter, especially loss of dative marking. Our evidence from several Heritage German varieties suggests that speakers have not merely lost case, but rather developed innovative structures to mark it. More specifically, Heritage German speakers produce dative forms in line with established patterns of Differential Object Marking (Bossong, 1985, 1991; Aissen, 2003), suggesting a reallocated mapping of case. We take this as evidence for innovative reanalysis in heritage grammars (Putnam and Sánchez, 2013). Following Kamp and Reyle (1993) and Wechsler (2011, 2014), the dative adopts a more indexical discourse function, forging a tighter connection between morphosyntax and semantic properties. Moribund grammars deploy linguistic resources in novel ways, a finding which can help move us beyond simple narratives of ‘attrition’ and ‘incomplete acquisition.’ PMID:26635649

Three-to Four-Year-Olds' Recognition That Symbols Have a Stable Meaning: Pictures Are Understood Before Written Words

ERIC Educational Resources Information Center

Apperly, Ian. A.; Williams, Emily; Williams, Joelle

2004-01-01

In 4 experiments 120 three-to four-year-old non readers were asked the identity of a symbolic representation as it appeared with different objects. Consistent with Bialystok (2000), many children judged the identity of written words to vary according to the object with which they appeared but few made such errors with recognizable pictures.…

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

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.

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

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.

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

The Ebola virus glycoprotein mediates entry via a non-classical dynamin-dependent macropinocytic pathway

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

Mulherkar, Nirupama; Raaben, Matthijs; Torre, Juan Carlos de la

2011-10-25

Ebola virus (EBOV) has been reported to enter cultured cell lines via a dynamin-2-independent macropinocytic pathway or clathrin-mediated endocytosis. The route(s) of productive EBOV internalization into physiologically relevant cell types remain unexplored, and viral-host requirements for this process are incompletely understood. Here, we use electron microscopy and complementary chemical and genetic approaches to demonstrate that the viral glycoprotein, GP, induces macropinocytic uptake of viral particles into cells. GP's highly-glycosylated mucin domain is dispensable for virus-induced macropinocytosis, arguing that interactions between other sequences in GP and the host cell surface are responsible. Unexpectedly, we also found a requirement for the largemore » GTPase dynamin-2, which is proposed to be dispensable for several types of macropinocytosis. Our results provide evidence that EBOV uses an atypical dynamin-dependent macropinocytosis-like entry pathway to enter Vero cells, adherent human peripheral blood-derived monocytes, and a mouse dendritic cell line.« less

Technical aspects of neurostimulation: Focus on equipment, electric field modeling, and stimulation protocols.

PubMed

Klooster, D C W; de Louw, A J A; Aldenkamp, A P; Besseling, R M H; Mestrom, R M C; Carrette, S; Zinger, S; Bergmans, J W M; Mess, W H; Vonck, K; Carrette, E; Breuer, L E M; Bernas, A; Tijhuis, A G; Boon, P

2016-06-01

Neuromodulation is a field of science, medicine, and bioengineering that encompasses implantable and non-implantable technologies for the purpose of improving quality of life and functioning of humans. Brain neuromodulation involves different neurostimulation techniques: transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), vagus nerve stimulation (VNS), and deep brain stimulation (DBS), which are being used both to study their effects on cognitive brain functions and to treat neuropsychiatric disorders. The mechanisms of action of neurostimulation remain incompletely understood. Insight into the technical basis of neurostimulation might be a first step towards a more profound understanding of these mechanisms, which might lead to improved clinical outcome and therapeutic potential. This review provides an overview of the technical basis of neurostimulation focusing on the equipment, the present understanding of induced electric fields, and the stimulation protocols. The review is written from a technical perspective aimed at supporting the use of neurostimulation in clinical practice. Copyright © 2016 Elsevier Ltd. All rights reserved.

Leptin Action on GABAergic Neurons Prevents Obesity and Reduces Inhibitory Tone to POMC Neurons

PubMed Central

Vong, Linh; Ye, Chianping; Yang, Zongfang; Choi, Brian; Chua, Streamson; Lowell, Bradford B.

2011-01-01

SUMMARY Leptin acts in the brain to prevent obesity. The underlying neurocircuitry responsible for this is poorly understood, in part due to incomplete knowledge regarding first order, leptin-responsive neurons. To address this, we and others have been removing leptin receptors from candidate first order neurons. While functionally relevant neurons have been identified, the observed effects have been small suggesting that most first order neurons remain unidentified. Here we take an alternative approach and test whether first order neurons are inhibitory (GABAergic, VGAT+) or excitatory (glutamatergic, VGLUT2+). Remarkably, the vast majority of leptin’s anti-obesity effects are mediated by GABAergic neurons; glutamatergic neurons play only a minor role. Leptin, working directly on presynaptic GABAergic neurons, many of which appear not to express AgRP, reduces inhibitory tone to postsynaptic POMC neurons. As POMC neurons prevent obesity, their disinhibition by leptin action on presynaptic GABAergic neurons likely mediates, at least in part, leptin’s anti-obesity effects. PMID:21745644

Tumor suppression in basal keratinocytes via dual non-cell-autonomous functions of a Na,K-ATPase beta subunit

PubMed Central

Hatzold, Julia; Beleggia, Filippo; Herzig, Hannah; Altmüller, Janine; Nürnberg, Peter; Bloch, Wilhelm; Wollnik, Bernd; Hammerschmidt, Matthias

2016-01-01

The molecular pathways underlying tumor suppression are incompletely understood. Here, we identify cooperative non-cell-autonomous functions of a single gene that together provide a novel mechanism of tumor suppression in basal keratinocytes of zebrafish embryos. A loss-of-function mutation in atp1b1a, encoding the beta subunit of a Na,K-ATPase pump, causes edema and epidermal malignancy. Strikingly, basal cell carcinogenesis only occurs when Atp1b1a function is compromised in both the overlying periderm (resulting in compromised epithelial polarity and adhesiveness) and in kidney and heart (resulting in hypotonic stress). Blockade of the ensuing PI3K-AKT-mTORC1-NFκB-MMP9 pathway activation in basal cells, as well as systemic isotonicity, prevents malignant transformation. Our results identify hypotonic stress as a (previously unrecognized) contributor to tumor development and establish a novel paradigm of tumor suppression. DOI: http://dx.doi.org/10.7554/eLife.14277.001 PMID:27240166

Hierarchical chemosensory regulation of male-male social interactions in Drosophila

PubMed Central

Wang, Liming; Han, Xiaoqing; Mehren, Jennifer; Hiroi, Makoto; Billeter, Jean-Christophe; Miyamoto, Tetsuya; Amrein, Hubert; Levine, Joel D.; Anderson, David J.

2011-01-01

Pheromones regulate male social behaviors in Drosophila, but the identities and behavioral role(s) of these chemosensory signals, and how they interact, are incompletely understood. Here we show that (Z)-7-tricosene (7-T), a male-enriched cuticular hydrocarbon (CH) previously shown to inhibit male-male courtship, is also essential for normal levels of aggression. The opposite influences of 7-T on aggression and courtship are independent, but both require the gustatory receptor Gr32a. Surprisingly, sensitivity to 7-T is required for the aggression-promoting effect of 11-cis-vaccenyl acetate (cVA), an olfactory pheromone, but 7-T sensitivity is independent of cVA. 7-T and cVA therefore regulate aggression in a hierarchical manner. Furthermore, the increased courtship caused by depletion of male CHs is suppressed by a mutation in the olfactory receptor Or47b. Thus, male social behaviors are controlled by gustatory pheromones that promote and suppress aggression and courtship, respectively, and whose influences are dominant to olfactory pheromones that enhance these behaviors. PMID:21516101

FOREST ECOLOGY. Pervasive drought legacies in forest ecosystems and their implications for carbon cycle models.

PubMed

Anderegg, W R L; Schwalm, C; Biondi, F; Camarero, J J; Koch, G; Litvak, M; Ogle, K; Shaw, J D; Shevliakova, E; Williams, A P; Wolf, A; Ziaco, E; Pacala, S

2015-07-31

The impacts of climate extremes on terrestrial ecosystems are poorly understood but important for predicting carbon cycle feedbacks to climate change. Coupled climate-carbon cycle models typically assume that vegetation recovery from extreme drought is immediate and complete, which conflicts with the understanding of basic plant physiology. We examined the recovery of stem growth in trees after severe drought at 1338 forest sites across the globe, comprising 49,339 site-years, and compared the results with simulated recovery in climate-vegetation models. We found pervasive and substantial "legacy effects" of reduced growth and incomplete recovery for 1 to 4 years after severe drought. Legacy effects were most prevalent in dry ecosystems, among Pinaceae, and among species with low hydraulic safety margins. In contrast, limited or no legacy effects after drought were simulated by current climate-vegetation models. Our results highlight hysteresis in ecosystem-level carbon cycling and delayed recovery from climate extremes. Copyright © 2015, American Association for the Advancement of Science.

Interleukin-22 promotes aerobic glycolysis associated with tumor progression via targeting hexokinase-2 in human colon cancer cells.

PubMed

Liu, Yulin; Xiang, Fan; Huang, Yongming; Shi, Liang; Hu, Chaojie; Yang, Yiming; Wang, Di; He, Nan; Tao, Kaixiong; Wu, Ke; Wang, Guobin

2017-04-11

Interleukin-22 has been explored extensively in human cancer, but its functions and underlying mechanisms are incompletely understood. Here, we show that aberrant interleukin-22 expression facilitates aerobic glycolysis in colon cancer cells. Elevated interleukin-22 mRNA expression was observed and positively correlated with hexokinase-2 in colon cancer tissues. In vitro, interleukin-22 enhanced glucose consumption and lactate production via targeting hexokinase-2 in colon cancer cells. Moreover, the transcriptional factor c-Myc and signal transducer and activator of transcription 3 were involved in interleukin-22-induced up-regulation of hexokinase-2. We further demonstrated that hexokinase-2 partly accounted for interleukin-22-mediated cellular proliferation in DLD-1 cells. In vivo, our data demonstrated that interleukin-22 significantly promoted tumor growth along with elevated expression of c-Myc and hexokinase-2 in mice. In summary, our findings provide a new perspective on the pro-inflammatory cytokine interleukin-22 in promoting aerobic glycolysis associated with tumor progression in human colon cancer cells.

Cytoskeletal protein transformation in HIV-1-infected macrophage giant cells.

PubMed

Kadiu, Irena; Ricardo-Dukelow, Mary; Ciborowski, Pawel; Gendelman, Howard E

2007-05-15

The mechanisms linking HIV-1 replication, macrophage biology, and multinucleated giant cell formation are incompletely understood. With the advent of functional proteomics, the characterization, regulation, and transformation of HIV-1-infected macrophage-secreted proteins can be ascertained. To these ends, we performed proteomic analyses of culture fluids derived from HIV-1 infected monocyte-derived macrophages. Robust reorganization, phosphorylation, and exosomal secretion of the cytoskeletal proteins profilin 1 and actin were observed in conjunction with productive viral replication and giant cell formation. Actin and profilin 1 recruitment to the macrophage plasma membrane paralleled virus-induced cytopathicity, podosome formation, and cellular fusion. Poly-l-proline, an inhibitor of profilin 1-mediated actin polymerization, inhibited cytoskeletal transformations and suppressed, in part, progeny virion production. These data support the idea that actin and profilin 1 rearrangement along with exosomal secretion affect viral replication and cytopathicity. Such events favor the virus over the host cell and provide insights into macrophage defense mechanisms used to contain viral growth and how they may be affected during progressive HIV-1 infection.

MODELS OF INSULIN RESISTANCE AND HEART FAILURE

PubMed Central

Velez, Mauricio; Kohli, Smita; Sabbah, Hani N.

2013-01-01

The incidence of heart failure (HF) and diabetes mellitus is rapidly increasing and is associated with poor prognosis. In spite of the advances in therapy, HF remains a major health problem with high morbidity and mortality. When HF and diabetes coexist, clinical outcomes are significantly worse. The relationship between these two conditions has been studied in various experimental models. However, the mechanisms for this interrelationship are complex, incompletely understood, and have become a matter of considerable clinical and research interest. There are only few animal models that manifest both HF and diabetes. However, the translation of results from these models to human disease is limited and new models are needed to expand our current understanding of this clinical interaction. In this review, we discuss mechanisms of insulin signaling and insulin resistance, the clinical association between insulin resistance and HF and its proposed pathophysiologic mechanisms. Finally, we discuss available animal models of insulin resistance and HF and propose requirements for future new models. PMID:23456447

Silencing alpha-fetoprotein inhibits VEGF and MMP-2/9 production in human hepatocellular carcinoma cell.

PubMed

Meng, Wenbo; Li, Xun; Bai, Zhongtian; Li, Yan; Yuan, Jinqiu; Liu, Tao; Yan, Jun; Zhou, Wence; Zhu, Kexiang; Zhang, Hui; Li, Yumin

2014-01-01

Alpha-fetoprotein not only serves as a diagnostic marker for liver cancer, but also posses a variety of biological functions. However, the role of Alpha-fetoprotein on tumor angiogenesis and cell invasion remains incompletely understood. In this study, we aimed to evaluate if Alpha-fetoprotein can regulate the major angiogenic factors and matrix metalloproteinases in human liver cancer cells. Alpha-fetoprotein silencing was achieved by Stealth RNAi. Expression of Alpha-fetoprotein was examined by a full-automatic electrochemistry luminescence immunity analyzer. Expression of VEGF, VEGFR-2, MMP-9, and MMP-2 was examined by Western blot and immunocytochemistry. Apoptosis was detected by TUNEL assay. Angiogenesis was detected by in vitro angiogenesis assay kit. Silencing of Alpha-fetoprotein led to an increased apoptosis, which was associated with a decreased expression of vascular endothelial growth factor, vascular endothelial growth factor receptor 2, matrix metalloproteinases-2/9. These results suggest that Alpha-fetoprotein may play a regulatory role on angiogenesis and cell invasion during liver cancer development.

A Regulatory Switch Alters Chromosome Motions at the Metaphase to Anaphase Transition

PubMed Central

Su, Kuan-Chung; Barry, Zachary; Schweizer, Nina; Maiato, Helder; Bathe, Mark; Cheeseman, Iain McPherson

2016-01-01

Summary To achieve chromosome segregation during mitosis, sister chromatids must undergo a dramatic change in their behavior to switch from balanced oscillations at the metaphase plate to directed poleward motion during anaphase. However, the factors that alter chromosome behavior at the metaphase-to-anaphase transition remain incompletely understood. Here, we perform time-lapse imaging to analyze anaphase chromosome dynamics in human cells. Using multiple directed biochemical, genetic, and physical perturbations, our results demonstrate that differences in the global phosphorylation states between metaphase and anaphase are the major determinant of chromosome motion dynamics. Indeed, causing a mitotic phosphorylation state to persist into anaphase produces dramatic metaphase-like oscillations. These induced oscillations depend on both kinetochore-derived and polar ejection forces that oppose poleward motion. Thus, our analysis of anaphase chromosome motion reveals that dephosphorylation of multiple mitotic substrates is required to suppress metaphase chromosome oscillatory motions and achieve directed poleward motion for successful chromosome segregation. PMID:27829144

Mannose-pepstatin conjugates as targeted inhibitors of antigen processing.

PubMed

Free, Paul; Hurley, Christopher A; Kageyama, Takashi; Chain, Benjamin M; Tabor, Alethea B

2006-05-07

The molecular details of antigen processing, including the identity of the enzymes involved, their intracellular location and their substrate specificity, are still incompletely understood. Selective inhibition of proteolytic antigen processing enzymes such as cathepsins D and E, using small molecular inhibitors such as pepstatin, has proven to be a valuable tool in investigating these pathways. However, pepstatin is poorly soluble in water and has limited access to the antigen processing compartment in antigen presenting cells. We have synthesised mannose-pepstatin conjugates, and neomannosylated BSA-pepstatin conjugates, as tools for the in vivo study of the antigen processing pathway. Conjugation to mannose and to neomannosylated BSA substantially improved the solubility of the conjugates relative to pepstatin. The mannose-pepstatin conjugates showed no reduction in inhibition of cathepsin E, whereas the neomannosylated BSA-pepstatin conjugates showed some loss of inhibition, probably due to steric factors. However, a neomannosylated BSA-pepstatin conjugate incorporating a cleavable disulfide linkage between the pepstatin and the BSA showed the best uptake to dendritic cells and the best inhibition of antigen processing.

Inside-out neuropharmacology of nicotinic drugs

PubMed Central

Henderson, Brandon J.; Lester, Henry A.

2015-01-01

Upregulation of neuronal nicotinic acetylcholine receptors (AChRs) is a venerable result of chronic exposure to nicotine; but it is one of several consequences of pharmacological chaperoning by nicotine and by some other nicotinic ligands, especially agonists. Nicotinic ligands permeate through cell membranes, bind to immature AChR oligomers, elicit incompletely understood conformational reorganizations, increase the interaction between adjacent AChR subunits, and enhance the maturation process toward stable AChR pentamers. These changes and stabilizations in turn lead to increases in both anterograde and retrograde traffic within the early secretory pathway. In addition to the eventual upregulation of AChRs at the plasma membrane, other effects of pharmacological chaperoning include modifications to endoplasmic reticulum stress and to the unfolded protein response. Because these processes depend on pharmacological chaperoning within intracellular organelles, we group them as “inside-out pharmacology”. This term contrasts with the better-known, acute, “outside-in” effects of activating and desensitizing plasma membrane AChRs. We review current knowledge concerning the mechanisms and consequences of inside-out pharmacology. PMID:25660637

ATX-LPA1 axis contributes to proliferation of chondrocytes by regulating fibronectin assembly leading to proper cartilage formation

PubMed Central

Nishioka, Tatsuji; Arima, Naoaki; Kano, Kuniyuki; Hama, Kotaro; Itai, Eriko; Yukiura, Hiroshi; Kise, Ryoji; Inoue, Asuka; Kim, Seok-Hyung; Solnica-Krezel, Lilianna; Moolenaar, Wouter H.; Chun, Jerold; Aoki, Junken

2016-01-01

The lipid mediator lysophosphatidic acid (LPA) signals via six distinct G protein-coupled receptors to mediate both unique and overlapping biological effects, including cell migration, proliferation and survival. LPA is produced extracellularly by autotaxin (ATX), a secreted lysophospholipase D, from lysophosphatidylcholine. ATX-LPA receptor signaling is essential for normal development and implicated in various (patho)physiological processes, but underlying mechanisms remain incompletely understood. Through gene targeting approaches in zebrafish and mice, we show here that loss of ATX-LPA1 signaling leads to disorganization of chondrocytes, causing severe defects in cartilage formation. Mechanistically, ATX-LPA1 signaling acts by promoting S-phase entry and cell proliferation of chondrocytes both in vitro and in vivo, at least in part through β1-integrin translocation leading to fibronectin assembly and further extracellular matrix deposition; this in turn promotes chondrocyte-matrix adhesion and cell proliferation. Thus, the ATX-LPA1 axis is a key regulator of cartilage formation. PMID:27005960

Diverse Soil Carbon Dynamics Expressed at the Molecular Level

NASA Astrophysics Data System (ADS)

van der Voort, T. S.; Zell, C. I.; Hagedorn, F.; Feng, X.; McIntyre, C. P.; Haghipour, N.; Graf Pannatier, E.; Eglinton, T. I.

2017-12-01

The stability and potential vulnerability of soil organic matter (SOM) to global change remain incompletely understood due to the complex processes involved in its formation and turnover. Here we combine compound-specific radiocarbon analysis with fraction-specific and bulk-level radiocarbon measurements in order to further elucidate controls on SOM dynamics in a temperate and subalpine forested ecosystem. Radiocarbon contents of individual organic compounds isolated from the same soil interval generally exhibit greater variation than those among corresponding operationally defined fractions. Notably, markedly older ages of long-chain plant leaf wax lipids (n-alkanoic acids) imply that they reflect a highly stable carbon pool. Furthermore, marked 14C variations among shorter- and longer-chain n-alkanoic acid homologues suggest that they track different SOM pools. Extremes in SOM dynamics thus manifest themselves within a single compound class. This exploratory study highlights the potential of compound-specific radiocarbon analysis for understanding SOM dynamics in ecosystems potentially vulnerable to global change.

Mfge8 promotes obesity by mediating the uptake of dietary fats and serum fatty acids.

PubMed

Khalifeh-Soltani, Amin; McKleroy, William; Sakuma, Stephen; Cheung, Yuk Yin; Tharp, Kevin; Qiu, Yifu; Turner, Scott M; Chawla, Ajay; Stahl, Andreas; Atabai, Kamran

2014-02-01

Fatty acids are integral mediators of energy storage, membrane formation and cell signaling. The pathways that orchestrate uptake of fatty acids remain incompletely understood. Expression of the integrin ligand Mfge8 is increased in human obesity and in mice on a high-fat diet, but its role in obesity is unknown. We show here that Mfge8 promotes the absorption of dietary triglycerides and the cellular uptake of fatty acid and that Mfge8-deficient (Mfge8(-/-)) mice are protected from diet-induced obesity, steatohepatitis and insulin resistance. Mechanistically, we found that Mfge8 coordinates fatty acid uptake through αvβ3 integrin- and αvβ5 integrin-dependent phosphorylation of Akt by phosphatidylinositide-3 kinase and mTOR complex 2, leading to translocation of Cd36 and Fatp1 from cytoplasmic vesicles to the cell surface. Collectively, our results imply a role for Mfge8 in regulating the absorption and storage of dietary fats, as well as in the development of obesity and its complications.

Food Insecurity and Food Resource Utilization in an Urban Immigrant Community.

PubMed

Greenwald, Howard P; Zajfen, Vanessa

2017-02-01

Risk and prevalence of food insecurity and use of food security resources are important but incompletely understood factors in immigrant health. Key informant interviews and a survey (N = 809) of housing units were conducted in a San Diego, California neighborhood with a high proportion of immigrant and low income families. The difference in food insecurity between immigrant and non-immigrant households was non-significant (20.1 vs. 15.7 %, p = n.s.), though immigrant families were more likely to use food security resources such as SNAP (32.7 vs. 22.9 %, p < .01) and food pantries (28.2 vs. 19.7 %, p < .001). Among immigrants, neither national origin nor years in the United States predicted food insecurity or use of most food security resources. In immigrant families, food insecurity often remains a challenge long after immigration, suggesting a potentially increasing need for food security resources as immigration into the United States continues.

Neuropharmacological sequelae of persistent CNS viral infections: lessons from Borna disease virus.

PubMed

Solbrig, Marylou V; Koob, George F

2003-03-01

Borna Disease Virus (BDV) is a neurotropic RNA virus that is worldwide in distribution, causing movement and behavior disorders in a wide range of animal species. BDV has also been reported to be associated with neuropsychiatric diseases of humans by serologic study and by recovery of nucleic acid or virus from blood or brain. Natural infections of horses and sheep produce encephalitis with erratic excited behaviors, hyperkinetic movement or gait abnormalities; naturally infected cats have ataxic "staggering disease." Experimentally infected primates develop hyperactivity, aggression, disinhibition, then apathy; prosimians (lower primates) have hyperactivity, circadian disruption, abnormal social and dominance behaviors, and postural disorders. However, the neuropharmacological determinants of BD phenotypes in laboratory and natural hosts are incompletely understood. Here we review how experimentally infected rodents have provided models for examining behavioral, pharmacologic, and biochemical responses to viral challenge, and how rodents experimentally infected as neonates or as adolescents are providing models for examining age-specific neuropharmacological adaptations to viral injury.

Invasion-Related Factors as Potential Diagnostic and Therapeutic Targets in Oral Squamous Cell Carcinoma—A Review

PubMed Central

Siriwardena, Samadarani B. S. M.; Tsunematsu, Takaaki; Qi, Guangying; Ishimaru, Naozumi; Kudo, Yasusei

2018-01-01

It is well recognized that the presence of cervical lymph node metastasis is the most important prognostic factor in oral squamous cell carcinoma (OSCC). In solid epithelial cancer, the first step during the process of metastasis is the invasion of cancer cells into the underlying stroma, breaching the basement membrane (BM)—the natural barrier between epithelium and the underlying extracellular matrix (ECM). The ability to invade and metastasize is a key hallmark of cancer progression, and the most complicated and least understood. These topics continue to be very active fields of cancer research. A number of processes, factors, and signaling pathways are involved in regulating invasion and metastasis. However, appropriate clinical trials for anti-cancer drugs targeting the invasion of OSCC are incomplete. In this review, we summarize the recent progress on invasion-related factors and emerging molecular determinants which can be used as potential for diagnostic and therapeutic targets in OSCC. PMID:29758011

Posttranscriptional Control of T Cell Effector Function by Aerobic Glycolysis

PubMed Central

Chang, Chih-Hao; Curtis, Jonathan D.; Maggi, Leonard B.; Faubert, Brandon; Villarino, Alejandro V.; O’Sullivan, David; Huang, Stanley Ching-Cheng; van der Windt, Gerritje J.W.; Blagih, Julianna; Qiu, Jing; Weber, Jason D.; Pearce, Edward J.; Jones, Russell G.; Pearce, Erika L.

2013-01-01

SUMMARY A “switch” from oxidative phosphorylation (OXPHOS) to aerobic glycolysis is a hallmark of T cell activation and is thought to be required to meet the metabolic demands of proliferation. However, why proliferating cells adopt this less efficient metabolism, especially in an oxygen-replete environment, remains incompletely understood. We show here that aerobic glycolysis is specifically required for effector function in T cells but that this pathway is not necessary for proliferation or survival. When activated T cells are provided with costimulation and growth factors but are blocked from engaging glycolysis, their ability to produce IFN-γ is markedly compromised. This defect is translational and is regulated by the binding of the glycolysis enzyme GAPDH to AU-rich elements within the 3′ UTR of IFN-γ mRNA. GAPDH, by engaging/disengaging glycolysis and through fluctuations in its expression, controls effector cytokine production. Thus, aerobic glycolysis is a metabolically regulated signaling mechanism needed to control cellular function. PMID:23746840

Phosphorylation of CPAP by Aurora-A Maintains Spindle Pole Integrity during Mitosis.

PubMed

Chou, En-Ju; Hung, Liang-Yi; Tang, Chieh-Ju C; Hsu, Wen-Bin; Wu, Hsin-Yi; Liao, Pao-Chi; Tang, Tang K

2016-03-29

CPAP is required for centriole elongation during S/G2 phase, but the role of CPAP in mitosis is incompletely understood. Here, we show that CPAP maintains spindle pole integrity through its phosphorylation by Aurora-A during mitosis. Depletion of CPAP induced a prolonged delay in mitosis, pericentriolar material (PCM) dispersion, and multiple mitotic abnormalities. Further studies demonstrated that CPAP directly interacts with and is phosphorylated by Aurora-A at serine 467 during mitosis. Interestingly, the dispersal of the PCM was effectively rescued by ectopic expression of wild-type CPAP or a phospho-mimic CPAP-S467D mutant, but not a non-phosphorylated CPAP-S467A mutant. Finally, we found that CPAP-S467D has a low affinity for microtubule binding but a high affinity for PCM proteins. Together, our results support a model wherein CPAP is required for proper mitotic progression, and phosphorylation of CPAP by Aurora-A is essential for maintaining spindle pole integrity. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Emerging therapies for idiopathic pulmonary fibrosis, a progressive age-related disease

PubMed Central

Mora, Ana L.; Rojas, Mauricio; Pardo, Annie; Selman, Moises

2018-01-01

Idiopathic pulmonary fibrosis (IPF) is a fatal age-associated disease that is characterized by progressive and irreversible scarring of the lung. The pathogenesis of IPF is not completely understood and current therapies are limited to those that reduce the rate of functional decline in patients with mild-to-moderate disease. In this context, new therapeutic approaches that substantially improve the survival time and quality of life of these patients are urgently needed. Our incomplete understanding of the pathogenic mechanisms of IPF and the lack of appropriate experimental models that reproduce the key characteristics of the human disease are major challenges. As ageing is a major risk factor for IPF, age-related cell perturbations such as telomere attrition, senescence, epigenetic drift, stem cell exhaustion, loss of proteostasis and mitochondrial dysfunction are becoming targets of interest for IPF therapy. In this Review, we discuss current and emerging therapies for IPF, particularly those targeting age-related mechanisms, and discuss future therapeutic approaches. PMID:29081515

Tumor cell-driven extracellular matrix remodeling drives haptotaxis during metastatic progression

PubMed Central

Oudin, Madeleine J.; Jonas, Oliver; Kosciuk, Tatsiana; Broye, Liliane C.; Guido, Bruna C.; Wyckoff, Jeff; Riquelme, Daisy; Lamar, John M.; Asokan, Sreeja B.; Whittaker, Charlie; Ma, Duanduan; Langer, Robert; Cima, Michael J.; Wisinski, Kari B.; Hynes, Richard O.; Lauffenburger, Douglas A.; Keely, Patricia J.; Bear, James E.; Gertler, Frank B.

2016-01-01

Fibronectin (FN) is a major component of the tumor microenvironment, but its role in promoting metastasis is incompletely understood. Here we show that FN gradients elicit directional movement of breast cancer cells, in vitro and in vivo. Haptotaxis on FN gradients requires direct interaction between α5β1 integrin and Mena, an actin regulator, and involves increases in focal complex signaling and tumor-cell-mediated extracellular matrix (ECM) remodeling. Compared to Mena, higher levels of the pro-metastatic MenaINV isoform associate with α5, which enables 3D haptotaxis of tumor cells towards the high FN concentrations typically present in perivascular space and in the periphery of breast tumor tissue. MenaINV and FN levels were correlated in two breast cancer cohorts, and high levels of MenaINV were significantly associated with increased tumor recurrence as well as decreased patient survival. Our results identify a novel tumor-cell-intrinsic mechanism that promotes metastasis through ECM remodeling and ECM guided directional migration. PMID:26811325

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

Tan, Bee Ling; Norhaizan, Mohd Esa

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.

Scleroderma: nomenclature, etiology, pathogenesis, prognosis, and treatments: facts and controversies.

PubMed

Fett, Nicole

2013-01-01

Scleroderma refers to a heterogeneous group of autoimmune fibrosing disorders. The nomenclature of scleroderma has changed dramatically in recent years, with morphea (localized scleroderma), limited cutaneous systemic sclerosis, diffuse cutaneous systemic sclerosis, and systemic sclerosis sine scleroderma encompassing the currently accepted disease subtypes. Major advances have been made in the molecular studies of morphea and systemic sclerosis; however, their etiologies and pathogenesis remain incompletely understood. Although morphea and systemic sclerosis demonstrate activation of similar inflammatory and fibrotic pathways, important differences in signaling pathways and gene signatures indicate they are likely biologically distinct processes. Morphea can cause significant morbidity but does not affect mortality, whereas systemic sclerosis has the highest disease-specific mortality of all autoimmune connective tissue diseases. Treatment recommendations for morphea and systemic sclerosis are based on limited data and largely expert opinions. Current collaborative efforts in morphea and systemic sclerosis research will hopefully lead to better understanding of the etiology and pathogenesis of these rare and varied diseases and improved treatment options. Published by Elsevier Inc.

Hypoxia signaling controls postnatal changes in cardiac mitochondrial morphology and function

PubMed Central

Neary, Marianne T.; Ng, Keat-Eng; Ludtmann, Marthe H.R.; Hall, Andrew R.; Piotrowska, Izabela; Ong, Sang-Bing; Hausenloy, Derek J.; Mohun, Timothy J.; Abramov, Andrey Y.; Breckenridge, Ross A.

2014-01-01

Fetal cardiomyocyte adaptation to low levels of oxygen in utero is incompletely understood, and is of interest as hypoxia tolerance is lost after birth, leading to vulnerability of adult cardiomyocytes. It is known that cardiac mitochondrial morphology, number and function change significantly following birth, although the underlying molecular mechanisms and physiological stimuli are undefined. Here we show that the decrease in cardiomyocyte HIF-signaling in cardiomyocytes immediately after birth acts as a physiological switch driving mitochondrial fusion and increased postnatal mitochondrial biogenesis. We also investigated mechanisms of ATP generation in embryonic cardiac mitochondria. We found that embryonic cardiac cardiomyocytes rely on both glycolysis and the tricarboxylic acid cycle to generate ATP, and that the balance between these two metabolic pathways in the heart is controlled around birth by the reduction in HIF signaling. We therefore propose that the increase in ambient oxygen encountered by the neonate at birth acts as a key physiological stimulus to cardiac mitochondrial adaptation. PMID:24984146

Neuroinflammatory Mechanisms of Connective Tissue Fibrosis: Targeting Neurogenic and Mast Cell Contributions

PubMed Central

Monument, Michael J.; Hart, David A.; Salo, Paul T.; Befus, A. Dean; Hildebrand, Kevin A.

2015-01-01

Significance: The pathogenesis of fibrogenic wound and connective tissue healing is complex and incompletely understood. Common observations across a vast array of human and animal models of fibroproliferative conditions suggest neuroinflammatory mechanisms are important upstream fibrogenic events. Recent Advances: As detailed in this review, mast cell hyperplasia is a common observation in fibrotic tissue. Recent investigations in human and preclinical models of hypertrophic wound healing and post-traumatic joint fibrosis provides evidence that fibrogenesis is governed by a maladaptive neuropeptide-mast cell-myofibroblast signaling pathway. Critical Issues: The blockade and manipulation of these factors is providing promising evidence that if timed correctly, the fibrogenic process can be appropriately regulated. Clinically, abnormal fibrogenic healing responses are not ubiquitous to all patients and the identification of those at-risk remains an area of priority. Future Directions: Ultimately, an integrated appreciation of the common pathobiology shared by many fibrogenic connective tissue conditions may provide a scientific framework to facilitate the development of novel antifibrotic prevention and treatment strategies. PMID:25785237

Platelets contribute to postnatal occlusion of the ductus arteriosus.

PubMed

Echtler, Katrin; Stark, Konstantin; Lorenz, Michael; Kerstan, Sandra; Walch, Axel; Jennen, Luise; Rudelius, Martina; Seidl, Stefan; Kremmer, Elisabeth; Emambokus, Nikla R; von Bruehl, Marie-Luise; Frampton, Jon; Isermann, Berend; Genzel-Boroviczény, Orsolya; Schreiber, Christian; Mehilli, Julinda; Kastrati, Adnan; Schwaiger, Markus; Shivdasani, Ramesh A; Massberg, Steffen

2010-01-01

The ductus arteriosus (DA) is a fetal shunt vessel between the pulmonary artery and the aorta that closes promptly after birth. Failure of postnatal DA closure is a major cause of morbidity and mortality particularly in preterm neonates. The events leading to DA closure are incompletely understood. Here we show that platelets have an essential role in DA closure. Using intravital microscopy of neonatal mice, we observed that platelets are recruited to the luminal aspect of the DA during closure. DA closure is impaired in neonates with malfunctioning platelet adhesion or aggregation or with defective platelet biogenesis. Defective DA closure resulted in a left-to-right shunt with increased pulmonary perfusion, pulmonary vascular remodeling and right ventricular hypertrophy. Our findings indicate that platelets are crucial for DA closure by promoting thrombotic sealing of the constricted DA and by supporting luminal remodeling. A retrospective clinical study revealed that thrombocytopenia is an independent predictor for failure of DA closure in preterm human newborns, indicating that platelets are likely to contribute to DA closure in humans.

Neurotensin increases mortality and mast cells reduce neurotensin levels in a mouse model of sepsis.

PubMed

Piliponsky, Adrian M; Chen, Ching-Cheng; Nishimura, Toshihiko; Metz, Martin; Rios, Eon J; Dobner, Paul R; Wada, Etsuko; Wada, Keiji; Zacharias, Sherma; Mohanasundaram, Uma M; Faix, James D; Abrink, Magnus; Pejler, Gunnar; Pearl, Ronald G; Tsai, Mindy; Galli, Stephen J

2008-04-01

Sepsis is a complex, incompletely understood and often fatal disorder, typically accompanied by hypotension, that is considered to represent a dysregulated host response to infection. Neurotensin (NT) is a 13-amino-acid peptide that, among its multiple effects, induces hypotension. We find that intraperitoneal and plasma concentrations of NT are increased in mice after severe cecal ligation and puncture (CLP), a model of sepsis, and that mice treated with a pharmacological antagonist of NT, or NT-deficient mice, show reduced mortality during severe CLP. In mice, mast cells can degrade NT and reduce NT-induced hypotension and CLP-associated mortality, and optimal expression of these effects requires mast cell expression of neurotensin receptor 1 and neurolysin. These findings show that NT contributes to sepsis-related mortality in mice during severe CLP and that mast cells can lower NT concentrations, and suggest that mast cell-dependent reduction in NT levels contributes to the ability of mast cells to enhance survival after CLP.

Synonymous codon changes in the oncogenes of the cottontail rabbit papillomavirus lead to increased oncogenicity and immunogenicity of the virus

PubMed Central

Cladel, Nancy M.; Budgeon, Lynn R.; Hu, Jiafen; Balogh, Karla K.; Christensen, Neil D.

2013-01-01

Papillomaviruses use rare codons with respect to the host. The reasons for this are incompletely understood but among the hypotheses is the concept that rare codons result in low protein production and this allows the virus to escape immune surveillance. We changed rare codons in the oncogenes E6 and E7 of the cottontail rabbit papillomavirus to make them more mammalian-like and tested the mutant genomes in our in vivo animal model. While the amino acid sequences of the proteins remained unchanged, the oncogenic potential of some of the altered genomes increased dramatically. In addition, increased immunogenicity, as measured by spontaneous regression, was observed as the numbers of codon changes increased. This work suggests that codon usage may modify protein production in ways that influence disease outcome and that evaluation of synonymous codons should be included in the analysis of genetic variants of infectious agents and their association with disease. PMID:23433866

δ-COP contains a helix C-terminal to its longin domain key to COPI dynamics and function

PubMed Central

Arakel, Eric C.; Richter, Kora P.; Clancy, Anne; Schwappach, Blanche

2016-01-01

Membrane recruitment of coatomer and formation of coat protein I (COPI)-coated vesicles is crucial to homeostasis in the early secretory pathway. The conformational dynamics of COPI during cargo capture and vesicle formation is incompletely understood. By scanning the length of δ-COP via functional complementation in yeast, we dissect the domains of the δ-COP subunit. We show that the μ-homology domain is dispensable for COPI function in the early secretory pathway, whereas the N-terminal longin domain is essential. We map a previously uncharacterized helix, C-terminal to the longin domain, that is specifically required for the retrieval of HDEL-bearing endoplasmic reticulum-luminal residents. It is positionally analogous to an unstructured linker that becomes helical and membrane-facing in the open form of the AP2 clathrin adaptor complex. Based on the amphipathic nature of the critical helix it may probe the membrane for lipid packing defects or mediate interaction with cargo and thus contribute to stabilizing membrane-associated coatomer. PMID:27298352

Repetitive trauma and nerve compression.

PubMed

Carragee, E J; Hentz, V R

1988-01-01

Repetitive movement of the upper extremity, whether recreational or occupational, may result in various neuropathies, the prototype of which is the median nerve neuropathic in the carpal canal. The pathophysiology of this process is incompletely understood but likely involves both mechanical and ischemic features. Experimentally increased pressures within the carpal canal produced reproducible progressive neuropathy. Changes in vibratory (threshold-type) sensibility appears to be more sensitive than two-point (innervation density-type) sensibility. The specific occupational etiologies of carpal neuropathy are obscured by methodologic and sociological difficulties, but clearly some occupations have high incidences of CTS. History and physical examination are usually sufficient for the diagnosis, but diagnostic assistance when required is available through electrophysiological testing, CT scanning, and possibly MRI. Each of these tests has limitations in both sensitivity and specificity. Treatment by usual conservative means should be combined with rest from possible provocative activities. Surgical release of the carpal canal is helpful in patients failing conservative therapy. Occupational modifications are important in both treatment and prevention of median neuropathy due to repetitive trauma.

Quantitative time-resolved analysis reveals intricate, differential regulation of standard- and immuno-proteasomes

PubMed Central

Liepe, Juliane; Holzhütter, Hermann-Georg; Bellavista, Elena; Kloetzel, Peter M; Stumpf, Michael PH; Mishto, Michele

2015-01-01

Proteasomal protein degradation is a key determinant of protein half-life and hence of cellular processes ranging from basic metabolism to a host of immunological processes. Despite its importance the mechanisms regulating proteasome activity are only incompletely understood. Here we use an iterative and tightly integrated experimental and modelling approach to develop, explore and validate mechanistic models of proteasomal peptide-hydrolysis dynamics. The 20S proteasome is a dynamic enzyme and its activity varies over time because of interactions between substrates and products and the proteolytic and regulatory sites; the locations of these sites and the interactions between them are predicted by the model, and experimentally supported. The analysis suggests that the rate-limiting step of hydrolysis is the transport of the substrates into the proteasome. The transport efficiency varies between human standard- and immuno-proteasomes thereby impinging upon total degradation rate and substrate cleavage-site usage. DOI: http://dx.doi.org/10.7554/eLife.07545.001 PMID:26393687

Lgr6 labels a rare population of mammary gland progenitor cells that are able to originate luminal mammary tumours

PubMed Central

Messal, Hendrik A.; Andersson, Agneta B.; Ruiz, E. Josue; Gerling, Marco; Douagi, Iyadh; Spencer-Dene, Bradley; Musch, Alexandra; Mitter, Richard; Bhaw, Leena; Stone, Richard; Bornhorst, Dorothee; Sesay, Abdul K.; Jonkers, Jos; Stamp, Gordon; Malanchi, Ilaria; Toftgård, Rune; Behrens, Axel

2018-01-01

The mammary gland is composed of a complex cellular hierarchy with unusual postnatal plasticity. The identities of stem/progenitor cell populations, as well as tumour-initiating cells that give rise to breast cancer, are incompletely understood. Here we show that Lgr6 marks rare populations of cells in both basal and luminal mammary gland compartments in mice. Lineage tracing analysis showed that Lgr6+ cells are unipotent progenitors, which expand clonally during puberty but diminish in adulthood. In pregnancy or upon stimulation with ovarian hormones, adult Lgr6+ cells regained proliferative potency and their progeny formed alveoli over repeated pregnancies. Oncogenic mutations in Lgr6+ cells resulted in expansion of luminal cells, culminating in mammary gland tumours. Conversely, depletion of Lgr6+ cells in the MMTV-PyMT model of mammary tumourigenesis significantly impaired tumour growth. Thus, Lgr6 marks mammary gland progenitor cells that can initiate tumours, and cells of luminal breast tumours required for efficient tumour maintenance. PMID:27798604

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

Mechanisms Underlying HIV-Associated Noninfectious Lung Disease.

PubMed

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

2017-11-01

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

Salmonella enterica serovar-specific transcriptional reprogramming of infected cells.

PubMed

Hannemann, Sebastian; Galán, Jorge E

2017-07-01

Despite their high degree of genomic similarity, different Salmonella enterica serovars are often associated with very different clinical presentations. In humans, for example, the typhoidal S. enterica serovar Typhi causes typhoid fever, a life-threatening systemic disease. In contrast, the non-typhoidal S. enterica serovar Typhimurium causes self-limiting gastroenteritis. The molecular bases for these different clinical presentations are incompletely understood. The ability to re-program gene expression in host cells is an essential virulence factor for typhoidal and non-typhoidal S. enterica serovars. Here, we have compared the transcriptional profile of cultured epithelial cells infected with S. Typhimurium or S. Typhi. We found that both serovars stimulated distinct transcriptional responses in infected cells that are associated with the stimulation of specific signal transduction pathways. These specific responses were associated with the presence of a distinct repertoire of type III secretion effector proteins. These observations provide major insight into the molecular bases for potential differences in the pathogenic mechanisms of typhoidal and non-typhoidal S. enterica serovars.

HCN2 channels in the ventral tegmental area regulate behavioral responses to chronic stress

PubMed Central

Zhong, Peng; Vickstrom, Casey R; Liu, Xiaojie; Hu, Ying; Yu, Laikang; Yu, Han-Gang

2018-01-01

Dopamine neurons in the ventral tegmental area (VTA) are powerful regulators of depression-related behavior. Dopamine neuron activity is altered in chronic stress-based models of depression, but the underlying mechanisms remain incompletely understood. Here, we show that mice subject to chronic mild unpredictable stress (CMS) exhibit anxiety- and depressive-like behavior, which was associated with decreased VTA dopamine neuron firing in vivo and ex vivo. Dopamine neuron firing is governed by voltage-gated ion channels, in particular hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Following CMS, HCN-mediated currents were decreased in nucleus accumbens-projecting VTA dopamine neurons. Furthermore, shRNA-mediated HCN2 knockdown in the VTA was sufficient to recapitulate CMS-induced depressive- and anxiety-like behavior in stress-naïve mice, whereas VTA HCN2 overexpression largely prevented CMS-induced behavioral deficits. Together, these results reveal a critical role for HCN2 in regulating VTA dopamine neuronal activity and depressive-related behaviors. PMID:29256865

Cost-effective conservation planning: lessons from economics.

PubMed

Duke, Joshua M; Dundas, Steven J; Messer, Kent D

2013-08-15

Economists advocate that the billions of public dollars spent on conservation be allocated to achieve the largest possible social benefit. This is "cost-effective conservation"-a process that incorporates both monetized benefits and costs. Though controversial, cost-effective conservation is poorly understood and rarely implemented by planners. Drawing from the largest publicly financed conservation programs in the United States, this paper seeks to improve the communication from economists to planners and to overcome resistance to cost-effective conservation. Fifteen practical lessons are distilled, including the negative implications of limiting selection with political constraints, using nonmonetized benefit measures or benefit indices, ignoring development risk, using incomplete cost measures, employing cost measures sequentially, and using benefit indices to capture costs. The paper highlights interrelationships between benefits and complications such as capitalization and intertemporal planning. The paper concludes by identifying the challenges at the research frontier, including incentive problems associated with adverse selection, additionality, and slippage. Copyright © 2013 Elsevier Ltd. All rights reserved.

Pathogenic Fungi Regulate Immunity by Inducing Neutrophilic Myeloid-Derived Suppressor Cells

PubMed Central

Rieber, Nikolaus; Singh, Anurag; Öz, Hasan; Carevic, Melanie; Bouzani, Maria; Amich, Jorge; Ost, Michael; Ye, Zhiyong; Ballbach, Marlene; Schäfer, Iris; Mezger, Markus; Klimosch, Sascha N.; Weber, Alexander N.R.; Handgretinger, Rupert; Krappmann, Sven; Liese, Johannes; Engeholm, Maik; Schüle, Rebecca; Salih, Helmut Rainer; Marodi, Laszlo; Speckmann, Carsten; Grimbacher, Bodo; Ruland, Jürgen; Brown, Gordon D.; Beilhack, Andreas; Loeffler, Juergen; Hartl, Dominik

2015-01-01

Summary Despite continuous contact with fungi, immunocompetent individuals rarely develop pro-inflammatory antifungal immune responses. The underlying tolerogenic mechanisms are incompletely understood. Using both mouse models and human patients, we show that infection with the human pathogenic fungi Aspergillus fumigatus and Candida albicans induces a distinct subset of neutrophilic myeloid-derived suppressor cells (MDSCs), which functionally suppress T and NK cell responses. Mechanistically, pathogenic fungi induce neutrophilic MDSCs through the pattern recognition receptor Dectin-1 and its downstream adaptor protein CARD9. Fungal MDSC induction is further dependent on pathways downstream of Dectin-1 signaling, notably reactive oxygen species (ROS) generation as well as caspase-8 activity and interleukin-1 (IL-1) production. Additionally, exogenous IL-1β induces MDSCs to comparable levels observed during C. albicans infection. Adoptive transfer and survival experiments show that MDSCs are protective during invasive C. albicans infection, but not A. fumigatus infection. These studies define an innate immune mechanism by which pathogenic fungi regulate host defense. PMID:25771792

Post-Polio Syndrome and the Late Effects of Poliomyelitis: Part 1. Pathogenesis, Biomechanical Considerations, Diagnosis, and Investigations.

PubMed

Lo, Julian K; Robinson, Lawrence R

2018-05-12

Post-Polio Syndrome (PPS) is characterized by new muscle weakness and/or muscle fatigability that occurs many years following the initial poliomyelitis illness. There are many theories that exist on the pathogenesis of PPS, which remains incompletely understood. In contrast, the Late Effects of Poliomyelitis are often a consequence of biomechanical alterations that occur as a result of polio-related surgeries, musculoskeletal deformities or weakness. Osteoporosis and fractures of the polio-involved limbs are common. A comprehensive clinical evaluation with appropriate investigations is essential to fulfilling the established PPS diagnostic criteria. PPS is a diagnosis of exclusion, in which a key clinical feature required for the diagnosis is new muscle weakness and/or muscle fatigability that is persistent for at least one year. Electromyographic and muscle biopsy findings including evidence of ongoing denervation cannot reliably distinguish between patients with or without PPS. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Gentle reenergization of electrons in merging galaxy clusters.

PubMed

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

2017-10-01

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.

Inflammation and wound healing: The role of the macrophage

PubMed Central

Koh, Timothy J.; DiPietro, Luisa Ann

2013-01-01

The macrophage is a prominent inflammatory cell in wounds, but its role in healing remains incompletely understood. Macrophages have been described to have many functions in wounds, including host defense, the promotion and resolution of inflammation, the removal of apoptotic cells, and the support of cell proliferation and tissue restoration following injury. Recent studies suggest that macrophages exist in several different phenotypic states within the healing wound, and that the influence of these cells on each stage of repair varies with the specific phenotypes. While the macrophage is beneficial to the repair of normally healing wounds, this pleotropic cell type may promote excessive inflammation and/or fibrosis in certain circumstances. Emerging evidence suggests that macrophage dysfunction is a component of the pathogenesis of non-healing and poorly healing wounds. Due to advances in the understanding of this multi-functional cell, the macrophage continues to be an attractive therapeutic target both to reduce fibrosis and scarring, and to improve healing of chronic wounds. PMID:21740602

Chamber identity programs drive early functional partitioning of the heart.

PubMed

Mosimann, Christian; Panáková, Daniela; Werdich, Andreas A; Musso, Gabriel; Burger, Alexa; Lawson, Katy L; Carr, Logan A; Nevis, Kathleen R; Sabeh, M Khaled; Zhou, Yi; Davidson, Alan J; DiBiase, Anthony; Burns, Caroline E; Burns, C Geoffrey; MacRae, Calum A; Zon, Leonard I

2015-08-26

The vertebrate heart muscle (myocardium) develops from the first heart field (FHF) and expands by adding second heart field (SHF) cells. While both lineages exist already in teleosts, the primordial contributions of FHF and SHF to heart structure and function remain incompletely understood. Here we delineate the functional contribution of the FHF and SHF to the zebrafish heart using the cis-regulatory elements of the draculin (drl) gene. The drl reporters initially delineate the lateral plate mesoderm, including heart progenitors. Subsequent myocardial drl reporter expression restricts to FHF descendants. We harnessed this unique feature to uncover that loss of tbx5a and pitx2 affect relative FHF versus SHF contributions to the heart. High-resolution physiology reveals distinctive electrical properties of each heart field territory that define a functional boundary within the single zebrafish ventricle. Our data establish that the transcriptional program driving cardiac septation regulates physiologic ventricle partitioning, which successively provides mechanical advantages of sequential contraction.

[Tropical sprue (author's transl)].

PubMed

Gras, C; Chapoy, P; Aubry, P

1981-01-01

Tropical sprue is a disease of the small intestine characterized by a malabsorption syndrome with a subtotal or partial mucosal atrophy. It is observed in Asia and Central America. It appears to be rare in Africa but its real frequency is unknown as small bowel biopsys are not routinely done. Bacterial overgrowth as well as giardiasis may be trigger factors of the disease the pathogenesis of which is still incompletely understood. The disease beginning as chronic diarrhea is later on characterized by an aphtoïd stomatitis and a macrocytic anemia. Treatment with antibiotics and folic acid is efficient and has a diagnostic value. If treatment is started lately, vitamin B 12 is then also necessary. In any intestinal syndrome observed in tropical areas without an ascertained etiologic diagnosis, peroral biopsie of the small intestine is requested. However, with the use of pediatric endoscope it will be possible to appreciate the respective incidence of tropical sprue and asymptomatic tropical sprue in Africa South of the Sahara.

Bacterial population and biodegradation potential in chronically crude oil-contaminated marine sediments are strongly linked to temperature.

PubMed

Bargiela, Rafael; Mapelli, Francesca; Rojo, David; Chouaia, Bessem; Tornés, Jesús; Borin, Sara; Richter, Michael; Del Pozo, Mercedes V; Cappello, Simone; Gertler, Christoph; Genovese, María; Denaro, Renata; Martínez-Martínez, Mónica; Fodelianakis, Stilianos; Amer, Ranya A; Bigazzi, David; Han, Xifang; Chen, Jianwei; Chernikova, Tatyana N; Golyshina, Olga V; Mahjoubi, Mouna; Jaouanil, Atef; Benzha, Fatima; Magagnini, Mirko; Hussein, Emad; Al-Horani, Fuad; Cherif, Ameur; Blaghen, Mohamed; Abdel-Fattah, Yasser R; Kalogerakis, Nicolas; Barbas, Coral; Malkawi, Hanan I; Golyshin, Peter N; Yakimov, Michail M; Daffonchio, Daniele; Ferrer, Manuel

2015-06-29

Two of the largest crude oil-polluted areas in the world are the semi-enclosed Mediterranean and Red Seas, but the effect of chronic pollution remains incompletely understood on a large scale. We compared the influence of environmental and geographical constraints and anthropogenic forces (hydrocarbon input) on bacterial communities in eight geographically separated oil-polluted sites along the coastlines of the Mediterranean and Red Seas. The differences in community compositions and their biodegradation potential were primarily associated (P < 0.05) with both temperature and chemical diversity. Furthermore, we observed a link between temperature and chemical and biological diversity that was stronger in chronically polluted sites than in pristine ones where accidental oil spills occurred. We propose that low temperature increases bacterial richness while decreasing catabolic diversity and that chronic pollution promotes catabolic diversification. Our results further suggest that the bacterial populations in chronically polluted sites may respond more promptly in degrading petroleum after accidental oil spills.

Bacterial population and biodegradation potential in chronically crude oil-contaminated marine sediments are strongly linked to temperature

PubMed Central

Bargiela, Rafael; Mapelli, Francesca; Rojo, David; Chouaia, Bessem; Tornés, Jesús; Borin, Sara; Richter, Michael; Del Pozo, Mercedes V.; Cappello, Simone; Gertler, Christoph; Genovese, María; Denaro, Renata; Martínez-Martínez, Mónica; Fodelianakis, Stilianos; Amer, Ranya A.; Bigazzi, David; Han, Xifang; Chen, Jianwei; Chernikova, Tatyana N.; Golyshina, Olga V.; Mahjoubi, Mouna; Jaouanil, Atef; Benzha, Fatima; Magagnini, Mirko; Hussein, Emad; Al-Horani, Fuad; Cherif, Ameur; Blaghen, Mohamed; Abdel-Fattah, Yasser R.; Kalogerakis, Nicolas; Barbas, Coral; Malkawi, Hanan I.; Golyshin, Peter N.; Yakimov, Michail M.; Daffonchio, Daniele; Ferrer, Manuel

2015-01-01

Two of the largest crude oil-polluted areas in the world are the semi-enclosed Mediterranean and Red Seas, but the effect of chronic pollution remains incompletely understood on a large scale. We compared the influence of environmental and geographical constraints and anthropogenic forces (hydrocarbon input) on bacterial communities in eight geographically separated oil-polluted sites along the coastlines of the Mediterranean and Red Seas. The differences in community compositions and their biodegradation potential were primarily associated (P < 0.05) with both temperature and chemical diversity. Furthermore, we observed a link between temperature and chemical and biological diversity that was stronger in chronically polluted sites than in pristine ones where accidental oil spills occurred. We propose that low temperature increases bacterial richness while decreasing catabolic diversity and that chronic pollution promotes catabolic diversification. Our results further suggest that the bacterial populations in chronically polluted sites may respond more promptly in degrading petroleum after accidental oil spills. PMID:26119183

ATX-LPA1 axis contributes to proliferation of chondrocytes by regulating fibronectin assembly leading to proper cartilage formation.

PubMed

Nishioka, Tatsuji; Arima, Naoaki; Kano, Kuniyuki; Hama, Kotaro; Itai, Eriko; Yukiura, Hiroshi; Kise, Ryoji; Inoue, Asuka; Kim, Seok-Hyung; Solnica-Krezel, Lilianna; Moolenaar, Wouter H; Chun, Jerold; Aoki, Junken

2016-03-23

The lipid mediator lysophosphatidic acid (LPA) signals via six distinct G protein-coupled receptors to mediate both unique and overlapping biological effects, including cell migration, proliferation and survival. LPA is produced extracellularly by autotaxin (ATX), a secreted lysophospholipase D, from lysophosphatidylcholine. ATX-LPA receptor signaling is essential for normal development and implicated in various (patho)physiological processes, but underlying mechanisms remain incompletely understood. Through gene targeting approaches in zebrafish and mice, we show here that loss of ATX-LPA1 signaling leads to disorganization of chondrocytes, causing severe defects in cartilage formation. Mechanistically, ATX-LPA1 signaling acts by promoting S-phase entry and cell proliferation of chondrocytes both in vitro and in vivo, at least in part through β1-integrin translocation leading to fibronectin assembly and further extracellular matrix deposition; this in turn promotes chondrocyte-matrix adhesion and cell proliferation. Thus, the ATX-LPA1 axis is a key regulator of cartilage formation.