Miracle-dz/UniFAR-FTUs huggingface dataset:
Sildenafil and B-Type Natriuretic Peptide Acutely Phosphorylate Titin and Improve Diastolic Distensibility In Vivo

Background— In vitro studies suggest that phosphorylation of titin reduces myocyte/myofiber stiffness. Titin can be phosphorylated by cGMP-activated protein kinase. Intracellular cGMP production is stimulated by B-type natriuretic peptide (BNP) and degraded by phosphodiesterases, including phosphodiesterase-5A. We hypothesized that a phosphodiesterase-5A inhibitor (sildenafil) alone or in combination with BNP would increase left ventricular diastolic distensibility by phosphorylating titin. Methods and Results— Eight elderly dogs with experimental hypertension and 4 young normal dogs underwent measurement of the end-diastolic pressure-volume relationship during caval occlusion at baseline, after sildenafil, and BNP infusion. To assess diastolic distensibility independently of load/extrinsic forces, the end-diastolic volume at a common end-diastolic pressure on the sequential end-diastolic pressure-volume relationships was measured (left ventricular capacitance). In a separate group of dogs (n=7 old hypertensive and 7 young normal), serial full-thickness left ventricular biopsies were harvested from the beating heart during identical infusions to measure myofilament protein phosphorylation. Plasma cGMP increased with sildenafil and further with BNP (7.31±2.37 to 26.9±10.3 to 70.3±8.1 pmol/mL; P<0.001). Left ventricular diastolic capacitance increased with sildenafil and further with BNP (51.4±16.9 to 53.7±16.8 to 60.0±19.4 mL; P<0.001). Changes were similar in old hypertensive and young normal dogs. There were no effects on phosphorylation of troponin I, troponin T, phospholamban, or myosin light chain-1 or -2. Titin phosphorylation increased with sildenafil and BNP, whereas titin-based cardiomyocyte stiffness decreased. Conclusion— Short-term cGMP-enhancing treatment with sildenafil and BNP improves left ventricular diastolic distensibility in vivo, in part by phosphorylating titin.
Interleukin-12 Promotes Pathologic Liver Changes and Death in Mice Coinfected with Schistosoma mansoni andToxoplasma gondii

ABSTRACT We previously demonstrated that mice concurrently infected withSchistosoma mansoni and Toxoplasma gondiiundergo accelerated mortality which is preceded by severe liver damage. Abnormally high levels of serum tumor necrosis factor alpha (TNF-α) in the dually infected mice suggested a role for this and related proinflammatory mediators in the pathologic alterations. In order to evaluate the factors involved in increased inflammatory-mediator production and mortality, interleukin-12−/−(IL-12−/−) mice were coinfected with S. mansoni and T. gondii, and survival and immune responses were monitored. These IL-12−/− mice displayed decreased liver damage and prolonged time to death relative to wild-type animals also coinfected with these parasites. Relative to the response of cells from the coinfected wild-type animals, levels of TNF-α, gamma interferon, and NO produced by splenocytes from coinfected IL-12−/− mice were reduced, and levels of IL-5 and IL-10 were increased, with the net result that the immune response of the dually infected IL-12−/− mice was similar to that of the wild-type mice infected with S. mansoni alone. While dually infected wild-type animals succumb in the absence of overt parasitemia, the delayed death in the absence of IL-12 is associated with relatively uncontrolled T. gondii replication. These data support the view that S. mansoni-infected mice are acutely sensitive to infection with T. gondii as a result of their increased hepatic sensitivity to high levels of proinflammatory cytokines; IL-12 and TNF-α are implicated in this process.
Regulation of Neurite Growth by Spontaneous Ca2+ Oscillations in Astrocytes

Astrocytes play a pivotal role in the regulation of neurite growth, but the intracellular signaling mechanism in astrocytes that mediates this regulation remains unclarified. We studied the relationship between spontaneous Ca2+ oscillations in astrocytes and the astrocyte-mediated neurite growth. We generated Ca2+ signal-deficient astrocytes in which spontaneous Ca2+ oscillations were abolished by a chronic inhibition of IP3 signaling. When hippocampal neurons were cultured on a monolayer of Ca2+ signal-deficient astrocytes, the growth of dendrites and axons was inhibited. Time-lapse imaging of the advancement of axonal growth cones indicated the involvement of membrane-bound molecules for this inhibition. Among six candidate membrane-bound molecules that may modulate neuronal growth, N-cadherin was downregulated in Ca2+ signal-deficient astrocytes. Although a blocking antibody to N-cadherin suppressed the axonal growth on control astrocytes, extrinsic N-cadherin expression rescued the suppressed axonal growth on Ca2+ signal-deficient astrocytes. These findings suggest that spontaneous Ca2+ oscillations regulate the astrocytic function to promote neurite growth by maintaining the expression of specific growth-enhancing proteins on their surface, and that N-cadherin is one of such molecules.
Environmental equity, air quality, socioeconomic status, and respiratory health: a linkage analysis of routine data from the Health Survey for England

Study objective: To assess relations between socioeconomic status and local air quality, and combined effects on respiratory health, in the context of environmental and health inequality. Design: Data on people taking part in the Health Survey for England were attributed with a small area index of air pollution using annual mean concentrations of nitrogen dioxide, sulphur dioxide, benzene, and particulates (PM10). Regression models were used to measure associations between social class, air quality, forced expiratory volume in one second (FEV1), and self reported asthma. Participants: Participants aged 16–79 in the Health Survey for England 1995, 1996, and 1997. Main results: Urban lower social class households were more likely to be located in areas of poor air quality, but the association in rural areas was, if anything reversed. Low social class and poor air quality were independently associated with decreased lung function (FEV1), but not asthma prevalence, after adjustment for a number of potential confounders. Social class effects were not attenuated by adjustment for air quality. In men, a differential effect of air pollution on FEV1 was found, with its effect in social classes III to V about double that in social classes I and II (p value for interaction = 0.04). This effect modification was not seen for women. Conclusions: Further evidence of environmental inequity in the UK is provided. The association between FEV1 and local air quality is of similar magnitude to that with social class, and the adverse effects of air pollution seem to be greater in men in lower social classes.
Major Depressive Disorder: Precursors, Predictors, and Coping Mechanism Among Undergraduate Students

Major Depressive Disorder: Precursors, Predictors, and Coping Mechanism Among Undergraduate Students by Grace Antia Bickham M.S., University of Nigeria, Nsukka, 1993 B.Ed., University of Ibadan, Ibadan, 1986 Dissertation Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy
Peripherally Inserted Central Catheters and Hemodialysis Outcomes.

BACKGROUND AND OBJECTIVES Use of peripherally inserted central catheters has expanded rapidly, but the consequences for patients who eventually require hemodialysis are undefined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Our national, population-based analysis included 33,918 adult Medicare beneficiaries from the US Renal Data System who initiated hemodialysis with central venous catheters as their sole vascular access in 2010 and 2011. We used linked Medicare claims to identify peripherally inserted central catheter exposures and evaluate the associations of peripherally inserted central catheter placement with transition to working arteriovenous fistulas or grafts and patient survival using a Cox model with time-dependent variables. RESULTS Among 33,918 individuals initiating hemodialysis with a catheter as sole access, 12.6% had received at least one peripherally inserted central catheter. Median follow-up was 404 days (interquartile range, 103-680 days). Among 6487 peripherally inserted central catheters placed, 3435 (53%) were placed within the 2 years before hemodialysis initiation, and 3052 (47%) were placed afterward. Multiple peripherally inserted central catheters were placed in 30% of patients exposed to peripherally inserted central catheters. Recipients of peripherally inserted central catheters were more likely to be women and have comorbid diagnoses and less likely to have received predialysis nephrology care. After adjustment for clinical and demographic factors, peripherally inserted central catheters placed before or after hemodialysis initiation were independently associated with lower likelihoods of transition to any working fistula or graft (hazard ratio for prehemodialysis peripherally inserted central catheter, 0.85; 95% confidence interval, 0.79 to 0.91; hazard ratio for posthemodialysis peripherally inserted central catheter, 0.81; 95% confidence interval, 0.73 to 0.89). CONCLUSIONS Peripherally inserted central catheter placement was common and associated with adverse vascular access outcomes. Recognition of potential long-term adverse consequences of peripherally inserted central catheters is essential for clinicians caring for patients with CKD.
Crossmodal Processing of Haptic Inputs in Sighted and Blind Individuals

In a previous behavioral study, it was shown that early blind individuals were superior to sighted ones in discriminating two-dimensional (2D) tactile angle stimuli. The present study was designed to assess the neural substrate associated with a haptic 2D angle discrimination task in both sighted and blind individuals. Subjects performed tactile angle size discriminations in order to investigate whether the pattern of crossmodal occipital recruitment was lateralized as a function of the stimulated hand. Task-elicited activations were also compared across different difficulty levels to ascertain the potential modulatory role of task difficulty on crossmodal processing within occipital areas. We show that blind subjects had more widespread activation within the right lateral and superior occipital gyri when performing the haptic discrimination task. In contrast, the sighted activated the left cuneus and lingual gyrus more so than the blind when performing the task. Furthermore, activity within visual areas was shown to be predictive of tactile discrimination thresholds in the blind, but not in the sighted. Activity within parietal and occipital areas was modulated by task difficulty, where the easier angle comparison elicited more focal occipital activity along with bilateral posterior parietal activity, whereas the more difficult comparison produced more widespread occipital activity combined with reduced parietal activation. Finally, we show that crossmodal reorganization within the occipital cortex of blind individuals was primarily right lateralized, regardless of the stimulated hand, supporting previous evidence for a right-sided hemispheric specialization of the occipital cortex of blind individuals for the processing of tactile and haptic inputs.
Behaviour in Latin American men: Implications for HIV/AIDS interventions

The single most deeply rooted feature of sexual culture in Latin America is the culture of machismo. Machismo is a complex ideological system that organizes gender relations hierarchically which establishes relations of power and domination between men and women. Same-sex relations between men are conceptualized within the framework of male-female relations. In Latin America the penetrating partner in same-sex interactions may maintain a sense of a fundamentally male identity. Thus he may not distinguish himself from other macho males. The receiving or effeminate partner faces the severest stigma in Latin America. Regardless of the type of sexual relations sexual practices are socially and culturally constructed within the context of sexual scripts. The broader conceptual frameworks of most HIV/AIDS prevention programs and interventions focus on psychologically grounded theories of individual behavior change rather than on more sociologically grounded approaches to community development and mobilization. Projects in Latin America have revealed many important insights that guide decision makers to reevaluate some elements of models that appear to contribute to the guidance of past HIV/AIDS behavioral interventions. Perhaps the concept of a behavioral intervention may be somewhat a misnomer because most AIDS prevention programs do not directly intervene at the level of behavior. Instead they tend to intervene at the level of social and cultural representations--the level of the subjective and intersubjective meanings held by people about their behaviors. The possibilities of behavior changes are conditioned by a range of social cultural economic and political factors or forces. These conditions may actually be beyond the possibility of any HIV/AIDS prevention program to effectively influence behavior. Nevertheless HIV/AIDS prevention programs should try to integrate as much as possible a concern with these factors into the design and implementation of prevention programs.
The interrelationships of ‘complex’ conodonts (Vertebrata)

Synopsis Little attention has been paid to the suprageneric classification for conodonts and existing schemes have been formulated without attention to homology, diagnosis and definition. We propose that cladistics providesan appropriate methodology to test existingschemes of classification and in which to explore the evolutionary relationships of conodonts. The development of a multielement taxonomy and a concept of homology based upon the position, not morphology, of elements within the apparatus provide the ideal foundation for the application of cladistics to conodonts. In an attempt to unravel the evolutionary relationships between ‘complex’ conodonts (prioniodontids and derivative lineages) we have compiled a data matrix based upon 95 characters and 61 representative taxa. The dataset was analysed using parsimony and the resulting hypotheses were assessed using a number of measures of support. These included bootstrap, Bremer Support and double‐decay; we also compared levels of homoplasy to those expected given the size of the dataset and to those expected in a random dataset. The dataset was analysed in three hierarchical tranches, representing three levels of certainty concerning multi‐element reconstructions and positional homologies. There is much agreement between the results derived from the three partitions, but some inconsistency, particularly in the precise composition of the three main evolutionary grades traditionally recognised (Prioniodontida, Prioniodinina, Ozarkodinina). This is considered to result from (a) the progressive inclusion of data that is increasingly uncertain and (b) the inclusion of increasingly distantly related taxa, introducing spurious hypotheses of homology. We tested for these by partitioning the dataset into the three main evolutionary grades and in each instance resolution was seen to increase substantially, especially among prioniodinins. Our concluding scheme of relationships is a tree derived from a compilation of the three component subtrees, which is directly compatible with the most‐parsimonious trees derived from the initial second tranche analysis with the exception of the position of Hibbardella. This is compared in detail to the main extant schemes of suprageneric classification. A formal scheme of suprageneric classification is presented and the distribution of characters with respect to component clades is considered as a basis for identifying diagnostic characters.
Knowing your limits - self-evaluation and prediction in object recognition

Allowing a robot to acquire 3D object models autonomously not only requires robust feature detection and learning methods but also mechanisms for guiding learning and assessing learning progress. In this paper we present probabilistic measures for observed detection success, predicted detection success and the completeness of learned models, where learning is incremental and online. This allows the robot to decide when to add a new keyframe to its view-based object model, where to look next in order to complete the model, predicting the probability of successful object detection given the model trained so far as well as knowing when to stop learning.
Quality of Life: Assessment, Analysis, and Interpretation

Principles of Measurement Scales. DEVELOPING AND TESTING QUESTIONNAIRES. Scores and Measurements: Validity, Reliability, Sensitivity. Multi-item Scales. Factor Analysis. Item Response Theory and Differential Item Functioning. Questionnaire Development and Scoring. ANALYSIS OF QoL DATA. Cross-sectional Analysis. Exploring Longitudinal Data. Modelling Longitudinal Data. Missing Data. Quality-adjusted Survival. PRACTICAL ASPECTS AND CLINICAL INTERPRETATION. Clinical Trials. Sample Sizes. Practical and Reporting Issues. Clinical Interpretation. Appendices. References. Index.
Molecular Phenotyping of Retinal Ganglion Cells

Classifying all of the ganglion cells in the mammalian retina has long been a goal of anatomists, physiologists, and cell biologists. The rabbit retinal ganglion cell layer was phenotyped using intrinsic small molecule signals (aspartate, glutamate, glycine, glutamine, GABA, and taurine) and glutamate receptor-gated 1-amino-4-guanidobutane excitation signals as the clustering dimensions for formal classification. Intrinsic signals alone yielded 7 ganglion cell superclasses and 1 amacrine cell superclass; the addition of excitation signals ultimately resolved 14 natural ganglion cell classes and 3 amacrine cell classes. Ganglion cells comprise two-thirds to three-quarters of the cells in the ganglion cell layer and exhibited distinct metabolic, coupling, and excitation phenotypes, as well as characteristic sizes, population fractions, and patterns. Metabolic signatures (mixtures of glutamate, aspartate, glutamine, and GABA) chemically discriminated ganglion from amacrine cells. Coupling signatures reflected heterologous coupling states across ganglion cells: (1) uncoupled, (2) coupled to GABAergic amacrine cells, and (3) coupled to glycinergic amacrine cells. Excitation signatures reflected differential channel permeation rates across classes after AMPA activation. Extraction of unique size and patterning features from the data sets further validated the robustness of the classification. Because the classifications were explicitly blinded to structure, this is strong evidence that molecular phenotype classes are natural classes. Correspondences of molecular phenotype classes to functional classes were inferred from size, coupling, encounter, and physiological attributes. Ganglion cell classes display markedly different ionotropic drives, which may partly explain the physiological brisk–sluggish spectrum of ganglion cell spiking patterns.
TamiR159 Directed Wheat TaGAMYB Cleavage and Its Involvement in Anther Development and Heat Response

In Arabidopsis and rice, miR159-regulated GAMYB-like family transcription factors function in flower development and gibberellin (GA) signaling in cereal aleurone cells. In this study, the involvement of miR159 in the regulation of its putative target TaGAMYB and its relationship to wheat development were investigated. First, we demonstrated that cleavage of TaGAMYB1 and TaGAMYB2 was directed by miR159 using 5′-RACE and a transient expression system. Second, we overexpressed TamiR159, TaGAMYB1 and mTaGAMYB1 (impaired in the miR159 binding site) in transgenic rice, revealing that the accumulation in rice of mature miR159 derived from the precursor of wheat resulted in delayed heading time and male sterility. In addition, the number of tillers and primary branches in rice overexpressing mTaGAMYB1 increased relative to the wild type. Our previous study reported that TamiR159 was downregulated after two hours of heat stress treatment in wheat (Triticum aestivum L.). Most notably, the TamiR159 overexpression rice lines were more sensitive to heat stress relative to the wild type, indicating that the downregulation of TamiR159 in wheat after heat stress might participate in a heat stress-related signaling pathway, in turn contributing to heat stress tolerance.
Effect of swimming intensity on subsequent cycling and overall triathlon performance

Objectives: To investigate the effects of different swimming intensities on subsequent cycling and overall triathlon performance. Methods: Nine highly trained, male triathletes completed five separate laboratory sessions comprising one graded exercise test, a swim time trial (STT), and three sprint distance triathlons (TRI). The swimming velocities of the three TRI sessions were 80–85% (S80), 90–95% (S90), and 98–102% (S100) of the STT velocity. Subsequent cycling and running were performed at a perceived maximal intensity. Swimming stroke mechanics were measured during the swim. Plasma lactate concentration and ratings of perceived exertion were recorded at the conclusion of the swim and over the course of subsequent cycling and running. Oxygen consumption was recorded during the cycle. Results: The S80 and S90 cycle times were faster than the S100 cycle time (p<0.05). The overall triathlon time of S80 was faster than that of S100 (p<0.05). The S100 swim was characterised by a greater stroke rate than S80 and S90 (p<0.05) and a greater plasma lactate concentration than S80 (p<0.01). Conclusion: A swimming intensity below that of a time trial effort significantly improves subsequent cycling and overall triathlon performance.
Recursive teaching dimension, VC-dimension and sample compression

This paper is concerned with various combinatorial parameters of classes that can be learned from a small set of examples. We show that the recursive teaching dimension, recently introduced by Zilles et al. (2008), is strongly connected to known complexity notions in machine learning, e.g., the self-directed learning complexity and the VC-dimension. To the best of our knowledge these are the first results unveiling such relations between teaching and query learning as well as between teaching and the VC-dimension. It will turn out that for many natural classes the RTD is upper-bounded by the VCD, e.g., classes of VC-dimension 1, intersection-closed classes and finite maximum classes. However, we will also show that there are certain (but rare) classes for which the recursive teaching dimension exceeds the VC-dimension. Moreover, for maximum classes, the combinatorial structure induced by the RTD, called teaching plan, is highly similar to the structure of sample compression schemes. Indeed one can transform any repetition-free teaching plan for a maximum class C into an unlabeled sample compression scheme for C and vice versa, while the latter is produced by (i) the corner-peeling algorithm of Rubinstein and Rubinstein (2012) and (ii) the tail matching algorithm of Kuzmin and Warmuth (2007).