gebhart/patrepeval huggingface dataset:
Activation of gp130 Transduces Hypertrophic Signal Through Interaction of Scaffolding/Docking Protein Gab1 With Tyrosine Phosphatase SHP2 in Cardiomyocytes (2003)

Grb2-associated binder-1 (Gab1) is a scaffolding/docking protein and contains a Pleckstrin homology domain and potential binding sites for Src homology (SH) 2 and SH3 domains. Gab1 is tyrosine phosphorylated and associates with protein tyrosine phosphatase SHP2 and p85 phosphatidylinositol 3-kinase on stimulation with various cytokines and growth factors, including interleukin-6. We previously demonstrated that interleukin-6-related cytokine, leukemia inhibitory factor (LIF), induced cardiac hypertrophy through gp130. In this study, we report the role of Gab1 in gp130-mediated cardiac hypertrophy. Stimulation with LIF induced tyrosine phosphorylation of Gab1, and phosphorylated Gab1 interacted with SHP2 and p85 in cultured cardiomyocytes. We constructed three kinds of adenovirus vectors, those carrying wild-type Gab1 (AdGab1WT), mutated Gab1 lacking SHP2 binding site (AdGab1F627/659), and beta-galactosidase (Adbeta-gal). Compared with cardiomyocytes infected with Adbeta-gal, longitudinal elongation of cardiomyocytes induced by LIF was enhanced in cardiomyocytes infected with AdGab1WT but inhibited in cardiomyocytes infected with AdGab1F627/659. Upregulation of BNP mRNA expression by LIF was evoked in cardiomyocytes infected with Adbeta-gal and AdGab1WT but not in cardiomyocytes infected with AdGab1F627/659. In contrast, Gab1 repressed skeletal alpha-actin mRNA expression through interaction with SHP2. Furthermore, activation of extracellular signal-regulated kinase 5 (ERK5) was enhanced in cardiomyocytes infected with AdGab1WT compared with cardiomyocytes infected with Adbeta-gal but repressed in cardiomyocytes infected with AdGab1F627/659. Coinfection of AdGab1WT with adenovirus vector carrying dominant-negative ERK5 abrogated longitudinal elongation of cardiomyocytes induced by LIF. Taken together, these findings indicate that Gab1-SHP2 interaction plays a crucial role in gp130-dependent longitudinal elongation of cardiomyoctes through activation of ERK5.
On Building Cooperative Intelligent Transportation Systems over Public Transports (2019)

Cooperative Intelligent Transportation Systems (CITS) have gained an increasing interest in the last few years. Within these systems, vehicles use wireless communications to cooperatively exchange information in the perspective of enhancing traffic efficiency and comfort. Public transport represents an excellent candidate for C-ITS support. Indeed, unlike private cars, public transport vehicles are inherently cooperative and can be easily augmented with wireless communication capabilities. In this paper, we analyze the communication contact opportunities between public transport buses. Understanding these contacts is a basic building block towards the design and deployment of intelligent, distributed and cooperative applications on top of bus public transport systems. We particularly investigate bus-to-bus contacts in the actual bus public transport of the entire Luxembourg city over a whole day. This city is a representative example of many other European cities. Our study shows that both space and time are chief factors in the characterization of bus-to-bus contacts. Different geographical regions and daytimes show varied contacts properties. Our analysis thus stresses the importance of considering large-scale scenarios when evaluating C-ITS.
Negative regulation ofDrosophilaJAK–STAT signalling by endocytic trafficking (2010)

Appropriate regulation of signal transduction pathways is essential for normal development and is often disrupted in disease. Therefore, many regulatory mechanisms and feedback loops have evolved to ensure appropriate signalling. One mechanism previously suggested to modulate a range of signal transduction pathways involves the internalisation and destruction of transmembrane receptors by the endocytic trafficking machinery. Strikingly, a recent report has suggested that the endocytic trafficking of the Drosophila JAK-STAT pathway receptor Domeless (Dome) does not act to downregulate pathway activity, but rather is necessary for in vivo signalling. Here, we examine this relationship to address the interaction of Drosophila JAK-STAT pathway signalling and endocytic trafficking. We show that Dome is trafficked through clathrin-mediated endocytosis and a directed RNAi screen identified several components of the endocytic machinery as negative regulators of pathway signalling. We demonstrate that Dome signals both from the plasma membrane and internalised vesicles and show, using knockdown experiments, that endocytic components negatively regulate JAK-STAT signalling in vivo. As such, disruption in endocytic trafficking represents a potent negative regulator of the disease relevant JAK-STAT signalling cascade.
Robust Learning for Deep Monocular Depth Estimation (2019)

Existing methods for deep monocular depth estimation are often trained with basic loss functions such as mean absolute error (MAE) or reverse Huber (BerHu). We revisit several basic loss functions to explore possibilities for improvement and show that the final depth estimation accuracy is dominated by pixels with small errors, which account for the vast majority. Based on this observation, we propose a new robust loss function that suppresses the contributions of pixels with higher errors by taking their square root. The loss function called the square root Huber (Ruber) is designed to be first-order differentiable on ℝ <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;0</sup> , so it can be directly applied to the end-to-end learning of a general type of neural network. Unlike the widely-used robust loss function called Huber, the Ruber loss function facilitates further refinement of the pixels with smaller errors by giving larger gradient values to the errors that are close to zero. Moreover, we show that the estimation accuracy can be further improved by introducing a second training step based on an edge-preserving loss. Experimental results with public indoor scene datasets demonstrate that our method outperforms major loss functions and can yield better accuracies than existing approaches in terms of root mean square error (RMSE).
Clinical Trial Principles and Endpoint Definitions for Paravalvular Leaks in Surgical Prosthesis (2017)

The VARC (Valve Academic Research Consortium) for transcatheter aortic valve replacement set the standard for selecting appropriate clinical endpoints reflecting safety and effectiveness of transcatheter devices, and defining single and composite clinical endpoints for clinical trials. No such standardization exists for circumferentially sutured surgical valve paravalvular leak (PVL) closure. This document seeks to provide core principles, appropriate clinical endpoints, and endpoint definitions to be used in clinical trials of PVL closure devices. The PVL Academic Research Consortium met to review evidence and make recommendations for assessment of disease severity, data collection, and updated endpoint definitions. A 5-class grading scheme to evaluate PVL was developed in concordance with VARC recommendations. Unresolved issues in the field are outlined. The current PVL Academic Research Consortium provides recommendations for assessment of disease severity, data collection, and endpoint definitions. Future research in the field is warranted.
Large-eddy simulation of turbulent mixed convection in a vertical annulus with a rotating inner cylinder (2007)

Large-eddy simulations of mixed convection in an upward turbulent flow inside a vertical annular pipe with a rotating inner cylinder were performed at Re Dh = 8900 and Pr = 0.71. The principal objective of this study was to investigate the combined effects of buoyancy and inner wall rotation on the turbulent structures. The incompressible filtered Navier–Stokes equations and energy equations were solved using a mixed fourth and second-order accurate finite difference method. Isoflux wall boundary conditions with low and high heating (buoyancy numbers, Bo = 0.18 and 0.5) were imposed. Two rotation rates (N = 0.1716 and 0.2574) were used and the radius ratio (R*) was 0.5. Various turbulent statistics were obtained to analyze the near-wall turbulent structures. The results show that strong heating of the system with a stationary inner wall causes distortions of the flow structure resulting in reduced turbulent intensities, shear stress, and turbulent heat flux, particularly near the wall. In contrast, rotation of the inner cylinder suppresses this substantial reduction in turbulent statistics.
Spatial Expression Patterns and Biochemical Properties Distinguish a Second myo-Inositol Monophosphatase IMPA2 from IMPA1 (2006)

Lithium is used in the clinical treatment of bipolar disorder, a disease where patients suffer mood swings between mania and depression. Although the mode of action of lithium remains elusive, a putative primary target is thought to be inositol monophosphatase (IMPase) activity. Two IMPase genes have been identified in mammals, the well characterized myo-inositol monophosphatase 1 (IMPA1) and myo-inositol monophosphatase 2 (IMPA2). Several lines of genetic evidence have implicated IMPA2 in the pathogenesis of not only bipolar disorder but also schizophrenia and febrile seizures. However, little is known about the protein, although it is predicted to have lithium-inhibitable IMPase activity based on its homology to IMPA1. Here we present the first biochemical study comparing the enzyme activity of IMPA2 to that of IMPA1. We demonstrate that in vivo, IMPA2 forms homodimers but no heterodimers with IMPA1. Recombinant IMPA2 exhibits IMPase activity, although maximal activity requires higher concentrations of magnesium and a higher pH. IMPA2 shows significantly lower activity toward myo-inositol monophosphate than IMPA1. We therefore screened for additional substrates that could be more efficiently dephosphorylated by IMPA2, but failed to find any. Importantly, when using myo-inositol monophosphate as a substrate, the IMPase activity of IMPA2 was inhibited at high lithium and restricted magnesium concentrations. This kinetics distinguishes it from IMPA1. We also observed a characteristic pattern of differential expression between IMPA1 and IMPA2 in a selection of tissues including the brain, small intestine, and kidney. These data suggest that IMPA2 has a separate function in vivo from that of IMPA1.
Computer extracted texture features on T2w MRI to predict biochemical recurrence following radiation therapy for prostate cancer (2014)

In this study we explore the ability of a novel machine learning approach, in conjunction with computer-extracted features describing prostate cancer morphology on pre-treatment MRI, to predict whether a patient will develop biochemical recurrence within ten years of radiation therapy. Biochemical recurrence, which is characterized by a rise in serum prostate-specific antigen (PSA) of at least 2 ng/mL above the nadir PSA, is associated with increased risk of metastasis and prostate cancer-related mortality. Currently, risk of biochemical recurrence is predicted by the Kattan nomogram, which incorporates several clinical factors to predict the probability of recurrence-free survival following radiation therapy (but has limited prediction accuracy). Semantic attributes on T2w MRI, such as the presence of extracapsular extension and seminal vesicle invasion and surrogate measure- ments of tumor size, have also been shown to be predictive of biochemical recurrence risk. While the correlation between biochemical recurrence and factors like tumor stage, Gleason grade, and extracapsular spread are well- documented, it is less clear how to predict biochemical recurrence in the absence of extracapsular spread and for small tumors fully contained in the capsule. Computer{extracted texture features, which quantitatively de- scribe tumor micro-architecture and morphology on MRI, have been shown to provide clues about a tumor's aggressiveness. However, while computer{extracted features have been employed for predicting cancer presence and grade, they have not been evaluated in the context of predicting risk of biochemical recurrence. This work seeks to evaluate the role of computer-extracted texture features in predicting risk of biochemical recurrence on a cohort of sixteen patients who underwent pre{treatment 1.5 Tesla (T) T2w MRI. We extract a combination of first-order statistical, gradient, co-occurrence, and Gabor wavelet features from T2w MRI. To identify which of these T2w MRI texture features are potential independent prognostic markers of PSA failure, we implement a partial least squares (PLS) method to embed the data in a low{dimensional space and then use the variable importance in projections (VIP) method to quantify the contributions of individual features to classification on the PLS embedding. In spite of the poor resolution of the 1.5 T MRI data, we are able to identify three Gabor wavelet features that, in conjunction with a logistic regression classifier, yield an area under the receiver operating characteristic curve of 0.83 for predicting the probability of biochemical recurrence following radiation therapy. In comparison to both the Kattan nomogram and semantic MRI attributes, the ability of these three computer-extracted features to predict biochemical recurrence risk is demonstrated.
Effects of heart isolation, voltage-sensitive dye, and electromechanical uncoupling agents on ventricular fibrillation (2003)

We tested whether the interventions typically required for optical mapping affect activation patterns during ventricular fibrillation (VF). A 21 x 24 unipolar electrode array (1.5 mm spacing) was sutured to the left ventricular epicardium of 16 anesthetized pigs, and four episodes of electrically induced VF (30-s duration) were recorded. The hearts were then rapidly excised and connected to a Langendorff perfusion apparatus. Four of the hearts were controls, in which 24 additional VF episodes were then mapped. In the remaining 12 hearts, four VF episodes were mapped after isolation, four more episodes were mapped after exposure to the voltage-sensitive dye di-4-ANEPPS, and six more episodes were mapped after exposure to the electromechanical uncoupling agents diacetyl monoxime (DAM; 20 mmol/l, n = 6) or cytochalasin D (CytoD; 10 micromol/l, n = 6). VF episodes were separated by 4 min. VF activation patterns were quantified using custom pattern analysis algorithms. From comparisons with time-corrected control data, all interventions significantly changed VF patterns. Most changes were broadly consistent with slowing and regularization due to loss of excitability. Heart isolation had the largest effect on VF patterns, followed by CytoD, DAM, and dye.
Cochlear implant speech intelligibility outcomes with structured and unstructured binary mask errors (2016)

It has been shown that intelligibility can be improved for cochlear implant (CI) recipients with the ideal binary mask (IBM). In realistic scenarios where prior information is unavailable, however, the IBM must be estimated, and these estimations will inevitably contain errors. Although the effects of both unstructured and structured binary mask errors have been investigated with normal-hearing (NH) listeners, they have not been investigated with CI recipients. This study assesses these effects with CI recipients using masks that have been generated systematically with a statistical model. The results demonstrate that clustering of mask errors substantially decreases the tolerance of errors, that incorrectly removing target-dominated regions can be as detrimental to intelligibility as incorrectly adding interferer-dominated regions, and that the individual tolerances of the different types of errors can change when both are present. These trends follow those of NH listeners. However, analysis with a mixed effects model suggests that CI recipients tend to be less tolerant than NH listeners to mask errors in most conditions, at least with respect to the testing methods in each of the studies. This study clearly demonstrates that structure influences the tolerance of errors and therefore should be considered when analyzing binary-masking algorithms.
WatchOut (2016)

Current interactions on a smartwatch are generally limited to a tiny touchscreen, physical buttons or knobs, and speech. We present WatchOut, a suite of interaction techniques that includes three families of tap and swipe gestures which extend input modalities to the watch's case, bezel, and band. We describe the implementation of a user-independent gesture recognition pipeline based on data from the watch's embedded inertial sensors. In a study with 12 participants using both a round- and square-screen watch, the average gesture classification accuracies ranged from 88.7% to 99.4%. We demonstrate applications of this richer interaction capability, and discuss the strengths, limitations, and future potential for this work.
<title>Application of Lorentz geometry to nonimaging optics: new 3D ideal concentrators</title> (1995)

A new family of 3D ideal nonimaging concentrators with rotational symmetry is presented. The formulation has been done using Lorentz geometry. The flow line concentrator and cone concentrator appear as particular cases with this approach.
Biotechnology for Fuels and Chemicals (2003)

In Biotechnology for Fuels and Chemicals: The Twenty-Fourth Symposium, leading US and international researchers from academia, industry, and government present state-of-the-art research on how biotechnology is being used to produce high-volume, low-price products from renewable resources, as well as to improve the environment. The focus of this symposium was on bioprocessing from multidisciplinary perspectives. Session topics include advanced feedstock production and processing, enzyme and microbial biocatalysts, bioprocess research and development, opportunities in biorefineries, and commercialization of biobased products. This symposium was particularly exciting because of the projects and concepts that were being commercialized on a large scale for lactic acid, propanedol, and ethanol. Cutting-edge and authoritative, Biotechnology for Fuels and Chemicals: The Twenty-Fourth Symposium provides an excellent overview of current research and development in the production of commodity fuels and chemicals via biological transformation
Cytokines, Antibodies, and Histopathological Profiles during Giardia Infection and Variant-Specific Surface Protein-Based Vaccination (2018)

Giardiasis is one of the most common human intestinal diseases worldwide. Several experimental animal models have been used to evaluate <i>Giardia</i> infections, with gerbils (<i>Meriones unguiculatus</i>) being the most valuable model due to their high susceptibility to <i>Giardia</i> infection, abundant shedding of cysts, and pathophysiological alterations and signs of disease similar to those observed in humans. Here, we report cytokine and antibody profiles both during the course of <i>Giardia</i> infection in gerbils and after immunization with a novel oral vaccine comprising a mixture of purified variant-specific surface proteins (VSPs). Transcript levels of representative cytokines of different immune profiles as well as macro- and microtissue alterations were assessed in Peyer's patches, mesenteric lymph nodes, and spleens. During infection, cytokine responses showed a biphasic profile: an early induction of Th1 (gamma interferon [IFN-γ], interleukin-1β [IL-1β], IL-6, and tumor necrosis factor [TNF]), Th17 (IL-17), and Th2 (IL-4) cytokines, together with intestinal alterations typical of inflammation, followed by a shift toward a predominant Th2 (IL-5) response, likely associated with a counterregulatory mechanism. Conversely, immunization with an oral vaccine comprising the entire repertoire of VSPs specifically showed high levels of IL-17, IL-6, IL-4, and IL-5, without obvious signs of inflammation. Both immunized and infected animals developed local (intestinal secretory IgA [S-IgA]) and systemic (serum IgG) humoral immune responses against VSPs; however, only infected animals showed evident signs of giardiasis. This is the first comprehensive report of cytokine expression and anti-<i>Giardia</i> antibody production during infection and VSP vaccination in gerbils, a reliable model of the human disease.
Regulatory aspects in modified-release drug delivery (2008)

Modified-release products are produced with the goal of delivering medicines that are efficacious, are acceptably safe and have a predictable time course of delivery. In this context, modified release refers to all types of formulations with modified release, including fast (rapid), delay, sustained release, targeted, and controlled-release formulations for the various routes of administration possible. Achieving regulatory approval is an integral part in the development and commercialization of any modified-release product. This overview chapter will emphasize conventional products, recognizing that although approaches differ somewhat between the major regulatory jurisdictions regulatory authorities will require documentation demonstrating that, in common with more standard preparations, such pharmaceutical products meet Good Manufacturing Practices (GMP); quality control specifications; and pharmaceutical product interchangeability (1). In general, such approval requires evidence that the following are well defined: n As an active drug substance in its properties, manufacture, characterization, control, choice of storage container, and stability n The drug product in terms of its formulation, manufacturing process, manufacture, excipient control, its control, choice of storage container and stability n The pharmacokinetics and biopharmaceutics and, possibly, pharmacodynamics of the drug product and/or n Demonstration of safety and efficacy by clinical trial The precise nature and form of the evidence does differ greatly between the countries providing regulatory approval. In general, two somewhat different but increasingly convergent strategies are used. The United States has very detailed process driven procedures that are applied in product approval as described in a later chapter by Marroum (2). In contrast, the European Union (EU) provides guidelines for what is seen as the norm for various delivery systems (3). Here, it is possible to depart from the guidance with justification. The Japanese (4) and Canadian (5) systems appear to have a number of aspects in common with the US system. In contrast, the Australian system is somewhat more flexible, largely following, and formally adopting, the European Medicines Agency (EMEA) guidelines (6) but utilizing other sources of guidance or adopting a case by case approach where appropriate. The World Health Organization (WHO) provides effectively an overall harmonizing system. Interestingly, EMEA, WHO, and FDA each have one formulation category referred to as Delayed Release (1). The second is referred to as Prolonged Release by EMEA and as Extended (controlled, prolonged, sustained) Release by WHO and FDA.