gebhart/patrepeval huggingface dataset:
Glucosylceramide synthase inhibition enhances vincristine-induced cytotoxicity (2001)

As a strategy to enhance tumor cell sensitivity to vincristine, we tested whether modulation of sphingolipid metabolism would alter vincristine cytotoxicity since this is linked to accumulation of the intermediate metabolite, ceramide. We blocked ceramide metabolism in a series of variably vincristine-resistant cell lines derived from CCRF-CEM leukemia cells using an inhibitor of glucosylceramide synthase, DL-threo-phenyl-2-hexadecanoylamino-3-pyrrolidino-1-propanol (PPPP). PPPP alone (1.0 microM), while nearly completely blocking glucosylceramide synthesis, was not toxic and did not increase cellular ceramide levels. Vincristine alone was toxic, caused apoptosis or programmed cell death (PCD) and caused an elevation in ceramide levels. Strikingly, the combination of PPPP and vincristine resulted in a further increase, over that of vincristine alone, of (i) cellular ceramide concentration, (ii) cytotoxicity associated with PCD and (iii) G2/M cell-cycle arrest. PPPP had no effect on P-glycoprotein expression or function. We conclude that vincristine cytotoxicity occurs in part through a ceramide-dependent mechanism, resulting in both G2/M block as well as PCD, and that the blockade of glucosylceramide synthase, in itself not toxic, causes augmented accumulation of ceramide resulting from vincristine exposure, which in turn maximizes ceramide-dependent, vincristine-induced cytotoxicity. Inhibition of glucosylceramide synthesis may be a means of circumventing drug resistance by enhancing signaling through a cell-death pathway.
Dual mechanism of vascular endothelial growth factor upregulation by hypoxia in human hepatocellular carcinoma (2001)

These data suggest hypoxia as a central stimulus of angiogenesis in human HCC through upregulation of VEGF gene expression by at least two distinct molecular mechanisms: activation of VEGF gene transcription and an increase in VEGF mRNA stability.
A fibrosarcoma model derived from mouse embryo cells: Growth properties and secretion of collagenase and metalloproteinase inhibitor (TIMP) by tumour cell lines (1984)

A new murine fibrosarcoma model has been developed in which it is possible to compare in vitro the behaviour of tumour cells with that of normal parental cells from which the tumour was originally derived by spontaneous transformation in vitro. Tumour cell lines were obtained which showed differing capacities for localized invasion of the skin following subcutaneous injection: these were categorized as either highly invasive or poorly invasive and were compared with the normal cells for (I) their respective saturation densities when grown on plastic, (2) their ability to grow in agar, and (3) their secretions of the metalloenzyme collagenase and the specific inhibitor of metalloproteinases (TIMP). Although increased in vitro saturation density showed some correlation with increased invasiveness in vivo, the most striking correlation was the 10- to 20-fold reduction in TIMP secretion by tumour cells of high invasive potential compared with normal cells or tumour cells with low invasive potential. No collagenase secretion by tumour cells was ever detected. It is proposed that local TIMP levels may play a crucial in the control of tumour invasion in vivo.
Thymus-Independent and Thymus-Dependent Responses to Polysaccharide Antigens (1992)

Immune responses to polysaccharide antigens are thymus-independent (TI). Conversion of a polysaccharide antigen to a thymus-dependent (TD) antigen by covalent coupling to an immunogenic protein carrier alters the response to the polysaccharide in several important ways. Of primary importance for the prevention of invasive diseases in infants caused by encapsulated bacteria is the shift of the peak antibody response to a much younger age. Another important change is the development of memory B cells primed and ready to respond to either the polysaccharide, as would be encountered during an infection, or to a second dose of the same antigen. Additional immunoglobulin isotypes not seen or seen as a minor component in response to the polysaccharide are also a feature of the TD response. Finally, the diversity of the antibody population is increased after immunization with a TD vaccine compared with that seen after immunization with a TI vaccine.
Pushing the Envelope for RGB-based Dense 3D Hand Pose Estimation via\n Neural Rendering (2019)

Estimating 3D hand meshes from single RGB images is challenging, due to\nintrinsic 2D-3D mapping ambiguities and limited training data. We adopt a\ncompact parametric 3D hand model that represents deformable and articulated\nhand meshes. To achieve the model fitting to RGB images, we investigate and\ncontribute in three ways: 1) Neural rendering: inspired by recent work on human\nbody, our hand mesh estimator (HME) is implemented by a neural network and a\ndifferentiable renderer, supervised by 2D segmentation masks and 3D skeletons.\nHME demonstrates good performance for estimating diverse hand shapes and\nimproves pose estimation accuracies. 2) Iterative testing refinement: Our\nfitting function is differentiable. We iteratively refine the initial estimate\nusing the gradients, in the spirit of iterative model fitting methods like ICP.\nThe idea is supported by the latest research on human body. 3) Self-data\naugmentation: collecting sized RGB-mesh (or segmentation mask)-skeleton\ntriplets for training is a big hurdle. Once the model is successfully fitted to\ninput RGB images, its meshes i.e. shapes and articulations, are realistic, and\nwe augment view-points on top of estimated dense hand poses. Experiments using\nthree RGB-based benchmarks show that our framework offers beyond\nstate-of-the-art accuracy in 3D pose estimation, as well as recovers dense 3D\nhand shapes. Each technical component above meaningfully improves the accuracy\nin the ablation study.\n
The background of INTERNIST I and QMR (1987)

During my tenure as Chairman of the Department of Medicine at the University of Pittsburgh, 1955 to 1970, two points became clear in regard to diagnosis in internal medicine. The first was that the knowledge base in that field had become vastly too large for any single person to encompass it. The second point was that the busy practitioner, even though he knew the items of information pertinent to his patients correct diagnosis, often did not consider the right answer particularly if the diagnosis was an unusual disease.
Chondroitin Sulfate in Sputum from Patients with Cystic Fibrosis and Chronic Bronchitis (1991)

In order to ascertain whether or not the presence of glycosaminoglycans in sputa of patients suffering from chronic bronchial disorders was related to tracheobronchial infection, an electrophoretic procedure was set up. The different acidic macromolecular components of sputum, namely nucleic acids, glycosaminoglycans, and bronchial glycopeptides could be identified in proteolyzed sputum using agarose electrophoresis before and after the action of different enzymes: nucleases, chondroitinases, hyaluronidase and heparinase. This procedure was used to analyze 13 sputum samples from patients suffering from cystic fibrosis (CF) and 12 sputum samples from patients suffering from chronic bronchitis. Chondroitin sulfate was identified in 11 infected sputum samples from patients with CF and also in the noninfected sputum from a patient with chronic bronchitis. These data suggest a relationship between the presence of chondroitin sulfate proteoglycans in sputum and severe tracheobronchial infection in CF.
Electronic Manipulation of Cells on Microchip-Based Devices (2001)

The development of integrated microfluidic bioanalytical systems demands all the analytical functions-such as sample collection, sample pretreatment, target cell isolation, and biomolecular extraction, amplification, and detection-to be performed on single or multiple microchips. A number of functions have been successfully realized on biochips, including, most notably, DNA amplification by PCR in microchambers and molecular separation by capillary electrophoresis in microchannels. In contrast, microfluidic sample preparation in terms of manipulation and separation of target cells from complex fluid samples such as human blood remains a significant challenge (Cheng et al., 1998a).
The pharmacokinetics and pharmacodynamics of warfarin in combination with ambrisentan in healthy volunteers (2009)

Multiple doses of ambrisentan had no clinically relevant effects on the pharmacokinetics and pharmacodynamics of a single dose of warfarin. Therefore, significant dose adjustments of either drug are unlikely to be required with co-administration.
Safety and immunogenicity of a Pseudomonas aeruginosa O-polysaccharide toxin A conjugate vaccine in humans. (1987)

Lipid A-free polysaccharide (PS) isolated from Pseudomonas aeruginosa immunotype 5 lipopolysaccharide (LPS) was covalently coupled to toxin A via reductive amination. The PS-toxin A conjugate was comprised of 29.8% PS and 70.2% toxin A, possessed a molecular weight of greater than 1 X 10(6), was nontoxic for animals and was nonpyrogenic for rabbits at a dose of 50 micrograms/kg body wt when administered intravenously. The conjugate evoked only mild, transient reactions upon subcutaneous administration to human volunteers. Vaccination engendered immunoglobulin G (IgG) antibody, which neutralized the cytotoxic effect of toxin A and promoted the uptake and killing of P. aeruginosa in the presence of human polymorphonuclear leukocytes. Passively transferred IgG isolated from the serum of immunized donors was far more effective at preventing fatal P. aeruginosa burn wound sepsis than paired preimmunization serum. These studies establish the potential usefulness of such a PS-toxin A conjugate as a vaccine against P. aeruginosa.
Interacting with big interfaces on small screens: a comparison of fisheye, zoom, and panning techniques (2004)

Mobile devices with small screens are becoming more common, and will soon be powerful enough to run desktop software. However, the large interfaces of desktop applications do not fit on the small screens. Although there are ways to redesign a UI to fit a smaller area, there are many cases where the only solution is to navigate the large UI with the small screen. The best way to do this, however, is not known. We compared three techniques for using large interfaces on small screens: a panning system similar to what is in current use, a two-level zoom system, and a fisheye view. We tested the techniques with three realistic tasks. We found that people were able to carry out a web navigation task significantly faster with the fisheye view, that the two-level zoom was significantly better for a monitoring task, and that people were slowest with the panning system. ways to solve this problem. First, applications can be redesigned for the smaller screen. Although there are examples of this approach (e.g., Pocket Word or Internet Explorer for PocketPC devices), it requires that multiple versions of the application be produced, and requires that users become familiar with a second GUI. There will also be cases where no redesigned version of an application is available—so another approach is needed. Key words: Large interfaces, small screens, mobile devices, screen space, zoom and pan, fisheye views. 1
Ventilator-induced lung injury: The anatomical and physiological framework (2010)

Since its introduction into the management of the acute respiratory distress syndrome, mechanical ventilation has been so strongly interwoven with its side effects that it came to be considered as invariably dangerous. Over the decades, attention has shifted from gross barotrauma to volutrauma and, more recently, to atelectrauma and biotrauma. In this article, we describe the anatomical and physiologic framework in which ventilator-induced lung injury may occur. We address the concept of lung stress/strain as applied to the whole lung or specific pulmonary regions. We challenge some common beliefs, such as separately studying the dangerous effects of different tidal volumes (end inspiration) and end-expiratory positive pressures. Based on available data, we suggest that stress at rupture is only rarely reached and that high tidal volume induces ventilator-induced lung injury by augmenting the pressure heterogeneity at the interface between open and constantly closed units. We believe that ventilator-induced lung injury occurs only when a given threshold is exceeded; below this limit, mechanical ventilation is likely to be safe.
Nanocomposites with Spatially Separated Functionalities for Combined Imaging and Magnetolytic Therapy (2010)

Compact nanostructures with highly integrated functionalities are of considerable current interest to drug delivery, multimodality imaging, and electronic devices. A key challenge, however, is how to combine individual components together without interfering or sacrificing their original electronic and optical properties. Here, we demonstrate a new class of nanocomposites with spatially separated functionalities. We further demonstrate magnetic field modulated imaging and an innovative application of this technology in cancer cell treatment, magnetolytic therapy, based on magnetically controlled mechanical damage to cell membranes.
The histone deacetylase inhibitor scriptaid enhances nascent mRNA production and rescues full-term development in cloned inbred mice (2009)

Since the birth of Cumulina, the first mouse clone produced by somatic cell nuclear transfer (SCNT), the success rate of cloning in mice has been extremely low compared with other species and most of the inbred mouse strains have never been cloned. Recently, our laboratory has found that treatment of SCNT mouse embryos with trichostatin A, a histone deacetylase inhibitor (HDACi), improved the full-term development of B6D2F1 mouse clones significantly. However, this was not effective for the inbred strains. Here, we show for the first time that by treating SCNT embryos with another HDACi, scriptaid, all the important inbred mouse strains can be cloned, such as C57BL/6, C3H/He, DBA/2, and 129/Sv. Moreover, the success of somatic nuclear reprogramming and cloning efficiency via nuclear transfer technique is clearly linked to the competent de novo synthesis of nascent mRNA in cloned mouse embryos.
High-oleic acid Australian Brassica napus and B. juncea varieties produced by co-suppression of endogenous Δ12-desaturases (2000)

Genetic engineering methods have been used successfully to modify the fatty acid profile of elite Australian germplasm of Brassica napus and B. juncea. Co-suppression plasmids carrying oleate desaturase genes from each species have been constructed and transferred into Australian elite breeding lines of B. napus and B. juncea using Agrobacterium tumifaciens plant-transformation techniques. Modifications to existing Brassica transformation protocols and the use of an intron-interrupted hygromycin-resistance gene as the selectable marker have resulted in improved transformation efficiencies. Silencing of the endogenous oleate desaturase genes has resulted in substantial increases in oleic acid levels, up to 89% in B. napus and 73% in B. juncea.
Multi-parental extension of the unimodal normal distribution crossover for real-coded genetic algorithms (2003)

The unimodal normal distribution crossover (UNDX) for the real-coded genetic algorithms (RCGA) proposed by Ono et al. (1997, 1998) shows an excellent performance in optimization problems of multi-modal and highly epistatic fitness functions in continuous search space. Further, theoretical analysis of the UNDX shows that the UNDX is a crossover operator that preserves the statistics such as the mean vector and the covariance matrix of the population well. The present paper proposes some design guidelines for crossover operators for RCGA. Then, based on these guidelines, a multi-parental extension of the UNDX is proposed so as to enhance its exploration ability. Performance of the extended UNDX is evaluated by numerical experiments.
Improving the accuracy of EKF-based visual-inertial odometry (2012)

In this paper, we perform a rigorous analysis of EKF-based visual-inertial odometry (VIO) and present a method for improving its performance. Specifically, we examine the properties of EKF-based VIO, and show that the standard way of computing Jacobians in the filter inevitably causes inconsistency and loss of accuracy. This result is derived based on an observability analysis of the EKF's linearized system model, which proves that the yaw erroneously appears to be observable. In order to address this problem, we propose modifications to the multi-state constraint Kalman filter (MSCKF) algorithm [1], which ensure the correct observability properties without incurring additional computational cost. Extensive simulation tests and real-world experiments demonstrate that the modified MSCKF algorithm outperforms competing methods, both in terms of consistency and accuracy.
The electric field induced in the brain by magnetic stimulation: a 3-d finite-element analysis of the effect of tissue heterogeneity and anisotropy (2003)

We investigate the effect of tissue heterogeneity and anisotropy on the electric field and current density distribution induced in the brain during magnetic stimulation. Validation of the finite-element (FE) calculations in a homogeneous isotropic sphere showed that the magnitude of the total electric field can be calculated to within an error of approximately 5% in the region of interest, even in the presence of a significant surface charge contribution. We used a high conductivity inclusion within a sphere of lower conductivity to simulate a lesion due to an infarct. Its effect is to increase the electric field induced in the surrounding low conductivity region. This boost is greatest in the vicinity of interfaces that lie perpendicular to the current flow. For physiological values of the conductivity distribution, it can reach a factor of 1.6 and extend many millimeters from the interface. We also show that anisotropy can significantly alter the electric field and current density distributions. Either heterogeneity or anisotropy can introduce a radial electric field component, not present in a homogeneous isotropic conductor. Heterogeneity and anisotropy are predicted to significantly affect the distribution of the electric field induced in the brain. It is, therefore, expected that anatomically faithful FE models of individual brains which incorporate conductivity tensor data derived from diffusion tensor measurements, will provide a better understanding of the location of possible stimulation sites in the brain.
Robust camera pose recovery using stochastic geometry (2001)

The Problem: The objective of 3-D machine vision is to infer geometric properties (e.g. shape and size) and photometric attributes (e.g. color, texture, reflectance) from a set of 2-D images. Every such vision task relies on accurate camera calibration, that is, knowledge of the camera’s intrinsic parameters (focal length, lens distortion, etc.) and extrinsic parameters—orientation, position, and scale relative to a fixed frame of reference. This research concerns the automatic recovery of precise extrinsic pose among a large set of images, assuming that accurate intrinsic parameters and rough estimates of extrinsic parameters are available. This work also investigates models of geometric uncertainty and the application of projective inference techniques. Motivation: The MIT City Project [2] employs a set of unique algorithms to produce accurate, metric reconstruction of urban landscapes from pose imagery, or images annotated with approximate geo-referenced position and orientation. All components of the system are completely automatic except for extrinsic camera registration, which is obtained via manual correspondence of point features across images followed by global bundle adjustment. The acquired data consists of a large set (tens of thousands) of images, making the the human-assisted component quite tedious. Thus the primary goal of this work is to provide fully automatic, scalable external registration. Previous Work: There exists an enormous body of work in automatic camera registration, which is most often coupled with the recovery of 3-D structure. Some techniques use known calibration targets to determine camera pose [1].
Transforming growth factor‐beta 1 (TGF‐β1) induces angiogenesis through vascular endothelial growth factor (VEGF)‐mediated apoptosis (2009)

VEGF and TGF-beta1 induce angiogenesis but have opposing effects on endothelial cells. VEGF protects endothelial cells from apoptosis; TGF-beta1 induces apoptosis. We have previously shown that VEGF/VEGF receptor-2 (VEGFR2) signaling mediates TGF-beta1 induction of apoptosis. This finding raised an important question: Does this mechanism stimulate or inhibit angiogenesis? Here we report that VEGF-mediated apoptosis is required for TGF-beta1 induction of angiogenesis. In vitro the apoptotic effect of TGF-beta1 on endothelial cells is rapid and followed by a long period in which the cells are refractory to apoptosis induction by TGF-beta1. Inhibition of VEGF/VEGFR2 signaling abrogates formation of cord-like structures by TGF-beta1 with an effect comparable to that of z-VAD, an apoptosis inhibitor. Similarly, genetic deficiency of VEGF abolishes TGF-beta1 upregulation of endothelial cell differentiation and formation of vascular structures in embryoid bodies. In vivo TGF-beta1 induces endothelial cell apoptosis as rapidly as in vitro. Inhibition of VEGF blocks TGF-beta1 induction of both apoptosis and angiogenesis, an effect similar to that of z-VAD. Thus, TGF-beta1 induction of angiogenesis requires a rapid and transient apoptotic effect mediated by VEGF/VEGFR2. This novel, unexpected role of VEGF and VEGFR2 indicates VEGF-mediated apoptosis as a potential target to control angiogenesis.
Hydrogenomics of the Extremely Thermophilic Bacterium Caldicellulosiruptor saccharolyticus (2008)

Caldicellulosiruptor saccharolyticus is an extremely thermophilic, gram-positive anaerobe which ferments cellulose-, hemicellulose- and pectin-containing biomass to acetate, CO(2), and hydrogen. Its broad substrate range, high hydrogen-producing capacity, and ability to coutilize glucose and xylose make this bacterium an attractive candidate for microbial bioenergy production. Here, the complete genome sequence of C. saccharolyticus, consisting of a 2,970,275-bp circular chromosome encoding 2,679 predicted proteins, is described. Analysis of the genome revealed that C. saccharolyticus has an extensive polysaccharide-hydrolyzing capacity for cellulose, hemicellulose, pectin, and starch, coupled to a large number of ABC transporters for monomeric and oligomeric sugar uptake. The components of the Embden-Meyerhof and nonoxidative pentose phosphate pathways are all present; however, there is no evidence that an Entner-Doudoroff pathway is present. Catabolic pathways for a range of sugars, including rhamnose, fucose, arabinose, glucuronate, fructose, and galactose, were identified. These pathways lead to the production of NADH and reduced ferredoxin. NADH and reduced ferredoxin are subsequently used by two distinct hydrogenases to generate hydrogen. Whole-genome transcriptome analysis revealed that there is significant upregulation of the glycolytic pathway and an ABC-type sugar transporter during growth on glucose and xylose, indicating that C. saccharolyticus coferments these sugars unimpeded by glucose-based catabolite repression. The capacity to simultaneously process and utilize a range of carbohydrates associated with biomass feedstocks is a highly desirable feature of this lignocellulose-utilizing, biofuel-producing bacterium.