gebhart/patrepeval huggingface dataset:
Pharmacologic interactions between the resistance‐modifying cyclosporine sdz psc 833 and etoposide (VP 16–213) enhance <i>In Vivo</i> cytostatic activity and toxicity (1992)

Cyclosporin A reverses multidrug resistance (MDR) and increases the in vivo cytostatic activity and toxicity of the anticancer agent etoposide (VP 16-213). SDZ PSC 833 (PSC 833), a non-immunosuppressive, non-toxic cyclosporin and very active modifier of P-gp 170-mediated MDR, elicits similar effects when administered with adriamycin. The underlying mechanisms, however, are not yet understood. The present pharmacological interaction study with PSC 833 and VP 16-213 was carried out to reveal the nature of this enhancement of cytostatic activity and toxicity. Rats pre-treated with either PSC-833 or solvent received a single dose of VP 16-213. Plasma levels of VP 16-213 were measured by high-performance liquid chromatography (HPLC). The resulting increase in cytostatic activity and toxicity of VP 16-213 mediated by PSC 833 was paralleled by marked changes in the pharmacokinetic parameters of VP 16-213 in vivo. Bioavailability and blood levels of VP 16-213 were significantly increased 30 min after administration if PSC 833 had been given before. The disappearance rate of VP 16-213 from the intravascular compartment was considerably slowed down by PSC 833. In drug-sensitive xenografts of human colon carcinoma, the PSC-833-induced pharmacologic changes in vivo could be counteracted by dose reduction of VP 16-213 while a full therapeutic potential was maintained. Doses of VP 16-213, 1.5 to 2 times smaller, combined with PSC 833, were as effective in terms of tumor-growth inhibition as the maximum tolerated dose of VP 16-213 alone. Thus, pharmacologic interactions between PSC 833 or other resistance modifiers and VP 16-213 and other cytostatic agents require careful attention if they are to be used in humans to overcome MDR.
Detecting cheaters for multiplayer games: theory, design and implementation[1] (2006)

Massively multiplayer game holds a huge market in the digital entertainment industry. Companies invest heavily in the game and graphics development since a successful online game can attract million of users, and this translates to a huge investment payoff. However, multiplayer online game is also subjected to various forms of hacks and cheats. Hackers can alter the graphic rendering to reveal information otherwise be hidden in a normal game, or cheaters can use software robot to play the game automatically and gain an unfair advantage. Currently, some popular online games release software patches or incorporate anti-cheating software to detect known cheats. This not only creates deployment difficulty but new cheats will still be able to breach the normal game logic until software patches are available. Moreover, the anti-cheating software themselves are also vulnerable to hacks. In this paper, we propose a scalable and efficient method to detect whether a player is cheating or not. The methodology is based on the dynamic Bayesian network approach. The detection framework relies solely on the game states and runs in the game server only. Therefore it is invulnerable to hacks and it is a much more deployable solution. To demonstrate the effectiveness of the propose method, we implement a prototype multiplayer game system and to detect whether a player is using the "aiming robot" for cheating or not. Experiments show that not only we can effectively detect cheaters, but the false positive rate is extremely low. We believe the proposed methodology and the prototype system provide a first step toward a systematic study of cheating detection and security research in the area of online multiplayer games.
Neuronal differentiation of PC12 cells as a result of prevention of cell death by <i>bcl</i>‐2 (1994)

Rat pheochromocytoma PC12 cells die when cultured in serum-free medium. Neurotrophic factors can rescue PC12 cells from cell death, and induce neuronal differentiation. To further investigate the relationship among cell death, survival, and differentiation, the bcl-2 cDNA, which is known to prevent apoptosis in various types of cells, was transfected into PC12 cells. Six monoclonal bcl-2-transfected cell lines were isolated and confirmed to express mRNA and protein product of bcl-2. The wild-type and bcl-2-transfected PC12 cells were kept to adhere to collagen-coated dishes at the initiation of serum-free experiments to avoid cellular damage due to detachment of the cells by trituration. Even under the conditions, the control PC12 cells mostly died within 24 h, when cultured in serum-free medium, whereas those expressing Bcl-2 survived even for 7 days in serum-free medium. Moreover, outgrowth of long processes in the bcl-2-transfected cells was only observed under the condition to keep the cells attached to the dishes in serum-free medium without any additive neurotrophic or growth factors. Neurofilament medium protein, which is a neuron-specific cytoskeletal component, was also expressed in the differentiated cells, suggesting that the long processes in bcl-2-transfected PC12 cells are neurites. However, neuronal differentiation of PC12 cells expressing Bcl-2 was not observed when cultured in serum-containing medium. Accordingly, survival of PC12 cells expressing Bcl-2 under the condition which cells usually die may be accompanied with neuronal differentiation.
Synthetic Medical Images from Dual Generative Adversarial Networks (2017)

Currently there is strong interest in data-driven approaches to medical image classification. However, medical imaging data is scarce, expensive, and fraught with legal concerns regarding patient privacy. Typical consent forms only allow for patient data to be used in medical journals or education, meaning the majority of medical data is inaccessible for general public research. We propose a novel, two-stage pipeline for generating synthetic medical images from a pair of generative adversarial networks, tested in practice on retinal fundi images. We develop a hierarchical generation process to divide the complex image generation task into two parts: geometry and photorealism. We hope researchers will use our pipeline to bring private medical data into the public domain, sparking growth in imaging tasks that have previously relied on the hand-tuning of models. We have begun this initiative through the development of SynthMed, an online repository for synthetic medical images.
[Effects of a partial exchange transfusion with Fluosol DA 20% on healthy pigs]. (1982)

In 9 animals 500 ml of blood was replaced with 500 ml of Fluosol DA 20%. An average of 19.2 ml per kg body weight of emulsion, i.e. 3.883 gm per kg body weight of fluorocarbons was given. On the eighth day following exchange transfusion the animals were killed and tissue samples taken from liver and lung for electron microscopy and chemical analysis. Biochemical parameters were measured in central venous blood prior to transfusion and on the 2nd, 3rd, 6th and 8th days. One animal died on the sixth day of study, hence only the results obtained from the remaining 8 animals were analysed. On removing the lungs a marked firmness of consistency and failure to collapse was noted. Electron microscopy revealed numerous phagocytic cells packed with foam-like substance, partly occluding the pulmonary capillaries. On chemical analysis a residue of 23.95 mg fluorocarbon per gm of lung tissue was found. Acid-base analysis of central venous blood showed a compensated respiratory acidosis on the 6th and 8th day. The hepatic reticulo-endothelial system was found to be laden with numerous vacuoles, to such a degree that the sinusoids were all practically fully occluded. Neither cell necrosis nor inflammatory reactions were observed.
Cell Surface Heparan Sulfate Proteoglycans Participate in Factor VIII Catabolism Mediated by Low Density Lipoprotein Receptor-related Protein (2001)

We have demonstrated previously that catabolism of a coagulation factor VIII (fVIII) from its complex with von Willebrand factor (vWf) is mediated by low density lipoprotein receptor-related protein (LRP) (Saenko, E. L., Yakhyaev, A. V., Mikhailenko, I., Strickland, D. K., and Sarafanov, A. G. (1999) J. Biol. Chem. 274, 37685-37692). In the present study, we found that this process is facilitated by cell surface heparan sulfate proteoglycans (HSPGs). This was demonstrated by simultaneous blocking of LRP and HSPGs in model cells, which completely prevented fVIII internalization and degradation from its complex with vWf. In contrast, the selective blocking of either receptor had a lesser effect. In vivo studies of clearance of (125)I-fVIII-vWf complex in mice also demonstrated that the simultaneous blocking of HSPGs and LRP led to a more significant prolongation of fVIII half-life (5.5-fold) than blocking of LRP alone (3.5-fold). The cell culture and in vivo experiments revealed that HSPGs are also involved in another, LRP-independent pathway of fVIII catabolism. In both pathways, HSPGs act as receptors providing the initial binding of fVIII-vWf complex to cells. We demonstrated that this binding occurs via the A2 domain of fVIII, since A2, but not other portions of fVIII or isolated vWf, strongly inhibited cell surface binding of fVIII-vWf complex, and the affinities of A2 and fVIII-vWf complex for the cells were similar. The A2 site involved in binding to heparin was localized to the region 558-565, based on the ability of the corresponding synthetic peptide to inhibit A2 binding to heparin, used as a model for HSPGs.
Transcriptional organization of bovine papillomavirus type 1 (1983)

Multiple bovine papillomavirus type 1 (BPV-1)-specific polyadenylated RNA species in a BPV-1-infected bovine fibropapilloma were identified and mapped. All of the RNA species were transcribed from the same DNA strand of the BPV-1 genome. Five RNA species previously identified in BPV-1-transformed mouse cells were also present in the bovine fibropapilloma. These five species measured 1,050, 1,150, 1,700, 3,800, and 4,050 bases, mapped within the 69% transforming segment of the BPV-1 genome, and shared a 3' coterminus at 0.53 map units (m.u.). The 5' ends of the bodies of these distinct transcripts were located at ca. 0.03, 0.09, 0.34, 0.39, and 0.41 m.u. Additional polyadenylated RNA species not present in BPV-1-transformed mouse cells were specific for the BPV-1-infected bovine fibropapilloma and measured 1,700, 3,700, 3,800, 6,700, and 8,000 bases. These wart-specific species shared a 3' coterminus at 0.90 m.u. The 5' termini of the bodies of the 1,700- and 3,800-base species mapped at 0.71 and 0.42 m.u., respectively. Exonuclease VII analysis failed to reveal any internal splicing in these two species; however, the presence of small remote 5' leader sequences could not be ruled out. The 3,700-base species hybridized to DNA fragments from the 69% transforming segment as well as from the 31% nontransforming segment of the BPV-1 genome; however, this species was not precisely mapped. The 5' termini of the two largest RNA species (6,700 and 8,000 bases in size) were located at ca. 0.01 and 0.90 m.u., respectively. Since the 5' ends of these mapped adjacent to a TATAAA sequence which could possibly serve as an element of a transcriptional promoter, it is possible that one or both of these species represent nonspliced precursor RNA molecules.
Novel Antiinflammatory Targets for Asthma: A Role for PPAR γ ? (2001)

The search for new treatments of asthma and related airway disorders is a continuing quest of pulmonologists, pharmacologists, and pharmaceutical industries documented from as early as 1600 BC (1). The approach of modern medicine has been to identify key procontractile compounds and mediators with the hope of obtaining antagonists to a major clinical outcome, namely the loss of respiratory volume (2). New approaches are needed because many of the current treatments (e.g., antileukotriene drugs, antihistamines, and steroids) are only effective in a portion of those afflicted with asthma and the side effects of these treatments have proved to be a formidable challenge (3, 4). More recently, it has been appreciated that inflammation plays a critical role in asthma, particularly the recruitment of specialized leukocytes, neutrophils, eosinophils, and lymphocytes to lung, and eventually to airways (5). Hence, one strategy may involve the identification of novel antiinflammatory agents that could dampen the clinical sequelae in various forms of asthma. It is in this context that we consider this perspective.
Computer-controlled optical scanning tile microscope (2006)

A new type of computer-controlled optical scanning, high-magnification imaging system with a large field of view is described that overcomes the commonly believed incompatibility of achieving both high magnification and a large field of view. The new system incorporates galvanometer scanners, a CCD camera, and a high-brightness LED source for the fast acquisition of a large number of a high-resolution segmented tile images with a magnification of 800x for each tile. The captured segmented tile images are combined to create an effective enlarged view of a target totaling 1.6 mm x 1.2 mm in area. The speed and sensitivity of the system make it suitable for high-resolution imaging and monitoring of a small segmented area of 320 microm x 240 microm with 4 microm resolution. Each tile segment of the target can be zoomed up without loss of the high resolution. This new microscope imaging system gives both high magnification and a large field of view. This microscope can be utilized in medicine, biology, semiconductor inspection, device analysis, and quality control.
Activation of cord T lymphocytes. I. Evidence for a defective T cell mitogenesis induced through the CD2 molecule. (1989)

A study was carried out on cord blood T cell activation via the CD2-mediated pathway. Despite similar percentages of circulating CD3+ and CD2+ cells in adult and cord blood, the proliferation of cord PBMC to the anti-CD3 mAb and cord T cells to anti-CD2 mAb were defective. The T cell CD3-surface structure was normally able to control CD2-mediated activation, as its modulation by a non-mitogenic anti-CD3 mAb blocked cord PBMC proliferation induced by anti-CD2 mAb. CD2-stimulated cord T cells did not proliferate and did not produce a significant amount of IL-2 in culture, although they expressed the IL-2R. This observation was confirmed by the optimal proliferation of CD2-induced cord T cells when rIL-2 was added. Despite the alternative T cell activation pathway is monocyte-independent in adults, the defective cord T cell activation via the CD2 molecule could also be bypassed by the addition of PMA, small amounts of either autologous or allogeneic adult and cord AC or simply rIL-1 alone. Our findings provide evidence for an intrinsic functional defect in cord CD2-mediated T cell activation, which is linked to an impaired increase of free cytoplasmic calcium, as confirmed by the effectiveness of calcium ionophore A23187 in restoring a good CD2-induced cord T cell proliferation and by measurement of cellular calcium uptake after activation via the CD2 molecule. The characteristics of cord T cells revealed by this study recall the thymocyte functional pattern and may represent functional expression of the previously described phenotypic immaturity of cord T cells.
Effect of hydrogenation on the metal-semiconductor phase transition in vanadium dioxide thin films (2007)

Hydrogen penetration into thin films of vanadium dioxide from aqueous solutions of mono-, di-, and tribasic alcohols is studied. It is shown that this process is reversible, has a catalytic character, and brings about a lowering of the metal-semiconductor phase transition temperature. It is established that the phase transition in a hydrogenated HxVO2 film is completely suppressed for x> 0.04.
Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells (2017)

Immunotherapy using checkpoint-blocking antibodies against targets such as CTLA-4 and PD-1 can cure melanoma and non-small cell lung cancer in a subset of patients. The presence of CD8 T cells in the tumor correlates with improved survival. We show that immuno-positron emission tomography (immuno-PET) can visualize tumors by detecting infiltrating lymphocytes and, through longitudinal observation of individual animals, distinguish responding tumors from those that do not respond to therapy. We used <sup>89</sup>Zr-labeled PEGylated single-domain antibody fragments (VHHs) specific for CD8 to track the presence of intratumoral CD8<sup>+</sup> T cells in the immunotherapy-susceptible B16 melanoma model in response to checkpoint blockade. A <sup>89</sup>Zr-labeled PEGylated anti<i>-</i>CD8 VHH detected thymus and secondary lymphoid structures as well as intratumoral CD8 T cells. Animals that responded to CTLA-4 therapy showed a homogeneous distribution of the anti-CD8 PET signal throughout the tumor, whereas more heterogeneous infiltration of CD8 T cells correlated with faster tumor growth and worse responses. To support the validity of these observations, we used two different transplantable breast cancer models, yielding results that conformed with predictions based on the antimelanoma response. It may thus be possible to use immuno-PET and monitor antitumor immune responses as a prognostic tool to predict patient responses to checkpoint therapies.
Cervical ripening with dehydroepiandrosterone sulphate (1982)

Dehydroepiandrosterone sulphate (DHEA-S) was given intravenously twice a week after 38 weeks gestation to ripen the uterine cervix in 20 nulliparae and 24 parous women who subsequently went into labour at term. The condition of the uterine cervix was assessed by Bishop scoring. The increase in the score in nulliparous women given DHEA-S was significantly greater than that in the control group, who were given placebo injections, on the 7th, 14th and 21st days. The increase in the parous women was significant only on the 7th day. In nulliparous women the dilatation, effacement and consistency improved significantly, while in the parous women the effect of DHEA-S was apparent only in the consistency. The duration of labour was significantly shortened by treatment with DHEA-S in nulliparae but this effect was not found in parous women. The interval between the first administration of DHEA-S and the onset of labour in nulliparae was significantly shorter than that in the control group. There were no serious side effects or complications. Our results suggest that DHEA-S may be used safely and effectively to ripen the uterine cervix and to trigger the onset of labour in late pregnancy.
The N Terminus of the Centromere H3-Like Protein Cse4p Performs an Essential Function Distinct from That of the Histone Fold Domain (2000)

Cse4p is an evolutionarily conserved histone H3-like protein that is thought to replace H3 in a specialized nucleosome at the yeast (Saccharomyces cerevisiae) centromere. All known yeast, worm, fly, and human centromere H3-like proteins have highly conserved C-terminal histone fold domains (HFD) but very different N termini. We have carried out a comprehensive and systematic mutagenesis of the Cse4p N terminus to analyze its function. Surprisingly, only a 33-amino-acid domain within the 130-amino-acid-long N terminus is required for Cse4p N-terminal function. The spacing of the essential N-terminal domain (END) relative to the HFD can be changed significantly without an apparent effect on Cse4p function. The END appears to be important for interactions between Cse4p and known kinetochore components, including the Ctf19p/Mcm21p/Okp1p complex. Genetic and biochemical evidence shows that Cse4p proteins interact with each other in vivo and that nonfunctional cse4 END and HFD mutant proteins can form functional mixed complexes. These results support different roles for the Cse4p N terminus and the HFD in centromere function and are consistent with the proposed Cse4p nucleosome model. The structure-function characteristics of the Cse4p N terminus are relevant to understanding how other H3-like proteins, such as the human homolog CENP-A, function in kinetochore assembly and chromosome segregation.
Solvation and Dynamics of Sodium and Potassium in Ethylene Carbonate from ab Initio Molecular Dynamics Simulations (2017)

The development of sodium and potassium batteries offers a promising way to meet the scaling and cost challenges of energy storage. However, compared to Li+, several intrinsic properties of Na+ and K+, including their solvation and dynamics in typical organic electrolytes utilized in battery applications, are less well-understood. Here, we report a systematic investigation of Na+ and K+ in ethylene carbonate (EC) using first-principles molecular dynamics simulations. Our simulations reveal significant differences in the solvation structure and dynamical properties of Na+ and K+ compared to Li+. We find that, in contrast to Li+ which exhibits a well-defined first solvation shell, the larger Na+ and K+ ions show more disordered and flexible solvation structures. These differences in solvation were found to significantly influence the ion dynamics, leading to larger diffusion coefficients of Na+ and K+ compared to Li+. Our simulations also reveal a clear and interesting analog in the behavior of the ions in EC and aqueous environments, particularly in the specific ion effects on the solvent dynamics. This work provides fundamental understanding of the intrinsic properties of Na+ and K+ in organic electrolytes, which may ultimately influence the intercalation mechanism at the electrode–electrolyte interface and therefore battery performance, lifetime, and safety.
Torque and histomorphometric evaluation of c.p. titanium screws blasted with 25- and 75-?m-sized particles of Al2O3 (1996)

A comparison was made between screw-shaped c.p. titanium implants blasted with either 25- or 75-microns particles of Al2O3. The implant surfaces were investigated with respect to topography and composition before implantation in rabbit bone. Grit blasting with 25- or 75-microns particles produced two different surface roughnesses, but no significant difference in the surface composition for the two surfaces. After 12 weeks insertion time in the rabbit tibia and femur, a higher removal torque and more bone-to-metal contact was found for the implants blasted with 75-microns particles compared with the 25-microns-blasted ones.
Micropatterned, clickable culture substrates enable in situ spatiotemporal control of human PSC-derived neural tissue morphology (2015)

We describe a modular culture platform that enables spatiotemporal control of the morphology of 2D neural tissues derived from human pluripotent stem cells (hPSCs) by simply adding clickable peptides to the media. It should be widely applicable for elucidating how spatiotemporal changes in morphology and substrate biochemistry regulate tissue morphogenesis.
3D Reconstruction of Buildings and Vegetation from Synthetic Aperture Radar (SAR) Images. (1998)

3D models of a landscape are useful for the evaluation of remote sensing data or for landscape planning. In this paper, it is shown that a 3D reconstruction of buildings and vegetation can be obtained from the shadows in synthetic aperture radar (SAR) images. First, elevated objects like buildings and higher vegetation (e. g. trees), and shadow regions are segmented in the SAR image. Then the shadows are assigned to suitable elevated objects. Since it is assumed that the height of the ground is known from a digital elevation model (DEM) or from other sensors, the heights of the elevated objects can be calculated from the estimated radial shadow lengths and the system parameters. The wrong positions of elevated objects in SAR images can be corrected afterwards. Finally, triangulation and texturing methods lead to a realistic 3D model of the landscape including buildings and vegetation. 1 Introduction Remote sensing of the earth&amp;apos;s surface with synthetic aperture radar (SAR) has several...