gebhart/patrepeval huggingface dataset:
Interaction of human platelets with laminin and identification of the 67 kDa laminin receptor on platelets (1991)

A microtitre adhesion assay has been developed to define parameters affecting the adherence of washed platelets to laminin. Adherence was optimally supported by Mg2+ and was inhibited by Ca2+ and by anti-laminin Fab fragments, but significant adhesion (75-90% of control) was found both in heparinized plasma containing physiological levels of bivalent cations and in plasma anti-coagulated with EGTA. Adherence was unaffected by platelet activation with ADP but was decreased by 50% by treatment with alpha-thrombin (1 unit/ml, 5 min). Adherence was unaffected by monospecific polyclonal antibodies to glycoprotein (GP) Ib and GPIV, and was normal with platelets from two patients with Glanzmann's thrombasthaenia, indicating that GPIb, the GPIIb/IIIa complex and GPIV are not involved in platelet-laminin interaction. Affinity chromatography of Triton-solubilized membranes on laminin-Sepharose followed by elution with 0.2 M-glycine/HCl (pH 2.85) identified a major band with a molecular mass of 67 kDa in the reduced and of 53 kDa in the unreduced form. This protein gave a positive reaction on Western blotting with a monospecific polyclonal antibody raised against the high-affinity laminin receptor isolated from human breast carcinoma tissue. The adhesion of platelets to laminin was inhibited by two monoclonal IgM antibodies specific to the LR-1 domain of the 67 kDa receptor. The binding protein was surface-oriented, as shown by flow cytofluorimetry and by the fact that it could be iodinated in intact platelets, but it was not labelled by the periodate-borotritide procedure, suggesting that it did not contain terminal sialic acid. The laminin-derived peptides Tyr-Ile-Gly-Ser-Arg and Cys-Asp-Pro-Gly-Tyr-Ile-Gly-Ser-Arg-NH2, which constitute a complementary binding domain in laminin for the 67 kDa receptor, themselves supported platelet adhesion, bound to the receptor and inhibited the adhesion of platelets to laminin. In addition, Fab fragments of anti-Tyr-Ile-Gly-Ser-Arg antibody inhibited platelet adhesion to laminin. These results demonstrate that the high-affinity 67 kDa laminin receptor previously identified in a range of normal and transformed cells and its complementary Tyr-Ile-Gly-Ser-Arg binding domain play an important role in the interaction of platelets with laminin.
Miniature Doppler probe using a unidirectional SAW transducer (2003)

A miniature Doppler probe using a unidirectional leaky-wave surface acoustic wave transducer is presented for application to the measurement of blood flow in a living body. The interdigital electrodes in four pairs were fabricated on piezoelectric materials with dimensions of 1.6 mm*2.2 mm. The transducer has a 5-MHz center frequency, a directivity of 13.5 dB to 18 dB, and an electroacoustic conversion efficiency of -27 dB. The utility of the probe was demonstrated in blood flow measurements. The probe eliminates the need for a stand-off incorporated with a conventional Doppler probe.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Mechanism of the Gossypol Inactivation of Pepsinogen (1973)

Abstract Previous experiments have shown that pepsinogen reacts with the cottonseed pigment gossypol in the presence of ethanol to form a stable complex with little or no potenitial pepsin activity. We now find the reaction is both temperature- and alcohol-dependent, suggesting a conformational change in the zymogen prior to reaction with gossypol. A yellow, ninhydrin-positive material has been recovered from the acid hydrolysate of borohydride-reduced, gossypol-inactivated pepsinogen. This material is identical with synthetic lysine-gossypol prepared by the reduction of the gossypol-lysine Schiff base. These results confirm that inactivation is due to Schiff base formation between the aldehyde functional groups of the gossypol and lysines 18 and 358 of the zymogen. Pyridoxal phosphate, another Schiff base-forming reagent, was found to protect pepsinogen from inactivation by gossypol. Gossypol has been found to be a good competitive inhibitor of pepsin with a Ki of 4.7 x 10-5 m when Z-Gly-Gly-Phe-Phe-3-(4-pyridyl)propyl-1-oxy was used as a substrate. Under the same conditions, pyridoxal phosphate does not inhibit pepsin at 1.25 x 10-3 m.
Lack of N regions in fetal and neonatal mouse immunoglobulin V-D-J junctional sequences. (1990)

Much of T and B lymphocyte receptor diversity derives from the addition of nontemplated N regions at the junctions of receptor gene elements, although fetal T cells expressing gamma/delta receptors lack N regions. I have sequenced immunoglobulin H chain variable regions of PCR-amplified DNA and cDNA from fetal and newborn mouse liver and spleen cells. These sequences showed an absence of N regions. Only 1/87 DNA sequences and 17/146 RNA sequences contained N regions, in striking contrast to adult Ig sequences. These data show that N region insertion is a developmentally regulated process in B cells as well as in T cells, and demonstrate that receptor diversity in neonatal B cells is limited by the absence of N regions as well as by biased usage of Vh genes.
S2E (2011)

This paper presents S2E, a platform for analyzing the properties and behavior of software systems. We demonstrate S2E's use in developing practical tools for comprehensive performance profiling, reverse engineering of proprietary software, and bug finding for both kernel-mode and user-mode binaries. Building these tools on top of S2E took less than 770 LOC and 40 person-hours each. S2E's novelty consists of its ability to scale to large real systems, such as a full Windows stack. S2E is based on two new ideas: selective symbolic execution, a way to automatically minimize the amount of code that has to be executed symbolically given a target analysis, and relaxed execution consistency models, a way to make principled performance/accuracy trade-offs in complex analyses. These techniques give S2E three key abilities: to simultaneously analyze entire families of execution paths, instead of just one execution at a time; to perform the analyses in-vivo within a real software stack--user programs, libraries, kernel, drivers, etc.--instead of using abstract models of these layers; and to operate directly on binaries, thus being able to analyze even proprietary software. Conceptually, S2E is an automated path explorer with modular path analyzers: the explorer drives the target system down all execution paths of interest, while analyzers check properties of each such path (e.g., to look for bugs) or simply collect information (e.g., count page faults). Desired paths can be specified in multiple ways, and S2E users can either combine existing analyzers to build a custom analysis tool, or write new analyzers using the S2E API.
Opportunities for information visualization (2000)

Information visualization has been an active research topic for more than a decade. Products are starting to appear. This article discusses some of the research and commercial opportunities for information visualization over the next decade.
Mechanisms and enzymes involved in SARS coronavirus genome expression (2003)

A novel coronavirus is the causative agent of the current epidemic of severe acute respiratory syndrome (SARS). Coronaviruses are exceptionally large RNA viruses and employ complex regulatory mechanisms to express their genomes. Here, we determined the sequence of SARS coronavirus (SARS-CoV), isolate Frankfurt 1, and characterized key RNA elements and protein functions involved in viral genome expression. Important regulatory mechanisms, such as the (discontinuous) synthesis of eight subgenomic mRNAs, ribosomal frameshifting and post-translational proteolytic processing, were addressed. Activities of three SARS coronavirus enzymes, the helicase and two cysteine proteinases, which are known to be critically involved in replication, transcription and/or post-translational polyprotein processing, were characterized. The availability of recombinant forms of key replicative enzymes of SARS coronavirus should pave the way for high-throughput screening approaches to identify candidate inhibitors in compound libraries.
Haploinsufficiency of delta-like 4 ligand results in embryonic lethality due to major defects in arterial and vascular development (2004)

Vascular development depends on the highly coordinated actions of a variety of angiogenic regulators, most of which apparently act downstream of vascular endothelial growth factor (VEGF). One potential such regulator is delta-like 4 ligand (Dll4), a recently identified partner for the Notch receptors. We generated mice in which the Dll4 gene was replaced with a reporter gene, and found that Dll4 expression is initially restricted to large arteries in the embryo, whereas in adult mice and tumor models, Dll4 is specifically expressed in smaller arteries and microvessels, with a striking break in expression just as capillaries merge into venules. Consistent with these arterial-specific expression patterns, heterozygous deletion of Dll4 resulted in prominent albeit variable defects in arterial development (reminiscent of those in Notch knockouts), including abnormal stenosis and atresia of the aorta, defective arterial branching from the aorta, and even arterial regression, with occasional extension of the defects to the venous circulation; also noted was gross enlargement of the pericardial sac and failure to remodel the yolk sac vasculature. These striking phenotypes resulting from heterozygous deletion of Dll4 indicate that vascular development may be as sensitive to subtle changes in Dll4 dosage as it is to subtle changes in VEGF dosage, because VEGF accounts for the only other example of haploid insufficiency, resulting in obvious vascular abnormalities. In summary, Dll4 appears to be a major trigger of Notch receptor activities previously implicated in arterial and vascular development, and it may represent a new opportunity for pro- and anti-angiogenic therapies.
Artistic Edge and Corner Enhancing Smoothing (2007)

Two important visual properties of paintings and painting-like images are the absence of texture details and the increased sharpness of edges as compared to photographic images. Painting-like artistic effects can be achieved from photographic images by filters that smooth out texture details, while preserving or enhancing edges and corners. However, not all edge preserving smoothers are suitable for this purpose. We present a simple nonlinear local operator that generalizes both the well known Kuwahara filter and the more general class of filters known in the literature as "criterion and value filter structure." This class of operators suffers from intrinsic theoretical limitations which give rise to a dramatic instability in presence of noise, especially on shadowed areas. Such limitations are discussed in the paper and overcome by the proposed operator. A large variety of experimental results shows that the output of the proposed operator is visually similar to a painting. Comparisons with existing techniques on a large set of natural images highlight conditions on which traditional edge preserving smoothers fail, whereas our approach produces good results. In particular, unlike many other well established approaches, the proposed operator is robust to degradations of the input image such as blurring and noise contamination.
Injectable, Interconnected, High‐Porosity Macroporous Biocompatible Gelatin Scaffolds Made by Surfactant‐Free Emulsion Templating (2014)

High‐porosity interconnected, thermoresponsive macroporous hydrogels are prepared from oil‐in‐water high internal phase emulsions (HIPEs) stabilized by gelatin‐ graft ‐poly( N ‐isopropylacrylamide). PolyHIPEs are obtained by gelling HIPEs utilizing the thermoresponsiveness of the copolymer components. PolyHIPEs properties can be controlled by varying the aqueous phase composition, internal phase volume ratio, and gelation temperature. PolyHIPEs respond to temperature changes experienced during cell seeding, allowing fibroblasts to spread, proliferate, and penetrate into the scaffold. Encapsulated cells survive ejection of cell‐laden hydrogels through a hypodermic needle. This system provides a new strategy for the fabrication of safe injectable biocompatible tissue engineering scaffolds. image
Infection and Immunity (2002)

This concise text explores the interactions between pathogens and the immune system. Taking a disease-based approach, it explains how micro-organisms adapted to growth in human hosts can evade the immune system and cause disease.The opening chapter overviews the innate and adaptive immune responses to microbes. Subsequent chapters are specific
A new generation of monoclonal and recombinant antibodies against cell-adherent prostate specific membrane antigen for diagnostic and therapeutic targeting of prostate cancer (2006)

Our results suggest that only the mAbs and scFvs, that were elicited with unpurified LNCaP lysate and not with purified PSMA will be useful agents for diagnostic imaging and therapeutic applications of prostate cancer.
Thrombus formation induced by antibodies to β2-glycoprotein I is complement dependent and requires a priming factor (2005)

We monitored the number of intravascular platelet-leukocyte aggregates (PLAs) and thrombotic occlusions (TOs) by intravascular microscopy in the mesentery of rats receiving antiphospholipid (aPL) immunoglobulin G (IgG) purified from the sera of patients with antiphospholipid syndrome. aPL IgG had no procoagulant effect, but it caused rapid endothelial deposition of fibrinogen, followed by PLA and TO in rats receiving an intraperitoneal injection of bacterial lipopolysaccharide 3 hours before IgG infusion. Anti-beta2-glycoprotein I-depleted aPL IgG failed to induce PLAs and TOs. C3 and C9 colocalized with aPL IgG on the mesenteric vessels. The number of PLAs and TOs was markedly reduced in C6-deficient rats and in animals treated with anti-C5 miniantibody, suggesting the contribution of the terminal complement (C) complex to the aPL antibody-mediated intravascular thrombosis. In conclusion, our data indicate that antibodies to beta2-glycoprotein I trigger coagulation subsequent to a priming proinflammatory factor and that the terminal C complex is the main mediator of the coagulation process.
Development and evaluation of the ATOS spontaneous speech conversational system (2002)

In this paper we report our development work in Spanish spontaneous speech conversational systems. We describe the automatic telephone operator service (ATOS) and present the improvements introduced into it to deal with spontaneous speech, which are: (a) a task independent dialogue manager, that can be adapted to a new semantic domain by changing a configuration file. It also generates a prediction about the user's expected utterance to constrain the language model used by the speech recognizer; (b) a language modeling strategy, which allows to adapt the statistical language model to a new task with just few hundreds of sentences. This strategy reduces a 27% the word error rate. We also report the results, conclusions and the speech database collected in the evaluation of the ATOS system, which has been tested by 30 real users.
Strategies for Compound Selection (2004)

In-house pharmaceutical collections are no longer sufficient for sampling chemical spaces. As novel bioactive chemotypes are successfully identified by virtual and high -throughput screening, the ability to rapidly sift through large numbers of chemicals prior to acquisition or experiment is required. Strategies for compound selection include some of the following steps: 1.) database assembly ('in silico' inventory); 2a.) structural integrity verification (keep unique structures only); 2b.) limited exploration of alternative chemical representations for the uniques (stereoisomers, tautomers, ionization states); 3.) property and structural filtering (remove unwanted structures); 4.) 3D-structure generation (for virtual screening or 3D-based similarity); 5a.) clustering or statistical design for selection; 5b.) similarity-based selection (if bioactives are known); 5c.) receptor-based selection (if target binding site is known); 6.) add a random subset to the final list.
Hybrid analysis of a spherical mechanism for a minimally invasive surgical (MIS) robot--design concepts for multiple optimizations. (2006)

Several criteria exist for determining the optimal design for a surgical robot. This paper considers kinematic performance metrics, which reward good kinematic performance, and dynamic performance metrics, which penalize poor dynamic performance. Kinematic and dynamic metrics are considered independently, and then combined to produce hybrid metrics. For each metric, the optimal design is the one that maximizes the performance metric over a specific design space. In the case of a 2-DOF spherical mechanism for a surgical robot, the optimal design determined by kinematic metrics is a robot arm with link angles (alpha(12)=90 degrees , alpha(23)=90 degrees ). The large link angles are the most dextrous, but have the greatest risk of robot-robot or robot-patient collisions and require the largest actuators. The link lengths determined by the dynamic metrics are much shorter, which reduces the risk of collisions, but tend to place the robot in singularities much more frequently. When the hybrid metrics are used, and a restriction that the arm must be able to reach a human's entire abdomen, the optimal design is around (alpha(12)=51 degrees, alpha(23)=54 degrees). The hybrid design provides a compromise between dexterity and compactness.
Heat sensitivity of human parvovirus B19 (2003)

The heat sensitivity of B19 in liquid was clearly different from that of CPV. Significantly, the efficiency to inactivate B19 and reduce its infectivity following heating in liquid was mainly affected by the composition of the solutions used for virus suspension.
<b>SUBCUTANEOUS TISSUE RESPONSES IN RATS TO INJECTION OF FINE PARTICLES OF SYNTHETIC HYDROXYAPATITE </b><b>CERAMIC</b> (1988)

To clarify tissue responses to hydroxyapatite ceramic (HAP), time course observation of lesions induced by subcutaneous injections of fine particles of HAP was performed by light and electron microscopy: The description was based on the division of the particles into smaller-sized and larger-sized ones. Smaller particles, ranging in diameter from 0.65 to a few micra and scattered in the tissue, were phagocytized by macrophages in extremely early stages. Phagocytized particles formed phagosomes and phago-lysosomes containing one or more particles. In later stages, macrophages laden with smaller particles were widely distributed and occasionally observed in perivascular areas. Some of the phagocytized particles were resolved in phago-lysosomes. In contrast, larger particles measuring several micra in diameter were not phagocytized, being instead surrounded by numerous macrophages and multinucleated giant cells. Infiltrating macrophages at the injection sites gathered densely, closely approximating one another by the interdigitation of numerous microprojections in a zipper-like manner. The formation of a fibrous capsule was not evident, though the fibroblasts were gradually increased in number in and around the lesions. These results suggest that HAP particles are recognized as foreign bodies and provoke foreign body reactions in cells, principally that in mononuclear phagocytes and their derivates.
Cancer Therapy with Trifunctional Antibodies: Linking Innate and Adaptive Immunity (2011)

Trifunctional antibodies (trAbs) are promising novel anticancer biologics with a particular mode of action capable of linking innate with adaptive immunity. Based on their unique structure, trifunctional IgG-like heterodimeric antibodies, consisting of nonhuman mouse and rat immunoglobulin halves are able to redirect T lymphocytes, as well as accessory cells, to the tumor site. This recruitment of immune cells is accompanied by cellular activation events elicited by anti-CD3, as well as Fcγ-receptor engagement of trAbs supported by a proinflammatory Th1-biased cytokine milieu. All necessary immunological factors required for long-term vaccination-like effects are stimulated along trAb-mediated therapeutic interventions. Thus, the concerted interplay of antibody-dependent cellular cytotoxicity plus the polyclonal T-cell cytotoxicity and Fcγ-receptor-driven induction of long-lasting immune responses after the initial tumor cell elimination represent the major hallmarks of trAb-mediated treatment of malignant diseases.
Characterization of the active site of histidine ammonia‐lyase from Pseudomonas putida (2001)

Elucidation of the 3D structure of histidine ammonia-lyase (HAL, EC 4.3.1.3) from Pseudomonas putida by X-ray crystallography revealed that the electrophilic prosthetic group at the active site is 3,5-dihydro-5-methylidene-4H-imidazol-4-one (MIO) [Schwede, T.F., Rétey, J., Schulz, G.E. (1999) Biochemistry, 38, 5355-5361]. To evaluate the importance of several amino-acid residues at the active site for substrate binding and catalysis, we mutated the following amino-acid codons in the HAL gene: R283, Y53, Y280, E414, Q277, F329, N195 and H83. Kinetic measurements with the overexpressed mutants showed that all mutations resulted in a decrease of catalytic activity. The mutants R283I, R283K and N195A were approximately 1640, 20 and 1000 times less active, respectively, compared to the single mutant C273A, into which all mutations were introduced. Mutants Y280F, F329A and Q277A exhibited approximately 55, 100 and 125 times lower activity, respectively. The greatest loss of activity shown was in the HAL mutants Y53F, E414Q, H83L and E414A, the last being more than 20 900-fold less active than the single mutant C273A, while H83L was 18 000-fold less active than mutant C273A. We propose that the carboxylate group of E414 plays an important role as a base in catalysis. To investigate a possible participation of active site amino acids in the formation of MIO, we used the chromophore formation upon treatment of HAL with l-cysteine and dioxygen at pH 10.5 as an indicator. All mutants, except F329A showed the formation of a 338-nm chromophore arising from a modified MIO group. The UV difference spectra of HAL mutant F329A with the MIO-free mutant S143A provide evidence for the presence of a MIO group in HAL mutant F329A also. For modelling of the substrate arrangement within the active site and protonation state of MIO, theoretical calculations were performed.
A UV-Independent Topical Small-Molecule Approach for Melanin Production in Human Skin (2017)

The presence of dark melanin (eumelanin) within human epidermis represents one of the strongest predictors of low skin cancer risk. Topical rescue of eumelanin synthesis, previously achieved in "redhaired" Mc1r-deficient mice, demonstrated significant protection against UV damage. However, application of a topical strategy for human skin pigmentation has not been achieved, largely due to the greater barrier function of human epidermis. Salt-inducible kinase (SIK) has been demonstrated to regulate MITF, the master regulator of pigment gene expression, through its effects on CRTC and CREB activity. Here, we describe the development of small-molecule SIK inhibitors that were optimized for human skin penetration, resulting in MITF upregulation and induction of melanogenesis. When topically applied, pigment production was induced in Mc1r-deficient mice and normal human skin. These findings demonstrate a realistic pathway toward UV-independent topical modulation of human skin pigmentation, potentially impacting UV protection and skin cancer risk.