gebhart/patrepeval huggingface dataset:
Handbook of Drug Screening (2001)

Key Factors for Successful High-Throughput Screening, John G. Houston Critical Components in High-Throughput Screening: Challenges and New Trends, Litao Zhang, Martyn N. Banks, and John G. Houston Hit-to-Probe-to-Lead Optimization Strategies: A Biology Perspective to Conquer the Valley of Death, Anuradha Roy, Byron Taylor, Peter R. McDonald, Ashleigh Price, and Rathnam Chaguturu Signal Detection Platforms for Screening in Drug Discovery, Ramakrishna Seethala Proteomic Analysis in Drug Discovery, Haiteng Deng, Yang Xu, and Linqi Zhang Screening and Characterization of G-Protein-Coupled Receptor Ligands for Drug Discovery, Ge Zhang and Mary Ellen Cvijic Nuclear Hormone Receptor Screening in Drug Discovery, Ramakrishna Seethala and Litao Zhang Emerging Novel High-Throughput Screening Technologies for Cell-Based Assays, Ilona Kariv, Alexander A. Szewczak, Nathan W. Bays, Nadya Smotrov, and Christopher M. Moxham In Vitro Strategies for Ion Channel Screening in Drug Discovery, Ravikumar Peri, Mark Bowlby, and John Dunlop Wheat from Chaff: General andMechanistic Triage of Screening Hits for Enzyme Targets, Mark R. Harpel Protein Kinases and Phosphatases, Pirthipal Singh MicroRNA Strategies in Drug Discovery, Wishva B. Herath, Dwi S. Karolina, Arunmozhiarasi Armugam, and Kandiah Jeyaseelan Strategies for Screening of Biologic Therapeutics, Ian Foltz and Francesca Civoli Cryopreserved Cells in Functional Cell-Based HTS Assays, Geetha Shankar and Kirk McMillan High-Content Screening with a Special Emphasis on Cytotoxicity and Cell Health Measurementsn Ralph J. Garippa and Ann F. Hoffman Effective Application of DrugMetabolism and Pharmacokinetics in Drug Discovery, Sharon Diamond and Swamy Yeleswaram Compound Management for Drug Discovery: An Overview, Moneesh Chatterjee and Martyn N. Banks Practical Approach to Quantitative High Throughput Screening, Wei Zheng, Ke Liu, and James Inglese Enabling the Large-Scale Analysis of Quantitative High-Throughput Screening Data, Noel T. Southall, Ajit Jadhav, Ruili Huang, Trung Nguyen, and Yuhong Wang Application of Nanobiotechnologies for Drug Discovery, K. K. Jain Index
Knowledge Based Understanding of Radiology Text (1988)

A data acquisition tool which will extract pertinent diagnostic information from radiology reports has been designed and implemented. Pertinent diagnostic information is defined as that clinical data which is used by the HELP medical expert system. The program uses a memory based semantic parsing technique to “understand” the text. Moreover, the memory structures and lexicon necessary to perform this action are automatically generated from the diagnostic knowledge base by using a special purpose compiler. The result is a system where data extraction from free text is directed by an expert system whose goal is diagnosis.
Immediate Partial Validation Mechanism of the Update Operations in XML Databases (2001)

Structural information is very important in XML document processing. The logical structure of XML document must be validated by parser whether it confirms to DTD or not when browsed or updated by applications. In most cases, parser validates whole XML documents and can&amp;apos;t validate parts of them. If applications will update an XML document that has been stored in the database, it causes decreases in performance due to the validation process.
A Study on the Optimal Mahalanobis Distance for Speech Recognition (2006)

In an effort to enhance the quality of feature vector classification and thereby reduce the recognition error rate of the speaker-independent speech recognition, we employ the Mahalanobis distance in the calculation of the similarity measure between feature vectors. It is assumed that the metric matrix of the Mahalanobis distance be diagonal for the sake of cost reduction in memory and time of calculation. We propose that the diagonal elements be given in terms of the variations of the feature vector components. Geometrically, this prescription tends to redistribute the set of data in the shape of a hypersphere in the feature vector space. The idea is applied to the speech recognition by hidden Markov model with fuzzy vector quantization. The result shows that the recognition is. improved by an appropriate choice of the relevant adjustable parameter. The Viterbi score difference of the two winners in the recognition test shows that the general behavior is in accord with that of the recognition error rate.
An Assessment of Hand Thermography in Vinyl Chloride Workers (1977)

Since Raynaud's phenomenon is an early and integral part of the condition of acro-osteolysis in vinyl chloride workers, a survey involving 143 workers and 56 controls was carried out to assess the feasibility of using hand thermography to detect changes from the normal pattern of vascularity. From the almost identical results between the control and the exposed subjects, and between groups within the exposed population, it appears that there is no detectable difference in thermographic appearances.
Miniature micromachined Fabry-Perot interferometers in silicon (1987)

A new technique for the manufacture of miniature Fabry-Perot interferometers in silicon for use in the near-infra-red region is described. Tuning and parallelism control were achieved electrostatically, yielding low drive voltages and finesses exceeding 90 at 1.4 μm. Such devices will prove useful for laser intracavity elements and wavelength demultiplexers in fibre telecommunication systems.
Inhibition of the Hedgehog Pathway in Advanced Basal-Cell Carcinoma (2009)

GDC-0449, an orally active small molecule that targets the hedgehog pathway, appears to have antitumor activity in locally advanced or metastatic basal-cell carcinoma. (ClinicalTrials.gov number, NCT00607724.)
Urban aerosols harbor diverse and dynamic bacterial populations (2006)

Considering the importance of its potential implications for human health, agricultural productivity, and ecosystem stability, surprisingly little is known regarding the composition or dynamics of the atmosphere's microbial inhabitants. Using a custom high-density DNA microarray, we detected and monitored bacterial populations in two U.S. cities over 17 weeks. These urban aerosols contained at least 1,800 diverse bacterial types, a richness approaching that of some soil bacterial communities. We also reveal the consistent presence of bacterial families with pathogenic members including environmental relatives of select agents of bioterrorism significance. Finally, using multivariate regression techniques, we demonstrate that temporal and meteorological influences can be stronger factors than location in shaping the biological composition of the air we breathe.
RasGRF2, a Guanosine Nucleotide Exchange Factor for Ras GTPases, Participates in T-Cell Signaling Responses (2007)

The Ras pathway is critical for the development and function of T lymphocytes. The stimulation of this GTPase in T cells occurs primarily through the Vav1- and phospholipase C-gamma1-dependent activation of RasGRP1, a diacylglycerol-responsive Ras GDP/GTP exchange factor. Here, we show that a second exchange factor, RasGRF2, also participates in T-cell signaling. RasGRF2 is expressed in T cells, translocates to immune synapses, activates Ras, and stimulates the transcriptional factor NF-AT (nuclear factor of activated T cells) through Ras- and phospholipase C-gamma1-dependent routes. T-cell receptor-, Vav1-, and Ca2+-elicited pathways synergize with RasGRF2 for NF-AT stimulation. The analysis of RasGRF2-deficient mice indicates that this protein is required for the induction of bona fide NF-AT targets such as the cytokines tumor necrosis factor alpha and interleukin 2, while it plays minor roles in Ras activation itself. The comparison of lymphocytes from Vav1-/-, Rasgrf2-/-, and Vav1-/-; Rasgrf2-/- mice demonstrates that the RasGRF2 pathway cooperates with the Vav1/RasGRP1 route in the blasting transformation and proliferation of mature T cells. These results identify RasGRF2 as an additional component of the signaling machinery involved in T-cell receptor- and NF-AT-mediated immune responses.
Photodynamic therapy of cancer. (1988)

PDT represents another modality for the treatment of human malignancy. Photoactivated hematoporphyrins have definite antitumor activity in both in vitro and in vivo experimental systems. Much of the early clinical work involved treatment of patients with advanced, recurrent disease who had not responded to conventional therapy. Because good responses with acceptable toxicity have been obtained in these patients, active investigation continued and is aimed at defining the most appropriate sites and applications for the technique. Because of the limited depth of light penetration in tissue, the most promising sites may be those where there is limited thickness of tumor, such as in superficial skin lesions or carcinomas in situ involving the aerodigestive tract, bronchial tree, or genitourinary tract. Other potential uses include those where PDT could be combined with surgical or chemotherapeutic debulking, such as pleural mesothelioma or advanced stage ovarian cancer. Whether PDT can be of benefit in surgical cases where the margins of resection are close is an interesting but speculative notion at the present time. Clinical trials with hematoporphyrin derivative PDT in the sites mentioned are in progress. Laboratory work to better understand HpD also continues, as well as investigations into alternative photosensitizers with improved tumor localization, less cutaneous photosensitivity, and absorption peaks at deeper penetrating wavelengths of light. Attempts at measuring singlet oxygen, if successful, will permit the development of more meaningful dosimetry in order to correlate response with actual tissue levels of the purported cytotoxic agent. Hopefully, these and other developments in the field of PDT will improve the treatment for patients with cancer.
Photodynamic therapy on keloid fibroblasts in tissue-engineered keratinocyte-fibroblast co-culture (2005)

A PDT dosimetry range was established, which reduces tissue contraction and collagen density while minimizing injury to fibroblasts.
Allosuppressor- and allohelper-T cells in acute and chronic graft-vs.-host (GVH) disease. III. Different Lyt subsets of donor T cells induce different pathological syndromes. (1983)

Previous work from this laboratory has led to the hypothesis that the stimulatory pathological symptoms of chronic graft-vs.-host disease (GVHD) are caused by alloreactive donor T helper (TH) cells, whereas the suppressive pathological symptoms of acute GVHD are caused by alloreactive T suppressor (TS) cells of the donor. In the present paper we analyzed the Lyt phenotypes of B10 donor T cells required for the induction of either acute or chronic GVHD in H-2-different (B10 X DBA/2)F1 recipients. First, nonirradiated F1 mice were used as the recipients. We found that unseparated B10 T cells induced only a moderate formation of systemic lupus erythematosus (SLE)-like autoantibodies, but a high percentage of lethal GVHD (LGVHD). In contrast, Lyt-1+2- donor T cells were unable to induce LGVHD in these recipients; these cells were capable, however, of inducing a vigorous formation of SLE-like autoantibodies and the formation of severe immune-complex glomerulonephritis. Lyt-1-2+ T cells were incapable of inducing either acute or chronic GVHD. In another experiment, the sensitivity and accuracy of the GVH system were increased by using irradiated F1 mice as recipients and by comparing donor-cell inocula that contained similar numbers of T lymphocytes. In addition, donor-cell inocula were used that had been tested for their allohelper and allosuppressor effects on F1 B cells in vitro. In the irradiated F1 recipients, too, unseparated donor T cells were superior to T cell subsets in inducing LGVHD; Lyt-1-2+ donor cells were completely and Lyt-1+2- donor cells were almost incapable of doing so. In contrast, Lyt-1+2- T cells, but neither unseparated T cells nor Lyt-1-2+ T cells, were capable of inducing a vigorous formation of SLE-like auto-antibodies. We conclude that the stimulatory pathological symptoms of chronic GVHD are caused by Lyt-1+2- allohelper T cells. In contrast, the development of the suppressive pathological symptoms of acute GVHD appears to involve alloreactive Lyt-1+2+ T suppressor cells.
Flavivirus membrane fusion (2006)

Flavivirus membrane fusion is mediated by a class II viral fusion protein, the major envelope protein E, and the fusion process is extremely fast and efficient. Understanding of the underlying mechanisms has been advanced significantly by the determination of E protein structures in their pre- and post-fusion conformations and by the elucidation of the quarternary organization of E proteins in the viral envelope. In this review, these structural data are discussed in the context of functional and biochemical analyses of the flavivirus fusion mechanism and its characteristics are compared with those of other class II- and class I-driven fusion processes.
Fc-Engineering for Modulated Effector Functions—Improving Antibodies for Cancer Treatment (2020)

The majority of monoclonal antibody (mAb) therapeutics possess the ability to engage innate immune effectors through interactions mediated by their fragment crystallizable (Fc) domain. By delivering Fc-Fc gamma receptor (FcγR) and Fc-C1q interactions, mAb are able to link exquisite specificity to powerful cellular and complement-mediated effector functions. Fc interactions can also facilitate enhanced target clustering to evoke potent receptor signaling. These observations have driven decades-long research to delineate the properties within the Fc that elicit these various activities, identifying key amino acid residues and elucidating the important role of glycosylation. They have also fostered a growing interest in Fc-engineering whereby this knowledge is exploited to modulate Fc effector function to suit specific mechanisms of action and therapeutic purposes. In this review, we document the insight that has been generated through the study of the Fc domain; revealing the underpinning structure-function relationships and how the Fc has been engineered to produce an increasing number of antibodies that are appearing in the clinic with augmented abilities to treat cancer.
Bacterial lipases (1994)

Many different bacterial species produce lipases which hydrolyze esters of glycerol with preferably long-chain fatty acids. They act at the interface generated by a hydrophobic lipid substrate in a hydrophilic aqueous medium. A characteristic property of lipases is called interfacial activation, meaning a sharp increase in lipase activity observed when the substrate starts to form an emulsion, thereby presenting to the enzyme an interfacial area. As a consequence, the kinetics of a lipase reaction do not follow the classical Michaelis-Menten model. With only a few exceptions, bacterial lipases are able to completely hydrolyze a triacylglycerol substrate although a certain preference for primary ester bonds has been observed. Numerous lipase assay methods are available using coloured or fluorescent substrates which allow spectroscopic and fluorimetric detection of lipase activity. Another important assay is based on titration of fatty acids released from the substrate. Newly developed methods allow to exactly determine lipase activity via controlled surface pressure or by means of a computer-controlled oil drop tensiometer. The synthesis and secretion of lipases by bacteria is influenced by a variety of environmental factors like ions, carbon sources, or presence of non-metabolizable polysaccharides. The secretion pathway is known for Pseudomonas lipases with P. aeruginosa lipase using a two-step mechanism and P. fluorescens lipase using a one-step mechanism. Additionally, some Pseudomonas lipases need specific chaperone-like proteins assisting their correct folding in the periplasm. These lipase-specific foldases (Lif-proteins) which show a high degree of amino acid sequence homology among different Pseudomonas species are coded for by genes located immediately downstream the lipase structural genes. A comparison of different bacterial lipases on the basis of primary structure revealed only very limited sequence homology. However, determination of the three-dimensional structure of the P. glumae lipase indicated that at least some of the bacterial lipases will presumably reveal a conserved folding pattern called the alpha/beta-hydrolase fold, which has been described for other microbial and human lipases. The catalytic site of lipases is buried inside the protein and contains a serine-protease-like catalytic triad consisting of the amino acids serine, histidine, and aspartate (or glutamate). The Ser-residue is located in a strictly conserved beta-epsilon Ser-alpha motif. The active site is covered by a lid-like alpha-helical structure which moves away upon contact of the lipase with its substrate, thereby exposing hydrophobic residues at the protein's surface mediating the contact between protein and substrate.(ABSTRACT TRUNCATED AT 400 WORDS)
Why Stacked Models Perform Effective Collective Classification (2008)

Collective classification techniques jointly infer all class labels of a relational data set, using the inferences about one class label to influence inferences about related class labels. Kou and Cohen recently introduced an efficient relational model based on stacking that, despite its simplicity, has equivalent accuracy to more sophisticated joint inference approaches. Using experiments on both real and synthetic data, we show that the primary cause for the performance of the stacked model is the reduction in bias from learning the stacked model on inferred labels rather than true labels. The reduction in variance due to conditional inference also contributes to the effect but it is not as strong. In addition, we show that the performance of the joint inference and stacked learners can be attributed to an implicit weighting of local and relational features at learning time.
The Proper Role of Nerves in Salivary Secretion: A Review (1987)

Consideration of the history of this subject has created a perspective which helps one to appreciate how errors in thinking have occurred and why some have persisted, despite subsequent improvements in information. The most enduring misconception has been that the drying of the mouth under stress is due to sympathetic inhibitory fibers, a view that must be eradicated, for such fibers do not exist. The inhibition is due to central influences from higher centers acting on the salivary centers and thereby suppressing reflex activity. Wide variations exist in the neuro-effector arrangements and in the cellular responses in different glands from different species. Myoepithelial cells are usually contracted by both parasympathetic and sympathetic nerves. The blood vessels also receive a dual innervation, but parasympathetic impulses cause vasodilatation as part of secretion, whereas the sympathetic vasoconstrictor fibers are part of a more generalized vascular control system and not a direct part of the reflex secretory sympathetic pathway. Parasympathetic drive usually provides the main stimulus for fluid formation by parenchymal cells, whereas sympathetic nerves tend to increase the output of pre-formed components from certain cells. Absence of nerve impulses causes variable atrophic and other metabolic effects on the parenchymal cells. Evidence is beginning to accrue that certain nerve impulses may influence resynthetic activities. Vacuolation, often found experimentally after strong stimulation, also occurs to a variable extent in certain cells as a normal part of reflex secretion and may therefore have an effect on the components entering the saliva. If rupture of vacuoles occurs, then this may contribute to the salivary amylase that is present in the blood. Recent evidence points to the possibility that, even in a monomorphic gland, not all of the components necessarily enter nerve-induced saliva in "parallel" proportions. Consideration of current information has enabled some provisional generalizations about the roles of the secretory nerves to be suggested in the summary, but they must not be considered immutable.
Plasma myostatin-immunoreactive protein is increased after prolonged bed rest with low-dose T3 administration. (1999)

It has been hypothesized that myostatin, a newly identified member of the transforming growth factor-beta (TGF-beta) family of proteins, acts as a negative regulator of skeletal muscle growth. Because bed rest induced muscle atrophy results from a decreased rate of muscle protein synthesis, we hypothesized that circulating levels of myostatin would be increased following prolonged bed rest. Twelve men (age, 35.8 +/- 4.6 yr; height, 175.7 +/- 2.3 cm; weight, 74.8 +/- 3.5 kg; mean +/- SE) were confined to bed for 25 days at 6 degrees head-down tilt while receiving triiodothyronine (T3; 50 micrograms/day) to accelerate protein loss. Total lean body and appendicular skeletal muscle mass were determined by dual energy x-ray absorptiometry (DEXA) before and after the bed rest period. Plasma myostatin-immunoreactive protein was measured in blood samples obtained after an overnight fast 5 days prior to, and on the 25th day of bed rest. Lean body mass decreased an average 2.2 kg (p < 0.0001). Appendicular skeletal muscle accounted for a majority of the lean body mass loss. On day 25 of bed rest, plasma myostatin-immunoreactive protein was 12% higher (p = 0.01) than measured at baseline. These data support the idea that myostatin regulates muscle growth in humans and that it may be a novel target for interventions aiming to reduce space flight induced muscle atrophy.
Anabolic Effect of Human Synthetic Parathyroid Hormone-(1-34) Depends on Growth Hormone* (1990)

We tested whether GH is required for the anabolic effect of PTH on bone, using sham-operated (sham) and hypophysectomized (HX) young male rats. HX rats were supplemented daily with 3% sucrose water, T4, and corticosterone. Rats received vehicle or human PTH-(1-34) at 8 micrograms/100 g, sc, once daily, alone or in combination with rat or ovine GH at 0.2 mg/100 g, sc, twice daily or 12 micrograms ovine GH/100 g.day by continuous sc infusion. After 12 days, rats were sedated, and blood, femurs, and tibias were removed. Femur trabecular and cortical bone calcium (Ca), dry weight (DW), and hydroxyproline were measured. PTH increased bone Ca, DW, and hydroxyproline in shams by approximately 30%, but consistently failed to induce an anabolic response in HX rats. GH alone stimulated systemic growth in HX rats and increased their bone Ca and DW by 2-fold. The anabolic effect of PTH was restored in HX rats given both PTH and GH. Total bone mass in these rats was approximately 20% more (P less than 0.05) than the bone mass of rats given GH alone. When food was restricted in shams to limit systemic growth, PTH still induced an increase in bone mass. We conclude that GH or GH-dependent factors, such as insulin-like growth factor-I, which increases in PTH-treated bones in vitro, are required for the anabolic response of bone to PTH in vivo.