gebhart/patrepeval huggingface dataset:
Crystal Structure of Rat DNA Polymerase β: Evidence for a Common Polymerase Mechanism (1994)

Structures of the 31-kilodalton catalytic domain of rat DNA polymerase beta (pol beta) and the whole 39-kilodalton enzyme were determined at 2.3 and 3.6 angstrom resolution, respectively. The 31-kilodalton domain is composed of fingers, palm, and thumb subdomains arranged to form a DNA binding channel reminiscent of the polymerase domains of the Klenow fragment of Escherichia coli DNA polymerase I, HIV-1 reverse transcriptase, and bacteriophage T7 RNA polymerase. The amino-terminal 8-kilodalton domain is attached to the fingers subdomain by a flexible hinge. The two invariant aspartates found in all polymerase sequences and implicated in catalytic activity have the same geometric arrangement within structurally similar but topologically distinct palms, indicating that the polymerases have maintained, or possibly re-evolved, a common nucleotidyl transfer mechanism. The location of Mn2+ and deoxyadenosine triphosphate in pol beta confirms the role of the invariant aspartates in metal ion and deoxynucleoside triphosphate binding.
Telemedicine and telepharmacy: Current status and future implications (1999)

Uses of telemedicine are described and potential roles for pharmacists are discussed. Telemedicine has been defined as "the use of electronic information and communications technologies to provide and support health care when distance separates the participants." Technologies included in telemedicine are videoconferencing, telephones, computers, the Internet, fax, radio, and television. Telepharmacy has the same basic definition but refers to pharmaceutical care provision. Although the videotelemedicine market is expected to grow considerably, lack of reimbursement and high costs are continuing obstacles. Pharmacy is using video-conferencing for education, training, and management purposes. The telephone has changed from a dial-and-talk instrument to a multimedia access tool. Medical devices are being attached to telephone lines to provide remote monitoring and therapy, and call centers are providing medication counseling, prior authorization, refill authorization, and formulary compliance monitoring. Although the Internet has quickly become a star performer, utilization by health care lags behind that of other industries. The Internet-fueled empowerment of consumers and their expectations for speed, access, and convenience are creating more unmet expectations of the traditional health care system. Pharmacy has both organizational and individual practitioner Web sites, but it is online drugstores that are attracting most attention. Potential benefits of telemedicine include improved access to care, greater efficiency in diagnosis and treatment, higher productivity, and market positioning for the coming century. Telemedicine will tax the economic, regulatory, legal, ethical, and clinical care expertise of the entire health care system. Studies of the effectiveness, cost, and societal implications of telemedicine are needed, along with practice models and standards, training programs, and solutions to regulatory, licensing, and legal questions. Securing reimbursement for cognitive services remains a problem for telemedicine and telepharmacy. Telemedicine presents profound opportunities and challenges to pharmacy and other health care professions.
Management of colorectal cancer (2014)

Colorectal cancer is one of the most frequent solid tumors in the Western world. Treatment options are dependent on the stage of the disease, the performance status of the patient, and increasingly the molecular makeup of the tumor. In countries with surveillance programs, the incidence rate as well as the mortality rate has gone down because of the earlier stages at which the tumors are detected. For rectal cancer, standard of care differs from that of colon cancer with regard to perioperative treatment. In the metastatic setting, treatment options are uniform for colorectal cancer. Over the years, treatment options have emerged from single-agent 5-fluorouracil (5-FU) treatment to combination regimens using 5-FU and oxaliplatin or irinotecan or both. Treatment efficacy in the metastatic setting has been increased with the introduction of targeted substances. These include (a) the anti-vascular endothelial growth factor-A (anti-VEGF-A) antibody bevacizumab, (b) the anti-epidermal growth factor receptor (anti-EGFR) antibodies cetuximab and panitumumab, (c) the anti-angiogenic multi-kinase inhibitor regorafenib, and (d) the anti-angiogenic compound aflibercept. Anti-EGFR antibodies have shown efficacy only in the subpopulations of tumors that do not have any mutation in KRAS and NRAS exon 2, 3, 4. Physicians have the choice in the first line to use anti-EGFR or anti-VEGF inhibitors in combination with chemotherapy based on treatment goals and patient performance. In recent years, tumor location has been shown to be prognostic and predictive for clinical outcome. Right-sided sporadic colon cancers differ significantly in molecular characteristics and, with the exception of microsatellite instability (MSI-H) tumors, are associated with poor prognosis. Tumors based on hereditary non-polyposis colorectal cancer, on the other hand, have excellent prognosis in stage II and III disease. Recent efforts have focused on the molecular classification of colorectal cancer with the purpose of establishing molecularly defined subgroups.
Histone Deacetylase Inhibitors: Latest Developments, Trends and Prospects (2005)

Histone deacetylases (HDACs) and histone acetyltransferases (HATs) are enzymes that catalyze the deacetylation and acetylation of lysine residues located in the NH(2) terminal tails of histones and non-histone proteins. Perturbation of this balance is often observed in human cancers and inhibition of HDACs has emerged as a novel therapeutic strategy against cancer. To date, more that 30 groups, academic and industrial, are involved in research related to these target enzymes. Over the past year, dozens of research papers and patent applications describing new HDAC inhibitors belonging to different structural classes have been disclosed. The present review highlights the latest developments in design and synthesis of HDAC inhibitors -- potential anti-cancer drugs.
Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later (2008)

Psilocybin has been used for centuries for religious purposes; however, little is known scientifically about its long-term effects. We previously reported the effects of a double-blind study evaluating the psychological effects of a high psilocybin dose. This report presents the 14-month follow-up and examines the relationship of the follow-up results to data obtained at screening and on drug session days. Participants were 36 hallucinogen-naïve adults reporting regular participation in religious/ spiritual activities. Oral psilocybin (30 mg/70 kg) was administered on one of two or three sessions, with methylphenidate (40 mg/70 kg) administered on the other session(s). During sessions, volunteers were encouraged to close their eyes and direct their attention inward. At the 14-month follow-up, 58% and 67%, respectively, of volunteers rated the psilocybin-occasioned experience as being among the five most personally meaningful and among the five most spiritually significant experiences of their lives; 64% indicated that the experience increased well-being or life satisfaction; 58% met criteria for having had a 'complete' mystical experience. Correlation and regression analyses indicated a central role of the mystical experience assessed on the session day in the high ratings of personal meaning and spiritual significance at follow-up. Of the measures of personality, affect, quality of life and spirituality assessed across the study, only a scale measuring mystical experience showed a difference from screening. When administered under supportive conditions, psilocybin occasioned experiences similar to spontaneously occurring mystical experiences that, at 14-month follow-up, were considered by volunteers to be among the most personally meaningful and spiritually significant of their lives.
IgM Heavy Chain Complementarity-Determining Region 3 Diversity Is Constrained by Genetic and Somatic Mechanisms Until Two Months After Birth (1999)

Due to the greater range of lengths available to the third complementarity determining region of the heavy chain (HCDR3), the Ab repertoire of normal adults includes larger Ag binding site structures than those seen in first and second trimester fetal tissues. Transition to a steady state range of HCDR3 lengths is not complete until the infant reaches 2 mo of age. Fetal constraints on length begin with a genetic predilection for use of short DH (D7-27 or DQ52) gene segments and against use of long DH (e.g., D3 or DXP) and JH (JH6) gene segments in both fetal liver and fetal bone marrow. Further control of length is achieved through DH-specific limitations in N addition, with D7-27 DJ joins including extensive N addition and D3-containing DJ joins showing a paucity of N addition. DH-specific constraints on N addition are no longer apparent in adult bone marrow. Superimposed upon these genetic mechanisms to control length is a process of somatic selection that appears to ensure expression of a restricted range of HCDR3 lengths in both fetus and adult. B cells that express Abs of an "inappropriate" length appear to be eliminated when they first display IgM on their cell surface. Control of N addition appears aberrant in X-linked agammaglobulinemia, which may exacerbate the block in B cell development seen in this disease. Restriction of the fetal repertoire appears to be an active process, forcing limits on the diversity, and hence range of Ab specificities, available to the young.
Layer-by-Layer Assembly of Sintered CdSexTe1–x Nanocrystal Solar Cells (2012)

Alloying is a versatile tool for engineering the optical and electronic properties of materials. Here, we explore the use of CdTe and CdSe nanocrystals in developing sintered CdSe(x)Te(1-x) alloys as bandgap tunable, light-absorbing layers for solution-processed solar cells. Using a layer-by-layer approach, we incorporate such alloyed materials into single- and graded-composition device architectures. Nanostructured solar cells employing CdSe(x)Te(1-x) layers are found to exhibit a spectral response deeper into the IR region than bulk CdTe devices as a result of optical bowing and achieve power conversion efficiencies as high as 7.1%. The versatility of the layer-by-layer approach is highlighted through the fabrication of compositionally graded solar cells in which the [Se]:[Te] ratio is varied across the device. Each of the individual layers can be clearly resolved through cross-sectional imaging and show limited interdiffusion. Such devices demonstrate the importance of band-alignment in the development of highly efficient, nanostructured solar cells.
Experimental verification of a form-birefringent polarization splitter (1991)

Experimental verification is made of a new polarization splitter which utilizes artificial anisotropic dielectrics. The splitter is composed of layers of periodically laminated SiO2/TiO2 thin films. The SiO2 and TiO2 films are alternately deposited by rf sputtering and reactive dc sputtering, respectively. The thickness of each layer is 50 nm, while the total number of the layers amounts to 2000. The measured polarization split angles are 5.7° (λ=0.63 μm) and 5.1° (λ=1.3 μm), being roughly the same as those predicted.
Scatter factor: molecular characteristics and effect on the invasiveness of epithelial cells. (1990)

The generation of invasiveness in transformed cells represents an essential step of tumor progression. We have previously shown that MDCK epithelial cells, which are deprived of intracellular adhesion by the addition of anti-Arc-1/uvomorulin antibodies, become invasive for collagen gels and embryonal heart tissue (Behrens, J., M. M. Mareel, F. M. Van Roy, and W. Birchmeier. 1989. J. Cell Biol. 108: 2435-2447.). Here we examined whether invasiveness is also induced by scatter factor, which is known to dissociate epithelial cells (Stoker, M., E. Gherardi, M. Perryman, and J. Gray. 1987. Nature (Lond.). 327:239-242.). Scatter factor was purified to homogeneity from conditioned medium of human fibroblasts by heparin-Sepharose chromatography, followed by cation exchange chromatography, gel filtration, or preparative SDS gel electrophoresis. We found that scatter factor represents a 92,000 mol wt glycoprotein which, apparently, is converted by limited proteolysis into disulfide-linked 62,000 and 34/32,000 mol wt subunits. Reversed phase HPLC and sequence analysis of tryptic peptides confirmed the suggested molecular structure, and revealed further that scatter factor exhibits sequence similarities to hepatocyte growth factor and to plasminogen. Purified scatter factor in fact induces the invasiveness into collagen matrices of MDCK epithelial cells, and induces or promotes the invasiveness of a number of human carcinoma cell lines. Apparently, the effect on the human cells depends on their respective degree of differentiation, i.e., cell lines with a less pronounced epithelial phenotype were more susceptible to the factor. Scatter factor does not seem to influence synthesis, steady-state level, and phosphorylation of the cell adhesion molecule Arc-1/uvomorulin. Thus, scatter factor represents a clearly defined molecular species which induces, in vitro, the progression of epithelial cells to a more motile, i.e., invasive phenotype.
SE3-Pose-Nets: Structured Deep Dynamics Models for Visuomotor Control (2018)

In this work, we present an approach to deep visuomotor control using structured deep dynamics models. Our model, a variant of SE3-Nets, learns a low-dimensional pose embedding for visuomotor control via an encoder-decoder structure. Unlike prior work, our model is structured: given an input scene, our network explicitly learns to segment salient parts and predict their pose embedding and motion, modeled as a change in the pose due to the applied actions. We train our model using a pair of point clouds separated by an action and show that given supervision only through point-wise data associations between the frames our network is able to learn a meaningful segmentation of the scene along with consistent poses. We further show that our model can be used for closed-loop control directly in the learned low-dimensional pose space, where the actions are computed by minimizing pose error using gradient-based methods, similar to traditional model-based control. We present results on controlling a Baxter robot from raw depth data in simulation and RGBD data in the real world and compare against two baseline deep networks. We also test the robustness and generalization performance of our controller under changes in camera pose, lighting, occlusion, and motion. Our method is robust, runs in real-time, achieves good prediction of scene dynamics, and outperforms baselines on multiple control runs. Video results can be found at: https://rse-lab.cs.washington.edu/se3-structured-deep-ctrl/.
Heteroatom-directed lithiations of chiral alkyl carbamates: A powerful tool for enantioselective synthesis (1996)

Abstract
Automated tools for testing computer system vulnerability (1992)

The National Institute of Standards and Technology (NIST) has a unique responsibility for computer systems technology within the Federal Government. NIST's Computer Systems Laboratory (CSL) devel- ops standards and guidelines, provides technical assistance, and conducts research for computers and related telecommunications systems to achieve more effective utilization of Federal information technol- ogy resources. CSL's responsibilities include development of technical, management, physical, and ad- ministrative standards and guidelines for the cost-effective security and privacy of sensitive unclassified information processed
Online Deception Detection Refueled by Real World Data Collection (2017)

The lack of large realistic datasets presents a bottleneck in online deception detection studies. In this paper, we apply a data collection method based on social network analysis to quickly identify high-quality deceptive and truthful online reviews from Amazon. The dataset contains more than 10,000 deceptive reviews and is diverse in product domains and reviewers. Using this dataset, we explore effective general features for online deception detection that perform well across domains. We demonstrate that with generalized features - advertising speak and writing complexity scores - deception detection performance can be further improved by adding additional deceptive reviews from assorted domains in training. Finally, reviewer level evaluation gives an interesting insight into different deceptive reviewers' writing styles.
A Pure Enteroglucagon, Oxyntomodulin (Glucagon 37), Stimulates Insulin Release in Perfused Rat Pancreas* (1984)

Oxyntomodulin, a gut peptide recently purified, has been tested in isolated perfused pancreases of normal rats. It was shown to stimulate insulin release monophasically in the presence of a low (6 mM) glucose concentration in the medium. Furthermore, oxyntomodulin potentiated glucose-induced insulin release (10 mM glucose) in a dose-dependent manner, although it was less powerful in this respect than equimolar concentrations of pancreatic glucagon. As oxyntomodulin belongs to the gut glucagon-like immunoreactants which are released during digestion, it is suggested that oxyntomodulin might be one of the factors that could functionally link the gut and the endocrine pancreas and contribute, at least in part, to the regulation of postprandial insulin release.
Antigen-specific Proteolysis by Hybrid Antibodies Containing Promiscuous Proteolytic Light Chains Paired with an Antigen-binding Heavy Chain (2009)

The antigen recognition site of antibodies consists of the heavy and light chain variable domains (V(L) and V(H) domains). V(L) domains catalyze peptide bond hydrolysis independent of V(H) domains (Mei, S., Mody, B., Eklund, S. H., and Paul, S. (1991) J. Biol. Chem. 266, 15571-15574). V(H) domains bind antigens noncovalently independent of V(L) domains (Ward, E. S., Güssow, D., Griffiths, A. D., Jones, P. T., and Winter, G. (1989) Nature 341, 544-546). We describe specific hydrolysis of fusion proteins of the hepatitis C virus E2 protein with glutathione S-transferase (GST-E2) or FLAG peptide (FLAG-E2) by antibodies containing the V(H) domain of an anti-E2 IgG paired with promiscuously catalytic V(L) domains. The hybrid IgG hydrolyzed the E2 fusion proteins more rapidly than the unpaired light chain. An active site-directed inhibitor of serine proteases inhibited the proteolytic activity of the hybrid IgG, indicating a serine protease mechanism. The hybrid IgG displayed noncovalent E2 binding in enzyme-linked immunosorbent assay tests. Immunoblotting studies suggested hydrolysis of FLAG-E2 at a bond within E2 located approximately 11 kDa from the N terminus. GST-E2 was hydrolyzed by the hybrid IgG at bonds in the GST tag. The differing cleavage pattern of FLAG-E2 and GST-E2 can be explained by the split-site model of catalysis, in which conformational differences in the E2 fusion protein substrates position alternate peptide bonds in register with the antibody catalytic subsite despite a common noncovalent binding mechanism. These studies provide proof-of-principle that the catalytic activity of a light chain can be rendered antigen-specific by pairing with a noncovalently binding heavy chain subunit.
Combination of prostate-specific antigen, clinical stage, and Gleason score to predict pathological stage of localized prostate cancer. A multi-institutional update. (1997)

The data represent a multi-institutional modeling and validation of the clinical utility of combining PSA level measurement, clinical stage, and Gleason score to predict pathological stage for a group of men with localized prostate cancer. Clinicians can use these nomograms when counseling individual patients regarding the probability of their tumor being a specific pathological stage; this will enable patients and physicians to make more informed treatment decisions based on the probability of a pathological stage, as well as risk tolerance and the values they place on various potential outcomes.
Studies of membrane, mammilary cores and cuticle of the hen egg shell (1970)

Synopsis Mammillary cores and outer shell membrane have been studied by comparing the weight and chemical composition of outer membrane with cores still attached and of outer membrane free from cores, from the same shells. Inner membrane and cuticle have also been investigated. The weights of inner and outer membrane are significantly correlated (P < 0.05). Both membranes contain galactosamine, glucosamine, sialic acid, glucose, mannose and fucose but in different proportions. Uronic acid is probably absent. An average of 3.3 mg of organic mammillary core material per shell (52 μg/cm2) was present in the shells investigated, but there was a trend suggesting that eggs laid by more mature hens may contain rather more. Cores are rich in hexo‐samine, sialic acid and hexose, but the probable absence of uronic acid suggests that chondroitin sulphates play no part in shell initiation. There were no major differences in the amino acid spectrum of membrane samples with and without cores. Galactosamine, glucosamine, sialic acid, galactose, glucose, mannose, fucose and an unidentified pentose are present in the cuticle. In some respects these sugars are combined differently from their combination in the adjacent outer levels of the matrix.
Phenotype of fatty Due to Gln269Pro Mutation in the Leptin Receptor (Lepr) (1996)

The rat fatty (fa) mutation produces profound obesity of early onset caused by hyperphagia, defective nonshivering thermogenesis, and preferential deposition of energy into adipose tissue. Genetic mapping studies indicate that fa and diabetes (db) are homologous loci in the rat and mouse genomes, respectively. It has been shown that db alleles carry mutations in the Lepr (leptin receptor) gene. This paper describes a point mutation in the fatty allele of Lepr. A nucleotide substitution at position 880 (A-->C) causes an amino acid substitution at position 269 (Gln-->Pro). The mutation generates a novel Msp I site that cosegregates with fa in 1,028 meioses examined in obese F2 progeny from two crosses (Bnx13M and WKYx13M) and is still segregating in three rat colonies. PCR-based mutagenesis was used to introduce the fa mutation into the mouse Lepr cDNA. Transient transfection studies indicate that the mutant Lepr cDNA has greatly reduced binding of leptin (Lep) at the cell surface. These data are strong evidence that the single nucleotide substitution in the fa allele of Lepr (Leprfa) is responsible for the obese phenotype.
A comparison of memetic algorithms, tabu search, and ant colonies for the quadratic assignment problem (2003)

A memetic algorithm (MA), i.e. an evolutionary algorithm making use of local search, for the quadratic assignment problem is presented. A new recombination operator for realizing the approach is described, and the behavior of the MA is investigated on a set of problem instances containing between 25 and 100 facilities/locations. The results indicate that the proposed MA is able to produce high quality solutions quickly. A comparison of the MA with some of the currently best alternative approaches-reactive tabu search, robust tabu search and the fast ant colony system-demonstrates that the MA outperforms its competitors on all studied problem instances of practical interest.