gebhart/patrepeval huggingface dataset:
REBAR: Low-variance, unbiased gradient estimates for discrete latent\n variable models (2017)

Learning in models with discrete latent variables is challenging due to high\nvariance gradient estimators. Generally, approaches have relied on control\nvariates to reduce the variance of the REINFORCE estimator. Recent work (Jang\net al. 2016, Maddison et al. 2016) has taken a different approach, introducing\na continuous relaxation of discrete variables to produce low-variance, but\nbiased, gradient estimates. In this work, we combine the two approaches through\na novel control variate that produces low-variance, \\emph{unbiased} gradient\nestimates. Then, we introduce a modification to the continuous relaxation and\nshow that the tightness of the relaxation can be adapted online, removing it as\na hyperparameter. We show state-of-the-art variance reduction on several\nbenchmark generative modeling tasks, generally leading to faster convergence to\na better final log-likelihood.\n
Transistor characteristics of 14-nm-gate-length EJ-MOSFETs (2000)

We have fabricated electrically variable shallow junction metal-oxide-silicon field-effect transistors (EJ-MOSFETs) to investigate transport characteristics of ultrafine gate MOSFETs. By using EB direct writing on an ultrahigh-resolution negative resist (calixarene), we could achieved a gate length of only 14 nm. Despite such an ultrafine gate, the device exhibited transistor operation at room temperature. From studying the devices with the gate lengths from 14 nm to 98 nm, we found that when the gate length was below 30 nm the subthreshold leakage current increased. The low-temperature measurements showed that the leakage current was caused by the classical thermal process and that quantum effects do not play an important role in subthreshold characteristics at room temperature.
Envelope stress is a trigger of CRISPR RNA-mediated DNA silencing in Escherichia coli (2010)

A widespread feature in the genomes of most bacteria and archaea is an array of clustered, regularly interspaced short palindromic repeats (CRISPRs) that, together with a group of CRISPR-associated (Cas) proteins, mediate immunity against invasive nucleic acids such as plasmids and viruses. Here, the CRISPR-Cas system was activated in cells expressing a plasmid-encoded protein that was targeted to the twin-arginine translocation (Tat) pathway. Expression of this Tat substrate resulted in upregulation of the Cas enzymes and subsequent silencing of the encoding plasmid in a manner that required the BaeSR two-component regulatory system, which is known to respond to extracytoplasmic stress. Furthermore, we confirm that the CasCDE enzymes form a stable ternary complex and appear to function as the catalytic core of the Cas system to process CRISPR RNA into its mature form. Taken together, our results indicate that the CRISPR-Cas system targets DNA directly as part of a defence mechanism in bacteria that is overlapping with but not limited to phage infection.
Therapy of human transitional cell carcinoma of the bladder by oral administration of the epidermal growth factor receptor protein tyrosine kinase inhibitor 4,5-dianilinophthalimide. (1997)

Epidermal growth factor receptor (EGF-R), a transmembrane glycoprotein that mediates the mitogenic response of cells to epidermal growth factor, is highly expressed on malignant human bladder cancer cells. The 4,5-dianilinophthalimides represent a novel class of inhibitors of the EGF-R family of tyrosine kinase with selectivity at the enzymatic and cellular levels. Two compounds of this class, CGP 54211 and CGP 53353, inhibited tyrosine kinase activity of the EGF-R in five different human transitional cell carcinoma lines. The compounds also produced cytostasis in vitro. Highly metastatic human 253J B-V cells were implanted in the bladder wall of nude mice. The daily oral administration of CGP 54211 inhibited the level of EGF-R phosphorylation in this tumor; necrosis and inhibition of tumor growth paralleled this inhibition.
Prevention of graft-versus-host disease by peptides binding to class II major histocompatibility complex molecules (1994)

Graft-versus-host disease across minor histocompatibility barriers was induced in two different models by transplanting allogeneic bone marrow and spleen cells into irradiated H-2-compatible recipient mice. In this report, we show that administration of peptides with high binding affinity for the respective class II major histocompatibility complex molecules after transplantation is capable of preventing the development of graft-versus-host disease in two different murine models. The peptides used were myelin basic protein residues 1 through 11 with alanine at position 4 (Ac 1–11[4A]) for I-Au (A alpha uA beta u), and the antigenic core sequence 323 through 339 of ovalbumin with lysine and methionine extension (KM core) for I-As (A alpha sA beta s). In both systems, the mechanism of prevention was found to be major histocompatibility complex-associated, because nonbinding control peptides did not have any effect. Engraftment of allogeneic bone marrow cells was shown by polymerase chain reaction analysis of DNA polymorphisms in a microsatellite region within the murine interleukin- 5 gene.
REPRODUCIBILITY OF THE NEW DIAGNOSTIC CRITERIA FOR IMPAIRED GLUCOSE TOLERANCE (1985)

Sixty-seven subjects with impaired glucose tolerance and 136 normoglycemic individuals defined according to the diagnostic criteria of the European Association for the Study of Diabetes were selected from among persons aged 40-59 years who participated in a health examination survey in Naples in 1980. A second oral glucose tolerance test was given under identical conditions between two and four months later with the participants having no knowledge of the results of the first test. Venous whole blood was utilized for blood glucose determination. At the second test, 93% of the control group were confirmed to be normoglycemic, but only 56% of the impaired glucose tolerance group were still intolerant. Reproducibility was poorest among subjects with blood glucose two hours after load of less than 140 mg/dl. Among these subjects, 47% reverted to normoglycemia at the second test. In contrast, 15% of those with blood glucose greater than or equal to 140 mg/dl two hours after load reverted to normoglycemia (chi 2 = 6.29, p less than 0.05). Subjects with impairment of glucose tolerance at the second test were reclassified according to the diagnostic criteria of the National Diabetes Data Group and the World Health Organization (WHO). Only 22 (46%) of the 48 individuals classified in the impaired glucose tolerance group according to the criteria of the European Association for the Study of Diabetes were so classified by the criteria of both the National Diabetes Data Group and WHO. The disagreement between the three diagnostic criteria was maximal in the lowest blood glucose range. It is concluded that the diagnosis of impaired glucose tolerance, despite the new diagnostic criteria, still has little reproducibility and uniformity.
Insulin lispro: a fast-acting insulin analog. (1998)

Research has established the importance of maintaining blood glucose levels near normal in patients with type 1 (insulin-dependent) diabetes mellitus. Short-acting insulin analogs are designed to overcome the limitations of regular short-acting insulins. Compared with regular human insulin, the analog insulin lispro offers faster subcutaneous absorption, an earlier and greater insulin peak and a more rapid postpeak decrease. Insulin lispro begins to exert its effects within 15 minutes of subcutaneous administration, and peak levels occur 30 to 90 minutes after administration. Duration of activity is less than five hours. Rates of insulin allergy, lipodystrophy, hypoglycemia and abnormal laboratory test results are essentially the same in patients using insulin lispro and in those using regular human insulin.
Voltage-mode CMOS quaternary latch circuit (1994)

A new voltage-mode CMOS quaternary threshold logic latch circuit that has been realised in a standard 2 µm p-well polysilicon-gate CMOS technology is presented. This circuit requantises quaternary logical voltages during a SETUP clock mode and latches the input value during the HOLD clock mode. Using a 5 V supply and logical voltage increments of 1.67 V, the quaternary latch has a worst-case total SETUP and HOLD time of ~5.7 ns, and best single-level transition total SETUP and HOLD time of ~0.9 ns.
Antifreeze Proteins:  Structures and Mechanisms of Function (1996)

ADVERTISEMENT RETURN TO ISSUEArticleNEXTAntifreeze Proteins: Structures and Mechanisms of FunctionYin Yeh and Robert E. FeeneyView Author Information Departments of Applied Science and Food Science and Technology, University of California, Davis, California 95616 Cite this: Chem. Rev. 1996, 96, 2, 601–618Publication Date (Web):March 28, 1996Publication History Received20 July 1995Revised3 January 1996Published online28 March 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/cr950260chttps://doi.org/10.1021/cr950260cresearch-articleACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views5714Altmetric-Citations452LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Adsorption,Crystallization,Crystals,Ice,Molecules Get e-Alerts
3-D lithography and metal surface micromachining for RF and microwave MEMS (2003)

A new metal surface micromachining technology utilizing 3-D lithography, electroplating, and mechanical polishing has been developed to fabricate arbitrary 3-D metal microstructures as post-IC processes at low temperature below 120/spl deg/C. Using this technology, various highly-suspended 3-D microstructures have been successfully demonstrated for RF and microwave MEMS applications. We have fabricated spiral inductors suspended 100 /spl mu/m over the substrate, coplanar waveguides suspended 50 /spl mu/m over the substrate, and complicated micro-coaxial lines which have 50 /spl mu/m-suspended center signal lines surrounded by ground shields of 100 /spl mu/m in height.
Thermoresponsive biohybrid materials synthesized by ATRP (2007)

The aqueous phase behaviour of poly(N-isopropylacrylamide)–protein conjugates prepared by atom transfer radical polymerization (ATRP) is reported.
Pyrolytic Deposition of Carbon Films Containing Nitrogen and/or Boron (1990)

Carbon films containing nitrogen and/or boron were prepared in a closed system by the pyrolysis of appropriate precursor materials. The decomposition products of the pyrolysis were identified and the resulting films were characterized by chemical and physical means. The electrical conductivity of the heteroatom‐containing films is similar to that of pure amorphous carbon films. Boron nitride was present in the C‐N‐B film as revealed by XPS and IR spectroscopy. Oxygen appeared to have a role in the adherence of the films to the silica substrate.
Tolerance to rat monoclonal antibodies. Implications for serotherapy. (1986)

The antiglobulin response is a major complication of mAb therapy. It has been suggested that, in clinical practice, this might be avoided by using human or chimeric mAbs, or by prior induction of tolerance to the therapeutic mAb. In this study, we show that it is possible to induce tolerance in mice to the constant regions of rat IgG2b mAbs by both classical deaggregation methods and by anti-L3T4 mAb therapy. Mice tolerant to IgG2b constant region determinants failed to make an antiglobulin response when immunized with a number of mAbs of the same isotype that had no binding specificity for mouse cells, but produced vigorous antiidiotypic responses to cell-binding mAbs. Binding of antibodies to hemopoietic cells rends their idiotypic determinants major immunogens even in the presence of tolerance to constant region epitopes. These findings suggest that the use of human or chimeric mAbs will not be sufficient to eliminate the antiglobulin response, and that additional methods need to be investigated.
A small multigene family encodes Gi signal-transduction proteins. (1987)

The guanine nucleotide-binding regulatory proteins known as G proteins are receptor-associated signal-transduction molecules that are implicated in the control of a variety of metabolic processes. Recent evidence suggests that G proteins may mediate B-lymphocyte responses to bacterial lipopolysaccharide and may also transduce signals from the T-cell antigen receptor. Since these receptors are uniquely expressed on lymphoid cells, we used molecular cloning strategies to ask whether lymphocytes contain specialized G-protein alpha subunits to assist in signal transduction. Comparison of our two deduced human alpha i amino acid sequences with those previously determined for bovine and rodent G proteins permits the identification of three closely related but distinct types of alpha i molecules that comprise a small multigene family. Using gene-specific probes, we found that both of our alpha i genes are expressed in most cell types but in differing ratios. Our data support the view that a modest repertoire of extremely closely related G proteins mediates the transduction of signals derived from multiple different receptor molecules.
Ras in Cancer and Developmental Diseases (2011)

Somatic, gain-of-function mutations in ras genes were the first specific genetic alterations identified in human cancer about 3 decades ago. Studies during the last quarter century have characterized the Ras proteins as essential components of signaling networks controlling cellular proliferation, differentiation, or survival. The oncogenic mutations of the H-ras, N-ras, or K-ras genes frequently found in human tumors are known to throw off balance the normal outcome of those signaling pathways, thus leading to tumor development. Oncogenic mutations in a number of other upstream or downstream components of Ras signaling pathways (including membrane RTKs or cytosolic kinases) have been detected more recently in association with a variety of cancers. Interestingly, the oncogenic Ras mutations and the mutations in other components of Ras/MAPK signaling pathways appear to be mutually exclusive events in most tumors, indicating that deregulation of Ras-dependent signaling is the essential requirement for tumorigenesis. In contrast to sporadic tumors, separate studies have identified germline mutations in Ras and various other components of Ras signaling pathways that occur in specific association with a number of different familial, developmental syndromes frequently sharing common phenotypic cardiofaciocutaneous features. Finally, even without being a causative force, defective Ras signaling has been cited as a contributing factor to many other human illnesses, including diabetes and immunological and inflammatory disorders. We aim this review at summarizing and updating current knowledge on the contribution of Ras mutations and altered Ras signaling to development of various tumoral and nontumoral pathologies.
High efficiency gene transfer into mammalian cells (1984)

We have generalized the protocol of gene transfer, greatly increasing the variety of cells that can be used as recipients of foreign genes. Our approach has been to use a transient assay system that allows rapid screening of expression of foreign DNA. When the initial steps of gene transfer have been optimized with the transient system, these defined conditions are used to yield efficient stable transformation. We have seen that primate cells, including human cells, can be used in gene transfer experiments at levels sensitive enough to allow detection of single copy gene function. Recently we have also used this approach successfully with undifferentiated embryonic cells.
Small-Molecule Inhibitors of the LEDGF/p75 Binding Site of Integrase Block HIV Replication and Modulate Integrase Multimerization (2012)

Targeting the HIV integrase (HIV IN) is a clinically validated approach for designing novel anti-HIV therapies. We have previously described the discovery of a novel class of integration inhibitors, 2-(quinolin-3-yl)acetic acid derivatives, blocking HIV replication at a low micromolar concentration through binding in the LEDGF/p75 binding pocket of HIV integrase, hence referred to as LEDGINs. Here we report the detailed characterization of their mode of action. The design of novel and more potent analogues with nanomolar activity enabled full virological evaluation and a profound mechanistic study. As allosteric inhibitors, LEDGINs bind to the LEDGF/p75 binding pocket in integrase, thereby blocking the interaction with LEDGF/p75 and interfering indirectly with the catalytic activity of integrase. Detailed mechanism-of-action studies reveal that the allosteric mode of inhibition is likely caused by an effect on HIV-1 integrase oligomerization. The multimodal inhibition by LEDGINs results in a block in HIV integration and in a replication deficiency of progeny virus. The allosteric nature of LEDGINs leads to synergy in combination with the clinically approved active site HIV IN strand transfer inhibitor (INSTI) raltegravir, and cross-resistance profiling proves the distinct mode of action of LEDGINs and INSTIs. The allosteric nature of inhibition and compatibility with INSTIs underline an interest in further (clinical) development of LEDGINs.
Identification of protein–protein interfaces by decreased amide proton solvent accessibility (1998)

Matrix-assisted laser desorption ionization-time-of-flight mass spectrometry was used to identify peptic fragments from protein complexes that retained deuterium under hydrogen exchange conditions due to decreased solvent accessibility at the interface of the complex. Short deuteration times allowed preferential labeling of rapidly exchanging surface amides so that primarily solvent accessibility changes and not conformational changes were detected. A single mass spectrum of the peptic digest mixture was analyzed to determine the deuterium content of all proteolytic fragments of the protein. The protein-protein interface was reliably indicated by those peptides that retained more deuterons in the complex compared with control experiments in which only one protein was present. The method was used to identify the kinase inhibitor [PKI(5-24)] and ATP-binding sites in the cyclic-AMP-dependent protein kinase. Three overlapping peptides identified the ATP-binding site, three overlapping peptides identified the glycine-rich loop, and two peptides identified the PKI(5-24)-binding site. A complex of unknown structure also was analyzed, human alpha-thrombin bound to an 83-aa fragment of human thrombomodulin [TMEGF(4-5)]. Five peptides from thrombin showed significantly decreased solvent accessibility in the complex. Three peptides identified the anion-binding exosite I, confirming ligand competition experiments. Two peptides identified a new region of thrombin near the active site providing a potential mechanism of how thrombomodulin alters thrombin substrate specificity.
Electrostatically Driven Immobilization of Peptides onto (Maleic Anhydride-alt-methyl Vinyl Ether) Copolymers in Aqueous Media (2000)

The covalent immobilization of a model peptide onto the MAMVE copolymer, via the formation of amide bonds, occurred in moderate yields in aqueous conditions. The improvement of the grafting reaction was achieved by adding at the amino terminus of the model peptide a sequence (tag) of three positively charged amino acids, lysine or arginine, and by taking profit of electrostatic attractive interactions between the negatively charged copolymer and the tagged peptides. The arginine tag was more efficient than the lysine tag for enhancing the immobilization reaction, proving that the effect was due to an electrostic driving force. On the basis of these results, a tentative mechanism is discussed, and Scatchard plots pointed out two regimes of binding. With the first, at low polymer load (up to 50% of saturation for a lysine tag and 60-70% for an arginine tag), the binding occurred with a positive cooperative effect, the already bound peptide participating to the binding of others. A second one for higher coverages, for which the binding occurred with a negative cooperativity, and saturation was reached in the presence of a large excess of peptide.
Infranet: Circumventing Web Censorship and Surveillance (2002)

An increasing number of countries and companies routinely block or monitor access to parts of the Internet. To counteract these measures, we propose Infranet, a system that enables clients to surreptitiously retrieve sensitive content via cooperating Web servers distributed across the global Internet. These Infranet servers provide clients access to censored sites while continuing to host normal uncensored content. Infranet uses a tunnel protocol that provides a covert communication channel between its clients and servers, modulated over standard HTTP transactions that resemble innocuous Web browsing. In the upstream direction, Infranet clients send covert messages to Infranet servers by associating meaning to the sequence of HTTP requests being made. In the downstream direction, Infranet servers return content by hiding censored data in uncensored images using steganographic techniques. We describe the design, a prototype implementation, security properties, and performance of Infranet. Our security analysis shows that Infranet can successfully circumvent several sophisticated censoring techniques. 1
Isolation of a monoclonal antibody that blocks attachment of the major group of human rhinoviruses (1986)

Reciprocal competition binding assays have previously demonstrated that 20 of 24 human rhinovirus serotypes tested compete for a single cellular receptor. These studies suggested that the vast majority of rhinovirus serotypes utilize a single cellular receptor. With HeLa cells as an immunogen, a mouse monoclonal antibody was isolated which had the precise specificity predicted by the competition binding study. The receptor antibody was shown to protect HeLa cells from infection by 78 of 88 human rhinovirus serotypes assayed. In addition, the receptor antibody protects HeLa cells from infection by three coxsackievirus A serotypes. The receptor antibody was unable to protect cells from infection by a wide range of other RNA and DNA viruses. Using the receptor antibody and human rhinovirus type 15, we determined that the cellular receptor utilized by the vast number of human rhinovirus serotypes is present only on cells of human origin, with the exception of chimpanzee-derived cells. The receptor antibody has a strong affinity for the cellular receptor as evidenced by its rapid binding kinetics and ability to displace previously bound human rhinovirus virions from receptors. No viral variants were identified which could bypass the receptor blockage.