gebhart/patrepeval huggingface dataset:
Atmospheric escape from HD 189733b observed in H I Lyman-α: detailed analysis of HST/STIS September 2011 observations (2013)

Observations of transits of the hot giant exoplanet HD 189733b in the unresolved H i Lyman-α line show signs of hydrogen escaping the upper atmosphere of the planet. New resolved Lyman-α observations obtained with the STIS spectrograph onboard the Hubble Space Telescope in April 2010 and September 2011 confirmed that the planet is evaporating, and furthermore discovered significant temporal variations in the physical conditions of its evaporating atmosphere. Here we present a detailed analysis of the September 2011 observations of HD 189733b, when an atmospheric signature was detected. We present specific methods to find and characterize this absorption signature of escaping hydrogen in the Lyman-α line, and to calculate its false-positive probability, found to be 3.6%. Taking advantage of the spectral resolution and high sensitivity of the STIS spectrograph, we also present new results on temporal and spectro-temporal variability of this absorption feature. We also report the observation of HD 189733b in other lines (Si iii at 1206.5 Å, N v at 1240 Å). Variations in these lines could be explained either by early occultation by a bow-shock rich in highly ionized species, or by stellar variations.
Biologic activities of the beta -chemokine TCA3 on neutrophils and macrophages. (1995)

Previous in vivo and in vitro studies demonstrated that the murine beta-chemokine TCA3 is a chemoattractant for monocytes/macrophages and neutrophils. The ability of TCA3 to activate these cell populations is now evaluated. Treatment with 10 to 20 nM rTCA3 induced a respiratory burst with the production of superoxide and hydrogen peroxide in both casein-elicited and unstimulated neutrophil and macrophage populations. In addition, TCA3 treatment induced the production of reactive nitrogen intermediates, whereas stimulation with higher concentrations (100 nM) of TCA3 induced the exocytosis of lysozyme and elastase in the presence of cytochalasin B (7 micrograms/ml). Subnanomolar concentrations (100 pM) of TCA3 also caused integrin-mediated increases of adhesiveness to fibrinogen by neutrophils and macrophages. Increased adhesiveness is the most sensitive assay for TCA3 bioactivity. TCA3 treatment appears to involve signaling through a G-protein-linked receptor as Pertussis toxin abolished the TCA3-mediated increase of adhesiveness and the production of reactive nitrogen intermediates. The dose dependence of the TCA3-mediated activities indicate a coordinated inflammatory response mediated by varying concentrations of TCA3.
A Focused DNA-Encoded Chemical Library for the Discovery of Inhibitors of NAD+-Dependent Enzymes (2019)

DNA-encoded chemical libraries are increasingly used in pharmaceutical research because they enable the rapid discovery of synthetic protein ligands. Here we explored whether target-class focused DNA-encoded chemical libraries can be cost-effective tools to achieve robust screening productivity for a series of proteins. The study revealed that a DNA-encoded library designed for NAD<sup>+</sup>-binding pockets (NADEL) effectively sampled the chemical binder space of enzymes with ADP-ribosyltransferase activity. The extracted information directed the synthesis of inhibitors for several enzymes including PARP15 and SIRT6. The high dissimilarity of NADEL screening fingerprints for different proteins translated into inhibitors that showed selectivity for their target. The discovery of patterns of enriched structures for six out of eight tested proteins is remarkable for a library of 58 302 DNA-tagged structures and illustrates the prospect of focused DNA-encoded libraries as economic alternatives to large library platforms.
Improved antitumor activity of immunotherapy with BRAF and MEK inhibitors in BRAF V600E melanoma (2015)

Combining immunotherapy and BRAF targeted therapy may result in improved antitumor activity with the high response rates of targeted therapy and the durability of responses with immunotherapy. However, the first clinical trial testing the combination of the BRAF inhibitor vemurafenib and the CTLA4 antibody ipilimumab was terminated early because of substantial liver toxicities. MEK [MAPK (mitogen-activated protein kinase) kinase] inhibitors can potentiate the MAPK inhibition in BRAF mutant cells while potentially alleviating the unwanted paradoxical MAPK activation in BRAF wild-type cells that lead to side effects when using BRAF inhibitors alone. However, there is the concern of MEK inhibitors being detrimental to T cell functionality. Using a mouse model of syngeneic BRAF(V600E)-driven melanoma, SM1, we tested whether addition of the MEK inhibitor trametinib would enhance the antitumor activity of combined immunotherapy with the BRAF inhibitor dabrafenib. Combination of dabrafenib and trametinib with pmel-1 adoptive cell transfer (ACT) showed complete tumor regression, increased T cell infiltration into tumors, and improved in vivo cytotoxicity. Single-agent dabrafenib increased tumor-associated macrophages and T regulatory cells (Tregs) in tumors, which decreased with the addition of trametinib. The triple combination therapy resulted in increased melanosomal antigen and major histocompatibility complex (MHC) expression and global immune-related gene up-regulation. Given the up-regulation of PD-L1 seen with dabrafenib and/or trametinib combined with antigen-specific ACT, we tested the combination of dabrafenib, trametinib, and anti-PD1 therapy in SM1 tumors, and observed superior antitumor effect. Our findings support the testing of triple combination therapy of BRAF and MEK inhibitors with immunotherapy in patients with BRAF(V600E) mutant metastatic melanoma.
Type 1 and 2 T helper cell-mediated colitis (2006)

Understanding the cellular and molecular mechanisms of crosstalk among T helper 1, 2, 17 and T regulatory 1 cells is central for the prevention or treatment of inflammatory bowel diseases.
The 9/4 secondary structure of eukaryotic selenocysteine tRNA: More pieces of evidence (1998)

Selenocysteine biosynthesis and its cotranslational incorporation into selenoproteins are achieved by a complex molecular machinery (reviewed in Hüttenhofer &amp; Böck, 1998). A major wheel in this mechanism is the tRNASec, which plays a pivotal role. It is first charged with serine by the conventional SerRS, the seryl-residue being further converted in situ to the selenocysteyl-residue by the selenocysteine synthase enzyme. The charged selenocysteyl-tRNASec delivers selenocysteine to the nascent polypeptide chain in response to a reprogrammed UGA codon. The classical elongation factors EF-Tu (in bacteria) or EF1-α (in eukaryotes) do not intervene at this stage. Instead, this process requires a selenocysteine-specific translation factor, called SELB in bacteria, but for which no eukaryotic homologue has been cloned yet. Interestingly, antideterminants against EF-Tu binding were found in the Escherichia coli tRNASec (Rudinger et al., 1996). Based on the several functions that this tRNA has to accomplish, it is reasonable to expect that the tRNASec secondary structure should exhibit distinctive structural features deviating from classical elongator tRNAs. In this regard, functional studies, structural probing, and sequence comparisons confirmed the earlier proposal that the bacterial tRNASec needs an 8-bp long amino acceptor stem and a 6-bp long D-stem to function, instead of the canonical 7 bp and 3/4 bp, respectively (Leinfelder et al., 1988; Baron et al., 1990, 1993; Tormay et al., 1994).
PayBreak (2017)

Similar to criminals in the physical world, cyber-criminals use a variety of illegal and immoral means to achieve monetary gains. Recently, malware known as ransomware started to leverage strong cryptographic primitives to hold victims' computer files "hostage" until a ransom is paid. Victims, with no way to defend themselves, are often advised to simply pay. Existing defenses against ransomware rely on ad-hoc mitigations that target the incorrect use of cryptography rather than generic live protection. To fill this gap in the defender's arsenal, we describe the approach, prototype implementation, and evaluation of a novel, automated, and most importantly proactive defense mechanism against ransomware. Our prototype, called PayBreak, effectively combats ransomware, and keeps victims' files safe.
A new method for peptide synthesis in the N→C direction: amide assembly through silver-promoted reaction of thioamides (2014)

The Ag(I)-promoted coupling of amino acids and peptides with amino ester thioamides generates peptide imides without epimerisation. The peptide imides undergo regioselective hydrolysis under mild conditions to generate native peptides. This method was employed to prepare the pentapeptide thymopentin in the N→C direction, in high yield and purity.
Ring-Opening Metathesis Polymerization of Functionalized Cyclooctenes by a Ruthenium-Based Metathesis Catalyst (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRing-Opening Metathesis Polymerization of Functionalized Cyclooctenes by a Ruthenium-Based Metathesis CatalystMarc A. Hillmyer, Walter R. Laredo, and Robert H. GrubbsCite this: Macromolecules 1995, 28, 18, 6311–6316Publication Date (Print):August 1, 1995Publication History Published online1 May 2002Published inissue 1 August 1995https://pubs.acs.org/doi/10.1021/ma00122a043https://doi.org/10.1021/ma00122a043research-articleACS PublicationsRequest reuse permissionsArticle Views3071Altmetric-Citations174LEARN 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 Get e-Alerts
Multi-institutional Validation Study of the American Joint Commission on Cancer (8th Edition) Changes for T and N Staging in Patients With Pancreatic Adenocarcinoma (2016)

The proposed 8th edition changes for T and N classification were statistically valid and may allow a more reproducible system of T staging. This system also stratifies patients more evenly across stages without sacrificing prognostic accuracy.
A monofunctional prephenate dehydrogenase created by cleavage of the 5' 109 bp of the tyrA gene from Erwinia herbicola (1992)

A cohesive phylogenetic cluster that is limited to enteric bacteria and a few closely related genera possesses a bifunctional protein that is known as the T-protein and is encoded by tyrA. The T-protein carries catalytic domains for chorismate mutase and for cyclohexadienyl dehydrogenase. Cyclohexadienyl dehydrogenase can utilize prephenate or L-arogenate as alternative substrates. A portion of the tyr A gene cloned from Erwinia herbicola was deleted in vitro with exonuclease III and fused in-frame with a 5' portion of lacZ to yield a new gene, denoted tyrA*, in which 37 N-terminal amino acids of the T-protein are replaced by 18 amino acids encoded by the polycloning site/5' portion of the lacZ alpha-peptide of pUC19. The TyrA* protein retained dehydrogenase activity but lacked mutase activity, thus demonstrating the separability of the two catalytic domains. While the Km of the TyrA* dehydrogenase for NAD+ remained unaltered, the Km for prephenate was fourfold greater and the Vmax was almost twofold greater than observed for the parental T-protein dehydrogenase. Activity with L-arogenate, normally a relatively poor substrate, was reduced to a negligible level. The prephenate dehydrogenase activity encoded by tyrA* was hypersensitive to feedback inhibition by L-tyrosine (a competitive inhibitor with respect to prephenate), partly because the affinity for prephenate was reduced and partly because the Ki value for L-tyrosine was decreased from 66 microM to 14 microM. Thus, excision of a portion of the chorismate mutase domain is shown to result in multiple extra-domain effects upon the cyclohexadienyl dehydrogenase domain of the bifunctional protein.(ABSTRACT TRUNCATED AT 250 WORDS)
A circular antibody-antigen complex is responsible for increased affinity shown by mixtures of monoclonal antibodies to human chorionic gonadotropin. (1983)

Mixtures of some pairs of monoclonal antibodies that have separate epitopes on the beta-subunit of hCG have increased affinity for the hormone relative to that of either antibody alone. A mathematical model developed to explain the phenomenon predicted that a circular tetrameric complex composed of each antibody and two molecules of hCG was responsible for the effect. This structure has now been identified experimentally by the following criteria: 1) the m.w. of the complex observed by electrophoresis (370,000 g/mol) and gel filtration (440,000 g/mol) was in agreement with the m.w. expected for a tetramer composed of two molecules of antibody and two molecules of hCG (i.e., 376,000 g/mol); 2) the ratio of individual antibodies to hCG measured with the use of 131I and 125I-labeled antibodies and/or hCG was 1:1:2; and 3) the complex failed to adhere to affinity columns containing either antibodies or hCG covalently coupled to Sepharose. These columns adsorbed B101, B102, hCG, and mixtures of B101 plus hCG or B102 plus hCG. The observations made with the affinity resins are compatible with a circular model for antigen-antibody complex in which the epitopes of the antigen and the binding site of the antibodies were mutually and completely obscured. Although not studied in detail, a similar complex was formed when the beta-subunit of hCG was substituted for the intact hormone. In addition, a mixture of antibodies that bound to the alpha- and beta-subunits of hCG (i.e., A102 and B102) and that had a higher affinity for the hormone than either antibody also gave rise to a similar species that could be detected after electrophoresis. A pair of antibodies that bind to separate epitopes on the beta-subunit (i.e., B101 and B103) and do not show enhanced affinity for hCG failed to form a stable complex that could be identified as a separate species after electrophoresis. Thus, the studies reported here confirm earlier theoretical predictions linking the increase in affinity observed on mixing monoclonal antibodies to the formation of a circular complex.
Cell therapy for ARDS: efficacy of endobronchial versus intravenous administration and biodistribution of MAPCs in a large animal model (2019)

Introduction Bone marrow-derived multipotent adult progenitor cells (MAPCs) are adult allogeneic adherent stem cells currently investigated clinically for use in acute respiratory distress syndrome (ARDS). To date, there is no agreement on which is the best method for stem cells delivery in ARDS. Here, we compared the efficacy of two different methods of administration and biodistribution of MAPC for the treatment of ARDS in a sheep model. Methods MAPC were labelled with [ 18 F] fluoro-29-deoxy-D-glucose and delivered by endobronchial (EB) or intravenous route 1 hour after lipopolysaccharide infusion in sheep mechanically ventilated. PET/CT images were acquired to determine the biodistribution and retention of the cells at 1 and 5 hours of administration. Results The distribution and retention of the MAPC was dependent on the method of cell administration. By EB route, PET images showed that MAPC remained at the site of administration and no changes were observed after 5 hours, whereas with intravenous route, the cells had broad biodistribution to different organs, being the lung the main organ of retention at 1 and 5 hours. MAPC demonstrated an equal effect on arterial oxygenation recovery by either route of administration. Conclusion The EB or intravenous routes of administration of MAPC are both effective for the treatment of ARDS in an acute sheep model, and the effect of MAPC therapy is not dependent of parenchymal integration or systemic biodistribution.
Hypertension and the Pathogenesis of Atherosclerosis (1995)

Hypertension is a risk factor for the development of atherosclerosis, although the mechanisms have not been well elucidated. As the cellular and molecular mechanisms of the pathogenesis of atherosclerosis and the effects of hypertension are being more clearly defined, it becomes apparent that the two processes have certain common mechanisms. The endothelium is a likely central focus for the effect of both diseases. There is increasing evidence that atherosclerosis should be viewed fundamentally as an inflammatory disease. Atherogenic stimuli such as hyperlipidemia appear to active the inflammatory response by causing expression of mononuclear leukocyte recruiting mechanisms. The gene for one of these, the vascular cell adhesion molecule-1, is controlled at least in part by transcriptional factors regulated by oxidative stress, which modifies the redox state of the endothelial cell. Alterations in the redox state of the arterial wall also may contribute to vascular smooth muscle cell growth. In a somewhat parallel fashion, there is evidence that hypertension may also exert oxidative stress on the arterial wall. This article reviews evidence that leads to the postulate that hypertension predisposes to and accelerates atherosclerosis at least in part because of synergy between elevated blood pressure and other atherogenic stimuli to induce oxidative stress on the arterial wall.
All i-line lift-off T-gate process and materials (2005)

An all i-line 0.22 um T-gate process is demonstrated. A resist structure suitable for metal deposition and lift-off is constructed sequentially with two different resist materials. The lithographic process is described in details in this paper.
A MEMS thermopneumatic silicone membrane valve (2002)

A technology for fabricating silicone rubber membranes and integrating them with other processes on a silicon wafer has been developed. Silicone rubber has been found to have exceptional mechanical properties including low modulus, high elongation, and good sealing. An integrated normally open valve using a silicone rubber membrane and 3M PF5060 liquid for thermopneumatic actuation has been fabricated and tested. For a 1.3 lpm air flow, 280 mW is required to close the valve at 20 PSI inlet pressure. Due to the high permeability of silicone rubber, most liquids used in thermopneumatic systems will be lost, necessitating more work to find a suitable barrier material compatible with silicone rubber.
Nature and Mechanisms of Cytoplasmic Male Sterility in Plants: a Review1 (1981)

Abstract Cytoplasmic male sterility (CMS) has been described in many of our cultivated crops and is commercially useful in the production of hybrids when pollen vectors will provide the necessary economic levels of seed production. In the more common type, the sporophytic, the development of the microspore is affected by the abnormal growth of the tapetum or mistiming of callose formation and, in corn at least, the mitochondrial complex is involved. In the gametophytic system the factor causing abortion of the pollen apparently resides in the microspore rather than in its environment. Other systems which suggest plasmid-like inclusions associated with CMS have been reported. Transfer to the cytosterile mechanism by cell fusion has been accomplished, but wider application of this technique waits on methods for development of plants from naked protoplasts In more species.
Galactose Oxidase from Polyporus circinatus, Fr (1959)

A new pathway for the metabolism of galactose which differs 'from the galactokinase-galactouridyl transferase scheme of Trucco
Further studies of androgenetic embryo production and plant regeneration from in vitro cultured anthers in maize (Zea mays L.) (1986)

International audience
6. Dose Adjustments Based on Pharmacogenetics of CYP450 Enzymes. (2008)

In today’s medicine, drug therapy represents an important tool to treat or control disease. Dosing drugs is based on the assumption that a particular dose will yield a predefined concentration in the circulation and thereby establish the desired therapeutic effect. The fact that liver and kidney function may affect this relationship is appreciated, as is the fact that the use of co-medication potentially may interfere with the relationship between dose and blood concentration. Also environmental factors, like diet, alcohol use, smoking behaviour and caffeine intake may alter the rate at which particular drugs are metabolized, and will thus affect exposure of individuals to these drugs. A factor that has been neglected for a long time is genetics: differences in genetic make up may affect the relation between drug dose and blood concentration. Variant alleles encoding drug transporters or drug metabolizing enzymes with altered activity, present in the population, will give rise to unexpectedly high or low blood concentrations in response to a particular dose of a drug in certain individuals. The variation in drug metabolizing capacity between individuals is known for quite some time, but only recently this is becoming available as a routine diagnostic to provide better therapy. An important group of enzymes involved in drug metabolism is the cytochrome P450 enzyme system, which is mainly (but not only) active in the liver and the intestine. It consists of a family of isoenzymes, each with their own substrate specificity, and catalyzes oxidative reactions in order make potentially toxic and harmful substances more soluble. Purpose is to protect the body against toxic substances. The most important cytochromes with respect to drug metabolism are CYP3A4, CYP2C9, CYP2C19 and CYP2D6. For these enzymes, however, several variant alleles encoding enzymes with decreased activity exist (see www.cypalleles.ki.se), giving rise to interindividual differences in capacity to metabolize drugs. The best known example in this family is the enzyme CYP2D6, for which even 10% of the Caucasian population is a poor metabolizer, due to inheritance of two inactive variant alleles.

The documented genetic variability in cytochrome P450 enzymes has increased considerably the last years, and it has become clear that inherited capabilities of drug metabolism by this important detoxifying system may be of importance for predicting outcome of drug treatment. Especially the fact that this concerns inherited information makes it possible to assess prospectively the drug metabolizing capacity of patients. Whereas detection of variant alleles is an important first step, the real clinical benefit should come from adjusting drug therapy based on this genetic information. It is at this stage where the field of pharmacogenetics nowadays finds itself.