gebhart/patrepeval huggingface dataset:
Linking genome and proteome by mass spectrometry: Large-scale identification of yeast proteins from two dimensional gels (1996)

The function of many of the uncharacterized open reading frames discovered by genomic sequencing can be determined at the level of expressed gene products, the proteome. However, identifying the cognate gene from minute amounts of protein has been one of the major problems in molecular biology. Using yeast as an example, we demonstrate here that mass spectrometric protein identification is a general solution to this problem given a completely sequenced genome. As a first screen, our strategy uses automated laser desorption ionization mass spectrometry of the peptide mixtures produced by in-gel tryptic digestion of a protein. Up to 90% of proteins are identified by searching sequence data bases by lists of peptide masses obtained with high accuracy. The remaining proteins are identified by partially sequencing several peptides of the unseparated mixture by nanoelectrospray tandem mass spectrometry followed by data base searching with multiple peptide sequence tags. In blind trials, the method led to unambiguous identification in all cases. In the largest individual protein identification project to date, a total of 150 gel spots-many of them at subpicomole amounts-were successfully analyzed, greatly enlarging a yeast two-dimensional gel data base. More than 32 proteins were novel and matched to previously uncharacterized open reading frames in the yeast genome. This study establishes that mass spectrometry provides the required throughput, the certainty of identification, and the general applicability to serve as the method of choice to connect genome and proteome.
A non-conservatively defensive strategy for urban autonomous driving (2016)

From the driving strategy point of view, a major challenge for autonomous vehicles in urban environment is to behave defensively to potential dangers, yet to not overreact to threats with low probability. As it is overwhelming to program the action rules case-by-case, a unified planning framework under uncertainty is proposed in this paper, which achieves a non-conservatively defensive strategy (NCDS) in various kinds of scenarios for urban autonomous driving. First, uncertainties in urban scenarios are simplified to two probabilistic cases, namely passing and yielding. Two-way-stop intersection is used as an exemplar scenario to illustrate the derivation of probabilities for different intentions of others via a logistic regression model. Then a deterministic planner is designed as the baseline. Also, a safe set is defined, which considers both current and preview safety. The planning framework under uncertainty is then proposed, in which safety is guaranteed and overcautious behavior is prevented. Finally, the proposed planning framework is tested by simulation in the exemplar scenario, which demonstrates that an NCDS can be realistically achieved by employing the proposed framework.
ARRY-334543, A potent, orally active small molecule inhibitor of EGFR and ErbB-2 (2005)

3399 The growth factor receptor tyrosine kinases EGFR (ErbB-1) and ErbB-2 (HER-2/neu) play a major role in controlling cell growth, differentiation and survival. These two receptor tyrosine kinases are often over-expressed and/or abnormally active in a wide variety of tumor types. Currently several drugs have been developed that selectively inhibit either EGFR or ErbB-2. Despite some clinical success with the selective agents, data suggest concomitant inhibition of both kinases maybe a more efficacious approach for the treatment of tumors. At the present time, there are no approved therapeutic agents that target both EGFR and ErbB-2, although several compounds are currently under investigation. In a series of experiments we demonstrate that ARRY-334543 is a novel, potent, orally active dual inhibitor of EGFR and ErbB-2. The compound is a reversible ATP-competitive inhibitor with nanomolar potency against both kinases in vitro. In cell-based assays using tumor cells that over-express EGFR (A431) or ErbB-2 (BT474), ARRY-334543 potently inhibited substrate phosphorylation. ARRY-334543 was shown to be highly selective for EGFR/ErbB-2, and did not show any significant activity when screened against a panel of 104 kinases. In murine xenograft models ARRY-334543 demonstrated significant dose-related (25, 50, 100 mg/kg) tumor growth inhibition in A431-derived tumors when administered orally, BID, for 21 days. Based on potency, selectivity and efficacy data, the compound is currently in development as an anti-cancer agent.
4-(3'-Bromo-4'hydroxylphenyl)-amino-6,7-dimethoxyquinazoline: a novel quinazoline derivative with potent cytotoxic activity against human glioblastoma cells. (1998)

The novel quinazoline derivative 4-(3'-bromo-4'-hydroxylphenyl)-amino-6,7-dimethoxyquinazoline (WHI-P154) exhibited significant cytotoxicity against U373 and U87 human glioblastoma cell lines, causing apoptotic cell death at micromolar concentrations. The in vitro antiglioblastoma activity of WHI-P154 was amplified > 200-fold and rendered selective by conjugation to recombinant human epidermal growth factor (EGF). The EGF-P154 conjugate was able to bind to and enter target glioblastoma cells within 10-30 min via receptor (R)-mediated endocytosis by inducing internalization of the EGF-R molecules. In vitro treatment with EGF-P154 resulted in killing of glioblastoma cells at nanomolar concentrations with an IC50 of 813 +/- 139 nM, whereas no cytotoxicity against EGF-R-negative leukemia cells was observed, even at concentrations as high as 100 microM. The in vivo administration of EGF-P154 resulted in delayed tumor progression and improved tumor-free survival in a severe combined immunodeficient mouse glioblastoma xenograft model. Whereas none of the control mice remained alive tumor-free beyond 33 days (median tumor-free survival, 19 days) and all control mice had tumors that rapidly progressed to reach an average size of > 500 mm3 by 58 days, 40% of mice treated for 10 consecutive days with 1 mg/kg/day EGF-P154 remained alive and free of detectable tumors for more than 58 days with a median tumor-free survival of 40 days. The tumors developing in the remaining 60% of the mice never reached a size > 50 mm3. Thus, targeting WHI-P154 to the EGF-R may be useful in the treatment of glioblastoma multiforme.
Role of sequences within the first intron in the regulation of expression of eukaryotic initiation factor 2 alpha. (1992)

Resting human peripheral blood T cells synthesize proteins at very low rates and contain very low levels of eukaryotic initiation factor (eIF) 2 alpha mRNA. During mitogenic activation, the level of eIF-2 alpha mRNA increases at least 50-fold, an effect thought to be due primarily to intranuclear stabilization of the primary transcript (Cohen, R. B., Boal, T. R., and Safer, B. (1990) EMBO J. 9, 3831-3837). Analysis of sequences within the first intron revealed a region with homology to the "initiator" (Inr) sequence first described by Smale and Baltimore (Smale, S. T., and Baltimore, D. (1989) Cell 57, 103-113). This Inr element is positioned 450 bases downstream of the eIF-2 alpha promoter and is oriented to generate an overlapping antisense transcript. Deletion or mutation of the Inr element results in a reproducible 5-8-fold increase in the activity of an eIF-2 alpha promoter-driven CAT reporter gene and a corresponding 2.5-fold decrease in activity of an antisense driven luciferase reporter gene in vivo in 293 cells. In vitro transcription analysis also reveals antisense transcripts which depend on an intact Inr element and whose 5' ends map to sequences surrounding the Inr consensus sequence. A potential role for double-stranded RNA generated by these overlapping divergent transcription units in the regulation of eIF-2 alpha gene expression in T cells is suggested.
A Comparative Study of Two Different Schemes to Dopant Segregation at NiSi/Si and PtSi/Si Interfaces for Schottky Barrier Height Lowering (2008)

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> An experimental study is presented to compare two different schemes used to incorporate a high concentration of dopants at the silicide/silicon interface for NiSi and PtSi, i.e., dopant segregation, with the purpose of lowering the Schottky barrier height (SBH) of the contact systems. Specifically, the interfacial dopant is introduced either through silicidation-induced dopant segregation (SIDS) or by silicide as diffusion source (SADS). For the latter, a postimplantation drive-in anneal is needed. For both silicide systems, the dopant segregation gives rise to a predominant effect, leading to an effective SBH that is independent of the original SBHs of PtSi and NiSi, which differs by 0.2 eV. Scheme SIDS is relatively simple in processing, but the silicidation process is dopant-dependent, leading to local variations of silicide formation. Scheme SADS addresses the adverse effect of dopant on silicidation by separating silicidation from dopant incorporation. </para>
Definition of a Second Bacillus subtilis pur Regulon Comprising the pur and xpt-pbuX Operons plus pbuG , nupG ( yxjA ), and pbuE ( ydhL ) (2003)

In Bacillus subtilis expression of genes or operons encoding enzymes and other proteins involved in purine synthesis is affected by purine bases and nucleosides in the growth medium. The genes belonging to the PurR regulon (purR, purA, glyA, guaC, pbuO, pbuG, and the pur, yqhZ-folD, and xpt-pbuX operons) are controlled by the PurR repressor, which inhibits transcription initiation. Other genes are regulated by a less-well-described transcription termination mechanism that responds to the presence of hypoxanthine and guanine. The pur operon and the xpt-pbuX operon, which were studied here, are regulated by both mechanisms. We isolated two mutants resistant to 2-fluoroadenine in which the pur operon and the xpt-pbuX operon are expressed at increased levels in a PurR-independent manner. The mutations were caused by deletions that disrupted a potential transcription terminator structure located immediately upstream of the ydhL gene. The 5' part of the ydhL leader region contained a 63-nucleotide (nt) sequence very similar to the 5' ends of the leaders of the pur and xpt-pbuX operons. Transcripts of these regions may form a common tandem stem-loop secondary structure. Two additional genes with potential leader regions containing the 63-nt sequence are pbuG, encoding a hypoxanthine-guanine transporter, and yxjA, which was shown to encode a purine nucleoside transporter and is renamed nupG. Transcriptional lacZ fusions and mutations in the 63-nt sequence encoding the possible secondary structures provided evidence that expression of the pur and xpt-pbuX operons and expression of the ydhL, nupG, and pbuG genes are regulated by a common mechanism. The new pur regulon is designated the XptR regulon. Except for ydhL, the operons and genes were negatively regulated by hypoxanthine and guanine. ydhL was positively regulated. The derived amino acid sequence encoded by ydhL (now called pbuE) is similar to the amino acid sequences of metabolite efflux pumps. When overexpressed, PbuE lowers the sensitivity to purine analogs. Indirect evidence indicated that PbuE decreases the size of the internal pool of hypoxanthine. This explains why the hypoxanthine- and guanine-regulated genes are expressed at elevated levels in a mutant that overexpresses pbuE.
Anti-GPIIb/IIIa Drugs: Current Strategies and Future Directions (2001)

Three platelet glycoprotein (GP) IIb/IIIa receptor antagonists have been approved as adjunctive therapy to decrease the ischemic complications of percutaneous coronary interventions (PCI) and/or unstable angina. They include the chimeric murine/human monoclonal antibody 7E3 Fab fragment (abciximab), a cyclic heptapeptide based on the KGD amino acid sequence (eptifibatide), and a nonpeptide mimetic of the RGD sequence (tirofiban). The agents are very effective in providing both short-term and long-term benefit after PCI, and one agent has also demonstrated a progressive long-term mortality benefit. The long-term mortality benefit is highly cost-effective when compared to other medical interventions. The benefits in treating unstable angina without PCI are less dramatic and robust, with some agents providing no benefit. Severe thrombocytopenia is an infrequent, but potentially serious, complication of therapy with all of the agents. The risk of major bleeding is increased only minimally or not at all by the drugs. Currently, a number of new indications for GPIIb/IIIa antagonists are under study, including acute myocardial infarction (+/- thrombolytic therapy, +/- PCI) and stroke. In addition to their impact on improving outcome, the results of clinical trials with these agents provide crucial insights into the contribution of GPIIb/IIIa-mediated platelet function in the pathophysiology of thrombotic vascular disease.
Influence of body weight on response of Fischer 344 rats to anthrax lethal toxin (1989)

Groups of Fischer 344 rats were injected intravenously with Bacillus anthracis culture supernatant containing crude anthrax toxin. Times to death of rats given identical toxin preparations varied directly with the weights of the rats (P = 0.0001). In contrast to previous reports, the data indicate that rat weight must be taken into account during in vivo assays of anthrax lethal toxin activity.
The New S Language (2018)

This book provides documentation for a new version of the S system released in 1988. The New S Language enhances the features that have made S popular: interactive computing, flexible graphics, data management and a large collection of functions. The New S language features make possible new applications and higher-level programming, including a single unified language, user-defined functions as first-class objects, symbolic computations, more accurate numerical calculations and a new approach to graphics. S now provides direct interfaces to the powerful tool of the UNIX operating system and to algorithms implemented in Fortran and C.
Allium sativum (garlic) suppresses leukocyte inflammatory cytokine production in vitro: Potential therapeutic use in the treatment of inflammatory bowel disease (2002)

By inhibiting Th1 and inflammatory cytokines while upregulating IL-10 production, treatment with garlic extract may help to resolve inflammation associated with IBD. An in vivo animal model study needs to be undertaken to determine the significance of these in vitro findings.
Evolutionary view of acyl-CoA diacylglycerol acyltransferase (DGAT), a key enzyme in neutral lipid biosynthesis (2011)

In this study, we identified several DGAT1 and DGAT2 homologs in eukaryote taxa. Overall, the data show that DGAT1 and DGAT2 are present in most eukaryotic organisms and belong to two different gene families. The phylogenetic and evolutionary analyses revealed that DGAT1 and DGAT2 evolved separately, with functional convergence, despite their wide molecular and structural divergence.
Proinflammatory Activities of S100: Proteins S100A8, S100A9, and S100A8/A9 Induce Neutrophil Chemotaxis and Adhesion (2003)

S100A8 and S100A9 are small calcium-binding proteins that are highly expressed in neutrophil and monocyte cytosol and are found at high levels in the extracellular milieu during inflammatory conditions. Although reports have proposed a proinflammatory role for these proteins, their extracellular activity remains controversial. In this study, we report that S100A8, S100A9, and S100A8/A9 caused neutrophil chemotaxis at concentrations of 10(-12)-10(-9) M. S100A8, S100A9, and S100A8/A9 stimulated shedding of L-selectin, up-regulated and activated Mac-1, and induced neutrophil adhesion to fibrinogen in vitro. Neutralization with Ab showed that this adhesion was mediated by Mac-1. Neutrophil adhesion was also associated with an increase in intracellular calcium levels. However, neutrophil activation by S100A8, S100A9, and S100A8/A9 did not induce actin polymerization. Finally, injection of S100A8, S100A9, or S100A8/A9 into a murine air pouch model led to rapid, transient accumulation of neutrophils confirming their activities in vivo. These studies 1) show that S100A8, S100A9, and S100A8/A9 are potent stimulators of neutrophils and 2) strongly suggest that these proteins are involved in neutrophil migration to inflammatory sites.
Imidazolium sulfonate-containing pentablock copolymer–ionic liquid membranes for electroactive actuators (2012)

Block copolymer–ionic liquid composite materials emerge as promising candidates for electromechanical transducer applications. Herein, a novel imidazolium sulfonate-containing pentablock copolymer–ionic liquid composite was prepared and fabricated into thermally stable electroactive actuators, which exhibit effective actuation response under a low applied potential of 4 V.
Induction of programmed cell death (apoptosis) by influenza virus infection in tissue culture cells (1993)

The process of cell death caused by influenza virus infection in cultured MDCK and HeLa cells was analysed. This infection gave rise to nuclear fragmentation and chromatin condensation accompanied by chromosomal DNA fragmentation into oligonucleosomes. Chromosomal DNA fragmentation progressed concomitantly with cell lysis of MDCK cells and HeLa cells, producing high and low yields of virus particles, respectively, indicating that the extent of cell lysis was not proportional to the virus production. The endonuclease inhibitor zinc blocked DNA fragmentation in MDCK cells. Cycloheximide inhibited DNA fragmentation as well as cell lysis. Inhibition occurred when the drug was added to the medium within 2 h after infection but not efficiently at 4 h or later. Infection induced the Fas Ag gene, which encodes a possible apoptosis-mediating molecule, in the early infectious stage followed by the expression of Fas Ag on the cell surface. These results suggested that influenza virus infection causes apoptotic death of cultured cells, and their fate might be determined at an early stage of the infection by induction of an apoptotic gene.
Botulinum neurotoxin types A and E require the SNARE motif in SNAP‐25 for proteolysis (1997)

Botulinum neurotoxins type A and E (BoNT/A and BoNT/E) are metalloproteases with a unique specificity for SNAP-25 (synaptosome-associated protein of 25 kDa), an essential protein component of the neuroexocytotic machinery. It has been suggested that this specificity is directed through the recognition of a nine residue sequence, termed SNARE motif, that is common to the other two SNARE proteins: VAMP (vesicle-associated membrane protein) and syntaxin, the only known substrates of the other six clostridial neurotoxins. Here we analyse the involvement of the four copies of the SNARE motif present in SNAP-25 in its interaction with BoNT/A and BoNT/E by following the kinetics of proteolysis of SNAP-25 mutants deleted of SNARE motifs. We show that a single copy of the motif is sufficient for BoNT/A and BoNT/E to recognise SNAP-25. While the copy of the motif proximal to the cleavage site is clearly involved in recognition, in its absence, other more distant copies of the motif are able to support proteolysis. Also, a non-neuronal isoform of SNAP-25, Syndet, is shown to be sensitive to BoNT/E, but not BoNT/A, whilst the SNAP-25 isoforms from Torpedo marmorata and Drosophila melanogaster were demonstrated not to be substrates of these metalloproteases.
Thiazolidinediones as anti-cancer agents. (2008)

The PPAR-gamma (PPAR-γ) activating thiazolidinedione (TZD) medications are a class of drugs used to improve lipid and glucose metabolism in type-2 diabetes. In addition to their known insulin sensitization action, these drugs have been shown to suppress tumor development in several in vitro and in vivo models. Among the proposed mechanisms for the anti-tumor effects of TZDs, apoptosis induction, cell cycle arrest, and differentiation have been extensively reported. Interestingly, some of the observed anti-tumor effects are independent of PPAR-γ activation. The following review will discuss studies employing TZDs as anti-cancer therapies for the most common types of cancers including, lung, breast, and colon and will explore the principal PPAR-γ-dependent and -independent mechanisms by which TZDs exert their anti-tumor effects.
Super-Hydrophobic Surface of Aligned Polyacrylonitrile Nanofibers (2002)

A water contact angle exceeding 170° is exhibited by the surface of aligned polyacrylonitrile (PAN) nanofibers without any surface treatment (the picture shows a cross-sectional view of the as-synthesized nanofibers). The nanofibers were obtained by simply extruding a PAN solution through an anodic alumina template into a solidifying solution. The factors that govern the hydrophobicity of aligned nanostructures are discussed.
The Orphan Receptor C5L2 Has High Affinity Binding Sites for Complement Fragments C5a and C5a des-Arg74 (2002)

The substantial variations in the responses of cells to the anaphylatoxin C5a and its desarginated form, C5adR(74), suggest that more than one type of cell surface receptor for these ligands might exist. However, only a single receptor for C5a and C5adR(74), CD88, has been characterized to date. Here we report that the orphan receptor C5L2/gpr77, which shares 35% amino acid identity with CD88, binds C5a with high affinity but has a 10-fold higher affinity for C5adR(74) than CD88. C5L2 also has a moderate affinity for anaphylatoxin C3a, but cross-competition studies suggest that C3a binds to a distinct site from C5a. C4a was able to displace C3a, suggesting that C5L2, like the C3a receptor, may have a low binding affinity for this anaphylatoxin. Unlike CD88 and C3a receptor, C5L2 transfected into RBL-2H3 cells does not support degranulation or increases in intracellular [Ca(2+)] and is not rapidly internalized in response to ligand binding. However, ligation of C5L2 by anaphylatoxin did potentiate the degranulation response to cross-linkage of the high affinity IgE receptor by a pertussis toxin-sensitive mechanism. These results suggest that C5L2 is an anaphylatoxin-binding protein with unique ligand binding and signaling properties.
Analysis of laser–melt pool–powder bed interaction during the selective laser melting of a stainless steel (2017)

The laser powder bed fusion (LPBF) or powder-bed additive layer manufacturing process is now recognized as a high-potential manufacturing process for complex metallic parts. However, many technical issues are still to overcome for making LPBF a fully viable manufacturing process. This is the case of surface finish and the systematic occurrence of porosities, which require postmachining steps. Up till now, the porosity origin remains unclear but is expected to be related to the stability of the process. As a LPBF part is made by the accumulation of hundreds of meters of small weld beads, it also appears to be important to understand all the phenomena that occur during the laser-powder-melt pool (MP) interaction for each single track. For this reason, in the first part of our study, using an instrumented LPBF setup and a fast camera analysis (&amp;gt;10 000 image/s), single tracks were fabricated and analyzed in real time and postmortem. Spatters ejections and powder denudation phenomena were observed together with variations of melt pool dimensions and melt-pool instabilities. In turn, the physical origin of this powder denudation and the dynamics of the MP were investigated and discussed.
The Effectiveness of Vaccination against Influenza in Healthy, Working Adults (1995)

Vaccination against influenza has substantial health-related and economic benefits for healthy, working adults.