gebhart/patrepeval huggingface dataset:
Chemical reactivity drives spatiotemporal organisation of bacterial metabolism (2014)

In this review, we examine how bacterial metabolism is shaped by chemical constraints acting on the material and dynamic layout of enzymatic networks and beyond. These are moulded not only for optimisation of given metabolic objectives (e.g. synthesis of a particular amino acid or nucleotide) but also for curbing the detrimental reactivity of chemical intermediates. Besides substrate channelling, toxicity is avoided by barriers to free diffusion (i.e. compartments) that separate otherwise incompatible reactions, along with ways for distinguishing damaging vs. harmless molecules. On the other hand, enzymes age and their operating lifetime must be tuned to upstream and downstream reactions. This time dependence of metabolic pathways creates time-linked information, learning and memory. These features suggest that the physical structure of existing biosystems, from operon assemblies to multicellular development may ultimately stem from the need to restrain chemical damage and limit the waste inherent to basic metabolic functions. This provides a new twist of our comprehension of fundamental biological processes in live systems as well as practical take-home lessons for the forward DNA-based engineering of novel biological objects.
Poly(acrylic acid) Undergoes Partial Esterification During RAFT Synthesis in Methanol and Interchain Disulfide Bridging Upon NaOH Treatment (2012)

Abstract In this work, poly(acrylic acid) was synthesized by reversible addition–fragmentation chain transfer (RAFT) polymerization using 4,4′‐azobis(4‐cyanopentanoic acid) and 4‐cyanopentanoic acid dithiobenzoate as a radical initiator and chain transfer agent, respectively. By varying the reactant ratios, we achieved poly(acrylic acid) with molecular weights up to 55 100 and polydispersities of ≈1.2. Upon characterization of the final products, we detected, as a side reaction, partial esterification of the carboxyl side chain groups when the polymerization was conducted in methanol. Treatment of the esterified polymer with base resulted in acrylic acid homopolymers, but also led to end‐group disulfide bridging, which was reversed using a reducing buffer.
Analysis of Primary Structural Determinants That Distinguish the Centromere-Specific Function of Histone Variant Cse4p from Histone H3 (1999)

Cse4p is a variant of histone H3 that has an essential role in chromosome segregation and centromere chromatin structure in budding yeast. Cse4p has a unique 135-amino-acid N terminus and a C-terminal histone-fold domain that is more than 60% identical to histone H3 and the mammalian centromere protein CENP-A. Cse4p and CENP-A have biochemical properties similar to H3 and probably replace H3 in centromere-specific nucleosomes in yeasts and mammals, respectively. In order to identify regions of Cse4p that distinguish it from H3 and confer centromere function, a systematic site-directed mutational analysis was performed. Nested deletions of the Cse4p N terminus showed that this region of the protein contains at least one essential domain. The C-terminal histone-fold domain of Cse4p was analyzed by changing Cse4p amino acids that differ between Cse4p and H3 to the analogous H3 residues. Extensive substitution of contiguous Cse4p residues with H3 counterparts resulted in cell lethality. However, all large lethal substitution alleles could be subdivided into smaller viable alleles, many of which caused elevated rates of mitotic chromosome loss. The results indicate that residues critical for wild-type Cse4p function and high-fidelity chromosome transmission are distributed across the entire histone-fold domain. Our findings are discussed in the context of the known structure of H3 within the nucleosome and compared with previous results reported for CENP-A.
Technetium-99m-galactosyl-neoglycoalbumin combined with iodine-123-Tyr-(A14)-insulin visualizes human hepatocellular carcinomas. (1995)

This hepatocyte receptor-specific, double-tracer method using 99mTc-NGA and 123I-Tyr-(A14)-insulin could become clinically useful in the diagnosis of HCC.
Simultaneous Gas Chromatography/Mass Spectrometry Assay of Methadone and 2-Ethyl-1, 5-Dimethyl-3,3-Diphenylpyrrolidine (EDDP) in Urine (1991)

An efficient extraction and gas chromatography/mass spectrometry (GC/MS) procedure has been developed for the simultaneous determination of methadone and 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolidine in urine samples. The merits of this procedure include (1) effective high-volume sample processing; (2) excellent gas chromatography characteristics; (3) high precision for quantitative methadone determination--1.0% coefficient of variation (CV) for GC/MS injection replicates and 1.2% for extraction replicates; (4) excellent linearity within the range (0 to 1200 ng/mL) studied; and (5) adequate detection limits (50 ng/mL) for most practical purposes. The detection limit for methadone may be improved 40-fold by using a different internal standard.
Clinical features and mutations in patients with dominant retinitis pigmentosa-1 (RP1). (2001)

Dominant RP1 alleles typically have premature nonsense codons occurring in the last exon of the gene and would be expected to encode mutant proteins that are only approximately one third the size of the wild-type protein, suggesting that a dominant negative effect rather than haploinsufficiency is the mechanism leading to RP caused by RP1 mutations. On average, patients with RP1 mutations have slightly better visual acuity than patients with dominant rhodopsin mutations; otherwise, they have similarly severe disease. The wide range in severity among patients with RP1 mutations indicates that other genetic or environmental factors modulate the effect of the primary mutation.
Solubility of nano-zinc oxide in environmentally and biologically important matrices (2011)

Increasing manufacture and use of engineered nanoparticles is leading to a greater probability for release of engineered nanoparticles into the environment and exposure to organisms. In particular, zinc oxide (ZnO) is toxic, although it is unclear whether this toxicity is due to the zinc oxide nanoparticles, dissolution to Zn(2+) , or some combination thereof. The goal of this study was to determine the relative solubilities of both commercially available and in-house synthesized ZnO in matrices used for environmental fate and transport or biological toxicity studies. Dissolution of ZnO was observed in nanopure water (7.18-7.40 mg/L dissolved Zn, as measured by filtration) and Roswell Park Memorial Institute medium (RPMI-1640) (∼5 mg/L), but much more dissolution was observed in Dulbecco's modified Eagle's medium, in which the dissolved Zn concentration exceeded 34 mg/L. Moderately hard water exhibited low Zn solubility, likely because of precipitation of a Zn carbonate solid phase. Precipitation of a Zn-containing solid phase in RPMI also appeared to limit Zn solubility. Equilibrium conditions with respect to ZnO solubility were not apparent in these matrices, even after more than 1,000 h of dissolution. These results suggest that solution chemistry exerts a strong influence on ZnO dissolution and can result in limits on Zn solubility from precipitation of less soluble solid phases.
Tumor necrosis factor alpha upregulates human microglial cell production of interleukin-10 in vitro (1995)

Interleukin (IL)-10 appears to play an important regulatory role in the systemic inflammatory response; however, production of IL-10 within the human central nervous system has not been described. Using cultures of human fetal microglial cells, the resident macrophages of the brain, we investigated the production and regulation of bioactive IL-10. Lipopolysaccharide stimulated acute release of tumor necrosis factor (TNF)-alpha (peak by 8 h) and delayed production of IL-10 (over a 48-h period) in microglial cell cultures. Treatment of microglial cell cultures with TNF-alpha and IL-6 resulted in a dose-dependent release of IL-10. These cytokines also induced expression of IL-10 mRNA. Treatment of microglial cell cultures with IL-10 markedly inhibited TNF-alpha and IL-6 production. These findings suggest that during inflammation within the brain, acute release of TNF-alpha and IL-6 by activated microglia could promote subsequent release of IL-10, which functions to minimize the potential neurotoxic effects of proinflammatory cytokines.
A novel method for the synthesis of 4‐isoquinolinols (1991)

Abstract 1‐Substituted 1,2‐dihydroisoquinolines, derived from isoquinoline and organolithium reagents, readily undergo autoxidation to lead to 4‐isoquinolinols in moderate yields.
Constitutive Activation of STAT5 by a Point Mutation in the SH2 Domain (2000)

We previously identified a constitutively active form of STAT (signal transducer and activator of transcription) 5A by polymerase chain reaction-driven random mutagenesis followed by retrovirus-mediated expression screening, which had two point mutations in the DNA-binding and transcriptional activation domains, and was designated STAT5A1*6. STAT5A1*6 showed markedly elevated DNA binding and transactivation activities with stable tyrosine phosphorylation and nuclear accumulation, and conferred autonomous cell growth on interleukin 3-dependent Ba/F3 cells. We now report another constitutively active mutant, STAT5A-N642H which has a single point mutation (N642H) in its SH2 domain, identified using the same strategy as that used to identify STAT5A1*6. STAT5A-N642H showed identical properties to those of STAT5A1*6 both biochemically and biologically. Interestingly the mutation in STAT5A-N642H resulted in restoration of the conserved critical histidine which is involved in the binding of phosphotyrosine in the majority of SH2-containing proteins. Introduction of an additional mutation (Y694F) to STAT5A-N642H, which disrupted critical tyrosine 694 required for dimerization of STAT5, abolished all the activities manifested by the mutant STAT5A-N642H, which indicates that dimerization is required for the activity of STAT5A-N642H as was the case for the wild-type STAT5A. The present findings also show that different mutations rendered STAT5A constitutively active, through a common mechanism, which is similar to that of physiological activation.
Analysis of Progression and LAM Bands Observed in Infrared and Raman Spectra of a Series of Vinylidene Fluoride Oligomers (2002)

Infrared and Raman spectra observed for a series of vinylidene fluoride oligomers with TGTḠ conformation have been analyzed focusing on the progression bands in the fingerprint region and the Raman bands of longitudinal acoustic mode in the low-frequency region. By the quantitative analysis of progression bands, the vibrational frequency−phase angle dispersion curves could be obtained on the basis of normal-coordinates treatment. From the analysis of longitudinal acoustic mode, the limiting Young's modulus of poly(vinylidene fluoride) crystal form II was evaluated to be 95.8 GPa. This value was found to be consistent with the modulus evaluated from the slope of acoustic branch of the above-mentioned dispersion curves.
TGF-β1 and TGF-β2 abundance in liver diseases of mice and men (2016)

TGF-β1 is a major player in chronic liver diseases promoting fibrogenesis and tumorigenesis through various mechanisms. The expression and function of TGF-β2 have not been investigated thoroughly in liver disease to date. In this paper, we provide evidence that TGF-β2 expression correlates with fibrogenesis and liver cancer development.Using quantitative realtime PCR and ELISA, we show that TGF-β2 mRNA expression and secretion increased in murine HSCs and hepatocytes over time in culture and were found in the human-derived HSC cell line LX-2. TGF-β2 stimulation of the LX-2 cells led to upregulation of the TGF-β receptors 1, 2, and 3, whereas TGF-β1 treatment did not alter or decrease their expression. In liver regeneration and fibrosis upon CCl4 challenge, the transient increase of TGF-β2 expression was accompanied by TGF-β1 and collagen expression. In bile duct ligation-induced fibrosis, TGF-β2 upregulation correlated with fibrotic markers and was more prominent than TGF-β1 expression. Accordingly, MDR2-KO mice showed significant TGF-β2 upregulation within 3 to 15 months but minor TGF-β1 expression changes. In 5 of 8 hepatocellular carcinoma (HCC)/hepatoblastoma cell lines, relatively high TGF-β2 expression and secretion were observed, with some cell lines even secreting more TGF-β2 than TGF-β1. TGF-β2 was also upregulated in tumors of TGFα/cMyc and DEN-treated mice. The analysis of publically available microarray data of 13 human HCC collectives revealed considerable upregulation of TGF-β2 as compared to normal liver.Our study demonstrates upregulation of TGF-β2 in liver disease and suggests TGF-β2 as a promising therapeutic target for tackling fibrosis and HCC.
Correlation of angiogenic biomarker signatures with clinical outcomes in metastatic colorectal cancer patients receiving capecitabine, oxaliplatin, and bevacizumab (2013)

A novel combination of capecitabine, oxaliplatin, and bevacizumab was evaluated in colorectal cancer patients enrolled in a phase II clinical trial. In this retrospective analysis, plasma samples from patients receiving capecitabine, oxaliplatin, and bevacizumab were analyzed to investigate biomarkers of clinical benefit. Forty-one protein biomarkers were tested in 38 patients at baseline and after two cycles of drug administration. Correlations among analytes were evaluated by Spearman analysis. Analyte levels at baseline and changes on-treatment were correlated with progression-free survival (PFS) and overall survival (OS) by univariate analysis. Multivariate analyses were determined using the Cox proportional hazard model. Time to event analyses were evaluated by Kaplan-Meier analysis and compared by log-rank test. Baseline levels of vWF and Ang-2 significantly correlated with PFS, while levels of VCAM-1, vWF, TSP-2, IL-8, MMP-2, and Ang-2 correlated with OS (P < 0.05). The fold change of IGF-1 levels from baseline to the end of cycle 2 was correlated with PFS, while fold changes of Ang-2, TSP-2, and TGF-β2 correlated with OS. A baseline signature of Ang-2, IGFBP-3, IL-6, and VCAM-1 identified a low-risk and high-risk group of patients (OS: 33.9 months vs. 18.1 months, respectively, P = 0.016). For treatment-related changes, a signature consisting of Ang-2, E-Cadherin, IL-6, MCP-1, OPN, and TGF-β1 was able to stratify patients into high- and low-risk groups (PFS: 7.7 months vs. 15.5 months, P = 0.004). Multiplex analysis of patient plasma in this trial identified several baseline- and treatment-related biomarkers associated with clinical outcome. These findings merit further exploration in larger, controlled clinical trials.
A framework for reducing the cost of instrumented code (2001)

Instrumenting code to collect profiling information can cause substantial execution overhead. This overhead makes instrumentation difficult to perform at runtime, often preventing many known offline feedback-directed optimizations from being used in online systems. This paper presents a general framework for performing instrumentation sampling to reduce the overhead of previously expensive instrumentation. The framework is simple and effective, using code-duplication and counter-based sampling to allow switching between instrumented and non-instrumented code.
Carotid Stenting With Cerebral Protection: First Clinical Experience Using the PercuSurge GuardWire System (1999)

Cerebral protection with the GuardWire device is easy, safe, and effective in protecting the brain from cerebral embolism. Larger studies are warranted.
ChemInform Abstract: 1,2,3,4‐Tetrahydroquinolines as Substrates for Mannich Compounds. (1998)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
High sensitivity silicon-based VIS/NIR photodetectors (2004)

We fabricate silicon-based photodiodes using a simple femtosecond-laser microstructuring technique. The detectors are ten times more sensitive than commercial silicon PlN photodiodes at visible wavelengths and can be used at wavelengths up to 1650 nm.
LEuro et le Franc CFA (2000)

Le franc des colonies françaises d’Afrique est devenu le franc de la Communauté Financière Africaine au moment des indépendances, en 1960. En 1948, le taux de change est fixé à 1 ancien franc = 0,5 FCFA puis, au moment de la création du nouveau franc, en 1959 à 1 FF = 50 FCFA. Il a fallu attendre la dévaluation du 1er janvier 1994 de 100% pour modifier une parité vieille de 46 ans. Le franc français vaut désormais 100 francs CFA.
Tyrphostin AG-490 inhibits cytokine-mediated JAK3/STAT5a/b signal transduction and cellular proliferation of antigen-activated human T cells (1999)

Janus kinase 3 (JAK3) is a cytoplasmic tyrosine kinase required for T cell development and activated by cytokines that utilize the interleukin-2 (IL-2) receptor common gamma chain (gamma(c)). Genetic inactivation of JAK3 is manifested as severe combined immunodeficiency disease (SCID) in humans and mice. These findings have suggested that JAK3 represents a pharmacological target to control certain lymphoid-derived diseases. Here we provide novel evidence that AG-490 potently inhibits the autokinase activity of JAK3 and tyrosine phosphorylation and DNA binding of signal transducer and activator of transcription 5a and 5b (STAT5a/b). Similar inhibitory effects were observed with other cytokines that use gamma(c). AG-490 also inhibited IL-2-mediated proliferative growth in human T cells with an IC50) = 25 microM that was partially recoverable. Moreover, we demonstrate that this inhibitor prevented tetanus toxoid antigen-specific T cell proliferation and expansion but failed to block activation of Zap70 or p56Lck after anti-CD3 stimulation of human T cells. Taken together, these findings suggest that AG-490 inhibits the JAK3-mediated Type II signaling pathway but not the T cell receptor-derived Type I pathway and possesses therapeutic potential for T cell-derived pathologies such as graft-versus-host disease, allergy, and autoimmune disorders.
Crystal structure of the SOCS2–elongin C–elongin B complex defines a prototypical SOCS box ubiquitin ligase (2006)

Growth hormone (GH) signaling is tightly controlled by ubiquitination of GH receptors, phosphorylation levels, and accessibility of binding sites for downstream signaling partners. Members of the suppressors of cytokine signaling (SOCS) family function as key regulators at all levels of this pathway, and mouse knockout studies implicate SOCS2 as the primary suppressor. To elucidate the structural basis for SOCS2 function, we determined the 1.9-A crystal structure of the ternary complex of SOCS2 with elongin C and elongin B. The structure defines a prototypical SOCS box ubiquitin ligase with a Src homology 2 (SH2) domain as a substrate recognition motif. Overall, the SOCS box and SH2 domain show a conserved spatial domain arrangement with the BC box and substrate recognition domain of the von Hippel-Lindau (VHL) tumor suppressor protein, suggesting a common mechanism of ubiquitination in these cullin-dependent E3 ligases. The SOCS box binds elongin BC in a similar fashion to the VHL BC box and shows extended structural conservation with the F box of the Skp2 ubiquitin ligase. A previously unrecognized feature of the SOCS box is revealed with the burial of the C terminus, which packs together with the N-terminal extended SH2 subdomain to create a stable interface between the SOCS box and SH2 domain. This domain organization is conserved in SOCS1-3 and CIS1, which share a strictly conserved length of their C termini, but not in SOCS4, 5, and 7, which have extended C termini defining two distinct classes of inter- and intramolecular SOCS box interactions.
Selective Formation of Homo- and Heterobivalent Peptidomimetics (2003)

Methodology is presented for assembling fluorescently labeled bivalent molecules from monovalent constituents, without side chain protection or coupling agents. To illustrate the procedure, a series of bivalent peptidomimetics directed toward the Trk receptors were prepared and screened via fluorescent activated cell sorting scan assays.
Trans -splicing and polyadenylation of let-7 microRNA primary transcripts (2004)

Members of the microRNA (miRNA) class of 22-nucleotide RNAs regulate the expression of target genes that contain sequences of antisense complementarity. Maturation of miRNAs involves cleavage of longer primary transcripts, but little is yet understood about how miRNA genes are transcribed and enter the processing pathway. We find that relatively long, polyadenylated transcripts encoded by the Caenorhabditis elegans let-7 gene undergo trans-splicing to the spliced leader 1 (SL1) RNA. Deletions, including removal of the trans-splice site, upstream of mature let-7 sequence result in stable accumulation of primary transcripts and compromised production of mature let-7 RNA in vivo. Our data show that multiple steps of let-7 miRNA biogenesis can be uncoupled, allowing for complex regulation in the production of a functional miRNA. Finally, the observation that let-7 primary transcripts undergo splicing highlights the importance of identifying the sequence of endogenous pri-miRNA substrates recognized by the cellular processing machinery.
Highly Stereoselective Reductions of α-Alkyl-1,3-diketones and α-Alkyl-β-keto Esters Catalyzed by Isolated NADPH-Dependent Ketoreductases (2005)

[reaction: see text] The biocatalytic reduction of alpha-alkyl-1,3-diketones and alpha-alkyl-beta-keto esters employing 1 of 20 different isolated NADPH-dependent ketoreductases proved to be a highly efficient method for the preparation of optically pure keto alcohols or hydroxy esters.
Sequence-Specific and Phosphorylation-Dependent Proline Isomerization: A Potential Mitotic Regulatory Mechanism (1997)

Pin1 is an essential and conserved mitotic peptidyl-prolyl isomerase (PPIase) that is distinct from members of two other families of conventional PPIases, cyclophilins and FKBPs (FK-506 binding proteins). In response to their phosphorylation during mitosis, Pin1 binds and regulates members of a highly conserved set of proteins that overlaps with antigens recognized by the mitosis-specific monoclonal antibody MPM-2. Pin1 is here shown to be a phosphorylation-dependent PPIase that specifically recognizes the phosphoserine-proline or phosphothreonine-proline bonds present in mitotic phosphoproteins. Both Pin1 and MPM-2 selected similar phosphorylated serine-proline-containing peptides, providing the basis for the specific interaction between Pin1 and MPM-2 antigens. Pin1 preferentially isomerized proline residues preceded by phosphorylated serine or threonine with up to 1300-fold selectivity compared with unphosphorylated peptides. Pin1 may thus regulate mitotic progression by catalyzing sequence-specific and phosphorylation-dependent proline isomerization.
Antibody-based depletion of Foxp3+ T cells potentiates antitumor immune memory stimulated by mTOR inhibition (2014)

Inhibition of mTOR signaling enhances antitumor memory T lymphocytes while increasing the frequency of immunosuppressive regulatory T cells (Tregs). We report here a strategy to further improve immunologic memory by controlling CD4<sup>+</sup> T cells with CD4-depleting monoclonal antibody therapy thereby improving CD8<sup>+</sup> memory T cell quality and function. We report that removal of Tregs is the mechanism underlying immunological memory formation in response to this combination immunotherapy.
722. The reaction of N-maleoylamino-acids with benzylamine (1962)

Y. Liwschitz, Y. Rabinsohn and A. Singerman, J. Chem. Soc., 1962, 3726 DOI: 10.1039/JR9620003726
An overview of the PTRAN analysis system for multiprocessing (2014)

No abstract available.