gebhart/patrepeval huggingface dataset:
TBP-DNA interactions in the minor groove discriminate between A:T and T:A base pairs (1994)

In this report, we test the hypothesis that TBP binds DNA promiscuously due to its manner of recognition of the DNA minor groove. The experiment performed was to select TBP-binding sequences from a pool of random double stranded oligonucleotides. Sixty two clones from this pool were sequenced. Surprisingly, the results show that TBP has a marked preference for stably binding one sequence (TATATAA) over all others, yet only four classes of TATA box were selected. The features of the selected sequences allow definition of a binding consensus for TBP. The DNA binding properties of TBP to the four TATA variants was examined, the results being in accord with the observed selection frequencies. However, the nature of TBP-DNA binding is strongly affected by ionic strength. We infer that recognition of DNA via the minor groove can be highly selective even where A:T and T:A discrimination is required. Models for how this might be accomplished are discussed.
Phase II study of single agent gemcitabine in patients with hormone refractory prostate cancer (HRPC) (2004)

4705 Background: Gemcitabine is effective in several solid tumor forms but only limited data have been reported in HRPC. Methods: The primary objective was to study the median time to treatment failure (TTF). Other objectives were to investigate symptom control, toxicity and survival. The eligibility criteria comprise presence of bone metastases, increasing PSA and performance status (WHO) ≤ 2. Gemcitabine was given as single agent therapy in a dose of 1250 mg/m2 on day 1+8 of a 3-week cycle. The dose was reduced to 1000 mg/m2 in case of WHO grade 2–3 hematologic toxicity or grade 3–4 non-hematologic toxicity. Treatment was given until objective tumor progression was documented, increasing PSA at two consecutive measurements, unacceptable toxicity or patients wish to withdraw from further treatment. Bone scan was done at base-line and during treatment at intervals according to praxis of the participating institutions. Chest X-ray and abdominal CT were done at base-line and if found positive every 9th week during treatment. Hematology, laboratory and PSA tests were done at base-line and before every new treatment cycle. A symptom questioner was completed by the patient at base-line and before every new treatment cycle. Results: 50 patients have received study treatment and are considered evaluable for TTF and toxicity. The median TTF is 2,7 (0.0–7.8) months with 14 events being censored. The median survival time is 14.7 (0.3–30.7) months with 23 events being censored. CR were noted in two measurable sites (lymph node and liver) in two patients. According to the patient self ratings, symptoms were held at the base-line level during therapy except fatigue which slightly increased over time. The median PSA value leveled out during therapy. One patient experiencing grade 4 thrombocytopenia and 2 patients grade 3 leucopenia. Subjective toxicity has been mild. Conclusion: Single agent gemcitabine seems to be an reasonably good option when symptom control is the main purpose for further therapy. No significant financial relationships to disclose.
The Human CD4+T Cell Response against Mumps Virus Targets a Broadly Recognized Nucleoprotein Epitope (2019)

Mumps outbreaks among vaccinated young adults stress the need for a better understanding of mumps virus (MuV)-induced immunity. Antibody responses to MuV are well characterized, but studies on T cell responses are limited. We recently isolated a MuV-specific CD4<sup>+</sup> T cell clone by stimulating peripheral blood mononuclear cells (PBMCs) from a mumps case with the viral nucleoprotein (MuV-N). In this study, we further explored the identity and relevance of the epitope recognized by the CD4<sup>+</sup> T cell clone and <i>ex vivo</i> by T cells in a cohort of mumps cases. Using a two-dimensional matrix peptide pool of 15-mer peptides covering the complete MuV-N, we identified the epitope recognized by the T cell clone as MuV-N<sub>110-124</sub> GTYRLIPNARANLTA, present in a well-conserved region of the viral protein. Upon peptide-specific stimulation, the T cell clone expressed the activation marker CD137 and produced gamma interferon, tumor necrosis factor, and interleukin-10 in a HLA-DR4-restricted manner. Moreover, the CD4<sup>+</sup> T cells exerted a cytotoxic phenotype and specifically killed cells presenting MuV-N<sub>110-124</sub> Furthermore, the identified peptide is widely applicable to the general population since it is predicted to bind various common HLA-DR molecules, and epitope-specific CD4<sup>+</sup> T cells displaying cytotoxic/Th1-type properties were found in all tested mumps cases expressing different HLA-DR alleles. This first broadly recognized human MuV-specific CD4<sup>+</sup> T cell epitope could provide a useful tool to detect and evaluate virus-specific T cell responses upon MuV infection or following vaccination.<b>IMPORTANCE</b> Recent outbreaks of mumps among vaccinated young adults have been reported worldwide. Humoral responses against mumps virus (MuV) are well characterized, although no correlate of protection has been elucidated, stressing the need to better understand cellular MuV-specific immunity. In this study, we identified the first MuV T cell epitope, which is derived from the viral nucleoprotein (MuV-N) and was recognized by a cytotoxic/Th1 CD4<sup>+</sup> T cell clone that was isolated from a mumps case. Moreover, the epitope was predicted to bind a broad variety of common HLA-DRB1 alleles, which was confirmed by the epitope-specific cytotoxic/Th1 CD4<sup>+</sup> T cell responses observed in multiple mumps cases with various HLA-DRB1 genotypes. The identified epitope is completely conserved among various mumps strains. These findings qualify this promiscuous MuV T cell epitope as a useful tool for further in-depth exploration of MuV-specific T cell immunity after natural mumps virus infection or induced by vaccination.
Glutamine synthetase of Mycobacterium tuberculosis: extracellular release and characterization of its enzymatic activity. (1994)

We have investigated the activity and extracellular release of glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2] of Mycobacterium tuberculosis. The purified, homogeneous M. tuberculosis glutamine synthetase appears to consist of 12 most likely identical subunits of M(r) 58,000, arranged in two superimpose hexagons. In the catalysis of L-glutamine, the enzyme has an apparent Km for L-glutamate of approximately 3 mM at the pH optimum of 7.5. M. tuberculosis releases a large proportion (approximately 30%) of its total measurable enzyme activity into the culture medium, a feature that is highly specific for pathogenic mycobacteria. Immunogold electron microscopy revealed that M. tuberculosis also releases the enzyme into its phagosome in infected human monocytes. Two potentially important roles for glutamine synthase in the pathogenesis of M. tuberculosis infection are (i) the synthesis of L-glutamine, a major component of the cell wall of pathogenic but not nonpathogenic mycobacteria, and (ii) the modulation of the ammonia level in the M. tuberculosis phagosome, which may in turn influence phagosomal pH and phagosomelysosome fusion.
Polymer-derived SiCN and SiOC ceramics – structure and energetics at the nanoscale (2012)

The complex nanodomain structure and energetic features of polymer-derived SiCN and SiOC ceramics have been investigated by multinuclear 1D and 2D solid-state NMR, micro-Raman, SAXS, XRD, HRTEM and oxidative high temperature oxide melt solution calorimetry, respectively. Structural models consistent with all these lines of evidence put emphasis on interconnected fractal domains stabilized by the mixed-bond-structure and interface bonding between nanodomains. The structural and thermodynamic role of hydrogen in the stabilization of interfacial bonding between the nanodomains in polysilylcarbodiimide-derived SiCN is reported as well.
The chemistry of triazine derivatives II. The acylation of 2,4,6‐trimethyl‐s‐triazine to triazinyl ketones and their facile isomerization to acetamidopyrimidines (1964)

Abstract A series of triazinyl ketones has been prepared by acylating 2,4,6‐trialkyl‐ s ‐triazines and these ketones have been isomerized to 4‐acylamidopyrimidine derivatives. A possible mechanism for this isomerization is suggested.
Valuable Versatile Reactivityof Thiaisatoic Anhydrides: Expedient SolidPhase Synthesisof Thieno[1,4]diazepine-2,5-diones (2008)

International audience
Study on Self-Sensor of Linear Moving Magnet Compressor's Piston Stroke (2009)

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> The mathematic model of the self-sensor was established by analyzing the moving magnet linear motor of linear compressor, and the measurement method of piston stroke was achieved. The piston stroke can be calculated by measuring the voltage and current of the linear motor coil. The self-sensor's circuit parameters were influenced by the parameters of the linear motor. For studying the performance of the self-sensor under the driving modes of variable-voltage control and variable time of flow control, piston stroke measurement and control software based on LabVIEW was designed, and the experimental study was carried out. The results show that using the linear motor as self-sensor is effective. Although the self-sensor has nonlinear problems at end of stroke and the electromagnetic interference, the steady-state error of self-sensor can be reduced by means of the better filter circuit and more accurately correcting the end of the piston stroke. So, this self-sensor can be satisfactorily employed with linear compressor. </para>
MEDI1873, a potent, stabilized hexameric agonist of human GITR with regulatory T-cell targeting potential (2017)

Glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) is part of a system of signals involved in controlling T-cell activation. Targeting and agonizing GITR in mice promotes antitumor immunity by enhancing the function of effector T cells and inhibiting regulatory T cells. Here, we describe MEDI1873, a novel hexameric human GITR agonist comprising an IgG1 Fc domain, a coronin 1A trimerization domain and the human GITRL extracellular domain (ECD). MEDI1873 was optimized through systematic testing of different trimerization domains, aglycosylation of the GITRL ECD and comparison of different Fc isotypes. MEDI1873 exhibits oligomeric heterogeneity and superiority to an anti-GITR antibody with respect to evoking robust GITR agonism, T-cell activation and clustering of Fc gamma receptors. Further, it recapitulates, <i>in vitro</i>, several aspects of GITR targeting described in mice, including modulation of regulatory T-cell suppression and the ability to increase the CD8<sup>+</sup>:CD4<sup>+</sup> T-cell ratio via antibody-dependent T-cell cytotoxicity. To support translation into a therapeutic setting, we demonstrate that MEDI1873 is a potent T-cell agonist <i>in vivo</i> in non-human primates, inducing marked enhancement of humoral and T-cell proliferative responses against protein antigen, and demonstrate the presence of GITR- and FoxP3-expressing infiltrating lymphocytes in a range of human tumors. Overall our data provide compelling evidence that MEDI1873 is a novel, potent GITR agonist with the ability to modulate T-cell responses, and suggest that previously described GITR biology in mice may translate to the human setting, reinforcing the potential of targeting the GITR pathway as a therapeutic approach to cancer.
Organization of Inorganic Nanoparticles Using Biotin−Streptavidin Connectors (1998)

Organizing inorganic matter at the nanometer and mesoscopic length scale represents a new challenge for materials chemistry. One potential strategy involves the use of biomolecular recognition in the coupling of complementary connecting units preattached to the surfaces of inorganic nanoparticles. In this paper, superparamagnetic iron oxide nanoparticles, synthesized within the 8 nm cavity of the protein ferritin, are reversibly organized into networks by intermolecular cross-linking of biotinylated molecules using high-affinity streptavidin binding. The extent and kinetics of aggregation are dependent on the concentrations and stoichiometry of the conjugated system.
Biological and clinical features in predicting efficacy of epidermal growth factor receptor tyrosine kinase inhibitors: a systematic review and meta-analysis. (2009)

At the present time, none of the biological features which have been evaluated in patients who have undergone therapy using TKIs is proven to be of predictive value; only K-ras mutations and smoking habits can be considered as a possible criteria for selection. Results of prospective randomized trials on biological markers are awaited.
Generalized autoimmune disease in interleukin‐2‐deficient mice is triggered by an uncontrolled activation and proliferation of CD4+ T cells (1995)

Interleukin-2-deficient mice (IL-2-/-) crossed to a BALB/c genetic background develop a lymphoproliferative syndrome with severe hemolytic anemia and die within 5 weeks of age. The presence of autoantibodies of various specificities and inflammatory lesions in several organs are indicative of a generalized auto-immune disease. No alterations of the immune system were observed in 6-day-old animals, but 10-day-old mice already showed an increased proliferation and polyclonal activation of lymphocytes. The treatment of IL-2-/- mice with anti-gp39(CD40L) antibody prevented the disease and indicated that the appearance of activated CD4- T cells (CD44high, CD69-) represents the first alteration of the immune system in IL-2-/- mice. Collectively, our results suggest that an essential role of IL-2 in vivo, which is not compensated by other cytokines, is the maintenance of self tolerance.
The Alternative Pathway Is Critical for Pathogenic Complement Activation in Endotoxin- and Diet-Induced Atherosclerosis in Low-Density Lipoprotein Receptor–Deficient Mice (2010)

These data demonstrate that amplification of complement activation by the alternative pathway in response to lipopolysaccharide or high-fat diet plays a proatherogenic role.
Inflection Generation as Discriminative String Transduction (2015)

We approach the task of morphological inflection generation as discriminative string transduction. Our supervised system learns to generate word-forms from lemmas accompanied by morphological tags, and refines them by referring to the other forms within a paradigm. Results of experiments on six diverse languages with varying amounts of training data demonstrate that our approach improves the state of the art in terms of predicting inflected word-forms.
Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53 (1997)

The tumor suppressor p53 is degraded by the ubiquitin‐proteasome system. p53 was polyubiquitinated in the presence of E1, UbcH5 as E2 and MDM2 oncoprotein. A ubiquitin molecule bound MDM2 through sulfhydroxy bond which is characteristic of ubiquitin ligase (E3)‐ubiquitin binding. The cysteine residue in the carboxyl terminus of MDM2 was essential for the activity. These data suggest that the MDM2 protein, which is induced by p53, functions as a ubiquitin ligase, E3, in human papillomavirus‐uninfected cells which do not have E6 protein.
Dual temperature and strain measurement with the combined fluorescence lifetime and Bragg wavelength shift approach in doped optical fiber (2002)

We have constructed fiber-optic sensors to measure temperature and strain by combining the properties of fiber Bragg gratings with the fluorescent lifetimes of various doped fibers. Sensors have been made with the fiber Bragg grating written directly into the doped fiber to ensure the collocation of the strain and temperature measurement points. Results are compared with those obtained previously from a Bragg grating written into standard photosensitive fiber spliced to doped fiber. Standard deviation errors of 7 microepsilon and 0.8 degrees C have been obtained for strain and temperature ranges of up to 1860 microepsilon and 120 degrees C, respectively.
Agrobacterium-mediated transformation of glycine max and regene ration of transgenic plants (2001)

A reproducible transformation system was developed for soybe an (Glycin e max) using as explants sections from the excised hypocotyls of seeds. A constr uct containing cauliflower mosaic virus 35S-neomycin phosphotransferase (nptII) and human β-1,4-galactosyltransferase (hGT) was introduced into soybean culti var using Agrobacterium tumefaciens- mediated transfermation procedures. Regenerat i on was via organogenesis and transformed plants were selected on medium containi ng 50 mg/L kanamycin and 100 mg/L of aminopenicillanic acia. Transgenic soybeans were raised in the glasshouse. The hGT genes was integrated into the chomosomal genome of primary transgenic soybean plants, The transformation of regenerated plants was confirmed by assays for neomycin phosphotransferase activity and Sout hern blotting analyses.
Dynamics of T Lymphocyte Responses: Intermediates, Effectors, and Memory Cells (2000)

The immune response is initiated in organized lymphoid tissues where antigen-loaded dendritic cells (DCs) encounter antigen-specific T cells. DCs function as packets of information that must be decoded by the T cell before an appropriate immune response can be mounted. We discuss how the dynamics of DC-T cell encounter and the mechanism of T cell differentiation make the decoding of this information stochastic rather than determinate. This results in the generation of both terminally differentiated effector cells and intermediates that play distinctive roles in protection, immunoregulation, and immunological memory.
Antimicrobial activities of 2-arylthio-N-alkylmaleimides (1992)

A variety of 2-arylthio-N-alkylmaleimides were prepared, and their antimicrobial activities were examined. Almost all of these compounds exhibited antibacterial activity against Gram-positive bacteria such asBacillus subtilis andStaphylococcus aureus. Some compounds such as 2-(halogeno-phenyl)-thio-N-methylmaleimides (4, 5, 6, 8 and 10) and 2-(2-carbamoylphenyl)thio-N-methylmaleimide(35) exhibited antibacterial activity againstEscherichia coli. All compounds tested were inactive againstPseudomonas aeruginosa except 2-(2-carbamoylphenyl)thio-N-methylmaleimide(35) which was marginally active. Activities against Gram-positive bacteria were not due to the effect of the substituent on the benzene ring, except in the instances 2-carboxy, 2-carbomethoxy, 2-amino groups and alkyl chains, however, activities against Gram-negative bacteria were due to phenylthio and the alkyl substituents. Some of 2-arylthio-N-alkylmaleimides were examined for their antifungal activities using eight strains of fungi, and they showed activity against these.
Design, Pharmacology, and NMR Structure of a Minimized Cystine Knot with Agouti-Related Protein Activity (2002)

The agouti-related protein (AGRP) is an endogenous antagonist of the melanocortin receptors MC3R and MC4R found in the hypothalamus and exhibits potent orexigenic activity. The cysteine-rich C-terminal domain of this protein, corresponding to AGRP(87-132), exhibits receptor binding affinity and antagonism equivalent to that of the full-length protein. The NMR structure of this active domain was recently determined and suggested that melanocortin receptor contacts were made primarily by two loops presented by a well-structured cystine knot domain within AGRP(87-132) [McNulty et al. (2001) Biochemistry 40, 15520-15527]. This hypothesis is tested here with NMR structure and activity studies of a 34-residue AGRP analogue designed to contain only the cystine knot domain. The designed miniprotein folds to a homogeneous product, retains the desired cystine knot architecture, functions as an antagonist, and maintains the melanocortin receptor pharmacological profile of AGRP(87-132). The AGRP-like activity of this molecule supports the hypothesis that indeed the cystine knot region possesses the melanocortin receptor contact points. Moreover, this potent AGRP analogue is synthetically accessible, may serve in the development of therapeutics for the treatment of diseases related to energy balance. and may also find use as a new reagent for probing melanocortin receptor structure and function.
X-ray powder diffraction study on ErNi 2 Ge 2 (1999)

An X-ray diffraction pattern for ErNi 2 Ge 2 at room temperature is reported. ErNi 2 Ge 2 is tetragonal with lattice parameters a =4.0191(2) Å, c =9.7643(2) Å, space group I 4/ mmm , and Z =2. The lattice parameters derived from Rietveld analysis agree well with the results of a least-squares refinement.
Intrinsic Rates and Activation Free Energies from Single-Molecule Pulling Experiments (2006)

We present a unified framework for extracting kinetic information from single-molecule pulling experiments at constant force or constant pulling speed. Our procedure provides estimates of not only (i) the intrinsic rate coefficient and (ii) the location of the transition state but also (iii) the free energy of activation. By analyzing simulated data, we show that the resulting rates of force-induced rupture are significantly more reliable than those obtained by the widely used approach based on Bell's formula. We consider the uniqueness of the extracted kinetic information and suggest guidelines to avoid over-interpretation of experiments.
In Vitro Inhibition of a Variety of Human Immunodeficiency Virus Isolates by a Broadly Reactive, V3-Directed Heteroconjugate Antibody (1992)

The cytotoxic efficacy of a heteroconjugate antibody composed of OKT3 cross-linked to a broadly reactive antibody directed against the GPGRAF sequence of the gp120 V3 region has been characterized. The heteroconjugate antibody could completely inhibit viral replication of both the IIIB and MN isolates of human immunodeficiency virus (HIV) at concentrations as low as 0.5 ng/ml. At an antibody concentration of 1 micrograms/ml, heteroconjugate-mediated cytotoxicity occurred at effector-to-target ratios as low as 0.006:1. Eight different HIV isolates were tested for in vitro inhibition by the anti-V3-OKT3 conjugate, and all but one were completely inhibited for at least 7 days. These results indicate that heteroconjugate antibodies are a potent, effective means by which HIV-infected cells can be killed and viral replication suppressed.
Potentiation of Hypoglycemic Effect of Sulfonylureas by Halofenate (1975)

We investigated the possibility of a drug interaction between the antilipemic agent halofenate and sulfonylureas. Twelve young, healthy men were given 1 g of tolbutamide by mouth before and after 12 days of double-blind treatment with 1 g per day of halofenate, or placebo. There was a significant increase in serum tolbutamide at eight, 10 and 12 hours (P less than 0.01) and a significant (P less than 0.01) decrease in serum glucose at one, four and six hours after halofenate treatment, but not after placebo. In a long-term, double-blind study of halofenate or clofibrate treatment of patients with Type IV hyperlipoproteinemia, diabetic patients receiving a sulfonylurea and halofenate either required a reduction in the dose of the sulfonylurea or demonstrated significantly improved control of hyperglycemia (P less than 0.05) or both. No appreciable decrease in serum glucose levels was noted in diabetic patients receiving sulfonylurea and clofibrate. This interaction between halofenate and sulfonylureas is clinically important, especially in view of the association of hyperlipemia and diabetes.