gebhart/patrepeval huggingface dataset:
Consequences of Intrathymic TCR Engagement by Partial Agonist on Selection Events and Peripheral T Cell Activation Program (1998)

Functions elicited from mature T cells depend on the nature of the Ag. Thus, an agonist induces a larger set of cytokine responses than a partial agonist. Additionally, Ags present in the thymus influence both the selection of TCRs generated by gene rearrangement and the potential functional program of developing thymocytes. This can be approached by analysing the development of T cells in mice expressing the same transgenic TCR (tgTCR) under different conditions of intrathymic selection. H-2Kbm8 was found to act as a partial agonist for CD8+ T cells expressing a tgTCR specific for the H-2Kb alloantigen. Intrathymic exposure to full or to partial agonist affected the development of thymocytes at different stages, consistent with the respective CD8-independent and -dependent characteristic of the tgTCR/Ag interaction. The presence of the partial agonist led to the accumulation of a major population of thymocytes (tgTCR(high) CD4- CD8(low)) originating from TCR engagement at the immature single-positive CD8(low) stage as evidenced by: 1) results from reaggregated thymic organ culture in the presence of H-2(k/bm8) thymic stromal cells; 2) the absence of CD4+ thymocytes, the development of which depends on rearrangements of endogenous TCR alpha genes; and 3) the identification of the CD8(low) thymocytes as cycling cells. Peripheral CD8(low) T cells selected in an H-2(k/bm8) thymus expressed a partial functional program in response to H-2Kb, akin to the response of CD8(high) T cells to a partial agonist. The analysis of the molecular bases for partial reactivity revealed a correlation with inefficient AP-1, but efficient NF-kappaB transactivation.
A model for the control of a multileaf collimator in radiation therapy treatment planning (2000)

A new approach for inverse treatment planning in radiation therapy with the multileaf collimator (MLC) technique is presented. The application of the MLC technique requires an algorithm for the computation of the positions or velocities of leaves as a function of time such that the prescribed dose in the patient space is obtained. The conventional method is to first determine the intensity distribution in the treatment space by applying some inverse treatment techniques. Then an MLC control algorithm which generates the determined intensity distribution is required. In this paper an MLC control algorithm not requiring an intensity distribution as an intermediate step is expressed. The algorithm uses the MLC leaf positions and delivery times (in multiple static treatments) directly in inverse treatment planning. The method is implemented to multiple static treatments but a modification to dynamical MLC techniques is possible. The numerical test is based on the search for a feasible solution but also the optimization (object function) based approach is formulated. The related feasible problem consists of a high-dimensional system of algebraic (in-) equations. It is solved by an iterative row action projection method. The applied algorithm is well suited and computationally robust for high-dimensional feasible problems.
Denatonium Benzoate as a Bitter Aversive Additive in Ethylene Glycol and Methanol-Based Automotive Products (1993)

&lt;div class="htmlview paragraph"&gt;Denatonium Benzoate (DB) is a bitterant used to reduce hazards and liability of accidental and intentional product ingestion. Annual reports of the American Association of Poison Control Centers indicate ethylene glycol and methanol poisoning incidences, including fatalities and hospitalizations, continue to occur. To mitigate poisoning severity to children and adults, addition of DB to these products has been explored and implemented by several manufactures. The stability and efficacy of DB in products are discussed together with studies on toxicity and environmental impact. It is concluded that DB renders these products bitter, is stable and compatible, and offers no significant toxicity or environmental hazards.&lt;/div&gt;
A multicenter, open-label, phase 3 trial to compare the efficacy and safety of lenvatinib (E7080) versus sorafenib in first-line treatment of subjects with unresectable hepatocellular carcinoma. (2014)

TPS4153 Background: Lenvatinib (L, E7080) is an oral multi-targeted tyrosine kinase inhibitor of VEGFR1-3, FGFR1-4, PDGFRβ, RET and KIT. Given the role of angiogenesis in hepatocellular carcinoma (HCC), a phase 1/2 open-label study evaluated the safety and efficacy of L in 46 patients with advanced disease and Childs-Pugh (CP) A liver function status (Kudo ILCA 2013). Patients were treated with a starting dose of L 12 mg qd (28-d cycles) until disease progression or development of unmanageable toxicities. Median time to progression (TTP) was 12.8 months (mo; 95% confidence interval [CI] 7.23–14.7) and median overall survival (OS) was 18.7 mo (95% CI 12.8–25.1). The most common adverse events were hypertension 76% (Gr3 54%), palmar-plantar erythrodysesthesia syndrome 61% (Gr3 7%), proteinuria 59% (Gr3 20%), anorexia 57% (Gr3 2%), thrombocytopenia 50% (Gr3 33%), and fatigue 48% (Gr3 0%). Overall response rate (ORR) was 37%; 45.7% had stable disease. Methods: Based on these phase 2 data, a global, randomized, open-label phase 3 trial was designed to determine if L is non-inferior or superior compared to sorafenib (S) in advanced HCC. Eligible patients (N=940) with Barcelona Clinic Liver Cancer Stage B or C HCC, CP A status, and ECOG 0-1 will be randomized 1:1 to either L 12 mg or 8 mg orally qd (based on body weight [BW]) or S 400 mg orally bid. Patients will be stratified by region; macroscopic portal vein invasion, extrahepatic spread, or both; ECOG-PS; and BW (<60 vs ≥60 kg). The primary endpoint is OS. Secondary endpoints include progression-free survival, TTP, ORR (modified RECIST criteria), safety and PK/PD. Given an estimated median OS for S of approximately 10 mo, a 2.5 mo improvement was derived to achieve a hazard ratio (HR) of 0.8. Statistical study power (using a non-inferiority test by the 95% CI lower-limit method on log HR for OS) was determined based on this HR and a non-inferiority margin of 1.08, corresponding to 60% retention of S effect vs placebo. Based on these assumptions, the study power to declare non-inferiority or superiority is approximately 97% and 82%, respectively. The overall false positive rate is 0.05 (2-sided). Clinical trial information: NCT01761266.
Chemoselectivity of Enzymes in Anhydrous Media is Strongly Solvent Dependent (1993)

Kinetics of monoacylation of different aminoalcohols with trifluoroethyl butyrate catalyzed by a dozen of proteases and lipases were investigated in a variety of anhydrous solvents. Chemoselectivity of these transformations (defined as the ratio of the rate of O-butyrylation to the rate of N-butyrylation, μO/μN) was found to be markedly dependent on the solvent under otherwise identical conditions. For example, with N-α-benzoyl-L-lysinol as the aminoalcohol, although Pseudomonas sp. lipoprotein lipase preferred the OH group and Mucor meheii lipase the NH2 group in all solvents tested, the extent of this preference varied up to 20 fold depending on the solvent. Moreover, for porcine pancreatic lipase, a solvent-induced inversion of chemoselectivity was observed. A mechanistic rationale was proposed which related the vO/vN values to physico-chemical properties of the solvent.
Kelvin probe force microscopy (1991)

Measurements of the contact potential difference between different materials have been performed for the first time using scanning force microscopy. The instrument has a high resolution for both the contact potential difference (better than 0.1 mV) and the lateral dimension (&amp;lt;50 nm) and allows the simultaneous imaging of topography and contact potential difference. Images of gold, platinum, and palladium surfaces, taken in air, show a large contrast in the contact potential difference and demonstrate the basic concept.
Reactivity and catalytic activity of tert-butoxy-aluminium hydride reagents (2014)

The reactivity and catalytic activities of the tert-butoxy aluminium hydride reagents [((t)BuO)xAlH3-x] [x = 1 (1), 2 (2)] and (L)Li[((t)BuO)2AlH2] [L = THF (3), 1,4-dioxane (4)] are investigated. The structural characterisation of the novel compounds 3 and 4 shows that the nature of the hydridic species present is affected dramatically by the donor ligand coordinating the Li(+) cation. Stoichiometric reaction of 1 with pyridine gives [(1,4-H-pyrid-1-yl)4Al](-)[(pyridine)4AlH2](+) (5) while reaction with the amine-borane Me2NHBH3 in the presence of PMDETA [(Me2NCH2CH2)2NMe] affords [(PMDETA)AlH2](+)[(BH3)2NMe2](-) (6). The reagents 1-4 catalyse the dehydrocoupling reaction of the amine-borane Me2NHBH3 into the ring compound [Me2NBH2]2, with the activity decreasing in the order 1≫2∼3 > 4. The greater reactivity of the neutral dihydride 1 provides the potential basis for future catalytic optimisation.
Analysis of Tyrosine Phosphorylation in Resident Peritoneal Cells During Diet Restriction by Laser Scanning Cytometry (2003)

Tyrosine phosphorylation plays a critical role in signal transduction pathways in immune cells. Laser scanning cytometer (LSC), a newly developed microscope-based cytofluorometer, may overcome shortcomings of Western blotting and flow cytometry in the detection of intracellular signaling transduction. The aims of this study were to visualize and quantitate intracellular phosphotyrosine in the peritoneal cells harvested from diet-restricted mice by LSC. In addition, using LSC, we identified the main cell type with activated tyrosine phosphorylation in response to an inflammatory stimulus and we investigated the intracellular distribution of tyrosine phosphorylation within the peritoneal macrophages. Mice were assigned to the ad libitum and diet-restricted, i.e., 75% restricted food intake, groups. After 7 days of pair feeding, the peritoneal cells were harvested. Tyrosine phosphorylation in the harvested cells with either N-formyl-methionyl-leucyle-phenylalanine (fMLP) or lipopolysaccharide (LPS) stimulation was examined using LSC. Tyrosine phosphorylation of peritoneal cells from the diet-restricted group was significantly higher than that from the ad libitum group, regardless of stimulation. Stimulation of peritoneal cells with either fMLP or LPS significantly increased tyrosine phosphorylation in the ad libitum group, but not in the diet-restricted group. The relocation feature of LSC revealed that the cells with distinct tyrosine phosphorylation were macrophages. Topographic analysis demonstrated that phosphotyrosine was localized mainly in the cytoplasm of these cells. In summary, LSC revealed that tyrosine phosphorylation is mainly in the cytoplasm of the peritoneal macrophages and is deranged by diet restriction. LSC is a powerful tool for the study of intracellular signaling transduction.
Splice site selection and ribonucleoprotein complex assembly during in vitro pre-mRNA splicing. (1988)

To study the determinants of splice site selection, we have inserted synthetic 5' and 3' splice sites at different positions within beta-globin genes and analyzed the resultant RNA substrates for in vitro splicing, factor binding, and complex assembly. We show that consensus 5' and 3' splice site sequences are insufficient to determine splice site utilization; in the presence or absence of the authentic site, the synthetic sites are variably active in a position-dependent manner. However, regardless of position or utilization, the synthetic 5' and 3' splice sites are bound by the appropriate splicing factors. Thus, binding of splicing factors is necessary but not sufficient for splice site utilization. Finally, we demonstrate that a block to efficient splicing can occur at multiple steps in the pathway of normal splicing complex assembly.
Selection for androgen receptor mutations in prostate cancers treated with androgen antagonist. (1999)

The role of androgen receptor (AR) mutations in androgen-independent prostate cancer (PCa) was determined by examining AR transcripts and genes from a large series of bone marrow metastases. Mutations were found in 5 of 16 patients who received combined androgen blockade with the AR antagonist flutamide, and these mutant ARs were strongly stimulated by flutamide. In contrast, the single mutant AR found among 17 patients treated with androgen ablation monotherapy was not flutamide stimulated. Patients with flutamide-stimulated AR mutations responded to subsequent treatment with bicalutamide, an AR antagonist that blocks the mutant ARs. These findings demonstrate that AR mutations occur in response to strong selective pressure from flutamide treatment.
A proton relaxation enhancement investigation of the binding of fatty acid spin labels to human serum albumin (1986)

Proton relaxation enhancement (PRE) values for fatty acid spin labels bound to human serum albumin have been investigated using the inversion-recovery method at 24 MHz. At 0.1 mM protein concentration and a label-to-protein ratio of one-to-one, the PRE value for 12-Doxylsterate-albumin complex is 7.8 +/- 2.3, whereas the PRE values for 5-Doxylstearate and 16-Doxylstearate-albumin complexes are 1.5 +/- 0.6 and 1.7 +/- 0.7, respectively. Addition of 10-fold excess of stearic acid reduced the PRE values nearly to 1, indicating that the strong enhancements arise from direct binding of fatty acid spin labels to human serum albumin. PRE values for all three labels exhibit maxima as a function of the label-to-protein ratio, suggesting multiple binding sites for fatty acid spin labels with labels in the tightest binding sites not resulting in the most effective relaxation. Based on the rates of reduction of ESR signal amplitudes by sodium ascorbate, the difference in PRE values for the three fatty acid spin labels bound to albumin is attributed to the difference in water accessibility of the nitroxide moieties at various positions along the acyl chain, being greater at the C-12 position than at C-5 or C-16 position. The PRE value of 8 for 12-Doxylstearate bound to human serum albumin indicates that this complex may be a suitable paramagnetic contrast agent for in vivo NMR imaging.
Efficient enzymatic production of rebaudioside A from stevioside (2015)

Stevioside and rebaudioside A are the chief diterpene glycosides present in the leaves of Stevia rebaudiana. Rebaudioside A imparts a desirable sweet taste, while stevioside produces a residual bitter aftertaste. Enzymatic synthesis of rebaudioside A from stevioside can increase the ratio of rebaudioside A to stevioside in steviol glycoside products, providing a conceivable strategy to improve the organoleptic properties of steviol glycoside products. Here, we demonstrate the efficient conversion of stevioside to rebaudioside A by coupling the activities of recombinant UDP-glucosyltransferase UGT76G1 from S. rebaudiana and sucrose synthase AtSUS1 from Arabidopsis thaliana. The conversion occurred via regeneration of UDP-glucose by AtSUS1. UDP was applicable as the initial material instead of UDP-glucose for UDP-glucose recycling. The amount of UDP could be greatly reduced in the reaction mixture. Rebaudioside A yield in 30 h with 2.4 mM stevioside, 7.2 mM sucrose, and 0.006 mM UDP was 78%.
Development of new classification criteria for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis (2014)

Macrophage activation syndrome (MAS) is a potentially fatal complication of systemic juvenile idiopathic arthritis (sJIA), whose prompt recognition and treatment are critical. However, early diagnosis of MAS is often challenging and none of the current diagnostic criteria is satisfactory. An international project aimed to develop a new set of classification criteria for MAS was recently started.
술어비일치 주격에 대하여: 고대러시아어 및 북부러시아방언의 비일치 주격을 중심으로 (2013)

This paper investigates licensing of the nominative case without accompanying predicate-agreement with the nominative DP in many languages, including Old Russian and Contemporary North Russian. I have examined morphological approaches, such as Disjunctive Case Hierarchy and Default Case, as well as syntactic analyses, centering on AGREE, to determine which solution more adequately explains the current data and the case system in general. The phenomenon of non-agreeing nominatives is more effectively accounted for in syntactic terms than morphologically. I argue that the non-finite Infl consists of a defective T and an intact AGR, the latter of which contains the nominative case and phi-features. When an AGREE relation is established between a non-finite Infl and a DP, phi-agreement is not morphologically realized on the predicate due to the absence of [+Tense], but the nominative case of the AGR is licensed to the DP. For the double nominative finite construction, the Infl enters the AGREE relation with two DPs (Multiple Agree). The Infl realizes phi-features of only one of the DPs \n\nwhile the nominative case is licensed to the both DPs. This proposal identifies \n\nPRO as pro, removing the control theory from the syntax. Given that the PRO \n\nis in fact pro, the problem of predicting overt nominatives in non-finite clauses \n\nis essentially reduced to an economy principle that balances the need of \n\nargument identification and the relative cost of argument realization.
Putative neutralization epitopes and broad cross-genotype neutralization of Hepatitis E virus confirmed by a quantitative cell-culture assay (2006)

Monolayers of Hep G2/C3A cells were inoculated with genotype 1 Hepatitis E virus (HEV) mixed with either anti-HEV or an appropriate control. After 5 or 6 days, cell monolayers were stained with anti-HEV and infected cells were identified by immunofluorescence microscopy and counted. Anti-HEV from vaccinated or infected rhesus monkeys neutralized the virus, as did mAbs that recognized epitopes on the C terminus of a recombinant vaccine protein. Antibodies were broadly cross-reactive, since convalescent serum from animals infected with any one of the four mammalian genotypes all neutralized the genotype 1 virus.
A Data-capture Tool for Mouse Pathology Phenotyping (2009)

The Mouse Disease Information System is a free Microsoft Access database (http://research.jax.org/faculty/sundberg/index.html) designed by veterinary pathologists to aid veterinary pathologists in data acquisition, analysis, and coordination of tissue-sample archives. Linking the system to the Mouse Anatomy and Mouse Pathology Ontologies provides controlled vocabulary (and spelling) for organ, tissue, and diagnosis. Severity scores provide a quantitative assessment of all lesions to enable quantitative trait locus analysis for large-scale studies. Individual diagnoses can be verified for their definition by online linkage to Pathbase.net. Histologic images can be accessed from Pathbase by using the Mouse Pathology Ontology directly for comparison with slides being viewed at the time of data entry and providing the user with a reference and a "virtual second opinion."
Intervertebral Disc Development Is Regulated by Wnt/β-catenin Signaling (2011)

The findings in this study suggest that proper regulation of Wnt/β-catenin signaling is required for development and organization of IVD.
Comparison of Commercial DNA Extraction Kits for Extraction of Bacterial Genomic DNA from Whole-Blood Samples (2003)

The demand for molecular diagnostic tests in medical microbiology has highlighted the need for efficient methods of DNA extraction. In addition, it is preferable for these methods to be automated. An example of such a requirement is for the confirmation of meningococcal disease where rapid, sensitive, and specific procedures are required for public health management purposes. Previous studies have shown that whole blood is the preferred method for the isolation of bacterial DNA in meningococcal disease, and in this study, we compare five commercially available kits for the extraction of bacterial genomic DNA from whole-blood samples. These include kits in a 96-well binding plate, 96-well filter plate, and metallic bead formats. The method for all five kits is described, and the sensitivity, specificity, ease of automation, and overall efficiency are determined.
Experimental Studies of the Pathogenesis of Infections Due to Pseudomonas aeruginosa: Description of a Burned Mouse Model (1975)

An experimental burned mouse model is described that is clinically relevant to burn wound sepsis caused by Pseudomonas aeruginosa. Mice subjected to a nonlethal burn by flame were challenged with P. aeruginosa. The LD50 after subcutaneous injection in the skin of the burn up to 24 hr after the burn was smaller than 10 organisms vs. 10-6 organisms in normal animals. By three days after the burn, the value returned to and exceeded that of normal animals. This dramatic change in the LD50 after the burn was not seen when mice were challenged with other organisms. Challenge with P. aeruginosa by different routes immediately after burning showed less dramatic decreases in the LD50. Enumeration of infecting organisms in the skin of the burn and in major organs suggests the possibility of a toxic event.
Chemistry of cyanoacetylenes. Part X. Further studies on the reactions of cyano-ynamines with hydrogen halides and bromine (1971)

4-Chloro-2,4-bis(diethylamino)- and -2,4-bis(dimethylamino)cyclobutene-1,3-dicarbonitrile [(I) and (II)], obtained from the corresponding 3-dialkylaminopropiononitriles and hydrogen chloride, suffered displacement of the chloro-substituent to give the triamines (III) and (IV) on treatment with morpholine and dimethylamine, respectively. Hydrolysis of the products gave the corresponding 2,4-bis(dialkylamino)-4-hydroxycyclobutene-1,3-dicarbonitriles (V) and (VI).Treatment of the 3-dialkylaminopropiononitriles with hydrogen bromide gave stereoisomeric mixtures of the 4-bromocyclobutenes corresponding to compounds (I) and (II), along with the corresponding NN-dialkyl-4-bromo-6-dialkylaminopyrimidine-2-acetamides. Similar treatment with dry bromine, however, afforded a complex mixture of cyclobutenes; the product distribution varied according to the molecular proportion of bromine used.
ChemInform Abstract: SYNTHESES WITH α‐METALATED ISOCYANIDES. XLVII. A REAGENT FOR NUCLEOPHILIC 1,3‐DIAMINOPROPYLATION (1981)

Abstract Das Tetrahydropyrimidin (I) wird in das Tosylat (II) übergeführt.
A General Model for the Transmembrane Proteins of HIV and Other Retroviruses (1989)

A hypothetical model of the transmembrane (TM) protein of human immunodeficiency virus (HIV) is proposed that is derived from the known structure of the influenza TM protein HA2. This model is consistent with computer algorithms of predicted protein structure and with known properties of TM proteins determined by sequence homology, site-directed mutations, peptide analogs, immunochemistry, or other biologic means. It is applicable to a wide variety of retroviral TM proteins differing widely in overall molecular weight.
Development of Tumor Targeting Bioprobes (111In-Chimeric L6 Monoclonal Antibody Nanoparticles) for Alternating Magnetic Field Cancer Therapy (2005)

This study shows that mAb-conjugated nanoparticles (bioprobes), when given i.v., escape into the extravascular space and bind to cancer cell membrane antigen, so that bioprobes can be used in concert with externally applied AMF to deliver thermoablative cancer therapy.
Recent applications of capillary electrochromatography (2001)

A review is presented of the most important recent applications of capillary electrochromatography (CEC) for the analysis of acidic, basic, and neutral compounds, of biomolecules, environmental substances, natural products, pharmaceuticals, and chiral compounds. Packed-column CEC (packed-CEC), open-tubular (OT-CEC), as well as pressure-assisted CEC (pseudo-CEC) are hereby considered. Papers published between July 1999 and April 2001 were taken into account. Applications before July 1999 have been reviewed in Electrophoresis 1999, 20, 3027-3065.