gebhart/patrepeval huggingface dataset:
Tumor-specific suppressor T-cells which inhibit the in vitro generation of cytolytic T-cells from immune and early tumor-bearing host spleens. (1986)

Spleen cells from DBA/2 mice, after immunization with syngeneic P815 mastocytoma cells and Corynebacterium parvum, respond to P815 in vitro with a brisk, secondary-type generation of cytotoxic cells. This cytotoxicity is mediated by antigen-specific T-lymphocytes and correlates with resistance to in vivo challenge. This model confirms the observations of previous investigators made in semisyngeneic hosts using an in vivo transfer model. Spleen cells from "early" tumor-bearing hosts (TBHs), 7-12 days after intradermal (i.d.) inoculation of 10(6) P815 cells alone, made a similar, but generally higher, cytotoxic T-lymphocyte (CTL) response in vitro. Spleen cells from "late" TBHs (18-28 days) completely suppressed the in vitro CTL response of immune cells (e.g., from 71% specific release in controls down to 8% at an effector: target ratio of 40:1). Early i.d. TBH spleen cells, because of their higher level response, appeared to be resistant to this suppression (85% release for controls and 84% when suppressor cells were added at 40:1). By testing early TBH CTL at lower effector: target ratios, however, suppression by late TBH spleen cells could be readily demonstrated. When TBHs were inoculated s.c. instead of i.d. or with lower doses of tumor cells, responses were lower and susceptibility of splenic CTLs to suppression was increased. At intermediate times after tumor inoculation (14-20 days), spleen cells from TBHs still can respond in vitro, but they are completely suppressed by spleen cells from late TBHs. The suppressor cells are antigen-specific, radiation-sensitive, Thy1+ cells.
Comparison of fenofibrate and pioglitazone effects on patients with nonalcoholic fatty liver disease (2017)

This study showed beneficial effects of fenofibrate and pioglitazone in patients with fatty liver. Further studies with larger study populations on the effects of these drugs on fatty liver, lipid profile, blood glucose, and insulin are suggested.
Stratified approaches to the treatment of asthma (2012)

While asthma is a chronic inflammatory disorder that is managed with inhaled controller and reliever drugs, there remains a large unmet need at the severe end of the disease spectrum. Here, a novel stratified approach to its treatment is reviewed, based upon identification of causal pathways, with a focus on biologics. A systematic search of the literature was made using Medline, and publications were selected on the basis of their relevance to the topic. Despite strong preclinical data for many of the more recently identified asthma targets, especially those relating to the T-helper 2 allergic pathway, clinical trials with specific biologics in moderate to severe asthma as a group have been disappointing. However, subgroup analyses based upon pathway-specific biomarkers suggest specific endotypes that are responsive. Application of hypothesis-free analytical approaches (the 'omics') to well-defined phenotypes is leading to the stratification of asthma along causal pathways. Refinement of this approach is likely to be the future for diagnosing and treating this group of diseases, as well as helping to define new causal pathways. The identification of responders and nonresponders to targeted asthma treatments provides a new way of looking at asthma diagnosis and management, especially with biologics that are costly. The identification of novel biomarkers linked to well-phenotyped patients provides a stratified approach to disease management beyond simple disease severity and involving causal pathways. In order to achieve this effectively, a closer interaction will be required between industry (therapeutic and diagnostic), academia and health workers.
Wafer bonding : mechanics-based models and experiments (2004)

Direct wafer bonding has emerged as an important technology in the manufacture of silicon-on-insulator substrates (SOI), microelectromechanical systems (MEMS), and three-dimensional inte-grated circuits (3D IC’s). While the process is currently employed in applications such as these, a lack of knowledge of the basic mechanics of the process has made developing robust processes and preventing process failures extremely challenging. The current work addresses this problem through the development and validation of mechanics-based models that connect the wafer geometry, etch pattern, clamping configuration, and work of adhesion to bonding failure. An energy-based bonding criterion, which allows the effect of flatness variations and etch pat-terns to be quantified, is presented and employed to develop analytical and numerical models. Analytical models, based on plate theory, are developed to examine the role of wafer-scale shape variations, etch patterns, and the clamping configuration. Finite element models are developed to verify the analytical models and to evaluate the bonding criterion for wafers with anisotropic elas-tic properties and arbitrary geometries. Experiments in which silicon substrates with wafer-scale shape variations and etch patterns were bonded demonstrate that the shape and size of the bonded
Textbook of hypertension (1994)

1. Epidemiology 2. Circulation in Hypertension 3. Pathogenesis 4. Target Organ Damage 5. Special Groups 6. Secondary Hypertension 7. Clinical Assessment 8. Treatment 9. The Hypertensive Patient in Society
Optimized implementation of memristor-based full adder by material implication logic (2014)

Recently memristor-based applications and circuits are receiving an increased attention. Furthermore, memristors are also applied in logic circuit design. Material implication logic is one of the main areas with memristors. In this paper an optimized memristor-based full adder design by material implication logic is presented. This design needs 27 memristors and less area in comparison with typical CMOS-based 8-bit full adders. Also the presented full adder needs only 184 computational steps which enhance former full adder design speed by 20 percent.
The Mechanism of Hydroaminoalkylation Catalyzed by Group 5 Metal Binaphtholate Complexes (2012)

The intermolecular hydroaminoalkylation of unactivated alkenes and vinyl arenes with secondary amines occurs readily in the presence of tantalum and niobium binaphtholate catalysts with high regio- and enantioselectivity (up to 98% ee). Mechanistic studies have been conducted in order to determine the kinetic order of the reaction in all reagents and elucidate the rate- and stereodetermining steps. The effects of substrate steric and electronic properties on the overall reaction rate have been evaluated. The reaction is first order in amine and the catalyst, while exhibiting saturation in alkene at high alkene concentration. Unproductive reaction events including reversible amine binding and arene C-H activation have been observed. The formation of the metallaaziridine is a fast reversible nondissociative process and the overall reaction rate is limited either by amide exchange or alkene insertion, as supported by reaction kinetics, kinetic isotope effects, and isotopic labeling studies. These results suggest that the catalytic activity can be enhanced by employing a more electron-deficient ligand backbone.
Photoaffinity Labelling of Arginine Kinase and Creatine Kinase with a gamma-P-Substituted Arylazido Analogue of ATP (1980)

1. An ATP analogue with a photoactivated azide group attached to the gamma-phosphate via an amide bond, ATP gamma-p-azidoanilide, appeared to have potential use as a photoaffinity label for the nucleotide-binding regions of ATP: guanidine phosphotransferases. Upon photolysis in the presence of lobster muscle arginine kinase and rabbit muscle creatine kinase, the analogue is converted to a potent inhibito of these two kinases. This photo-dependent inhibition is specific as it cannot be induced by azidoaniline, a mixture of azidoaniline and ATP or by ATP gamma-p-aminoanilide. Preirradiated under suitable conditions, the photoanalogue still shows a transitory inhibitory effect which, however, slowly vanishes with time (t0.5 = 3 h). 2. The photoinhibition is significantly decreased by the presence of ATP or ADP but is completely prevented by the addition of a mixture of nucleotide and guanidine substrates. Differential spectroscopy and affinity chromatography on Sepharose-ATP demonstrated the inability of photoinactivated arginine kinase and creatine kinase to recognize their nucleotide substrates. 3. Experiments with [14C]ATP gamma-p-azidoanilide indicated that photolysis is associated with an irreversible and stoichiometric binding of the ATP analogue to the enzymes. Autoradiographs made with the peptide maps corresponding to the tryptic digests of each 14C-labelled photomodified enzyme showed an unexpected highly specific labelling of the proteins. 4. Thiiol titrations of the kinases which have been subjected to various photolysis conditions led to the conclusion that the arylnitrene moiety of the photoanalogue is covalently attached to the single reactive cysteinyl side chain present in the active-site region of the two homologous kinases. This amino acid residue appears, therefore, to be located near the phosphate chain binding subsite occupied by the ATP analogue and probably also by the natural nucleotide substrates.
Haptic interface for virtual reality based laparoscopic surgery training environment (1997)

These Ecole polytechnique federale de Lausanne EPFL, n° 1734 (1997)Laboratoire de systemes robotiques 2 Reference doi:10.5075/epfl-thesis-1734Print copy in library catalog Record created on 2005-03-16, modified on 2017-05-10
Melanocortin Tetrapeptide Ac-His-DPhe-Arg-Trp-NH2 Modified at the Para Position of the Benzyl Side Chain (DPhe): Importance for Mouse Melanocortin-3 Receptor Agonist versus Antagonist Activity (2008)

The melanocortin-3 and -4 receptors (MC3R, MC4R) have been implicated in energy homeostasis and obesity. Whereas the physiological role of the MC4R is extensively studied, little is known about the MC3R. One caveat is the limited availability of ligands that are selective for the MC3R. Previous studies identified Ac-His-DPhe(p-I)-Arg-Trp-NH 2, which possessed partial agonist/antagonist pharmacology at the mMC3R while retaining full nanomolar agonist pharmacology at the mMC4R. These data allowed for the hypothesis that the DPhe position in melanocortin tetrapeptides can be used to examine ligand side-chain determinants important for differentiation of mMC3R agonist versus antagonist activity. A series of 15 DPhe (7) modified Ac-His-DPhe (7)-Arg-Trp-NH 2 tetrapeptides has been synthesized and pharmacologically characterized. Most notable results include the identification of modifications that resulted in potent antagonists/partial agonists at the mMC3R and full, potent agonists at the mMC4R. These SAR studies provide experimental evidence that the molecular mechanism of antagonism at the mMC3R differentiates this subtype from the mMC4R.
Targeting SREBP-1-driven Lipid Metabolism to Treat Cancer (2014)

Metabolic reprogramming is a hallmark of cancer. Oncogenic growth signaling regulates glucose, glutamine and lipid metabolism to meet the bioenergetics and biosynthetic demands of rapidly proliferating tumor cells. Emerging evidence indicates that sterol regulatory element-binding protein 1 (SREBP-1), a master transcription factor that controls lipid metabolism, is a critical link between oncogenic signaling and tumor metabolism. We recently demonstrated that SREBP-1 is required for the survival of mutant EGFR-containing glioblastoma, and that this pro-survival metabolic pathway is mediated, in part, by SREBP-1-dependent upregulation of the fatty acid synthesis and low density lipoprotein (LDL) receptor (LDLR). These results have identified EGFR/PI3K/Akt/SREBP-1 signaling pathway that promotes growth and survival in glioblastoma, and potentially other cancer types. Here, we summarize recent insights in the understanding of cancer lipid metabolism, and discuss the evidence linking SREBP-1 with PI3K/Akt signaling-controlled glycolysis and with Myc-regulated glutaminolysis to lipid metabolism. We also discuss the development of potential drugs targeting the SREBP-1- driven lipid metabolism as anti-cancer agents.
Aspartic proteinases : retroviral and cellular enzymes (1998)

Plenary: The Aspartic Proteinases: An Historical Overview T.L. Blundell, et al. Retroviral Aspartic Proteinases I: The Regulation of Sequential Processing of HIV-1 Gag by the Viral Protease S.C. Pettit, et al. A Cellular Anti-Apoptosis Protein Is Cleaved by the HIV-1 Protease B.D.Korant, et al. Retroviral Aspartic Proteinases II: In Vitro Selection and Characterization of VX-478 Resistant HIV-1 Variants S. Pazhanisamy, et al. Sensitivity to Inhibition and Catalytic Efficiency of HIV Proteinase Mutants S.I. Wilson et al. Mammalian Aspartic Proteinases: Comparison of the Specificity of the Aspartic Proteinases Towards Internally Consistent Sets of Oligopeptide Substrates B.M. Dunn, et al. Aspartic Proenzymes and Activation: Proteolytic and Non-Proteolytic Activation of Prorenin T.L. Reudelhuber, et al. Microbial Aspartic Proteinases: Aspergillus niger Acid Proteinase A-Structure and Function K. Takahashi, et al. Parasite Aspartic Proteinase: Structural Analysis of Plasmespin II: A Comparison with Human Aspartic Proteases A.M. Silva. Plant Aspartic Proteinases: Structural and Functional Aspects of Cardosins C. Faro, et al. 86 Additional Articles. Index.
G-band frequency-scanned antenna arrays (2010)

Beam steering antenna arrays have many applications, from object tracking and localization to landing systems [1]. The main requirements for such a system are usually a wide scanning angle, low beamwidth and constant gain. Beam steering can be obtained electronically, by controlling the relative phase shift between the array elements. This can be achieved by delay elements, as in phased arrays, or by sweeping the carrier frequency [1–4]. The latter are usually easier to implement, but require a wider operating bandwidth for the same scanning angle. In this work, frequency scanned arrays for wide-angle scanning are described. By operating at G-band, the overall size and weight of the antenna can be reduced, thus making it suitable for space applications. Two architectures, based on slotted waveguides and microcoaxial line fed slots, are introduced to provide a wider scanning angle than conventional structures. The devices are fabricated using the PolyStrata process, which enable low-loss feeds at millimeter-wave frequencies. The PolyStrata process involves sequential deposition of copper layers and photoresist on a silicon wafer [5]. Copper layer thicknesses range from 10µm to 100 µm, with gap-to-height and width-to-height aspect ratios of 1:1.2 and 1:1.5, respectively. After the desired layers are deposited, the photoresist filling is rinsed away (“released”) through 200 µm long holes. This process can be used to fabricate air-supported coaxial lines and waveguides at G-band, with slot antennas acting as release holes.
mtDNA variation of aboriginal Siberians reveals distinct genetic affinities with Native Americans. (1993)

The mtDNA variation of 411 individuals from 10 aboriginal Siberian populations was analyzed in an effort to delineate the relationships between Siberian and Native American populations. All mtDNAs were characterized by PCR amplification and restriction analysis, and a subset of them was characterized by control region sequencing. The resulting data were then compiled with previous mtDNA data from Native Americans and Asians and were used for phylogenetic analyses and sequence divergence estimations. Aboriginal Siberian populations exhibited mtDNAs from three (A, C, and D) of the four haplogroups observed in Native Americans. However, none of the Siberian populations showed mtDNAs from the fourth haplogroup, group B. The presence of group B deletion haplotypes in East Asian and Native American populations but their absence in Siberians raises the possibility that haplogroup B could represent a migratory event distinct from the one(s) which brought group A, C, and D mtDNAs to the Americas. Our findings support the hypothesis that the first humans to move from Siberia to the Americas carried with them a limited number of founding mtDNAs and that the initial migration occurred between 17,000-34,000 years before present.
A simple method for the detection of two types of thiaminase-producing colonies (1986)

A plate method which can detect two types of thiaminase-producing colonies was developed. After growing bacterial colonies on a plate with good thiaminase production for 2–4 days, soft agar was overlayed which contained the substrate thiamin, and substituting base (pyridoxine) for type I enzyme, and a buffer of appropriate pH for each type of enzyme. The plate was incubated at 37°C for 1–2 h for Bacillus thiaminolyticus and clostridia, and at 60°C for 2 h for Bacillus aneurinolyticus. Good results were obtained for laboratory strains of average thiaminase activity.
A Hausdorff chirality measure (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA Hausdorff chirality measureAndrzej B. Buda and Kurt MislowCite this: J. Am. Chem. Soc. 1992, 114, 15, 6006–6012Publication Date (Print):July 1, 1992Publication History Published online1 May 2002Published inissue 1 July 1992https://pubs.acs.org/doi/10.1021/ja00041a016https://doi.org/10.1021/ja00041a016research-articleACS PublicationsRequest reuse permissionsArticle Views908Altmetric-Citations121LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Immune Responses in Healthy and Allergic Individuals Are Characterized by a Fine Balance between Allergen-specific T Regulatory 1 and T Helper 2 Cells (2004)

The mechanisms by which immune responses to nonpathogenic environmental antigens lead to either allergy or nonharmful immunity are unknown. Single allergen-specific T cells constitute a very small fraction of the whole CD4+ T cell repertoire and can be isolated from the peripheral blood of humans according to their cytokine profile. Freshly purified interferon-gamma-, interleukin (IL)-4-, and IL-10-producing allergen-specific CD4+ T cells display characteristics of T helper cell (Th)1-, Th2-, and T regulatory (Tr)1-like cells, respectively. Tr1 cells consistently represent the dominant subset specific for common environmental allergens in healthy individuals; in contrast, there is a high frequency of allergen-specific IL-4-secreting T cells in allergic individuals. Tr1 cells use multiple suppressive mechanisms, IL-10 and TGF-beta as secreted cytokines, and cytotoxic T lymphocyte antigen 4 and programmed death 1 as surface molecules. Healthy and allergic individuals exhibit all three allergen-specific subsets in different proportions, indicating that a change in the dominant subset may lead to allergy development or recovery. Accordingly, blocking the suppressor activity of Tr1 cells or increasing Th2 cell frequency enhances allergen-specific Th2 cell activation ex vivo. These results indicate that the balance between allergen-specific Tr1 cells and Th2 cells may be decisive in the development of allergy.
Genomic Alterations in Ectopic and Eutopic Endometria of Women with Endometriosis (2006)

The correct classification of tissue samples into two groups suggests that these two subtypes of endometriosis may have distinct genomic alteration profiles and are thus distinct entities, as previously proposed. The shared alterations are likely the ones that harbor genes responsible for an increased propensity of endometrial debris to implant to the ectopic sites and for early events that lead to the establishment of lesions. Alternatively, these shared alterations may harbor genes that are dysregulated in both eutopic and ectopic endometria. The identified genomic alterations should help to zero in genes involved in the pathogenesis of endometriosis in future studies.
AB928, a novel dual adenosine receptor antagonist, combined with chemotherapy or AB122 (anti-PD-1) in patients (pts) with advanced tumors: Preliminary results from ongoing phase I studies. (2019)

2604 Background: AB928, a selective, small-molecule A 2a R/A 2b R antagonist, potently blocks the immunosuppressive effects of high adenosine concentrations in the tumor microenvironment. Preclinically, combining adenosine receptor inhibition with either chemotherapy or anti-PD-1 resulted in greater tumor control, suggesting AB928 may have additive activity when paired with either of these agents in cancer pts. Methods: Three dose-escalation (3+3 design) studies are assessing the safety, pharmacokinetics (PK), pharmacodynamics, and clinical activity of increasing doses of AB928 (75, 150, 200 mg orally once daily) in combination with: standard pegylated liposomal doxorubicin in triple-negative breast cancer (TNBC) and ovarian cancer (OC); standard mFOLFOX6 in gastroesophageal cancer (GEC) and colorectal cancer (CRC); and AB122 (240 mg every 2 weeks) in various advanced tumors. Following identification of the recommended phase 2 dose of AB928 in combination with chemotherapy or AB122 in dose escalation, the following tumor cohorts may be expanded (15-40 pts/cohort) to further test the combinations: TNBC and OC, GEC and CRC, and renal cell carcinoma. Results: As of 01Feb2019, 9 pts were treated across the 3 studies, and time on treatment ranged from 1-182 days (table). Overall, AB928 combination therapy was well tolerated. Two pts underwent post-baseline disease assessment; both had stable disease. Preliminary data indicate that AB928 PK and adenosine receptor coverage in cancer pts are similar to what was previously assessed in healthy volunteers. AB122 PK and PD-1 coverage are equally unaffected by AB928 co-administration. Updated data, including biomarker data, will be presented at the meeting. Conclusions: Early results showed a favorable safety profile of AB928 combination therapy. All 3 studies are actively recruiting pts. Clinical trial information: NCT03719326; NCT03720678; NCT03629756. [Table: see text]
From meiosis to postmeiotic events: Uncovering the molecular roles of the meiosis‐specific recombinase Dmc1 (2009)

In meiosis, the accurate segregation of maternal and paternal chromosomes is accomplished by homologous recombination. A central player in meiotic recombination is the Dmc1 recombinase, a member of the RecA/Rad51 recombinase superfamily, which is widely conserved from viruses to humans. Dmc1 is a meiosis-specific protein that functions with the ubiquitously expressed homolog, the Rad51 recombinase, which is essential for both mitotic and meiotic recombination. Since its discovery, it has been speculated that Dmc1 is important for unique aspects of meiotic recombination. Understanding the distinctive properties of Dmc1, namely, the features that distinguish it from Rad51, will further clarify the mechanisms of meiotic recombination. Recent structural, biochemical, and genetic findings are now revealing the molecular mechanisms of Dmc1-mediated homologous recombination and its regulation by various recombination mediators.