gebhart/patrepeval huggingface dataset:
A wideband two-layer radio access network using DECT technology in the uplink (1999)

This article describes a novel architecture of a broadband radio access network using the two-layer network solution. The proposed downlink is compliant with the DVB-S standards, and a DECT custom solution is used in the return channel. The idea we present is based on the use of a "single carrier with equalization" system in order to directly link the end-user terminal, avoiding the most expensive part of the cabling network: the last mile. The article reports, some considerations concerning the advantages and disadvantages of the novel architecture. Successively, aspects such as frequency plan, architecture of the base station, local repeater, and user terminal, in combination with some practical studies, are discussed.
Abstract 979: Discovery of the JAK1 selective kinase inhibitor AZD4205 (2017)

Abstract Janus kinases are a family of four enzymes; JAK1, JAK2, JAK3 and tyrosine kinase 2 (TYK2) that are critical in cytokine signalling, with constitutive activation of JAK/STAT pathways associated with a wide variety of malignancies. Elevated JAK/STAT signalling leading to increased activation of STAT3 is reported in a wide variety of cancers, including breast, liver, prostate, colorectal, head and neck, oesophageal, pancreatic, bladder, and non-small cell lung, and is implicated in the pathogenesis of diffuse large B-cell lymphoma and nasopharyngeal carcinomas. Overall, up to 70% of human tumours are linked to persistent elevated STAT3 activity which can be associated with poorer prognosis in many of these settings. In addition, elevated pSTAT3 is observed in response to chemotherapy treatment, and also in response to treatment with inhibitors of oncogenic signalling pathways such as EGFR, MAPK and AKT, and is associated with resistance or poorer response to agents targeting these pathways. In many of these cases, JAK1 is believed to be a primary driver of STAT3 phosphorylation and signalling, suggesting inhibition of JAKs as a therapeutic approach to treat these potential resistance mechanisms. The mixed JAK1/2 kinase inhibitor ruxolitinib is approved for the treatment of myeloproliferative neoplasms including intermediate or high risk myelofibrosis and polycythemia vera and has been tested in a variety of tumor settings. Since JAK2 is essential for the signal transduction downstream of erythropoietin, thrombopoietin and related receptors that control erythrocyte and megakaryocyte expansion, dosing of inhibitors that target JAK2 can be limited by toxicities such as thrombocytopenia and anaemia. Starting from a non-kinome selective screening hit, structure-based design was used to optimise a series of aminopyrimidines that led to JAK1-selective candidate drug AZD4205. This compound demonstrates ATP competitive binding with IC50’s in a high ATP concentration enzyme assay against JAK1 of 73 nM (Ki = 2.8 nM), with high selectivity against JAK2 and JAK3 with IC50’s of 13,233 nM and &amp;gt;30,000 nM respectively. In addition it showed potent inhibition of p-STAT3 in a cell based assay of JAK1 activity with an IC50 of 128 nM and excellent selectivity across the kinome. In summary, AZD4205 is a highly potent JAK1-selective kinase inhibitor with excellent preclinical pharmacokinetics with potential for further clinical development. The optimization from screening hit to first disclosure of this candidate drug will be presented. Citation Format: Jason G. Kettle, Qibin Su, Neil Grimster, Sameer Kawatkar, Scott Throner, Richard Woessner, Huawei Chen, Geraldine Bebernitz, Kristen Bell, Erica Anderson, Linette Ruston, Jon Winter-Holt, Paul Lyne, Melissa Vasbinder, Claudio Chuaqui. Discovery of the JAK1 selective kinase inhibitor AZD4205 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 979. doi:10.1158/1538-7445.AM2017-979
Intracellular Targeting and Structural Conservation of a Prohormone-Processing Endoprotease (1989)

The prohormone-processing endoprotease (KEX2 gene product) of the yeast Saccharomyces cerevisiae is a membrane-bound, 135,000-dalton glycoprotein, which contains both asparagine-linked and serine- and threonine-linked oligosaccharide and resides in a secretory compartment. Analysis of mutant kex2 genes truncated at their 3' end indicates that carboxyl terminal domains of the enzyme are required for its proper localization within the cell. A human gene product, "furin," shares 50% identity with the catalytic domain of Kex2 protease and is, therefore, a candidate for a human prohormone-processing enzyme.
TORT AND PROPERTY LAW—THE MASSACHUSETTS SUPREME JUDICIAL COURT SOUNDS THE DEATH KNELL FOR SECTION 14—Simon v. Solomon, 385 Mass 91, 431 N.E.2d 556 (1982) (1983)

An issue recently presented to the Massachusetts Supreme Judi cial Court was whether a landlord could be held liable for a tenant's emotional distress.This issue arose in Simon v. Solomon, I along with questions involving warranty of habitability, the covenant of quiet enjoyment,2 and Chapter 186, Section 14 of the Massachusetts General Laws. 3 Celeste Solomon was a tenant in a federally subsidized base ment apartment, managed by Gem Realty Company (Gem).4On thirty separate occasions, between April 1974 and November 1976, raw sewage and water ran into her apartment, covering the floors of the livingroom, bedroom and hallway.sWith flooding ankle deep, Ms. Solomon testified that she sometimes left her bed at night to check on her young children only to step into cold sewage and water. 6On each occasion, Ms. Solomon would spend the rest of the night awake, waiting to call Gem so that workers would come to pump out the apartment.?Although Ms. Solomon suffered no actual physical injury, she became withdrawn, depressed, and unable to care for her children. 8Because of the persistent flooding of the apartment, Ms. Solomon sent her children to live with relatives and claimed that she spent much of her time in her bedroom crying,
Soluble proteins delivered to dendritic cells via pH-sensitive liposomes induce primary cytotoxic T lymphocyte responses in vitro. (1992)

Effective immunity to many infectious agents, particularly viruses, requires a CD8+ cytotoxic T lymphocyte (CTL) response. Understanding how to achieve CTL induction with soluble proteins is important for vaccine development since such antigens are usually not processed appropriately to induce CTL. In the present report, we have demonstrated that a potent primary CTL response against a soluble protein can be achieved by delivering antigen in pH-sensitive liposomes to dendritic cells (DC) either in vivo or in vitro. Since the pH-sensitive liposome delivery system is efficient and easy to use, the approach promises to be valuable both in the study of basic mechanisms in antigen processing, and as a practical means of immunization.
Three-dimensional endocardial impedance mapping: a new approach for myocardial infarction assessment (2001)

Precise identification of infarcted myocardial tissue is of importance in diagnostic and interventional cardiology. A three-dimensional, catheter-based endocardial electromechanical mapping technique was used to assess the ability of local endocardial impedance in delineating the exact location, size, and border of canine myocardial infarction. Electromechanical mapping of the left ventricle was performed in a control group (n = 10) and 4 wk after left anterior descending coronary artery ligation (n = 10). Impedance, bipolar electrogram amplitude, and endocardial local shortening (LS) were quantified. The infarcted area was compared with the corresponding regions in controls, revealing a significant reduction in impedance values [infarcted vs. controls: 168.8 +/- 11. 7 and 240.7 +/- 22.3 Omega, respectively (means +/- SE), P < 0.05] bipolar electrogram amplitude (1.8 +/- 0.2 mV, 4.4 +/- 0.7 mV, P < 0. 05), and LS (-2.36 +/- 1.6%, 11.9 +/- 0.9%, P < 0.05). The accuracy of the impedance maps in delineating the location and extent of the infarcted region was demonstrated by the high correlation with the infarct area (Pearson's correlation coefficient = 0.942) and the accurate identification of the infarct borders in pathology. By accurately defining myocardial infarction and its borders, endocardial impedance mapping may become a clinically useful tool in differentiating healthy from necrotic myocardial tissue.
Quantitative PCR Analysis for Fruit Juice Authentication Using PCR and Laboratory-on-a-Chip Capillary Electrophoresis According to the Hardy−Weinberg Law (2009)

DNA-based analysis for the authentication of fruit juices was evaluated using the Polymerase Chain Reaction (PCR) and laboratory-on-a-chip capillary electrophoresis (LOC). A PCR restriction fragment length polymorphism (RFLP) assay demonstrated the detection of grapefruit juice in orange juice, although the assay was relatively insensitive with a limit of detection of 10% v/v. A PCR heteroduplex assay for detecting mandarin juice in orange juice was successfully applied to the LOC system and demonstrated greater sensitivity with a limit of detection of 2.5% v/v. Results for both assays using authentic juice mixtures were consistent with that expected following the random reannealing of PCR-amplified DNA at PCR plateau according to the principles of the Hardy−Weinberg law. Calculations of theoretical and expected yields of homoduplex and heteroduplexes indicated that the heteroduplexes were underestimated by 1.5-fold on the LOC. Although the LOC can provide good quantitative end-point analytical data from PCR methods, care must be taken in data interpretation because different data interpretation applies dependent on the attainment of the PCR plateau.
Vascular endothelial growth factor: Crystal structure and functional mapping of the kinase domain receptor binding site (1997)

Vascular endothelial growth factor (VEGF) is a homodimeric member of the cystine knot family of growth factors, with limited sequence homology to platelet-derived growth factor (PDGF) and transforming growth factor beta2 (TGF-beta). We have determined its crystal structure at a resolution of 2.5 A, and identified its kinase domain receptor (KDR) binding site using mutational analysis. Overall, the VEGF monomer resembles that of PDGF, but its N-terminal segment is helical rather than extended. The dimerization mode of VEGF is similar to that of PDGF and very different from that of TGF-beta. Mutational analysis of VEGF reveals that symmetrical binding sites for KDR are located at each pole of the VEGF homodimer. Each site contains two functional "hot spots" composed of binding determinants presented across the subunit interface. The two most important determinants are located within the largest hot spot on a short, three-stranded sheet that is conserved in PDGF and TGF-beta. Functional analysis of the binding epitopes for two receptor-blocking antibodies reveal different binding determinants near each of the KDR binding hot spots.
Critical Evaluation of in Vitro Methods for Estimating Digestibility in Simple-Stomach Animals (1991)

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Effectiveness of Ionizing Radiation in Reducing Furan and Acrylamide Levels in Foods (2006)

Furan and acrylamide are two possible carcinogens commonly found in many thermally processed foods. The possibility of using ionizing radiation to reduce the levels of thermally induced furan and acrylamide in water and selected foods was investigated. Aqueous furan solutions, and foods (frankfurters, sausages, infant sweet potatoes) that contained furan were irradiated to various doses of gamma-rays. Water and oil spiked with acrylamide and potato chips (a known acrylamide-containing food) were also irradiated. In addition, possible irradiation-induced formation of acrylamide in glucose and asparagine solutions was analyzed. Results showed that irradiation at 1.0 kGy destroyed almost all furan in water. In frankfurters, sausages, and infant sweet potatoes, the rate of irradiation-induced destruction of furan was much lower than the rate in water, although significant reductions in furan levels were observed in all foods. Irradiation at 2.5-3.5 kGy, doses that can inactivate 5-log of most common pathogens, reduced furan levels in the food samples by 25-40%. Similarly to furan, acrylamide in water was also sensitive to irradiation. After 1.5 kGy of irradiation, most of the acrylamide was degraded. Irradiation, however, had a very limited effect on acrylamide levels in oil and in potato chips, even at a dose of 10 kGy. No detectable acrylamide was formed in the mixture of asparagine and glucose upon irradiation. These results suggest that a low dose of irradiation easily destroys furan and acrylamide in water. In real foods, however, the reduction of furan was less effective than in water, whereas the reduction in acrylamide was minimal.
Breast and Ovarian Cancer (2003)

espite years of intensive study and substantial progress in understanding susceptibility to breast and ovarian cancer, these diseases remain important causes of death in women. However, several recent critical advances -sequencing of the human genome and the development of high-throughput techniques for identifying DNA-sequence variants, changes in copy numbers, and global expression profiles -have dramatically accelerated the pace of research aimed at preventing and curing these diseases. We review some of the important discoveries in the genetics of breast and ovarian cancer, ongoing studies to isolate additional susceptibility genes, and early work on molecular profiling involving microarrays.
Androgens and esophageal cancer: What do we know? (2015)

Significant disparities exist between genders for the development and progression of several gastro-intestinal (GI) diseases including cancer. Differences in incidence between men vs women for colon, gastric and hepatocellular cancers suggest a role for steroid sex hormones in regulation of GI carcinogenesis. Involvement of intrinsic gender-linked mechanisms is also possible for esophageal adenocarcinoma as its incidence is disproportionally high among men. However, the cause of the observed gender differences and the potential role of androgens in esophageal carcinogenesis remains unclear, even though the cancer-promoting role of androgen receptors (AR) shown in other cancers such as prostate and bladder suggests this aspect warrants exploration. Several studies have demonstrated expression of ARs in esophageal cancer. However, only one study has suggested a potential link between AR signaling and outcome - poorer prognosis. Two groups have analyzed data from cohorts with prostate cancer and one of these found a decreased incidence of esophageal squamous and adenocarcinoma after androgen deprivation therapy. However, very limited information is available about the effects of androgen and AR-initiated signaling on esophageal cancer cell growth in vitro and in vivo. Possible mechanisms for androgens/AR involvement in the regulation of esophageal cancer growth are considered, and the potential use of AR as a prognostic factor and clinical target is highlighted, although insufficient evidence is available to support clinical trials of novel therapies. As esophageal adenocarcinoma is a gender linked cancer with a large male predominance further studies are warranted to clarify the role of androgens and ARs in shaping intracellular signaling and genomic responses in esophageal cancer.
Beyond 100G Ethernet (2010)

With 100G technologies standardized, in the context of both Ethernet and the optical transport network (OTN), 100G router ports and 100G optical transport interfaces are commercially available. At the same time, heavily data-centric users are starting to ask for higher-rate interfaces. First speculations include 400G as well as 1T as the next possible Ethernet standards. In this article we discuss interface technology options for Ethernet and OTN beyond 100G in light of the current 100G standards, taking into account likely evolution paths of interface technologies over the next 10 years.
On the flexure of thin cylindrical shells and other "thin" sections (1927)

Abstract It is a generally appreciated deduction from St. Venant’s solution of the flexure problem that a beam in which the material is disposed at a distance from the neutral axis is superior to the solid section in economy of material. St. Yenant’s solution, however, suggests that this advantage increases without limit as the thickness of the material is reduced and the distance from the neutral axis is increased. It has, of course, been generally realised that this conclusion is not supported by ordinary engineering practice, and recent experience in the use of high tensile steels and problems of aircraft structure have emphasised the desirability of a further examination of the flexure problem. St. Venant’s solutions are obtained when the equations of equilibrium of an isotropic elastic solid are made linear by the neglect of terms of higher orders than the first: and by Kirchhoff’s theorem of determinancy these solutions may then be considered unique and stable. To attack problems of stability it is necessary, as is shown by R. V. Southwell in his ‘General Theory of Elastic Stability,’ to include some of the second order effects. It is, in fact, only when these become considerable that Kirchhoff’s theorem fails and instability becomes possible. By this general treatment various classes of instability are obtained or indicated, but the only ones susceptible to analysis or of practical interest (on account of the “elastic limit” which is a feature of all practical materials) are those in which at the moment of instability the strains are still small. Bryant has shown that this will only occur, as in the case of thin rods and shells, when one dimension of the body is small compared with others.
A role for ActA in epithelial cell invasion by Listeria monocytogenes (2001)

We assessed the role of the actin-polymerizing protein, ActA, in host cell invasion by Listeria monocytogenes. An in frame DeltaactA mutant was constructed in a hyperinvasive strain of prfA* genotype, in which all genes of the PrfA-dependent virulence regulon, including actA, are highly expressed in vitro. Loss of ActA production in prfA* bacteria reduced entry into Caco-2, HeLa, MDCK and Vero epithelial cells to basal levels. Reintroduction of actA into the DeltaactA prfA* mutant fully restored invasiveness, demonstrating that ActA is involved in epithelial cell invasion. ActA did not contribute to internalization by COS-1 fibroblasts and Hepa 1-6 hepatocytes. Expression of actA in Listeria innocua was sufficient to promote entry of this non-invasive species into epithelial cell lines, but not into COS-1 and Hepa 1-6 cells, indicating that ActA directs an internalization pathway specific for epithelial cells. Scanning electron microscopy of infected Caco-2 human enterocytes suggested that this pathway involves microvilli. prfA* bacteria, but not wild-type bacteria (which express PrfA-dependent genes very weakly in vitro) or prfA* DeltaactA bacteria, efficiently invaded differentiated Caco-2 cells via their apical surface. Microvilli played an active role in the phagocytosis of the prfA* strain, and actA was required for their remodelling into pseudopods mediating bacterial uptake. Thus, ActA appears to be a multifunctional virulence factor involved in two important aspects of Listeria pathogenesis: actin-based motility and host cell tropism and invasion.
Regulation of immunity by lysosphingolipids and their G protein–coupled receptors (2004)

T and B lymphocytes, as well as endothelial cells, express distinctive profiles of G protein–coupled receptors for sphingosine 1–phosphate, which is a major regulator of T cell development, B and T cell recirculation, tissue homing patterns, and chemotactic responses to chemokines. The capacity of drugs that act on type 1 sphingosine 1–phosphate receptors to suppress organ graft rejection in humans and autoimmunity in animal models without apparent impairment of host defenses against infections suggests that this system is a promising target for new forms of immunotherapy.
Different Electrostatic Potentials Define ETGE and DLG Motifs as Hinge and Latch in Oxidative Stress Response (2007)

Nrf2 is the regulator of the oxidative/electrophilic stress response. Its turnover is maintained by Keap1-mediated proteasomal degradation via a two-site substrate recognition mechanism in which two Nrf2-Keap1 binding sites form a hinge and latch. The E3 ligase adaptor Keap1 recognizes Nrf2 through its conserved ETGE and DLG motifs. In this study, we examined how the ETGE and DLG motifs bind to Keap1 in a very similar fashion but with different binding affinities by comparing the crystal complex of a Keap1-DC domain-DLG peptide with that of a Keap1-DC domain-ETGE peptide. We found that these two motifs interact with the same basic surface of either Keap1-DC domain of the Keap1 homodimer. The DLG motif works to correctly position the lysines within the Nrf2 Neh2 domain for efficient ubiquitination. Together with the results from calorimetric and functional studies, we conclude that different electrostatic potentials primarily define the ETGE and DLG motifs as a hinge and latch that senses the oxidative/electrophilic stress.
QTL analysis of Cercospora leaf spot resistance in sugar beet (1999)

Abstract The inheritance of Cercospora leaf spot resistance in sugar beet was investigated by means of quantitative trait loci (QTL) analysis of a segregating population of 193 individuals, using 110 AFLP and 35 restriction fragment length polymorphism (RFLP) markers. Five QTL were found through composite interval mapping on linkage groups 1, 2, 3, and 9, respectively, two of which were linked on linkage group 3. The significance of these QTL was tested by permutation analysis The QTL had mostly additive, but also certain negative dominance effects; all the resistance alleles came from the Cercospora ‐resistant parent. Each quantitative trait locus accounted for 7‐18% of the phenotypic variation, leaving 37% of the variation unexplained. The results are discussed in relation to the potential use of marker‐assisted breeding for Cercospora leaf spot resistance in sugar beet.
Dabigatran Associated with Increased Bleeding During Atrial Fibrillation Ablation (2012)

In warfarin recipients with therapeutic international normalized ratios (INRs), uninterrupted warfarin treatment during radiofrequency ablation for
Endothelium and inflammation. (2005)

During the past decade, our understanding of the pathophysiology of coronary heart disease (CAD) has undergone a remarkable evolution. To date atherosclerosis is considered an inflammatory disease, whose the endothelial dysfunction represents an early key event. When the arterial endothelium encounters certain bacterial products or risk factors, such as dyslipidemia, vasoconstrictor hormones involved in hypertension, the products of glycoxidation associated with hyperglycemia, or proinflammatory cytokines derived from excess adipose tissue, these cells increase the expression of adhesion molecules that promote the sticking of blood leukocytes to the inner surface of the arterial wall. Once in the arterial intima these cells communicate with endothelium and smooth muscle cells, under the influence of mediators of inflammation and immunity, such as the cytokines and complements components, prostanoids and leukotrienes. Thus, the activated endothelium promotes the development of the atherosclerotic disease process, i.e., vascular inflammation and thrombosis by producing vasoconstrictor substances, by inducing the expression of adhesive receptors for leukocytes and platelets, the production of tissue factor and endothelin, and by increasing the production of the plasminogen activator inhibitor-1. Emerging data support the concept that assessment of endothelial vasomotion may be a useful biomarker for atherosclerotic vascular disease.