gebhart/patrepeval huggingface dataset:
Abstract 1876: Preclinical efficacy of fibroblast growth factor ligand trap HGS1036 in lung carcinoma models with genomic amplification of <i>FGFR1</i> (2012)

Abstract Lung cancer is the most common cause of cancer-related death in industrialized countries. In 2010, it is estimated that cancer of the lung and bronchus will be responsible for 157,300 deaths in the US (Jermal et al. 2010). A number of recent publications have reported the genomic amplification of the fibroblast growth factor receptor 1 gene (FGFR1) in lung cancer (Weiss et al. 2010; Voortman et al. 2010). Subtype analysis indicates that approximately 22% of squamous non-small cell lung cell carcinomas (NSCLC) and 27-33% of small cell lung cancer (SCLC) have amplification of the FGFR1 gene. Amplification of the FGFR1 gene in lung cancer cell lines is associated with over-expression of the FGFR1 receptor protein and increased signaling through the FGFR1 pathway resulting in increased cell proliferation and tumorigenesis. HGS1036 (formerly FP-1039) is a soluble fusion protein consisting of the extracellular domain of human FGFR1 isoform α-IIIc linked to the Fc region of human immunoglobulin G1 (IgG1). HGS1036 acts as a ligand “trap” that sequesters multiple fibroblast growth factor (FGF) family ligands, blocking their ability to bind to and activate multiple FGF receptors. We investigated the preclinical efficacy of HGS1036 in preclinical lung cancer models with genomic FGFR1 amplification as a novel therapeutic strategy. A panel of lung cancer cell lines (n=5) were identified that displayed genomic FGFR1 amplification on chromosome 8. Two of the cell lines, DMS53 and DMS114, were derived from the tumors of patients with SCLC. The other three cell lines, NCI-H1581, NCI-H520 and NCI-H1703, were derived from the tumors of patients with NSCLC. Examination of in vitro drug sensitivity indicated that all 5 cell lines were sensitive to HGS1036. Treatment of NCI-H1581, NCI-H520, NCI-H1703, DMS53 and DMS114 cells with HGS1036 in vitro resulted in a 52%, 71%, 46%, 47% and 82% reduction in cell proliferation, respectively, as determined by CellTiterGlo. Sensitivity to HGS1036 in vitro generally correlated with FGFR1 copy number and total FGFR1 protein expression. HGS1036 treatment of mice bearing FGFR1 amplified lung cancer xenografts resulted in tumor growth inhibition in all five FGFR1-amplified models examined (p=&lt;0.01). The degree of tumor growth inhibition, as assessed by area-under-the-curve analysis, varied from 31-84% depending on the FGFR1 amplified lung model examined. These experiments demonstrate that lung tumor cell lines with genomic FGFR1 amplification can be sensitive to FGF-ligand blockade by HGS1036 and provide preclinical rationale for the clinical study of HGS1036 in the treatment of lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1876. doi:1538-7445.AM2012-1876
OX40- and CD27-Mediated Costimulation Synergizes with Anti–PD-L1 Blockade by Forcing Exhausted CD8+ T Cells To Exit Quiescence (2014)

Exhaustion of chronically stimulated CD8(+) T cells is a significant obstacle to immune control of chronic infections or tumors. Although coinhibitory checkpoint blockade with anti-programmed death ligand 1 (PD-L1) Ab can restore functions to exhausted T cell populations, recovery is often incomplete and dependent upon the pool size of a quiescent T-bet(high) subset that expresses lower levels of PD-1. In a model in which unhelped, HY-specific CD8(+) T cells gradually lose function following transfer to male bone marrow transplantation recipients, we have explored the effect of shifting the balance away from coinhibition and toward costimulation by combining anti-PD-L1 with agonistic Abs to the TNFR superfamily members, OX40 and CD27. Several weeks following T cell transfer, both agonistic Abs, but especially anti-CD27, demonstrated synergy with anti-PD-L1 by enhancing CD8(+) T cell proliferation and effector cytokine generation. Anti-CD27 and anti-PD-L1 synergized by downregulating the expression of multiple quiescence-related genes concomitant with a reduced frequency of T-bet(high) cells within the exhausted population. However, in the presence of persistent Ag, the CD8(+) T cell response was not sustained and the overall size of the effector cytokine-producing pool eventually contracted to levels below that of controls. Thus, CD27-mediated costimulation can synergize with coinhibitory checkpoint blockade to switch off molecular programs for quiescence in exhausted T cell populations, but at the expense of losing precursor cells required to maintain a response.
Correction: A β-Lactam Antibiotic Dampens Excitotoxic Inflammatory CNS Damage in a Mouse Model of Multiple Sclerosis (2011)

In multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE), impairment of glial ''Excitatory Amino Acid Transporters'' (EAATs) together with an excess glutamate-release by invading immune cells causes excitotoxic damage of the central nervous system (CNS).In order to identify pathways to dampen excitotoxic inflammatory CNS damage, we assessed the effects of a b-lactam antibiotic, ceftriaxone, reported to enhance expression of glial EAAT2, in ''Myelin Oligodendrocyte Glycoprotein'' (MOG)-induced EAE.Ceftriaxone profoundly ameliorated the clinical course of murine MOG-induced EAE both under preventive and therapeutic regimens.However, ceftriaxone had impact neither on EAAT2 protein expression levels in several brain areas, nor on the radioactive glutamate uptake capacity in a mixed primary glial cell-culture and the glutamate-induced uptake currents in a mammalian cell line mediated by EAAT2.Moreover, the clinical effect of ceftriaxone was preserved in the presence of the EAAT2-specific transport inhibitor, dihydrokainate, while dihydrokainate alone caused an aggravated EAE course.This demonstrates the need for sufficient glial glutamate uptake upon an excitotoxic autoimmune inflammatory challenge of the CNS and a molecular target of ceftriaxone other than the glutamate transporter.Ceftriaxone treatment indirectly hampered T cell proliferation and proinflammatory INFc and IL17 secretion through modulation of myelin-antigen presentation by antigen-presenting cells (APCs) e.g.dendritic cells (DCs) and reduced T cell migration into the CNS in vivo.Taken together, we demonstrate, that a b-lactam antibiotic attenuates disease course and severity in a model of autoimmune CNS inflammation.The mechanisms are reduction of T cell activation by modulation of cellular antigen-presentation and impairment of antigen-specific T cell migration into the CNS rather than or modulation of central glutamate homeostasis.
Novel thermooxidatively stable poly(ether‐imide‐benzoxazole) and poly(ester‐imide‐benzoxazole) (1994)

Abstract 4‐Hydroxy‐5‐nitrophthalimides were produced via nucleophilic aromatic substitution (NAS) of 4,5‐dichloro phthalimide substituents by potassium nitrite. The use of a N ‐phenyl‐phthalimide having a protected 4′‐hydroxyl group allows concurrent deprotection and nitro reduction to amine to give the 4‐hydroxy‐5‐amino‐ N ‐(4′‐hydroxyphenyl) phthalimide. This key intermediate is the precursor to a poly (ether‐imide‐benzoxazole), and is the condensable monomer for a poly (ester‐imide‐benzoxazole). Benzoxazole monomer formation via condensation with p ‐fluorobenzoyl chloride afforded 2‐(4′‐fluorophenyl)‐5,6,‐ N ‐[4′(‐hydroxyphenyl) imide]‐benzoxazole, which was polymerized under NAS conditions to produce a poly(ether‐imide‐benzoxazole) having an endothermic transition at 454°C with weight retention of 90% at 500°C in both air and nitrogen. Solution polycondensation of the 4‐hydroxy‐5‐amino‐ N ‐(4′‐hydroxyphenyl) phthalimide monomer with isophthaloyl chloride afforded a poly(ester‐amide‐imide) which was isolated and thermally cyclodehydrated in the solid state under vacuum to give a poly(ester‐imide‐benzoxazole) having 95% weight retention at 500°C in both air and nitrogen, with no detectable DSC transitions up to 500°C. © 1994 John Wiley & Sons, Inc.
Seclogmon : Security in cloud computing using activity log for consumer data protection (2017)

Cloud security encompass under its umbrella very extensive set of service level agreements (SLA's), methodologies which are used to secure user data, applications and resources that are connected via cloud. But, still the clients are handicapped with very little support and knowledge about what actually happens to their data after they have pushed it on to the cloud. Data ownership is important issue, especially while dealing with an enormous amount of data. This allows cloud provides to create their own terms and conditions, which at times may seem arbitrary. We proposed a novel approach which will maintain logging and monitoring for helping cloud consumers to identify any abnormal activity and resolve the problems accordingly. But, logging has a wide application too, therefore it depends on the user how and what he logs and monitors. To aid the consumers all cloud service providers maintain logs and generate a huge amount of information, much of which is redundant, awkwardly formatted, but there are hidden clues that can help the consumer to understand that they are having, or more importantly, about to have a problem. Using these logs the work creates a tool which parses these logs and provides user the apt amount of information and allows them to understand their activities and job behavior on cloud. It helps them to report any anomaly in the use of their cloud job and infrastructure effectively.
Phosphazene-catalyzed intramolecular cyclization of nitrogen-tethered alkynyl esters (2013)

Intramolecular cyclization of nitrogen-tethered alkynyl esters catalyzed by phosphazene organosuperbases P2-tBu and P4-tBu was investigated. Both acyclic and cyclic substrates underwent 5-exo-dig and 5-endo-dig cyclization. This reaction is a rare example of the intramolecular addition of enolates of simple esters to alkynes.
Switching characteristics of a piezoelectrical actuated evanescent-wave directional coupler (1987)

A single-mode-fibre evanescent-wave coupler can be used as an optical switch. The fabrication and technical features of such a device are described. Extension of this switch to wavelength multiplexing is presented.
Analysis of IPSEC VPNs performance in a multimedia environment (2008)

Internet Protocol Security (IPSec) is a standard for securing internet communication and, a widely deployed mechanism for implementing Virtual Private Networks (VPNs). This paper present the performance analysis of IPSec VPNs for videoconference in real time multimedia traffic over a secure communication links by implementing an IPSec-based VPNs technology. The impact of IPSec VPNs on multimedia under a stress traffic condition with particular attention to transmission delay has been evaluated and the results shows that degradation occurs as IPSec VPNs encrypted with AES could not offer good performance in latency to the videoconference.
Stabilitty of Anti-periodic Solutions for Certain Shunting Inhibitory Cellular Neural Networks (2011)

In this paper, the existence and exponential stability of anti-periodic solutions for shunting inhibitory cellular neural networks (SICNNs) with continuously distributed delays are considered by constructing suitable Lyapunov fuctions and applying some critial analysis techniques. Our results remove restrictive conditions of the global Lipschitz and bounded conditions of activation functions and new sufficient conditions ensuring the existence and exponential stability of anti-periodic solutions for SICNNs are obtained. Moreover, an example is given to illustrate the feasibility of the conditions in our results.
MET-Independent Lung Cancer Cells Evading EGFR Kinase Inhibitors Are Therapeutically Susceptible to BH3 Mimetic Agents (2011)

Targeted therapies for cancer are inherently limited by the inevitable recurrence of resistant disease after initial responses. To define early molecular changes within residual tumor cells that persist after treatment, we analyzed drug-sensitive lung adenocarcinoma cell lines exposed to reversible or irreversible epidermal growth factor receptor (EGFR) inhibitors, alone or in combination with MET-kinase inhibitors, to characterize the adaptive response that engenders drug resistance. Tumor cells displaying early resistance exhibited dependence on MET-independent activation of BCL-2/BCL-XL survival signaling. Further, such cells displayed a quiescence-like state associated with greatly retarded cell proliferation and cytoskeletal functions that were readily reversed after withdrawal of targeted inhibitors. Findings were validated in a xenograft model, showing BCL-2 induction and p-STAT3[Y705] activation within the residual tumor cells surviving the initial antitumor response to targeted therapies. Disrupting the mitochondrial BCL-2/BCL-XL antiapoptotic machinery in early survivor cells using BCL-2 Homology Domain 3 (BH3) mimetic agents such as ABT-737, or by dual RNAi-mediated knockdown of BCL-2/BCL-XL, was sufficient to eradicate the early-resistant lung-tumor-cells evading targeted inhibitors. Similarly, in a xenograft model the preemptive cotreatment of lung tumor cells with an EGFR inhibitor and a BH3 mimetic eradicated early TKI-resistant evaders and ultimately achieved a more durable response with prolonged remission. Our findings prompt prospective clinical investigations using BH3-mimetics combined with targeted receptor kinase inhibitors to optimize and improve clinical outcomes in lung-cancer treatment.
Structure and function of anti-DNA autoantibodies derived from a single autoimmune mouse. (1987)

Four monoclonal anti-DNA antibodies derived from a single autoimmune MRL/lpr mouse were studied. Three of these antibodies showed similarities in DNA binding; the fourth had a much higher specific activity for single-stranded DNA and, in addition, was unique in binding double-stranded DNA and cardiolipin. Complete nucleotide sequences of heavy- and light-chain variable regions demonstrated that all four antibodies are clonally related. The sequences also showed numerous somatic mutations, the distribution of which suggests that positive selection by antigen operated on these clonally related autoantibodies.
Reflection contributions to the dispersion artefact in FTIR spectra of single biological cells (2009)

Fourier transform infrared spectra of a single cell in transflection geometry are seen to vary significantly with position on the cell, showing a distorted derivative-like lineshape in the region of the optically dense nucleus. A similar behaviour is observable in a model system of the protein albumin doped in a potassium bromide disk. It is demonstrated that the spectrum at any point is a weighted sum of the sample reflection and transmission and that the dominance of the reflection spectrum in optically dense regions can account for some of the spectral distortions previously attributed to dispersion artefacts. Rather than being an artefact, the reflection contribution is ever present in transflection spectra and it is further demonstrated that the reflection characteristics can be used for cellular mapping.
Ouabain-specific antibodies: immunochemical properties and reversal of Na+, K+-activated adenosine triphosphatase inhibition (1972)

Antibodies with high affinity and specificity for the cardiac glycoside ouabain were raised in rabbits. The antigen used was a conjugate of ouabain linked through its rhamnose moiety to terminal alpha-amino groups of poly D,L alanyl-human serum albumin. Ouabain-specific antibodies were present as early as 3 wk, and rose steadily in titer over the initial 20-33 wk of immunization. Levels as high as 6.5 mg specific immunoglobulin per ml antiserum were reached in one rabbit at the end of 45 wk. The average intrinsic association constants for ouabain were 1.3 x 10(9) M(-1) and 1.6 x 10(9) M(-1) in antisera studied in detail, and there was evidence of restricted heterogeneity of binding site affinities. A high degree of specificity was demonstrated. Significant cross-reactivity occurred only with other cardioactive steroid compounds such as acetyl strophanthidin, digoxin, and digitoxin, while endogenous steroids did not cross-react even when present in 1000-fold excess. A rapid and convenient radioimmunoassay procedure for plasma or urine ouabain concentrations was developed using these antibodies. Competition between ouabain-(3)H tracer and unlabeled ouabain for specific antibody binding sites allowed the measurement of ouabain concentrations as low as 0.1 ng/ml or less without need for extraction procedures. The high association constants observed in these studies permit antibody reversal of established myocardial effects of ouabain. Both blockade and reversal of ouabain inhibition of canine myocardial microsomal Na(+), K(+)-activated ATPase by antibody were documented, suggesting a possible mechanism for reversal of cellular effects.
Large scale deletions in the GPC3 gene may account for a minority of cases of Simpson-Golabi-Behmel syndrome. (1997)

Our results suggest that large scale deletions may be less common in SGBS than was originally thought. One patient, with an exon 4 and 5 deletion, lacked the characteristic facial dysmorphic features. This raises the possibility of involvement of GPC3 gene defects in a wider range of overgrowth disorders.
Reno-protective effect of N-acetyl cysteine in patients with impaired renal function undergoing coronary angiography and interventions. (2006)

We conclude that prophylactit administration of N-Acetyl Cysteine along with hydration diminishes the incidence of deterioration of renal function induced by contrast agents in patients with renal insufficiency during coronary angiographic procedures.
Playing Fast Not Loose: Evaluating team-level pace of play in ice hockey using spatio-temporal possession data (2019)

Pace of play is an important characteristic in hockey as well as other team sports. We provide the first comprehensive study of pace within the sport of hockey, focusing on how teams and players impact pace in different regions of the ice, and the resultant effect on other aspects of the game. First we examined how pace of play varies across the surface of the rink, across different periods, at different manpower situations, between different professional leagues, and through time between seasons. Our analysis of pace by zone helps to explain some of the counter-intuitive results reported in prior studies. For instance, we show that the negative correlation between attacking speed and shots/goals is likely due to a large decline in attacking speed in the OZ. We also studied how pace impacts the outcomes of various events. We found that pace is positively-correlated with both high-danger zone entries (e.g. odd-man rushes) and higher shot quality. However, we find that passes with failed receptions occur at higher speeds than successful receptions. These findings suggest that increased pace is beneficial, but perhaps only up to a certain extent. Higher pace can create breakdowns in defensive structure and lead to better scoring chances but can also lead to more turnovers. Finally, we analyzed team and player-level pace in the NHL, highlighting the considerable variability in how teams and players attack and defend against pace. Taken together, our results demonstrate that measures of team-level pace derived from spatio-temporal data are informative metrics in hockey and should prove useful in other team sports.
Biphasic effect of p21Cip1 on smooth muscle cell proliferation: Role of PI 3-kinase and Skp2-mediated degradation (2005)

Taken together, this data demonstrates that a balance between PI 3-kinase-driven upregulation and Skp2-mediated degradation controls the level of p21Cip1, which regulates VSMC proliferation in a biphasic manner. Low levels of p21Cip1 are also essential to counter apoptosis during cell-cycle progression.
A Depleted Base Transistor (1978)

Normally-off JFET's, in which depletion layers in the channel touch each other by a built-in potential, have been found to perform a bipolar current amplifying action in a gate/base current operation mode. We named this normally-off JFET a depleted base transistor (DBT). Current amplification factors for two DBT samples were ∼500 and ∼2000 at Ic=5 mA and VCE=5 V. Differing from an npn bipolar transistor, DBT still keeps hFE of about 100 at -200°C, and that at temperatures higher than -50°C, this current amplification factor shows negative temperature dependence. DBT's operated upside-down showed hFE of 10 and 30, respectively at Ic=5 mA and VCE=0.5 V. It was confirmed that an equivalent I2L gate composed of a pnp transistor and a DBT, performs an inverter operation with a sufficient noise margin and that a five-gate ring oscillator, using these I2L gates, shows an oscillation waveform.
Over‐expression of polycomb group protein EZH2 relates to decreased expression of p16 <sup>INK4a</sup> in cholangiocarcinogenesis in hepatolithiasis (2008)

Polycomb group protein EZH2 and Bmi1 are reportedly involved in the progression of malignant tumours. We examined the participation of EZH2 in multi-step cholangiocarcinogenesis in hepatolithiasis with respect to tumour suppressor gene p16 INK4a. We examined 20 hepatolithiatic livers with intrahepatic cholangiocarcinoma (ICC) and 10 histologically normal livers. Neoplastic biliary lesions were classified into biliary intraepithelial neoplasm (BilIN-1, 2 and 3) and invasive carcinoma. We selected 15 foci of invasive carcinoma, 8 BilIN-3 (carcinoma in situ), 12 BilIN-2 (high-grade dysplasia), 32 BilIN-1 (low-grade dysplasia) and 37 non-neoplastic biliary epithelia from these livers. Expression of p16 INK4a, EZH2 and Bmi1 were surveyed in these foci. P16 INK4a promoter methylation was examined in microdissected tissues. Taking advantage of two cell lines of CC (HuCTT-1 and TFK-1) and small interfering RNA (siRNA), the effects of the knockdown of EZH2 on p16 INK4a methylation of CC cells were examined. Expression of p16 INK4a, which was frequent in BilIN1, was decreased in BilIN-2/3 and invasive carcinoma, while EZH2 expression showed step-wise increase from BilIN-1, -2 and -3 to invasive carcinoma (p < 0.01). P16 INK4a promoter hypermethylation was related to aberrant expression of EZH2. The knockdown of EZH2 in cultured CC cells decreased p16 INK4a methylation and decreased binding of EZH2 to the p16 INK4a gene promoter. The latter suggested that direct binding of EZH2 is involved in the regulation of the p16 INK4a gene. Our data suggest that over-expression of EZH2 may induce hypermethylation of p16 INK4a promoter followed by decreased expression of p16 INK4a in the multi-step cholangiocarcinogenesis through intraepithelial neoplasm in hepatolithiasis.