gebhart/patrepeval huggingface dataset:
Bevacizumab (Bev) in combination with XELOX or FOLFOX4: Updated efficacy results from XELOX-1/ NO16966, a randomized phase III trial in first-line metastatic colorectal cancer (2007)

4028 Background: NO16966 is the first phase III trial to evaluate the combination of Bev with oxaliplatin-based chemotherapy (FOLFOX4 or the XELOX regimen) in the first-line setting. Methods: 1401 pts were randomized to receive FOLFOX4 (oxaliplatin, 5-FU, leucovorin as described previously) or XELOX (oxaliplatin 130mg/m 2 iv, capecitabine 1000mg/m 2 bid oral d1–14, q3w) plus Bev (5mg/kg q 2 weeks for FOLFOX, 7.5mg/kg q 3 weeks for XELOX) or Placebo in a 2x2 factorial design. Results: The addition of Bev to oxaliplatin-based chemotherapy demonstrated a significant benefit in terms of PFS in the primary analysis (HR 0.83; 97.5% CI 0.72- 0.95, p=0.0023). Prespecified analysis of PFS on treatment (defined as progressive disease or death within 28 days from the last dose of study treatment) and PFS analysis based on tumor assessments by an independent review committee (IRC) were consistent with the benefit observed in the primary analysis. PFS results are shown in Table 1 . 34% of patients have died and the median follow-up for survival at this time is 18.6 months. Mature overall survival data will be presented at the meeting. Conclusions: This large, international phase III trial demonstrates that the addition of Bev to oxaliplatin-based chemotherapy regimens significantly improves PFS. [Table: see text] [Table: see text]
The Need for Highly Purified Products to Treat Hemophilia B (1995)

Thromboembolic complications of prothrombin complex concentrate (PCC) therapy were first reported by Kasper in 1973 [N Engl J Med 1973;289:160]. The following contaminants were discussed as possible contributors to the thrombogenicity risk: the presence of other zymogens in PCCs, the presence of activated factor IX or activated factor X, or the presence of phospholipids from platelets resulting from insufficient centrifugation of the donor plasma. Activated factor IX is now accepted as a major causative factor. After numerous additional reports of thromboembolic complications in patients treated with PCCs, the International Society on Thrombosis and Haemostasis (ISTH) Scientific and Standardization Committee (SSC) Thrombogenicity Registry was established in 1988. Lusher collected 72 cases worldwide for the SSC/ISTH in 1988 and 1989. Thromboembolic complications and myocardial infarctions, however, continue to be serious problems associated with PCC therapy--even in the 1990s--underscoring the urgent need for high-purity factor IX products. Results from several studies by Mannucci, Bauer, and other authors demonstrated that patients treated with high-purity products developed no activation of prothrombin or thrombin, as indicated by appearance of thrombogenicity markers such as fibrinopeptide A and the amino-terminal fragments of prothrombin (F1 + 2). Other authors demonstrated that in patients at high risk for thrombotic complications, particularly those with liver disease, or postsurgery, or in those requiring repeated treatments, high-purity concentrates appear to be safe, regarding both thrombosis and risk of virus transmission.
Effects of coagulation factor deficiency on plasma coagulation kinetics determined via thrombelastography®: critical roles of fibrinogen and factors II, VII, X and XII (2005)

The fundamental finding of this study is that coagulation factor deficiencies affect TEG parameters in both a factor-dependent and activation-dependent fashion. Utilizing both celite and TF activation improves the diagnostic power of TEG. Based on such TEG data, more targeted administration of blood products could potentially help improve perioperative hemostatic outcomes.
Deinterlacing Using Hierarchical Motion Analysis (2010)

A motion-compensated deinterlacing scheme based on hierarchical motion analysis is presented. According to deinterlacing steps, our contribution can be divided into four parts: motion estimation, motion state analysis, motion consistency analysis, and finer-grained interpolation. In motion estimation, we introduce a Gaussian noise model for choosing the best motion vector for each block, and make a tradeoff between utilizing previous de-interlaced frames and avoiding error propagation. A directional interpolation method is also introduced in this part for backward fields. In motion state analysis, we define two motion states for each pixel, thus achieve a compromise between traditional block-based strategies and the extreme pixel-based case. In motion consistency analysis, we propose to measure both the motion vector consistency and the motion state consistency in order to determine whether the previous two parts should be performed again with a different block size. In finer-grained interpolation, we utilize a combination of recursive median filters to generate the final results. Experimental results show that all of the proposed techniques are effective, either objectively or subjectively. As a result, we can achieve much higher image quality, with an average gain of about 1.83 dB in terms of peak signal-to-noise ratio. Moreover, the increased computation complexity is marginal.
Efficient C−B Bond Formation Promoted by N-Heterocyclic Carbenes: Synthesis of Tertiary and Quaternary B-Substituted Carbons through Metal-Free Catalytic Boron Conjugate Additions to Cyclic and Acyclic α,β-Unsaturated Carbonyls (2009)

Metal-free nucleophilic activation of a B-B bond has been exploited in the development of a highly efficient method for conjugate additions of commercially available bis(pinacolato)diboron to cyclic or acyclic alpha,beta-unsaturated carbonyls. The reactions are readily catalyzed by a simple N-heterocyclic carbene (NHC) present at 2.5-10 mol %. A variety of cyclic and acyclic unsaturated ketones and esters can serve as substrates. The transformations deliver beta-boryl carbonyls bearing tertiary or quaternary B-substituted carbons in up to >98% yield. Preliminary studies indicate that although related Cu-NHC-catalyzed reactions are equally efficient, the metal-free variant is more functional-group-tolerant; in contrast to the Cu-catalyzed reactions, the metal-free processes proceed readily in the presence of a terminal alkyne and do not promote concomitant diboration of an aldehyde. Representative functionalization of the resulting boron enolates demonstrates the strong influence of the Lewis acidic B atom of the beta-boronate.
Two Monomers of Yeast Transcription Factor ADRI Bind a Palindromic Sequence Symmetrically to Activate ADH2 Expression (1991)

ADR1 is a transcription factor from Saccharomyces cerevisiae that regulates ADH2 expression through a 22-bp palindromic sequence (UAS1). Size fractionation studies revealed that full-length ADR1 and a truncated ADR1 protein containing the first 229 amino acids, which has the complete DNA-binding domain, ADR1:17-229, exist as monomers in solution. However, two complexes were formed with target DNA-binding sites. UV-cross-linking studies suggested that these two complexes represent one and two molecules of ADR1 bound to DNA. Studies of ADR1 complexes formed with wild-type UAS1, asymmetrically altered UAS1, and one half of UAS1 showed that ADR1 can bind to one half of UAS1 and gives rise to a complex containing one molecule of ADR1. Dimethyl sulfate interference studies were consistent with this interpretation and in addition indicated that purine contact sites in each half of UAS1 were identical. Increasing the distance between the two halves of UAS1 had at most a minor effect of the thermodynamics of formation of the two complexes. These data are more consistent with ADR1 binding as two independent monomers, one to each half of UAS1. However, binding of two ADR1 monomers at UAS1 is apparently essential for transactivation in vivo. Further, we have identified a stretch of 18 amino acid residues amino terminal to the zinc two-finger domains of ADR1 which is essential for DNA-binding activity. Single amino acid substitutions of residues in this region resulted in severely reduced DNA-binding activity.
Soluble Monomeric P-Selectin Containing Only the Lectin and Epidermal Growth Factor Domains Binds to P-Selectin Glycoprotein Ligand-1 on Leukocytes (1997)

Abstract Under shear stress, leukocytes use P-selectin glycoprotein ligand-1 (PSGL-1) to tether to and roll on P-selectin expressed on activated platelets or endothelial cells. P-selectin has an NH2-terminal lectin domain, an epidermal growth factor (EGF)-like motif, nine consensus repeats (CRs), a transmembrane domain, and a cytoplasmic tail. To determine whether the CRs are required for P-selectin to bind PSGL-1, we expressed a soluble protein (Lec-EGF) that contained only the lectin and EGF domains, plus a short C-terminal epitope tag. Electron microscopy and hydrodynamic analysis confirmed that Lec-EGF was monomeric, as previously shown for soluble P-selectin (sPS) that contained the lectin and EGF domains plus all nine CRs. Fluid-phase Lec-EGF or sPS inhibited binding of oligomeric125I-labeled membrane-derived P-selectin (mPS) to PSGL-1 on neutrophils and binding of 125I-PSGL-1 to immobilized mPS. The IC50 for inhibiting binding of mPS to neutrophils was fivefold greater for Lec-EGF than for sPS, whereas the IC50 for inhibiting binding of mPS to purified PSGL-1 was indistinguishable for Lec-EGF and sPS. Under static or shear conditions, neutrophils used PSGL-1 to tether to or roll on Lec-EGF that was captured by an immobilized monoclonal antibody to the C-terminal epitope. These data show that P-selectin requires only the lectin and EGF domains to bind to PSGL-1.
Regional Polysterism in the GTP-Bound Form of the Human c-Ha-Ras Protein, (1997)

The backbone 1H, 13C, and 15N resonances of the c-Ha-Ras protein [a truncated version consisting of residues 1-171, Ras(1-171)] bound with GMPPNP (a slowly hydrolyzable analogue of GTP) were assigned and compared with those of the GDP-bound Ras(1-171). The backbone amide resonances of amino acid residues 10-13, 21, 31-39, 57-64, and 71 of Ras(1-171).GMPPNP, but not those of Ras(1-171).GDP, were extremely broadened, whereas other residues of Ras(1-171).GMPPNP exhibited amide resonances nearly as sharp as those of Ras(1-171). GDP. The residues exhibiting the extreme broadening, except for residues 21 and 71, are localized in three functional loop regions [loops L1, L2 (switch I), and L4 (switch II)], which are involved in hydrolysis of GTP and interactions with other proteins. From the temperature and magnetic field strength dependencies of the backbone amide resonance intensities, the extreme broadening was ascribed to the exchange at an intermediate rate on the NMR time scale. It was shown that the Ras(1-171) protein bound with GTP or GTPgammaS (another slowly hydrolyzable analogue of GTP) exhibits the same type of broadening. Therefore, it is a characteristic feature of the GTP-bound form of Ras that the L1, L2, and L4 loop regions, but not other regions, are in a rather slow interconversion between two or more stable conformers. This phenomenon, termed a "regional polysterism", of these loop regions may be related with their multifunctionality: the GTP-dependent interactions with several downstream target groups such as the Raf and RalGDS families and also with the GTPase activating protein (GAP) family. In fact, the binding of Ras(1-171).GMPPNP with the Ras-binding domain (residues 51-131) of c-Raf-1 was shown to eliminate the regional polysterism nearly completely. It was indicated, therefore, that each target/regulator selects its appropriate conformer among those presented by the "polysteric" binding interface of Ras. As the downstream target groups exhibit no apparent sequence homology to each other, it is possible that one target group prefers a conformer different from that preferred by another group. The involvement of loop L1 in the regional polysterism might suggest that the negative regulators, GAPs, bind to the polysteric binding interface (loops L2 and L4) of Ras and cooperatively select a conformer suitable for transition of the GTPase catalytic center, involving loops L1 and L4, into the highly active state.
Convolution engine (2015)

General-purpose processors, while tremendously versatile, pay a huge cost for their flexibility by wasting over 99% of the energy in programmability overheads. We observe that reducing this waste requires tuning data storage and compute structures and their connectivity to the data-flow and data-locality patterns in the algorithms. Hence, by backing off from full programmability and instead targeting key data-flow patterns used in a domain, we can create efficient engines that can be programmed and reused across a wide range of applications within that domain. We present the Convolution Engine (CE)---a programmable processor specialized for the convolution-like data-flow prevalent in computational photography, computer vision, and video processing. The CE achieves energy efficiency by capturing data-reuse patterns, eliminating data transfer overheads, and enabling a large number of operations per memory access. We demonstrate that the CE is within a factor of 2--3× of the energy and area efficiency of custom units optimized for a single kernel. The CE improves energy and area efficiency by 8--15× over data-parallel Single Instruction Multiple Data (SIMD) engines for most image processing applications.&lt;!-- END_PAGE_1 --&gt;
Charge-sensitive TCP and rate control in the Internet (2002)

We investigate the fundamental problem of achieving the system optimal rates in a distributed environment, which maximize the total user utility, using only the information available at the end hosts. This is done by decomposing the system problem into two subproblems-network and user problems-and introducing an incentive-compatible pricing scheme, while maintaining proportional fairness. We demonstrate that when users update their parameters by solving their own optimization problem, at an equilibrium the system optimum is achieved. Furthermore, this algorithm does not require any explicit feedback from the network and can be deployed over the Internet with modifications only on the end hosts. In the second part of the paper we model as a noncooperative game the case where the choice of each user's action has nonnegligible effect on the price per unit flow at the resources and investigate the Nash equilibria of the game. We show, in the simple case of a single bottleneck, that there exists a unique Nash equilibrium of the game. Further, as the number of users increases, the unique Nash equilibrium approaches the system optimum.
Los atentados de Londres del 7 y 21 de julio de 2005: ¿una "nueva normalidad" o lo ya previsto? (2006)

Los atentados perpetrados por terroristas suicidas en el metro y en un autobús de Londres el 7 de julio de 2005 así como los sucesivos atentados con bomba – en los que no llegaron a detonar los explosivos– cometidos en el metro de Londres el 21 de julio fueron atentados para los que no se dio ninguna alerta desde los servicios de inteligencia. Dichos atentados se produjeron después de que el Centro Conjunto de Análisis del Terrorismo decidiera “recalibrar” el nivel de amenaza en el Reino Unido en junio de 2005, que pasó de un nivel “severo general” a un nivel “sustancial”.
MIC Overlay Coupler Design Using Spectral Domain Techniques (1978)

A quasi-TEM analysis of dielectric overlay microstrip is described for an overlay extending several conductor Iinewidths beyond the coupled lines. This method permits the analysis of numerous variations of overlay coupler geometries. The relevant spectral domain Green's function is given and used to generate a set of design curves when the overlay is identical in thickness and dielectric constant to the main substrate. A trial 8.34-dB coupler was built. Significant improvement in isolation was noted with the overlay when compared to the equivalently designed uncompensated coupler. The measured values of isolation agree very well with predicted values.
Mycobacterium avium ss paratuberculosis-associated Diseases (2012)

The relation of Mycobacterium avium ss paratuberculosis (MAP) to Crohn's Disease (CD) and other MAP-associated conditions remains controversial. New data, coupled with the analogous Helicobacter pylori (H. pylori) story, has permitted us to piece together the MAP puzzle and move forward with a more scientific way of treating inflammatory bowel disease, particularly CD. As infection moves centre stage in inflammatory bowel disease, the dated "aberrant reaction" etiology has lost scientific credibility. Now, our growing understanding of MAP-associated diseases demands review and articulation. We focus here on (1) the concept of MAP-associated diseases; (2) causality, Johne Disease, the "aberrant reaction" hypothesis; and (3) responses to published misconceptions questioning MAP as a pathogen in CD.
Shotgun sequencing of the human transcriptome with ORF expressed sequence tags (2000)

Theoretical considerations predict that amplification of expressed gene transcripts by reverse transcription-PCR using arbitrarily chosen primers will result in the preferential amplification of the central portion of the transcript. Systematic, high-throughput sequencing of such products would result in an expressed sequence tag (EST) database consisting of central, generally coding regions of expressed genes. Such a database would add significant value to existing public EST databases, which consist mostly of sequences derived from the extremities of cDNAs, and facilitate the construction of contigs of transcript sequences. We tested our predictions, creating a database of 10,000 sequences from human breast tumors. The data confirmed the central distribution of the sequences, the significant normalization of the sequence population, the frequent extension of contigs composed of existing human ESTs, and the identification of a series of potentially important homologues of known genes. This approach should make a significant contribution to the early identification of important human genes, the deciphering of the draft human genome sequence currently being compiled, and the shotgun sequencing of the human transcriptome.
Experimental Allergic Encephalomyelitis (1976)

Experimental allergic encephalomyelitis is a disease of cell-mediated immunity and can be transferred passively to virgin recipients by lymphoid cells from sensitized donors. The rabbit eye contains myelinated medullary rays that can be visualized ophthalmoscopically. Intraocular injection of autologous lymph node cells from myelin basic protein (BP)-immunized rabbits into the vitreous leads to readily visualized optic neuritis while injection of cells from adjuvant immunized control rabbits does not. Microscopical study confirmed the presence of myelin destruction in recipients of cells from BP-sensitized donors. This eye chamber technique provides a simple model for the study of demyelination in vivo under direct observation.
On the physics of ultrashort single-electron pulses for time-resolved microscopy and diffraction (2013)

Pump–probe electron diffraction and ultrafast microscopy, based on laser excitation and probing with electrons, can provide a four-dimensional visualization of atomic motion in space and time. Electron pulses consisting of only single electrons have recently been used in order to avoid the deterioration of temporal resolution by Coulomb forces. Here it is discussed how one can define the pulse duration, the beam size and divergence, the transverse and longitudinal coherences, the energy spread and temporal dispersion, and the relation between bandwidth and shortest possible pulse duration, for single electrons and in practical context. Relations are provided on how to estimate these parameters from measurable quantities in a single-electron diffraction or microscopy experiment.
Targeting A2 adenosine receptors in cancer (2017)

Tumor cells use various ways to evade anti-tumor immune responses. Adenosine, a potent immunosuppressive metabolite, is often found elevated in the extracellular tumor microenvironment. Therefore, targeting adenosine-generating enzymes (CD39 and CD73) or adenosine receptors has emerged as a novel means to stimulate anti-tumor immunity. In particular, the A2 (A2a and A2b) adenosine receptors exhibit similar immunosuppressive and pro-angiogenic functions, yet have distinct biological roles in cancer. In this review, we describe the common and distinct biological consequences of A2a and A2b adenosine receptor signaling in cancer. We discuss recent pre-clinical studies and summarize the different mechanisms-of-action of adenosine-targeting drugs. We also review the rationale for combining inhibitors of the adenosine pathway with other anticancer therapies such immune checkpoint inhibitors, tumor vaccines, chemotherapy and adoptive T cell therapy.
Inhibitors of Acyl CoA:Cholesterol Acyltransferase (1996)

Conformational restriction of previously disclosed acyclic (diphenylethyl)diphenylacetamides led to the discovery of several potent inhibitors of acyl CoA:cholesterol acyltransferase (ACAT). cis-[2-(4-Hydroxyphenyl)-1-indanyl]diphenylacetamide (4a) was the most potent ACAT inhibitor identified (IC50 = 0.04 microM in an in vitro rat hepatic microsomal ACAT assay, ED50 = 0.72 mg/kg/day in cholesterol-fed hamster.
Components for the implementation of free-space optical crossbars (1996)

We describe an optical system developed to form the basis of a 64 × 64 free-space optical matrix-matrix crossbar switch. The design and performance of each of the main optical components is discussed: lenses, diffractive optical elements, and polarizing beamsplitters, together with the optomechanical hardware design. For these components, throughput levels of -6.9 dB have been achieved, which is compatible with full system operation at 10(-12) bit error rates at ≥270 Mbits s(-1).
EFFECT OF INTRAVENOUS INFUSION OF OMEGA-3 AND OMEGA-6 LIPID EMULSIONS ON EQUINE MONOCYTE FATTY ACID COMPOSITION AND INFLAMMATORY MEDIATOR PRODUCTION IN VITRO (2000)

The effect of intravenous administration of lipid emulsions enriched with omega-3 (n3) and omega-6 (n6) fatty acids on equine monocyte phospholipid fatty acid composition and the synthesis of inflammatory mediators in vitro was evaluated. In a randomized crossover design, horses were infused intravenously with 20% lipid emulsions containing n3 or n6 fatty acids. Monocytes were isolated from the horses before and 0 h, 8 h, 24 h, and 7 days after lipid infusion. Monocyte fatty acid analysis demonstrated incorporation of the parenteral n3 and n6 fatty acids in monocyte phospholipids immediately after infusion, with changes in the fatty acid composition persisting for up to 7 days after infusion. In vitro production of the inflammatory mediators thromboxane B2/thromboxane B3 (TXB(2/3)) and tumor necrosis factor-alpha (TNFalpha) by peripheral blood monocytes was diminished by n3 lipid infusion and was unchanged or increased by n6 lipid infusion. The results of this study demonstrate that short-term infusions of n3 and n6 fatty acid-enriched lipid emulsions alter the fatty acid composition of equine monocyte phospholipids and modify the inflammatory response of these cells in vitro. These results also support further investigation into the use of parenteral n3 fatty acids as part of the supportive therapy of patients with multiple organ dysfunction (MODS) or systemic inflammatory response syndrome (SIRS).