gebhart/patrepeval huggingface dataset:
Comparison of Recombinant and Synthetically Formed Monoclonal Antibody-β-Lactamase Conjugates for Anticancer Prodrug Activation (1999)

Conjugates of the L49 monoclonal antibody (binds to the p97 antigen on melanomas and carcinomas) were formed by attaching Enterobacter cloacae beta-lactamase (bL) to the L49-Fab' fragment using a heterobifunctional cross-linking reagent or by linking the enzyme to L49-sFv using DNA recombinant technology. The conjugates thus formed, L49-Fab'-bL and L49-sFv-bL, were designed to activate cephalosporin containing anticancer prodrugs at the surfaces of antigen positive tumor cells. Results from in vitro experiments using two lung carcinoma cell lines demonstrated that the conjugates were equally active in effecting the release of phenylenediamine mustard from the cephalosporin nitrogen mustard prodrug CCM. While treatment with either of the conjugates combined with the maximum tolerated doses of CCM led to cures of established SN12P renal cell carcinoma tumors in nude mice, only the L49-sFv-bL conjugate maintained its ability to do so at 1/4 the maximum tolerated dose of CCM. L49-sFv-bL was also superior to L49-Fab'-bL in the 1934J renal cell carcinoma tumor model and was shown to be quite active in two in vivo models of human lung carcinoma. These results demonstrate that the recombinant fusion protein leads to more pronounced therapeutic windows than the chemical conjugate and is active in an array of human tumor models.
Reflexiones sobre la Sentencia del Tribunal Constitucional [Pleno_] número 1/2018, de 11 de enero (RTC 2018, 1) (2018)

espanolEsta sentencia del Tribunal Constitucional aborda la cuestion de si el articulo 76-e) de la Ley del Contrato de Seguro, al establecer, en determinados supuestos, la sumision obligatoria l arbitraje en el seguro de defensa juridica por la sola voluntad del asegurado supone la infraccion del articulo 24.1 en relacion con el articulo 117.3 de la Constitucion. El Tribunal Constitucional, en distintas ocasiones, ha venido considerando contrario al derecho de tutela judicial efectiva la imposicion obligatoria e imperativa del sometimiento a arbitraje. De acuerdo con esta doctrina, el Tribunal Constitucional concluye que, aunque el articulo 76-e) responde a la idea plausible de fomentar el arbitraje como medio para la solucion de conflictos, asi como a la idea de conceder una especial proteccion al asegurado en su condicion de consumidor, esta finalidad no evita la restriccion al derecho fundamental que el arbitraje obligatorio supone. La anulacion del articulo 76-e) de la Ley del Contrato de Seguro plantea algunas delicadas cuestiones que conviene analizar. La mas importante es, sin duda, la de que la anulacion del precepto coloca a nuestro pais en situacion de incumplimiento parcial de la Directiva 87/344/CE. EnglishThis judgement of the Constitutional Court addresses the question whether article 76-e) of the Insurance Contract Law, by establishing, in certain cases, mandatory submission to arbitration in the legal expenses insurance upon the sole will of the insured, violates article 24.1 in relation to article 117.3 of the Constitution. The Constitutional Court, on different occasions, has been considering the compulsory and mandatory imposition of arbitration to be contrary to the right of effective judicial protection. According to this doctrine the Constitutional Court concludes that, although article 76-e) responds to the plausible idea of promoting arbitration as a means of resolving conflicts, as well as the idea of granting special protection to the insured as a consumer, this purpose does not prevent the consideration of this limitation as a restriction to the fundamental right of effective judicial protection on the part of the insurer that compulsory arbitration implies. Therefore, the Constitutional Court declares void article 76-e) of the Insurance Contract Law. This decision raises some delicate issues that should be analyzed. The most important is that the annulment of the provision places our country in a situation of partial non-compliance with Directive 87/344 / EC.
Release of Histamine from Dural Mast Cells by Substance P and Calcitonin Gene-Related Peptide (1997)

The aim of the present study was to examine if the neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) can stimulate histamine release from mast cells in the dura mater and thereby play a role in cranial vasoregulation and local neurogenic inflammation. Dura mater mast cells were compared with peritoneal mast cells in the rat. Histamine was released from dura mater mast cells by compound 48/80, SP and CGRP but from peritoneal mast cells only by compound 48/80 and SP. NPY and VIP released quite small amounts of histamine from dural mast cells. The release of SP and CGRP from rat dura mater mast cells was blocked by the receptor antagonists FK888 and CGRP8-37 respectively, suggesting receptor mediated release mechanisms. None of the stimuli released histamine from human or porcine dural mast cells, possibly because the sampling procedure injures and incapacitates the cells.
The link between nanoscale feature development in a negative resist and the Hansen solubility sphere (2009)

Abstract By systematically studying development of a high resolution, negative electron beam resist, hexa‐methyl acetoxy calix(6)arene, we have elicited a more general understanding of the underlying development mechanisms for negative resists. Using the three dimensional Hansen solubility parameters for more than 40 solvents, we have constructed a Hansen solubility sphere (HSS). From this sphere, we have estimated the Flory Huggins interaction parameter for solvents with hexa‐methyl acetoxy calix(6)arene and found a correlation between resist development contrast, nanoscale patterned feature quality, and the polymer‐solvent solubility. Conducting Atomic Force Microscopy (AFM) in a liquid cell, we have measured swelling for hexa‐methyl acetoxy calix(6)arene in four solvents. The swelling measurements indicate that the HSS gives an indication of the Flory‐Huggins interaction parameter. These measurements provide new insights into the development behavior of nanoscale features – necessary for obtaining the ultimate lithographic resolution. In addition, it demonstrates a methodology for choosing appropriate polymer‐solvent combinations for nanoscience applications. © 2009 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 47: 2091–2105, 2009
Design, Fabrication, and Testing of a Capsule With Hybrid Locomotion for Gastrointestinal Tract Exploration (2010)

This paper describes a novel solution for the active locomotion of a miniaturized endoscopic capsule in the gastrointestinal (GI) tract. The authors present the design, development, and testing of a wireless endocapsule with hybrid locomotion, where hybrid locomotion is defined as the combination between internal actuation mechanisms and external magnetic dragging. The capsule incorporates an internal actuating legged mechanism, which modifies the capsule profile, and small permanent magnets, which interact with an external magnetic field, thus imparting a dragging motion to the device. The legged mechanism is actuated whenever the capsule gets lodged in collapsed areas of the GI tract. This allows modification of the capsule profile and enables magnetic dragging to become feasible and effective once again. A key component of the endoscopic pill is the internal mechanism, endowed with a miniaturized brushless motor and featuring compact design, and adequate mechanical performance. The internal mechanism is able to generate a substantial force, which allows the legs to open against the intestinal tissue that has collapsed around the capsule body. An accurate simulation of the performance of the miniaturized motor under magnetic fields was carried out in order to define the best configuration of the internal permanent magnets (which are located very close to the motor) and the best tradeoff operating distance for the external magnet, which is responsible for magnetically dragging the capsule. Finally, a hybrid capsule was developed generating 3.8 N at the tip of the legged mechanism and a magnetic link force up to 135 mN. The hybrid capsule and its wireless control were extensively tested <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in vitro</i> , <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">ex vivo</i> , and <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in vivo</i> , thus confirming fulfilment of the design specifications and demonstrating a good ability to manage collapsed areas of the intestinal tract.
Community-acquired pneumonia immunization trial in adults (CAPiTA) (2014)

Pneumococcal disease, including pneumonia, is a major global public health problem, and older people are at greater risk, particularly for severe disease and complications. Conjugate vaccines have shown efficacy against invasive pneumococcal disease (IPD) and otitis media in children, but have not been evaluated healthy elderly. The CAPiTA study was designed was to demonstrate the efficacy of 13-valent pneumococcal conjugate vaccine (13vPnC) in prevention of a first episode of vaccine-type pneumococcal community-acquired pneumonia (CAP) (primary objective). The secondary objectives were to demonstrate efficacy in prevention of a first episode of nonbacteremic/noninvasive vaccine-type pneumococcal CAP and of vaccine-type invasive IPD. This was a randomized, double-blind clinical trial in 84,496 participants 65 and older in the Netherlands. Key eligibility criteria were no previous pneumococcal vaccination and immune competence. Participants were randomized 1:1 to receive 13vPnC or placebo. They were enrolled at community-based sites and home visits, and surveillance for CAP and IPD was conducted at hospitals in the areas of enrollment. A serotype-specific urinary antigen detection assay was used to identify episodes of vaccine-type CAP. Safety was also evaluated. The study started in September 2008, and reached the protocol defined 130 case accrual numbers of first episode of Vaccine Type CAP at the end of August 2013. The primary and secondary endpoints of this study will be presented. At the time abstract submission, the data were not yet available. (Funded by Pfizer, Inc.; ClinicalTrials.govnumber NCT00744263.)
Electrochemical treatment of mouse and rat fibrosarcomas with direct current (1997)

Electrochemical treatment (ECT) of cancer utilizes direct current to produce chemical changes in tumors. ECT has been suggested as an effective alternative local cancer therapy. However, a methodology is not established, and mechanisms are not well studied. In vivo studies were conducted to evaluate the effectiveness of ECT on animal tumor models. Radiation-induced fibrosarcomas were implanted subcutaneously in 157 female C3H/HeJ mice. Larger rat fibrosarcomas were implanted on 34 female Fisher 344 rats. When the spheroidal tumors reached 10 mm in the mice, two to five platinum electrodes were inserted into the tumors at various spacings and orientations. Ten rats in a pilot group were treated when their ellipsoidal tumors were about 25 mm long; electrode insertion was similar to the later part of the mouse study, i.e., two at the base and two at the center. A second group of 24 rats was treated with six or seven electrodes when their tumors were about 20 mm long; all electrodes were inserted at the tumor base. Of the 24 rats, 12 of these were treated once, 10 were treated twice, and 2 were treated thrice. All treated tumors showed necrosis and regression for both mice and rats; however, later tumor recurrence reduced long-term survival. When multiple treatments were implemented, the best 3 month mouse tumor cure rate was 59.3%, and the best 6 month rat tumor cure rate was 75.0%. These preliminary results indicate that ECT is effective on the radiation-induced fibrosarcoma (RIF-1) mouse tumor and rat fibrosarcoma. The effectiveness is dependent on electrode placement and dosage. Bioelectromagnetics 18:14–24, 1997. © 1997 Wiley-Liss, Inc.
Expression of a single‐chain Fv antibody against abscisic acid creates a wilty phenotype in transgenic tobacco (1995)

The plant hormone abscisic acid (ABA) participates in the control of several important physiological processes in plants such as stomata regulation, seed dormancy and stress tolerance. A new strategy was developed to study these phenomena by blocking abscisic acid with intracellularly expressed specific single-chain variable fragment (scFv) antibodies. Here evidence is presented that the expression of single-chain Fv antibodies against abscisic acid in the endoplasmic reticulum of transgenic tobacco cells leads to a wilty phenotype. Stomatal conductance is increased at high CO2 concentrations dependent on the level of antibody expression in leaves. Symptoms of abscisic acid deficiency were generated in the transformants although they have even higher levels of abscisic acid than wild-type plants.
Preoperative Plasma HER2 and Epidermal Growth Factor Receptor for Staging and Prognostication in Patients with Clinically Localized Prostate Cancer (2007)

Preoperative plasma HER2 and EGFR were associated with prostate cancer progression after radical prostatectomy. Plasma HER2 and EGFR may provide a tool for predicting long-term recurrence-free survival and early metastasis.
Markets Versus Monopolies in Education: The Historical Evidence (1996)

A common point of contention among educators and economists is the likely effect a free market would have on modern education. Most supporters of public schooling maintain that the field would either be adversely affected by competition and choice, or that the effects would be insubstantial. Conversely, a significant number of critics argue that education, like all other human exchanges, would respond to market incentives with improved performance, increased attention to the needs of families, and greater innovation. Historical evidence is presented indicating that teachers and schools are indeed affected by the financial incentives of the systems in which they operate. In particular, the data show that economic pressures have forced schools in competitive markets to meet the needs of families, through methodological advancements and diversity in curriculum, while centralized bureaucratic systems have generally been coercive and pedagogically stagnant.
Small heat shock proteins are molecular chaperones. (1993)

Small heat shock proteins (sHsp) with a molecular mass of 15-30 kDa are ubiquitous and conserved. Up to now their function has remained enigmatic. Increased expression under heat shock conditions and their protective effect on cell viability at elevated temperatures suggest that they may have a function in the formation or maintenance of the native conformation of cytosolic proteins. To test this hypothesis we studied the influence of murine Hsp25, human Hsp27, and bovine alpha-B-crystallin (an eye lens protein homologous to sHsps) on the unfolding and refolding of citrate synthase and alpha-glucosidase in vitro. Here we show that all sHsps investigated act as molecular chaperones in these folding reactions. At stoichiometric amounts they maximally prevent the aggregation of citrate synthase and alpha-glucosidase under heat shock conditions and stabilize the proteins. Furthermore, they promote the functional refolding of these proteins after urea denaturation similar to GroE and Hsp90. The interaction both with unfolding and refolding proteins seems to be ATP-independent.
Cloning and expression of a Bacillus subtilis division initiation gene for which a homolog has not been identified in another organism (1989)

The Bacillus subtilis 168 division initiation genes defined by the temperature-sensitive mutations ts-1 and ts-12 were cloned into a 10.5-kilobase EcoRI fragment of DNA in the lambda EMBL4 vector. The two genes were separated by approximately 3 kilobases. The gene in which the ts-1 mutation resides was shown to be the same as the B. subtilis homolog of the Escherichia coli ftsZ gene. The other gene was named divIB. It showed no homology to any previously identified gene and coded for a protein of 30.1 kilodaltons which was probably membrane bound.
High Sensitivity Gravitational Wave Antenna with Parametric Transducer Readout (1995)

A high- $Q$ niobium resonant mass gravitational radiation antenna with a superconducting parametric transducer and noncontacting readout is shown to achieve a noise temperature of about 2 mK using a zero order predictor filter. The predicted intrinsic cold damping of a parametric transducer is confirmed, along with predicted backaction limits on the sensitivity. While the antenna has the highest intrinsic $Q$ factor and lowest noise temperature ever observed in a full scale antenna, the possibility of further improvements is demonstrated.
MemX: Virtualization of Cluster-Wide Memory (2010)

We present MemX -- a distributed system that virtualizes cluster-wide memory to support data-intensive and large memory workloads in virtual machines (VMs). MemX provides a number of benefits in virtualized settings: (1) VM workloads that access large datasets can perform low-latency I/O over virtualized cluster-wide memory; (2) VMs can transparently execute very large memory applications that require more memory than physical DRAM present in the host machine; (3) MemX reduces the effective memory usage of the cluster by de-duplicating pages that have identical content; (4) existing applications do not require any modifications to benefit from MemX such as the use of special APIs, libraries, recompilation, or relinking; and (5) MemX supports live migration of large-footprint VMs by eliminating the need to migrate part of their memory footprint resident on other nodes. Detailed evaluations of our MemX prototype show that large dataset applications and multiple concurrent VMs achieve significant performance improvements using MemX compared against virtualized local and iSCSI disks.
CO-releasing molecules (CORM-2)-liberated CO attenuates leukocytes infiltration in the renal tissue of thermally injured mice (2008)

CO delivered by CORM-2 attenuates leukocytes infiltration in the kidney of burned mice by interfering with NF-kBeta activation, protein expression of ICAM-1 and therefore suppressing endothelial cells pro-adhesive phenotype.
Photodynamic Synovectomy Using Benzoporphyrin Derivative in an Antigen‐induced Arthritis Model for Rheumatoid Arthritis (1998)

ABSTRACT Experimental photodynamic therapy (PDT) has recently been adapted for the treatment of inflammatory and rheumatoid arthritis. The biodistribution of benzoporphyrin derivative monoacid ring A (BPD‐MA) and the effect of percutaneous light activation via intra‐articular bare cleaved optical fibers was investigated using a rabbit‐antigen‐induced arthritis model. Qualitative evaluation of intra‐articular photosensitizer clearance was performed with laser‐induced fluorescence from 0 to 6 h following intravenous injection. The compound was rapidly taken up within the joint and then cleared steadily over the 6 h interval. Biodistribution was determined by fluorescence microscopy and spectrofluoroscopic extraction techniques 3 h following intravenous injection of 2 mg/kg BPD‐MA. The biodistribution study demonstrated elevated levels of BPD‐MA in synovium (0.35 μg/g) and muscle (0.35μg/g). Fluorescence microscopy demonstrated presence of the compound within pathologic synovium but absence of the photosensitizer within meniscus, ligament, bone and articular cartilage. Tissue effects were evaluated histologically at 2 and 4 weeks posttreatment. BPD‐MA‐mediated PDT caused synovial necrosis in the region of light activation in 50% of treatment knees at 2 weeks and 43% at 4 weeks. No damage to nonpathologic tissues was observed. These studies indicate that selective destruction of synovium can be achieved by the light‐activated photosensitizing agent BPD‐MA without damage to articular cartilage or periarticular soft tissues. PDT needs to be further evaluated to optimize treatment parameters to provide for a new minimally invasive synovectomy technique.
Therapeutic Vaccination Using Cationic Liposome-Adjuvanted HIV Type 1 Peptides Representing HLA-Supertype-Restricted Subdominant T Cell Epitopes: Safety, Immunogenicity, and Feasibility in Guinea-Bissau (2013)

We have designed a therapeutic HIV-1 vaccine concept based on peptides together with the adjuvant CAF01. Peptides represented 15 HLA-supertype-restricted subdominant and conserved CD8 T cell epitopes and three CD4 T-helper cell epitopes. In this phase I clinical trial, safety and immunogenicity were assessed in untreated HIV-1-infected individuals in Guinea-Bissau, West Africa. Twenty-three HIV-1-infected individuals were randomized to receive placebo (n=5) or vaccine (n=18). Safety was appraised by clinical follow-up combined with monitoring of biochemistry, hematology, CD4 T cell counts, and HIV-1 viral loads. T cell immunogenicity was monitored longitudinally by interferon (IFN)-γ ELISpot. New vaccine-specific T cell responses were induced in 6/14 vaccinees for whom ELISpot data were valid. CD4 T cell counts and viral loads were stable. The study shows that therapeutic immunization is feasible and safe in Guinea-Bissau and that it is possible to redirect T cell immunity with CAF01-adjuvanted HIV-1 peptide vaccine during untreated HIV-1 infection in some patients. However, relatively few preexisting and vaccine-induced HIV-1 T cell responses to CD8 T cell epitopes were detected against HIV-1 using IFN-γ ELISpot in this chronically infected African population.
Effectiveness of Influenza Vaccine in the Community-Dwelling Elderly (2007)

During 10 seasons, influenza vaccination was associated with significant reductions in the risk of hospitalization for pneumonia or influenza and in the risk of death among community-dwelling elderly persons. Vaccine delivery to this high-priority group should be improved.
Magnetic fields applied to collagen-coated ferric oxide beads induce stretch-activated Ca2+ flux in fibroblasts (1995)

The ability to apply controlled forces to the cell membrane may enable elucidation of the mechanisms and pathways involved in signal transduction in response to applied physical stimuli. We have developed a magnetic particle-electromagnet model that allows the application of controlled forces to the plasma membrane of substrate-attached fibroblasts. The system allows applied forces to be controlled by the magnitude of the magnetic field and by the surface area of cell membrane covered with collagen-coated ferric beads. Analysis by single-cell ratio fluorimetry of fura 2-loaded cells demonstrated large calcium transients (50-300 nM) in response to the magnetic force applications. Experiments using either the stretch-activated channel blocker gadolinium chloride or ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid to eliminate external calcium ions, or addition of extracellular manganese ions, indicated that there was a calcium influx through putative stretch-activated channels. The probability of a calcium influx in single cells was increased by higher surface bead loading and the degree of cell spreading. Depolymerization of actin filaments by cytochalasin D increased the amplitude of calcium response twofold. The regulation of calcium flux by filamentous actin content and by cell spreading indicates a possible modulatory role for the cytoskeleton in channel sensitivity. Magnetic force application to beads on single cells provides a controlled model to study mechanisms and heterogeneity in physical force stimulation of cation-permeable channels.