gebhart/patrepeval huggingface dataset:
Management of acute decompensated heart failure (2007)

Acute decompensated heart failure represents a heterogeneous group of disorders that typically present as dyspnea, edema and fatigue. Despite the high prevalence of this condition and its associated major morbidity and mortality, diagnosis can be difficult, and optimal treatment remains poorly defined. Identification of the acute triggers for the decompensation as well as noninvasive characterization of cardiac filling pressures and output is central to management. Diuretics, vasodilators, continuous positive airway pressure and inotropes can be used to alleviate symptoms. However, few agents currently available for the treatment of acute decompensated heart failure have been definitively shown in large prospective randomized clinical trials to provide meaningful improvements in intermediate-term clinical outcomes. Multiple novel therapies are being developed, but previous treatment failures indicate that progress in the management of acute decompensated heart failure is likely to be slow.
E4orf3 Is Necessary for Enhanced S-Phase Replication of Cell Cycle-Restricted Subgroup C Adenoviruses (2003)

E1B-55K-mutant or E4orf6-mutant adenoviruses replicate more effectively after infecting cells in S phase than after infecting cells in G(1). Enhanced S-phase replication of the E4orf6-mutant viruses requires the E4orf3 gene. This report demonstrates that the E4orf3 gene is also required for enhanced S-phase replication of the E1B-55K-mutant virus.
Comparison of the effects of antibody-coated liposomes, IVIG, and anti-RBC immunotherapy in a murine model of passive chronic immune thrombocytopenia (2006)

The present work evaluated antibody-coated liposomes as a new treatment strategy for immune thrombocytopenic purpura (ITP) through the use of a mouse model of the disease. Effects of antimethotrexate antibody (AMI)-coated liposomes and intravenous immunoglobulin (IVIG)-coated liposomes (15, 30, 60 micromol lipid/kg) were compared with the effects of IVIG (0.4, 1, 2 g/kg) and anti-red blood cell (anti-RBC) monoclonal antibody immunotherapy (TER119, 5, 15, 25, and 50 microg/mouse) on MWReg30-induced thrombocytopenia. Each treatment was found to attenuate thrombocytopenia in a dose-dependent manner and, consistent with previous work, IVIG was found to increase antiplatelet antibody clearance in a dose-dependent manner. TER119 demonstrated greater effects on thrombocytopenia relative to other therapies (peak platelet counts: 224% +/- 34% of initial platelet counts for 50 microg TER119/mouse versus 160% +/- 34% for 2 g/kg IVIG, 88% +/- 36% for 60 micromol lipid/kg AMI-coated liposomes, and 80% +/- 25% for 60 micromol lipid/kg IVIG-coated liposomes). However, the effects of TER119 were associated with severe hemolysis, as TER119 decreased RBC counts by approximately 50%. The present work demonstrated that antibody-coated liposomes attenuated thrombocytopenia in this model at a much lower immunoglobulin dose than that required for IVIG effects and, in contrast with TER119, antibody-coated liposomes increased platelet counts without altering RBC counts.
Structure, mechanism and function of prenyltransferases (2002)

In this review, we summarize recent progress in studying three main classes of prenyltransferases: (a) isoprenyl pyrophosphate synthases (IPPSs), which catalyze chain elongation of allylic pyrophosphate substrates via consecutive condensation reactions with isopentenyl pyrophosphate (IPP) to generate linear polymers with defined chain lengths; (b) protein prenyltransferases, which catalyze the transfer of an isoprenyl pyrophosphate (e.g. farnesyl pyrophosphate) to a protein or a peptide; (c) prenyltransferases, which catalyze the cyclization of isoprenyl pyrophosphates. The prenyltransferase products are widely distributed in nature and serve a variety of important biological functions. The catalytic mechanism deduced from the 3D structure and other biochemical studies of these prenyltransferases as well as how the protein functions are related to their reaction mechanism and structure are discussed. In the IPPS reaction, we focus on the mechanism that controls product chain length and the reaction kinetics of IPP condensation in the cis-type and trans-type enzymes. For protein prenyltransferases, the structures of Ras farnesyltransferase and Rab geranylgeranyltransferase are used to elucidate the reaction mechanism of this group of enzymes. For the enzymes involved in cyclic terpene biosynthesis, the structures and mechanisms of squalene cyclase, 5-epi-aristolochene synthase, pentalenene synthase, and trichodiene synthase are summarized.
Experimental support for Schachar's hypothesis of accommodation. (1993)

To determine the physical effect of a change in the equatorial lenticular diameter on optical power, sclera-ciliary bodies of bovine eyes were stretched radially. The effective optical power and lenticular equatorial diameter were measured. We found that an increase in the equatorial diameter of the bovine lens produced an increase in its effective optical power. Our results directly contradict Helmholtz's hypothesis of accommodation and its modifications. These results support Schachar's hypothesis of accommodation, which states that there is increased zonular tension during accommodation.
<title>Parallel immunoassays on HydroGel biochips using microspot arrays</title> (2002)

Parallel immunoassay enable simultaneous detection of many analytes forma small volume of sample fluid. The use of exceedingly small quantities of capture antibody immobilized in microspots facilitates ambient analyte assay conditions. Under these assy conditions, the fractional occupancy of capture antibody is independent of sample volume. Analyte concentrations are thus measured with greater sensitivity and potentially greater speed. The small drop size delivered by the Packard BioChip Arrayer, a non-contact piezoelectric robotic dispenser, enables the production of arrays consisting of high reproducible microspots of antibodies. The Packard HyrdoGel coated slide is a porous substrate based on a polymer matrix that provides a 3D hydrophilic environment similar to free solution suitable for biomolecular interactions. This substrate has been used to develop fluorescence-based detection immunoassay in multiplex with high sensitivity and offers advantages of increased probe capacity, functionality and accessability for other biomolecular screening applications. Images are captured with the ScanArray confocal laserscanner, which offers the use to choose from a wide range of fluorescent dyes with high resolution and sensitivity, and analyzed with QuantArray microarray analysis software, which enables researchers to easily and accurately visualize and quantitate gene expression and proteomics data.
A mutational analysis of the polypyrimidine tract of introns. Effects of sequence differences in pyrimidine tracts on splicing (1993)

The polypyrimidine (py) tract of introns is required for efficient spliceosome assembly and splicing of pre-mRNAs. A detailed mutational analysis of the py tract of an adenovirus 2 intron was carried out. Utilizing a "precursor in pieces" vector system, it was possible to synthesize py tract mutant pre-mRNAs that were otherwise identical. The mutant pre-mRNAs that were otherwise identical. The mutant pre-mRNAs were analyzed for in vitro splicing, for formation of splicing complexes, and for binding to proteins in the HeLa nuclear extract. Chimeric pre-mRNAs that contained the yeast branch point consensus sequence (UAC-UAAC) and altered py tracts were also analyzed. Mutational analysis showed the following. First, any mutation in the py tract that affected splicing did so by interferring with complex A formation in spliceosome assembly. Second, introduction of purines into the py tract is detrimental only if the length of the tract is shortened and if there is a reduction in the number of consecutive uracil residues. Third, uracil and cytosine do not have equivalent functions in the py tract. Our results with chimeric pre-mRNAs also show that a strong py tract can partially replace a weak branch point sequence and a strong branch point sequence can partially replace a weak py tract. Finally, the one surprising finding obtained when examining protein binding was that a mutant pre-mRNA did not bind to heterogeneous nuclear ribonucleoprotein C proteins and yet spliced close to wild type level.
Immunogenicity of a soluble partially purified oncofetal antigen from murine fibrosarcoma in syngeneic mice. (1989)

A tumor/fetal associated antigen, termed oncofetal antigen (OFA), conserved in the tumor and fetal tissue of rodents and humans, was extracted from murine fibrosarcoma cells and tumors and was fractionated on an Ultrogel AcA34 gel filtration column. A monoclonal antibody 115 specific for the OFA identified three peaks of antigenic activity in the eluted fractions, designated fractions (Fr.) I, II, and III, in the molecular weight range of greater than 160, 90, and 44 kDa, respectively. Most of the activity resided in the high molecular weight fraction, Fr. I. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and gel scanning of Fr. I showed multiple bands, one of which, constituting about 5.6% of the total protein bands in Fr. I, was the 44 kDa oncofetal antigen, apparently present in this fraction in a soluble complex form. Lectin binding studies and isoelectric focusing showed that the 44 kDa OFA is a glycoprotein, whose pI is 6.8. Spleen and peritoneal exudate cells of BALB/c mice immunized with Fr. I protected naive syngeneic mice, in adoptive transfer experiments, from developing tumors when challenged with syngeneic fibrosarcoma tumor cells, MCA-1315. Also, immune spleen cells were cytotoxic to the tumor target cells, MCA-1315, in a 51Cr release assay at several different effector to target cell ratios. This is the first description of a conserved, true, oncofetal antigen capable of inducing tumor transplantation resistance in syngeneic rodents in a semipurified form.
Vaccinia virus semaphorin A39R is a 50–55 kDa secreted glycoprotein that affects the outcome of infection in a murine intradermal model (2001)

Vaccinia virus (VV) protein A39R has amino acid similarity to the extracellular domain of a glycosylphosphatidylinositol-linked cell surface semaphorin (SEMA7A/CDw108) that has an immunological expression profile and binding properties, thereby implicating A39R as an immunomodulator. Previously, a closely related A39R protein expressed by ectromelia virus was shown to induce cytokine production and up-regulate ICAM-1 expression in mouse monocytes in vitro. In this study, we show that the A39R gene of VV strain Copenhagen (COP) encodes a 50-55 kDa secreted glycoprotein and is expressed late during infection. The A39R protein was secreted by eight of 15 strains of VV, but not by strain Western Reserve (WR). To analyse the VV A39R function, several recombinant viruses were made, including an A39R deletion mutant of VV COP and a WR mutant containing the A39R sequence from COP. Loss of the gene from COP did not affect virus growth in vitro, or VV virulence in a mouse intranasal model, and had only a slight effect on lesion size in an intradermal model. In contrast, expression of COP A39R by VV WR was associated with an increase in the severity and persistence of skin lesions after intradermal infection of mice. Finally, a histological examination of mouse skin infected with recombinant viruses suggested that A39R has direct or indirect pro-inflammatory properties.
An adaptation of Relief for attribute estimation in regression (1997)

Heuristic measures for estimating the quality of attributes mostly assume the independence of attributes so in domains with strong dependencies between attributes their performance is poor. Relief and its extension ReliefF are capable of correctly estimating the quality of attributes in classification problems with strong dependencies between attributes. By exploiting local information provided by different contexts they provide a global view. We present the analysis of ReliefF which lead us to its adaptation to regression (continuous class) problems. The experiments on artificial and real-world data sets show that Regressional ReliefF correctly estimates the quality of attributes in various conditions, and can be used for non-myopic learning of the regression trees. Regressional ReliefF and ReliefF provide a unified view on estimating the attribute quality in regression and classification. 1 Introduction The majority of current propositional inductive learning systems predict discret...
A new model of LPC excitation for producing natural-sounding speech at low bit rates (2005)

The excitation for LPC speech synthesis usually consists of two separate signals - a delta-function pulse once every pitch period for voiced speech and white noise for unvoiced speech. This manner of representing excitation requires that speech segments be classified accurately into voiced and unvoiced categories and the pitch period of voiced segments be known. It is now well recognized that such a rigid idealization of the vocal excitation is often responsible for the unnatural quality associated with synthesized speech. This paper describes a new approach to the excitation problem that does not require a priori knowledge of either the voiced-unvoiced decision or the pitch period. All classes of sounds are generated by exciting the LPC filter with a sequence of pulses; the amplitudes and locations of the pulses are determined using a non-iterative analysis-by-synthesis procedure. This procedure minimizes a perceptual-distance metric representing subjectively-important differences between the waveforms of the original and the synthetic speech signals. The distance metric takes account of the finite-frequency resolution as well as the differential sensitivity of the human ear to errors in the formant and inter-formant regions of the speech spectrum.
Extracellular ATP activates mast cells via a mechanism that is different from the activation induced by the cross-linking of Fc receptors (1996)

In this study, the extracellular ATP (ATPo)-induced biochemical events were elucidated by comparing them with either the Fc epsilon RI- or Fc gamma R-induced events in the mouse mast cell line MC9. The omission of extracellular Ca2+ almost completely abolished the elevation of intracellular Ca2+ ([Ca2+]i) in the ATPo-stimulated cells, but only suppressed the second phase of the increase of [Ca2+]i in FcR-stimulated cells, thus suggesting that the ATPo-induced elevation of [Ca2+]i is totally dependent on the entry of extracellular Ca2+. Pretreatment with genistein, which inhibits protein kinases, especially protein tyrosine kinase, inhibited the FcR-triggered increase of [Ca2+]i, but not the ATPo-triggered one; however, such pretreatment did suppress both ATPo- and FcR-mediated beta-hexosaminidase release. An immunoblot analysis revealed that both ATPo and the cross-linking of FcRs led to tyrosine phosphorylation of 44- and 110-kDa proteins, which thus suggested that these tyrosine-phosphorylated proteins are involved in a modulation of the degranulation process following an elevation of [Ca2+]i. Pretreatment with PMA inhibited the FcR-induced [Ca2+]i increase, while not inhibiting the ATPo-induced one, thus suggesting that ATPo can mobilize [Ca2+]i even when protein kinase C (PKC) has already been activated. Pretreatment of calphostin C, a specific PKC inhibitor, had little effect on the ATPo-mediated beta-hexosaminidase secretion, thus indicating that the ATPo-induced degranulation is not mediated by PKC. Taken together, these results demonstrate that ATPo activates MC9 mast cells by a mechanism that is different from the activation induced by the cross-linking of FcRs.
Individualised cancer therapeutics: dream or reality? Therapeutics construction (2005)

The analysis of DNA microarray and proteomic data, and the subsequent integration into functional expression sets, provides a circuit map of the hierarchical cellular networks responsible for sustaining the viability and environmental competitiveness of cancer cells, that is, their robust systematics. These technologies can be used to 'snapshot' the unique patterns of molecular derangements and modified interactions in cancer, and allow for strategic selection of therapeutics that best match the individual profile of the tumour. This review highlights technology that can be used to selectively disrupt critical molecular targets and describes possible vehicles to deliver the synthesised molecular therapeutics to the relevant cellular compartments of the malignant cells. RNA interference (RNAi) involves a group of evolutionarily conserved gene silencing mechanisms in which small sequences of double-stranded RNA or intrinsic antisense RNA trigger mRNA cleavage or translational repression, respectively. Although RNAi molecules can be synthesised to 'silence' virtually any gene, even if upregulated, a mechanism for selective delivery of RNAi effectors to sites of malignant disease remains challenging. The authors will discuss gene-modified conditionally replicating viruses as candidate vehicles for the delivery of RNAi.
Efficacy of Chemokine Receptor Inhibition in Treating IL-36α–Induced Psoriasiform Inflammation (2019)

Several types of psoriasiform dermatitis are associated with increased IL-36 cytokine activity in the skin. A rare, but severe, psoriasis-like disorder, generalized pustular psoriasis (GPP), is linked to loss-of-function mutations in the gene encoding IL-36RA, an important negative regulator of IL-36 signaling. To understand the effects of IL-36 dysregulation in a mouse model, we studied skin inflammation induced by intradermal injections of preactivated IL-36α. We found the immune cells infiltrating IL-36α-injected mouse skin to be of dramatically different composition than those infiltrating imiquimod-treated skin. The IL-36α-induced leukocyte population comprised nearly equal numbers of CD4<sup>+</sup> αβ T cells, neutrophils, and inflammatory dendritic cells, whereas the imiquimod-induced population comprised γδ T cells and neutrophils. Ligands for chemokine receptors CCR6 and CXCR2 are increased in both GPP and IL-36α-treated skin, which led us to test an optimized small-molecule antagonist (CCX624) targeting CCR6 and CXCR2 in the IL-36α model. CCX624 significantly reduced the T cell, neutrophil, and inflammatory dendritic cell infiltrates and was more effective than saturating levels of an anti-IL-17RA mAb at reducing inflammatory symptoms. These findings put CCR6 and CXCR2 forward as novel targets for a mechanistically distinct therapeutic approach for inflammatory skin diseases involving dysregulated IL-36 signaling, such as GPP.
Socket location in total hip replacement Preoperative computed tomography and computer simulation (1988)

For choosing the size and location of the acetabular component, we have developed a three-dimensional simulation system based on computerized tomography and a microcomputer. In 34 cases of coxarthrosis secondary to congenital dysplasia or dislocation, the system provided valuable preoperative information.
Trichomonas vaginalis in Selected US Sexually Transmitted Disease Clinics (2013)

Trichomoniasis is common among STD clinic patients. In this analysis, most STD clinics tested symptomatic women seeking care, in accordance with national guidelines. All HIV-infected women should be screened annually. Additional evidence and national guidance are needed regarding potential benefits of T. vaginalis screening in other asymptomatic women.
Designing a positioning system for finding things and people indoors (1998)

Despite extraordinary advances in Global Positioning System (GPS) technology, millions of square meters of indoor space are out of reach of Navstar satellites. Their signals, originating high above the Earth, are not designed to penetrate most construction materials, and no amount of technical wizardry is likely to help. So the greater part of the world's commerce, being conducted indoors, cannot be followed by GPS satellites. Here, the authors describe how tracking people and assets indoors has now moved from the realm of science fiction to reality, thanks to a radiofrequency identification technique now being introduced to the market.
High Dynamic Range from Multiple Images: Which Exposures to Combine?∗ (2003)

Many computer vision algorithms rely on precise estimates of scene radiances obtained from an image. A simple way to acquire a larger dynamic range of scene radiances is by combining several exposures of the scene. The number of exposures and their values have a dramatic impact on the quality of the combined image. At this point, there exists no principled method to determine these values. Given a camera with known response function and dynamic range, we wish to find the exposures that would result in a set of images that when combined would emulate an effective camera with a desired dynamic range and a desired response function. We first prove that simple summation combines all the information in the individual exposures without loss. We select the exposures by minimizing an objective function that is based on the derivative of the response function. Using our algorithm, we demonstrate the emulation of cameras with a variety of response functions, ranging from linear to logarithmic. We verify our method on several real scenes. Our method makes it possible to construct a table of optimal exposure values. This table can be easily incorporated into a digital camera so that a photographer can emulate a wide variety of high dynamic range cameras by selecting from a menu. 1 Capturing a Flexible Dynamic Range Many computer vision algorithms require accurate estimates of scene radiance such as color constancy [9], inverse rendering [13, 1] and shape recovery [17, 8, 18]. It is difficult to capture both the wide range of radiance values real scenes produce and the subtle variations within them using a low cost digital camera. This is because any camera must assign a limited number of brightness values to the entire range of scene radi-
Hepatocyte Transplantation: An Alternative System for Evaluating Cell Survival and Immunoisolation (1993)

To evaluate systems for barrier immunoisolation of transplanted hepatocytes, we used transgenic mouse hepatocytes that secrete HBsAg. Hepatocytes were rapidly encapsulated in chitosan, a cationic polymer derived by deacetylation of chitin. Chitosan was allowed to electrostatically bond with anionic sodium alginate for creating an outer bipolymer membrane of the capsules. After encapsulation, hepatocyte viability remained unchanged for seven days in vitro with secretion of HBsAg into the culture medium throughout this period. Following intraperitoneal transplantation of encapsulated hepatocytes, HBsAg promptly appeared in blood of recipients. In congeneic recipients, serum HBsAg peaked at two weeks. Hepatocytes were present in recovered chitosan capsules and expressed HBsAg mRNA. In allogeneic recipients, however, serum HBsAg disappeared within one week and recovered chitosan capsules showed lymphomononuclear cells but not hepatocytes. Transplantation of chitosan encapsulated HbsAg secreting hepatocytes failed to induce an anti-HBs response, suggesting modulation of the host immune response. These results indicate that transplantation systems using genetically modified hepatocytes which secrete gene products in the blood of recipients should facilitate evaluation of hepatocyte encapsulation.
Efficacy and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: results of the randomized, double‐blind, phase III NAVIGATE trial (2017)

Patients treated with ustekinumab who did not achieve an IGA of 0/1 by week 16 derived significant benefit from switching to guselkumab.