gebhart/patrepeval huggingface dataset:
Rapid-onset clinical and mechanistic effects of anti-C5aR treatment in the mouse collagen-induced arthritis model (2014)

Preclinical evidence supports targeting the C5a receptor (C5aR) in rheumatoid arthritis (RA). To support ongoing clinical development of an anti-C5aR monoclonal antibody, we have investigated for the first time the mechanism of action and the pharmacodynamics of a blocking anti-murine C5aR (anti-mC5aR) surrogate antibody in mouse collagen-induced arthritis (CIA). First, efficacy was demonstrated in a multiple-dose treatment study. Almost complete inhibition of clinical disease progression was obtained, including reduced bone and cartilage destruction in anti-mC5aR-treated mice. Then, the mechanism of action was examined by looking for early effects of anti-mC5aR treatment in single-dose treatment studies. We found that 48 h after single-dose treatment with anti-mC5aR, the neutrophil and macrophage infiltration into the paws was already reduced. In addition, several inflammatory markers, including tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-17A were reduced locally in the paws, indicating reduction of local inflammation. Furthermore, dose-setting experiments supported a beneficial clinical effect of dosing above the C5aR saturation level. In conclusion, these preclinical data demonstrated rapid onset effects of antibody blockade of C5aR. The data have translational value in supporting the Novo Nordisk clinical trials of an anti-C5aR antibody in rheumatoid arthritis patients, by identifying potential biomarkers of treatment effects as well as by providing information on pharmacodynamics and novel insights into the mechanism of action of monoclonal antibody blockade of C5aR.
Applied logistic regression (1990)

From the reviews of the First Edition. An interesting, useful, and well-written book on logistic regression models... Hosmer and Lemeshow have used very little mathematics, have presented difficult concepts heuristically and through illustrative examples, and have included references.- Choice Well written, clearly organized, and comprehensive... the authors carefully walk the reader through the estimation of interpretation of coefficients from a wide variety of logistic regression models . . . their careful explication of the quantitative re-expression of coefficients from these various models is excellent. - Contemporary Sociology An extremely well-written book that will certainly prove an invaluable acquisition to the practicing statistician who finds other literature on analysis of discrete data hard to follow or heavily theoretical.-The Statistician In this revised and updated edition of their popular book, David Hosmer and Stanley Lemeshow continue to provide an amazingly accessible introduction to the logistic regression model while incorporating advances of the last decade, including a variety of software packages for the analysis of data sets. Hosmer and Lemeshow extend the discussion from biostatistics and epidemiology to cutting-edge applications in data mining and machine learning, guiding readers step-by-step through the use of modeling techniques for dichotomous data in diverse fields. Ample new topics and expanded discussions of existing material are accompanied by a wealth of real-world examples-with extensive data sets available over the Internet.
Structural analysis of chick-embryo cartilage proteoglycan by selective degradation with chondroitin lyases (chondroitinases) and endo-β-d-galactosidase (keratanase) (1980)

Digestion of chick-embryo cartilage proteoglycan (type H) with chondroitin AC II lyase or keratanase, in the presence of EDTA, N-ethylmaleimide, phenylmethanesulphonyl fluoride and pepstatin, resulted in the removal of the bulk of the chondroitin sulphate or keratan sulphate chains respectively, without altering the protein portion of the macromolecule. An exhaustive treatment of the proteoglycan with chondroitin AC II lyase followed by digestion with keratanase yielded a core fraction having the enzymically modified linkage oligosaccharides. Zonal sedimentation of this core preparation on a sucrose gradient in 0.5% SDS resulted in a single narrow band with a sedimentation coefficient of 6S. In 4 M-guanidinium chloride, the core preparation showed a tendency to aggregate to multiple-molecular-weight forms which could dissociate in the presence of Triton X-100. The results indicate that the preponderance of glycosaminoglycans in the proteoglycan molecule is a main reason for both polydispersity and hydrophilicity of the proteoglycan preparation, and further suggest that the enzymic procedures could prove useful as a method to obtain new information about the structure and properties of proteoglycan core molecules.
Microsomal Heme Oxygenase (1969)

Abstract This study characterizes microsomal heme oxygenase, a previously undescribed enzyme which catalyzes the oxidation of heme at the α-methene bridge to form biliverdin. This step is then coupled with soluble NADPH-dependent biliverdin reductase to form bilirubin; microsomal heme oxygenase is rate-limiting in this pathway. By all analytical criteria, the product of this reaction is bilirubin. Most, if not all, of the bilirubin is of the IX α configuration, which is the sole isomeric form of bilirubin occurring physiologically. Heme oxygenase is localized specifically to the microsomal fraction, has an absolute and stoichiometric requirement for NADPH and molecular oxygen, generates carbon monoxide in amounts equimolar to bilirubin, and is inhibited by carbon monoxide. These and other data suggest that this enzyme is a mixed function oxygenase. The enzyme is most active with protohemin IX or methemalbumin; substrates with less activity are methemoglobin, the α and β chains of hemoglobin, deuterohemin IX, coprohemin I, and the hemoglobin-haptoglobin complex, in this order. Oxyhemoglobin, carboxyhemoglobin, myoglobin, and free porphyrins are not acted upon by the enzyme. The apparent Km for protohemin IX is 5.0 µm, and for the other substrates ranges from 4.5 to 5.1 µm. Sodium dodecyl sulfate, lipase, phospholipase, trypsin, potassium cyanide, sodium azide, and p-hydroxymercuribenzoate inhibit the enzyme. The kinetics and tissue distribution of this enzyme suggest that it is of major importance in the physiological degradation of hemoglobin and other hemoproteins to bile pigment.
Surface Macromolecular Microarchitecture Design:  Biocompatible Surfaces via Photo-Block-Graft-Copolymerization Using N,N-Diethyldithiocarbamate (1999)

The photo-block-graft-copolymerization method using an iniferter, benzyl N,N-diethyldithiocarbamate, was utilized to design a biomedically functional surface for fabricated devices. Ultraviolet light irradiation under sequential charge of vinyl monomers, such as acrylic acid (AA), n-butyl methacrylate (BMA), N,N-dimethylacrylamide (DMAAm), N-[3-(dimethylamino)propyl]acrylamide (DMAPAAm), or styrene (ST), produced block-grafted surfaces, in which different polymer blocks were sequentially formed on polyST (PST) partially derivatized with N,N-diethyldithiocarbamate groups. Examination of a cross-sectional view under a transmission electron microscope (TEM) revealed a bilayered structure of the PST-b-PDMAAm block-graft copolymer. Three different AB-type block-graft-copolymerized surfaces were prepared for biomedical applications, where block A was the bottom layer and block B the top layer: (1) For heparin immobilization, a polyPDMAPAAm (PDMAPAAm) (A)−polyDMAAm (PDMAAm) (B) block-graft-copolymerized surface was prepared, where the block A layer contained ionically immobilized heparin and the block B layer functioned as a protective layer to suppress protein adsorption and cell adhesion. (2) For protein immobilization, a PDMAAm (A)-polyAA (PAA) (B) block-graft-copolymerized surface was prepared, where the block B layer covalently fixed the protein and the block A layer functioned as a protective layer to prevent contact of the protein with the substrate. (3) For a drug-releasing surface, a PDMAAm (A)-polyBMA (PBMA) (B) block-graft-copolymerized surface was prepared, where the block A layer contained the drug and the block B layer functioned as a barrier to regulate drug release. These macromolecularly designed surfaces were characterized by X-ray photoelectron spectroscopy, and the immobilization of heparin and protein was visualized by light microscopy, after staining with toluidine blue (for heparin), and fluorescence microscopy (for protein).
Cochlear Fluid Space Dimensions for Six Species Derived From Reconstructions of Three‐Dimensional Magnetic Resonance Images (1999)

The quantification of cochlear fluid spaces provided by this study will enable the more accurate calculation of drug and other solute movements in fluids of the inner ear during experimental or clinical manipulations.
Symmetrical dimethylarginine methylation is required for the localization of SMN in Cajal bodies and pre-mRNA splicing (2002)

The nuclear structures that contain symmetrical dimethylated arginine (sDMA)-modified proteins and the role of this posttranslational modification is unknown. Here we report that the Cajal body is a major epitope in HeLa cells for an sDMA-specific antibody and that coilin is an sDMA-containing protein as analyzed by using the sDMA-specific antibody and matrix-assisted laser desorption ionization time of flight mass spectrometry. The methylation inhibitor 5'-deoxy-5'-methylthioadenosine reduces the levels of coilin methylation and causes the appearance of SMN-positive gems. In cells devoid of Cajal bodies, such as primary fibroblasts, sDMA-containing proteins concentrated in speckles. Cells from a patient with spinal muscular atrophy, containing low levels of the methyl-binding protein SMN, localized sDMA-containing proteins in the nucleoplasm as a discrete granular pattern. Splicing reactions are efficiently inhibited by using the sDMA-specific antibody or by using hypomethylated nuclear extracts, showing that active spliceosomes contain sDMA polypeptides and suggesting that arginine methylation is important for efficient pre-mRNA splicing. Our findings support a model in which arginine methylation is important for the localization of coilin and SMN in Cajal bodies.
A Comparison between Brachial and Echocardiographic Systolic Time Intervals (2013)

Systolic time interval (STI) is an established noninvasive technique for the assessment of cardiac function. Brachial STIs can be automatically determined by an ankle-brachial index (ABI)-form device. The aims of this study are to evaluate whether the STIs measured from ABI-form device can represent those measured from echocardiography and to compare the diagnostic values of brachial and echocardiographic STIs in the prediction of left ventricular ejection fraction (LVEF) <50%. A total of 849 patients were included in the study. Brachial pre-ejection period (bPEP) and brachial ejection time (bET) were measured using an ABI-form device and pre-ejection period (PEP) and ejection time (ET) were measured from echocardiography. Agreement was assessed by correlation coefficient and Bland-Altman plot. Brachial STIs had a significant correlation with echocardiographic STIs (r = 0.644, P<0.001 for bPEP and PEP; r = 0.850, P<0.001 for bET and ET; r = 0.708, P<0.001 for bPEP/bET and PEP/ET). The disagreement between brachial and echocardiographic STIs (brachial STIs minus echocardiographic STIs) was 28.55 ms for bPEP and PEP, -4.15 ms for bET and ET and -0.11 for bPEP/bET and PEP/ET. The areas under the curve for bPEP/bET and PEP/ET in the prediction of LVEF <50% were 0.771 and 0.765, respectively. Brachial STIs were good alternatives to STIs obtained from echocardiography and also helpful in prediction of LVEF <50%. Brachial STIs automatically obtained from an ABI-form device may be helpful for evaluation of left ventricular systolic dysfunction.
Second Generation of Antisense Oligonucleotides: From Nuclease Resistance to Biological Efficacy in Animals (1996)

From efforts to improve the biophysical properties of antisense oligonucleotides by incorporating backbone- or sugar-modified nucleoside analogs, 2'-O-methoxyethyl ribonucleosides 8b were identified as building blocks for a second generation of antisense oligonucleotides. Compounds containing these modifications were demonstrated to combine the benefit of a high binding affinity to the RNA complement with a large increase in nuclease resistance, allowing the use of regular phosphodiester linkages. Chimeric oligonucleotides with 2'-O-methoxyethyl ribonucleosides, 8b, in the wings and a central DNA-phosphorothioate window were shown to efficiently downregulate C-'raf' kinase and PKC-α messenger-RNA in tumor cell lines resulting in a profound inhibition of cell proliferation. The same compounds were able to effectively reduce the growth of tumors in animal models at low concentrations indicating the potential utility of these second generation antisense oligonucleotides for therapeutic applications.
Cyclin D1 Overexpression versus Response to Induction Chemotherapy in Squamous Cell Carcinoma of the Head and Neck—Preliminary Report (2001)

The aim of this study was to investigate whether there is an association between overexpression of cyclin D1 and response to therapy. Immunohistochemical overexpression of cyclin D1 was determined in paraffin-embedded specimens from diagnostic biopsies of 89 primary cases of squamous cell carcinoma of the head and neck (SCCHN), using a polyclonal antiserum. The tumor response rates were estimated after curative treatment (i.e. surgery and/or radiotherapy and/or chemotherapy). Patients whose tumors were overexpressing cyclin D1 showed complete or partial response to neoadjuvant chemotherapy with cisplatin/5-FU. In addition, a majority of cyclin D1 negative tumors did not respond at all to this treatment (p = 0.02, Fisher's exact test). This study indicates that immunohistochemical assessment of cyclin D1 expression in SCCHN could be a new predictive marker to select a subgroup of patients that will benefit from neoadjuvant chemotherapy.
Ex vivo gene therapy for Alzheimer's disease and spinal cord injury. (1997)

Gene transfer is a potential means of treating chronic neurologic disorders and injury related neural degeneration. One approach for transferring genes to the CNS is to genetically modify cells in vitro and then transplant the cells to the CNS. For example, fibroblasts can be infected with a replication-defective retrovirus expressing a transgene, and can then be transplanted into the brain or spinal cord, thereby providing neurotrophic factors and substrates for axonal growth and elongation. In this review we discuss the grafting of neurotrophic factor secreting autologous fibroblasts in the rat and primate CNS. NGF secreting grafts have been shown to prevent degeneration of cholinergic neurons in the basal forebrain of primates and to induce sprouting of sensory, motor, and noradrenergic neurites after spinal cord injury. These results suggest the potential usefulness of ex vivo gene transfer for the treatment of Alzheimer's disease and spinal cord injury.
Subsurface tissue lesions created using an Nd:YAG laser and a sapphire contact cooling probe (2004)

Noninvasive laser procedures targeting tissue structures for thermal coagulation within a few millimeters of the tissue surface are feasible and may expand the use of combined laser/cooling techniques for applications in urology and general surgery. In vivo animal studies are currently in development to optimize the laser and cooling parameters for potential clinical applications.
Amorphous and Polycrystalline Photoconductors for Direct Conversion Flat Panel X-Ray Image Sensors (2011)

In the last ten to fifteen years there has been much research in using amorphous and polycrystalline semiconductors as x-ray photoconductors in various x-ray image sensor applications, most notably in flat panel x-ray imagers (FPXIs). We first outline the essential requirements for an ideal large area photoconductor for use in a FPXI, and discuss how some of the current amorphous and polycrystalline semiconductors fulfill these requirements. At present, only stabilized amorphous selenium (doped and alloyed a-Se) has been commercialized, and FPXIs based on a-Se are particularly suitable for mammography, operating at the ideal limit of high detective quantum efficiency (DQE). Further, these FPXIs can also be used in real-time, and have already been used in such applications as tomosynthesis. We discuss some of the important attributes of amorphous and polycrystalline x-ray photoconductors such as their large area deposition ability, charge collection efficiency, x-ray sensitivity, DQE, modulation transfer function (MTF) and the importance of the dark current. We show the importance of charge trapping in limiting not only the sensitivity but also the resolution of these detectors. Limitations on the maximum acceptable dark current and the corresponding charge collection efficiency jointly impose a practical constraint that many photoconductors fail to satisfy. We discuss the case of a-Se in which the dark current was brought down by three orders of magnitude by the use of special blocking layers to satisfy the dark current constraint. There are also a number of polycrystalline photoconductors, HgI(2) and PbO being good examples, that show potential for commercialization in the same way that multilayer stabilized a-Se x-ray photoconductors were developed for commercial applications. We highlight the unique nature of avalanche multiplication in a-Se and how it has led to the development of the commercial HARP video-tube. An all solid state version of the HARP has been recently demonstrated with excellent avalanche gains; the latter is expected to lead to a number of novel imaging device applications that would be quantum noise limited. While passive pixel sensors use one TFT (thin film transistor) as a switch at the pixel, active pixel sensors (APSs) have two or more transistors and provide gain at the pixel level. The advantages of APS based x-ray imagers are also discussed with examples.
<title>Coding of hyperspectral imagery using adaptive classification and trellis-coded quantization</title> (1997)

A system is presented for compression of hyperspectral imagery. Specifically, DPCM is used for spectral decorrelation, while an adaptive 2D discrete cosine transform coding scheme is used for spatial decorrelation. Trellis coded quantization is used to encode the transform coefficients. Side information and rate allocation strategies are discussed. Entropy-constrained codebooks are designed using a modified version of the generalized Lloyd algorithm. This entropy constrained system achieves a compression ratio of greater than 70:1 with an average PSNR of the coded hyperspectral sequence approaching 41 dB.
Identification and Characterization of thecpsLocus ofStreptococcus suisSerotype 2: the Capsule Protects against Phagocytosis and Is an Important Virulence Factor (1999)

To study the role of the capsule of Streptococcus suis serotype 2 in virulence, we generated two isogenic mutants disturbed in capsule production. For that purpose, we first cloned and characterized a major part of the capsular polysaccharide biosynthesis (cps) locus of S. suis serotype 2. Based on the established sequence, 14 open reading frames (ORFs), designated Orf2Z, Orf2Y, Orf2X, and Cps2A to Cps2K, were identified. Twelve ORFs belonged to a single transcriptional unit. The gene products of 11 of these ORFs showed similarity to proteins involved in polysaccharide biosynthesis of other gram-positive microorganisms. Nonencapsulated isogenic mutants were generated in the cps2B and cps2EF genes by insertional mutagenesis. In contrast to the wild-type S. suis serotype 2 strain, the nonencapsulated strains were highly sensitive to ingestion by porcine alveolar lung macrophages in vitro. More importantly, the nonencapsulated mutant strains were completely avirulent in young germfree pigs after intranasal inoculation. These observations indicate that the capsule of S. suis serotype 2 plays an essential role in the pathogenesis of S. suis serotype 2 infections.
Pilot Evaluation of Energy Savings from Residential Energy Demand Feedback Devices (2008)

This report discusses instantaneous feedback on household electrical demand has shown promise to reduce energy consumption. This report reviews past research and describes a two year pilot evaluation of a low cost residential energy feedback system installed in twenty case study homes in FL.
Analysis of the Mechanism and Regulation of Lactose Transport and Metabolism in Clostridium acetobutylicum ATCC 824 (2007)

Although the acetone-butanol-ethanol fermentation of Clostridium acetobutylicum is currently uneconomic, the ability of the bacterium to metabolize a wide range of carbohydrates offers the potential for revival based on the use of cheap, low-grade substrates. We have investigated the uptake and metabolism of lactose, the major sugar in industrial whey waste, by C. acetobutylicum ATCC 824. Lactose is taken up via a phosphoenolpyruvate-dependent phosphotransferase system (PTS) comprising both soluble and membrane-associated components, and the resulting phosphorylated derivative is hydrolyzed by a phospho-beta-galactosidase. These activities are induced during growth on lactose but are absent in glucose-grown cells. Analysis of the C. acetobutylicum genome sequence identified a gene system, lacRFEG, encoding a transcriptional regulator of the DeoR family, IIA and IICB components of a lactose PTS, and phospho-beta-galactosidase. During growth in medium containing both glucose and lactose, C. acetobutylicum exhibited a classical diauxic growth, and the lac operon was not expressed until glucose was exhausted from the medium. The presence upstream of lacR of a potential catabolite responsive element (cre) encompassing the transcriptional start site is indicative of the mechanism of carbon catabolite repression characteristic of low-GC gram-positive bacteria. A pathway for the uptake and metabolism of lactose by this industrially important organism is proposed.
Design and Synthesis of Cyclopenta[g]quinazoline-Based Antifolates as Inhibitors of Thymidylate Synthase and Potential Antitumor Agents, (2000)

Following the development of raltitrexed, the synthesis of nonpolyglutamatable inhibitors of TS that do not use the reduced folate carrier (RFC) for cellular entry should provide compounds which overcome mechanisms of resistance to folate-based inhibitors of TS that are associated with decreased/altered folylpolyglutamate synthetase (FPGS) expression and/or an impaired RFC. Examination of a computer graphics model of the humanized Escherichia coli TS enzyme with quinazoline inhibitors of TS, such as 1 bound in the active site of the enzyme, suggested that conformational restriction introduced by bridging the C9 with C7 to form a pentacycle may be beneficial for binding to TS. That led to the synthesis of a series of potent cyclopenta[g]quinazoline-based inhibitors of the enzyme in which the glutamyl residue associated with classical antifolates was replaced with a variety of glutamate-derived ligands; the most potent inhibitor being the L-Glu-gamma-D-GluT(alpha) derivative 7j. In the mouse L1210:1565 cell line (mutant RFC), the majority of these compounds had activity equal or only slightly greater compared with the parental L1210 cell line, indicating a reduced dependence on the RFC for cellular uptake in the L1210 cell line.
The relationship of human wound vascular endothelial growth factor (VEGF) after breast cancer surgery to circulating VEGF and angiogenesis. (2003)

Much higher local concentrations of angiogenic factors may need to be antagonized for effective antiangiogenic therapy, and there is great heterogeneity between patients. The small peripheral blood changes compared with large tumor fluid changes show that there is a tissue barrier. This has relevance for design of antiangiogenic therapy trials, highlighting the need for individually tailored treatment with biologically targeted interventions.