gebhart/patrepeval huggingface dataset:
Complications Associated with the Technique of Pedicle Screw Fixation A Selected Survey of ABS Members (1993)

A limited survey analysis of 617 surgical cases in which pedicle screw implants were used was undertaken to ascertain the incidence and variety of associated complications. The different implant systems used included variable spinal plating (n = 249), Edwards (n = 143), and AO fixateur interne (n = 101). The most common intraoperative problem was unrecognized screw misplacement (5.2%). Fracturing of the pedicle during screw insertion and iatrogenic cerebrospinal fluid leak occurred in 4.2% of cases. The postoperative deep infection rate was 4.2%. Transient neuropraxia occurred in 2.4% of cases, and permanent nerve root injury occurred in 2.3% of cases. Previously unreported injury to nerve roots occurred late in the postoperative course in three cases. Screw breakage occurred in 2.9% of cases. All other complications had an incidence of less than 2%. The authors conclude that pedicle screw placement may be associated with significant intraoperative and postoperative complications. This information is of value to surgeons using pedicle implant systems as well as to their patients. Repeat surgery is associated with greater numbers of complications.
In vitro phenotypes to elvitegravir and dolutegravir in primary macrophages and lymphocytes of clonal recombinant viral variants selected in patients failing raltegravir (2013)

All INIs showed comparable antiretroviral activity in both cell types even if single mutations were associated with a different level of susceptibility in vitro to raltegravir and elvitegravir in macrophages. In particular, dolutegravir was capable of inhibiting with similar potency infection of raltegravir-resistant variants with Y143 or N155 pathways in both HIV-1 major cell reservoirs.
Laser flash photolysis of hydrogen peroxide to oxidize protein solvent-accessible residues on the microsecond timescale (2005)

Footprinting of proteins by hydroxyl radicals generated on the millisecond to minute timescales to probe protein surfaces suffers from the uncertainty that radical reactions cause the protein to unfold, exposing residues that are protected in the native protein. To circumvent this possibility, we developed a method using a 248 nm KrF excimer laser to cleave hydrogen peroxide at low concentrations (15 mM, 0.04%), affording hydroxyl radicals that modify the protein in less than a microsecond. In the presence of a scavenger (20 mM glutamine), the radical lifetimes decrease to approximately 1 microsecond, yet the reaction timescales are sufficient to provide significant oxidation of the protein. These times are arguably faster than super-secondary protein structure can unfold as a result of the modification. The radical formation step takes place in a nanoliter flow cell so that only one laser pulse irradiates each bolus of sample. The oxidation sites are located using standard analytical proteomics, requiring less than a nanomole of protein. We tested the method with apomyoglobin and observed modifications in accord with solvent accessibility data obtained from the crystal structure of holomyoglobin. Additionally, the results indicate that the F-helix is conformationally flexible in apomyoglobin, in accord with NMR results. We also find that the binding pocket is resistant to modifications, indicating that the protein pocket closes in the absence of the heme group-conclusions that cannot be drawn from current structural methods. When developed further, this method may enable the determination of protein-ligand interfaces, affinity constants, folding pathways, and regions of conformational flexibility.
Erythropoietin Treatment of Anemia Associated with Multiple Myeloma (1990)

Anemia is a common complication of multiple myeloma. It resolves early in the disease if chemotherapy induces a complete remission, but persists if the disease progresses, causing disabling symptoms and often requiring blood transfusions. We treated 13 patients with myeloma-associated anemia by administering recombinant human erythropoietin three times a week for six months. Eleven patients (85 percent) had steady increases in hemoglobin levels and eventual correction of the anemia. Their symptoms of anemia subsided, and they reported a heightened sense of well-being. No patient had any adverse side effects, particularly episodes of hypertension. Monitoring of the serum M component showed a predominantly stable tumor load without apparent interaction between the underlying disease and the response to erythropoietin therapy. The number of erythroid burst-forming units in the bone marrow and peripheral blood and the level of erythropoiesis in bone marrow smears increased significantly during therapy. Pretreatment serum levels of erythropoietin were higher in the patients who did not respond and in those who required more than two months of treatment before they responded. Serum iron, ferritin, and transferrin concentrations reflected responses to treatment. We conclude that recombinant human erythropoietin is a promising therapeutic tool for treating myeloma-associated anemia.
Improved biological activity of a mutant endostatin containing a single amino-acid substitution (2004)

Human endostatin has an internal Asn-Gly-Arg (NGR) motif at position 126-128 following a proline at position 125. Asn-Gly-Arg-containing peptides have been shown to target tumour vasculature and inhibit aminopeptidase N activity. We previously compared the in vitro and in vivo biological activities of native endostatin and endostatin with a proline to alanine mutation (P125A-endostatin). P125A-endostatin exhibited greater inhibition of both endothelial cell proliferation and human ovarian cancer growth compared to native endostatin. Here we explore further the effects on biological activity of the P125A mutation, and show that aminopeptidase N is not involved. To determine whether the increased biological activity of the mutant was due to unmasking of downstream NGR-sequence, effect of endostatin on aminopeptidase N activity was investigated. Neither the native nor the P125A-endostatin inhibited aminopeptidase N. However, synthetic peptides consisting of the S118-T131 region of endostatin inhibited aminopeptidase N. These results suggest that the internal NGR site in native or mutant endostatin is not accessible to aminopeptidase N, and that this activity is not involved in the enhanced biological activity of the P125A form. P125A-endostatin bound to endothelial cells more efficiently than native endostatin and exhibited greater inhibition of not only proliferation but also migration of endothelial cells. P125A-endostatin also localised into tumour tissue to a higher degree than the native protein, and displayed greater inhibition of growth of colon cancer in athymic mice. Both proteins inhibited tumour cell-induced angiogenesis effectively. Real-time PCR analysis showed that both native and P125A-endostatin decreased expression of key proangiogenic growth factors. Vascular endothelial growth factor and angiopoietin 1 were downregulated more by the mutant. These studies suggest that the region around P125 can be modified to improve the biological activity of endostatin.
Analysis and design of metabolic reaction networks via mixed‐integer linear optimization (1996)

Abstract Improvements in bioprocess performance can be achieved by genetic modifications of metabolic control structures. A novel optimization problem helps quantitative understanding and rational metabolic engineering of metabolic reaction pathways. Maximizing the performance of a metabolic reaction pathway is treated as a mixed‐integer linear programming formulation to identify changes in regulatory structure and strength and in cellular content of pertinent enzymes which should be implemented to optimize a particular metabolic process. A regulatory superstructure proposed contains all alternative regulatory structures that can be considered for a given pathway. This approach is followed to find the optimal regulatory structure for maximization of phenylalanine selectivity in the microbial aromatic amino acid synthesis pathway. The solution suggests that from the eight feedback inhibitory loops in the original regulatory structure of this pathway, inactivation of at least three loops and overexpression of three enzymes will increase phenylalanine selectivity by 42%. Moreover, novel regulatory structures with only two loops, none of which exists in the original pathway, could result in a selectivity up to 95%.
Synthesis and antitumor activity of an inhibitor of fatty acid synthase (2000)

Compared to normal human tissues, many common human cancers, including carcinoma of the colon, prostate, ovary, breast, and endometrium, express high levels of fatty acid synthase (FAS, EC ), the primary enzyme responsible for the synthesis of fatty acids. This differential expression of FAS between normal tissues and cancer has led to the notion that FAS is a target for anticancer drug development. Recent studies with C75, an inhibitor of fatty acid synthesis, have shown significant antitumor activity with concomitant inhibition of fatty acid synthesis in tumor tissue and normal liver. Importantly, histopathological analysis of normal tissues after C75 treatment showed no adverse effects on proliferating cellular compartments, such as bone marrow, gastrointestinal tract, skin, or lymphoid tissues. In this study, we describe the de novo synthesis of C75 based on the known mechanism of action of cerulenin and the theoretical reaction intermediates of the beta-ketoacyl synthase moiety of FAS. In addition, we demonstrate that C75 is a synthetic, chemically stable inhibitor of FAS. C75 inhibits purified mammalian FAS with characteristics of a slow-binding inhibitor and also inhibits fatty acid synthesis in human cancer cells. Treatment of human breast cancer cells with [5-(3)H]C75 demonstrates that C75 reacts preferentially with FAS in whole cells. Therefore, we have shown that the primary mechanism of the antitumor activity of C75 is likely mediated through its interaction with, and inhibition of, FAS. This development will enable the in vivo study of FAS inhibition in human cancer and other metabolic diseases.
<title>Development of the tris-chelated polypyridyl ruthenium (II) complex as a solid state light emitter</title> (1998)

A series of tris-chelated polypyridylruthenium (II) complex- containing polyurethanes has been synthesized and evaluated as emitters in solid-state thin film devices. These new materials were found to give rise to luminance levels of about 200 cd/m<SUP>2</SUP> with external quantum efficiencies in the 0.5-1 percent range. Transient capacitance and conductance measurements were made to elucidate the origin of the slow device response times of these materials. Much faster-responding devices were fabricated by depositing a ruthenium complex onto a hole-transported layer of poly(p- phenylene vinylene).
Using the web for language independent spellchecking and autocorrection (2009)

We have designed, implemented and evaluated an end-to-end system spellchecking and autocorrection system that does not require any manually annotated training data. The World Wide Web is used as a large noisy corpus from which we infer knowledge about misspellings and word usage. This is used to build an error model and an n-gram language model. A small secondary set of news texts with artificially inserted misspellings are used to tune confidence classifiers. Because no manual annotation is required, our system can easily be instantiated for new languages. When evaluated on human typed data with real misspellings in English and German, our web-based systems outperform baselines which use candidate corrections based on hand-curated dictionaries. Our system achieves 3.8% total error rate in English. We show similar improvements in preliminary results on artificial data for Russian and Arabic.
Subband-coded image reconstruction for lossy packet networks (1997)

Transmission of digital subband-coded images over lossy packet networks presents a reconstruction problem at the decoder. This paper presents two techniques for reconstruction of lost subband coefficients, one for low-frequency coefficients and one for high-frequency coefficients. The low-frequency reconstruction algorithm is based on inherent properties of the hierarchical subband decomposition. To maintain smoothness and exploit the high intraband correlation, a cubic interpolative surface is fit to known coefficients to interpolate lost coefficients. Accurate edge placement, crucial for visual quality, is achieved by adapting the interpolation grid in both the horizontal and vertical directions as determined by the edges present. An edge model is used to characterize the adaptation, and a quantitative analysis of this model demonstrates that edges can be identified by simply examining the high-frequency bands, without requiring any additional processing of the low-frequency band. High-frequency reconstruction is performed using linear interpolation, which provides good visual performance as well as maintains properties required for edge placement in the low-frequency reconstruction algorithm. The complete algorithm performs well on loss of single coefficients, vectors, and small blocks, and is therefore applicable to a variety of source coding techniques.
Reduced Protection from Simian Immunodeficiency Virus SIV mac251 Infection Afforded by Memory CD8 + T Cells Induced by Vaccination during CD4 + T-Cell Deficiency (2008)

Adaptive CD4(+) and CD8(+) T-cell responses have been associated with control of human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) replication. Here, we have designed a study with Indian rhesus macaques to more directly assess the role of CD8 SIV-specific responses in control of viral replication. Macaques were immunized with a DNA prime-modified vaccinia virus Ankara (MVA)-SIV boost regimen under normal conditions or under conditions of antibody-induced CD4(+) T-cell deficiency. Depletion of CD4(+) cells was performed in the immunized macaques at the peak of SIV-specific CD4(+) T-cell responses following the DNA prime dose. A group of naïve macaques was also treated with the anti-CD4 depleting antibody as a control, and an additional group of macaques immunized under normal conditions was depleted of CD8(+) T cells prior to challenge exposure to SIV(mac251). Analysis of the quality and quantity of vaccine-induced CD8(+) T cells demonstrated that SIV-specific CD8(+) T cells generated under conditions of CD4(+) T-cell deficiency expressed low levels of Bcl-2 and interleukin-2 (IL-2), and plasma virus levels increased over time. Depletion of CD8(+) T cells prior to challenge exposure abrogated vaccine-induced protection as previously shown. These data support the notion that adaptive CD4(+) T cells are critical for the generation of effective CD8(+) T-cell responses to SIV that, in turn, contribute to protection from AIDS. Importantly, they also suggest that long-term protection from disease will be afforded only by T-cell vaccines for HIV that provide a balanced induction of CD4(+) and CD8(+) T-cell responses and protect against early depletion of CD4(+) T cells postinfection.
The Mediator Complex Subunit 1 Enhances Transcription of Genes Needed for Adrenal Androgen Production (2009)

There are three enzymes involved in the biosynthesis of the adrenal androgen dehydroepiandrosterone (DHEA) sulfate. Cholesterol side-chain cleavage (CYP11A1) and 17alpha-hydroxylase/17,20-lyase (CYP17) metabolize cholesterol into DHEA, whereas steroid sulfotransferase family 2A1 (SULT2A1) is responsible for conversion of DHEA to DHEA sulfate. We previously examined the mechanisms regulating CYP11A1, CYP17, and SULT2A1 transcription and found that each is regulated, in part, by the transcription factor GATA-6. Previous studies suggested that mediator complex subunit 1 (MED1, also called PPARBP or TRAP220) is a cofactor involved in not only the regulation of nuclear receptors but also the activation of GATA-6 transcription. Herein we demonstrated a role for MED1 in the regulation of CYP11A1, CYP17, and SULT2A1 transcription. Transient transfection assays with SULT2A1 deletion and mutation promoter constructs allowed the determination of specific the GATA-6 binding cis-regulatory elements necessary for transactivation of SULT2A1 transcription. Binding of MED1 and GATA-6 was confirmed by coimmunoprecipitation/Western analysis and chromatin immunoprecipitation assay. We demonstrated expression of MED1 mRNA and protein in the human adrenal and determined that knockdown of MED1 expression via specific small interfering RNA attenuated CYP11A1, CYP17, and SULT2A1 expression levels in H295R cells. In addition, we demonstrated that MED1 enhanced GATA-6 stimulated transcription of promoter constructs for each of these genes. Moreover, the activity of MED1 for SULT2A1 promoter was mediated by GATA-6 via the -190 GATA-binding site. These data support the hypothesis that MED1 and GATA-6 are key regulators of SULT2A1 expression, and they play important roles in adrenal androgen production.
Therapeutic hypothermia after cardiac arrest (2001)

This review discusses the mechanisms of neurologic damage during and after global cerebral ischemia caused by cardiac arrest. The different pathways of membrane destruction by radicals, free fatty acids, excitatory amino acids (neurotransmitters), calcium, glucose metabolism, and oxygen availability and demand in relation to metabolic rate are briefly discussed. The main focus of this review paper, however, lies in therapeutic (resuscitative) hypothermia after cardiac arrest. Two pioneering studies of the 1950s and four recent publications (in part preliminary results of ongoing studies) in humans are discussed in detail. The conclusions are as follows: (1) hypothermia holds promise as the only specific brain therapy after cardiac arrest so far; (2) hyperthermia is not tolerable after successful resuscitation; and (3) if the ongoing European multicenter trial of hypothermia after cardiac arrest finds a significant benefit to mild hypothermia, withholding hypothermia may be ethically hard to defend.
Experimental intramammary inoculation with Mycoplasma bovis in vaccinated and unvaccinated cows: effect on the mycoplasmal infection and cellular inflammatory response. (1986)

The effect of vaccination on mycoplasmal infection and the cellular inflammatory response was evaluated in 4 vaccinated and 4 control cows experimentally challenged in 2 of 4 quarters with live Mycoplasma bovis. In unchallenged quarters during the first three weeks after experimental challenge exposure, 6 of 8 quarters on control cows, and 7 of 8 quarters on vaccinated cows became infected with low numbers (10(2)-10(4) cfu/ml) of M bovis. During the same period all challenge-infused quarters on both control and vaccinated animals became infected with high numbers (10(9) cfu/ml) of M bovis. Thereafter, all quarters on vaccinated cows became culture-negative for M bovis, while 2 of 8 unchallenged quarters, and 4 of 8 challenged quarters on 3 of 4 control cows remained infected. A cellular inflammatory response as measured by the California Mastitis Test accompanied the experimental infection in proportion to the infection level except in challenged quarters on vaccinated cows after the first three weeks post challenge in which the cellular inflammatory response remained high despite the advent of negative M bovis culture results. This study indicates that the course of experimental M bovis mastitis can be affected by vaccination, and that vaccination results in an adverse cellular inflammatory response in challenged quarters.
Effects of Pressure, Temperature, Adsorbent Surface, and Mobile Phase Composition on the Supercritical Fluid Chromatographic Fractionation of Monodisperse Polystyrenes (1978)

No significant differences have been found in the separation behavior of oligomers of monodisperse polystyrene samples when using n-pentane as the mobile phase and a phenyl or an n-octadecyl bonded stationary phase. For low-molecular weight polystyrenes used in this study, there was no evidence of steric exclusion effects when using non-derivatized silica. In all cases, the addition of either isopropanol or cyclohexane as a moderator was found to produce more nearly complete elution of the polystyrene oligomers from the stationary phases. Concentrations of isopropanol above 5% v/v caused no further change while increasingly higher percentages of cyclohexane caused capacity ratios of higher molecular weight species to decrease. Finally, non-linear pressure programming was found to produce more nearly regular elution of an oligomeric series while linear downward temperature programming was found to produce irregular elution behavior near the critical temperature.
Dysregulation of Protein Phosphorylation/Dephosphorylation in Alzheimer′s Disease: A Therapeutic Target (2006)

Studies during the last two decades have provided new insights into the molecular mechanism of Alzheimer's disease (AD). One of the milestone findings in AD research was the demonstration that neurofibrillary degeneration characterized by tau pathology is central to the pathogenesis of AD and other tauopathies and that abnormal hyperphosphorylation of tau is pivotal to neurofibrillary degeneration. This article reviews the recent research advances in tau pathology and the underlying dysregulation of the protein phosphorylation/dephosphorylation system. An updated model of the mechanism of neurofibrillary degeneration is also presented, and a promising therapeutic target to treat AD by correcting dysregulation of protein phosphorylation/dephosphorylation is discussed.
Pitx2 confers left morphological, molecular, and functional identity to the sinus venosus myocardium (2011)

Pitx2 drives left/right patterning of the SV myocardium through multiple developmental steps. Overall, Pitx2 plays a crucial functional role by negatively modulating a nodal-type programme in the left SV myocardium.
WRAPLE: The Weighted Repair Assistance Program Learning Extension (1986)

The weighted repair assistance program learning extension, or WRAPLE, is a maintenance aid to help technicians isolate faults - a necessary step in system repair. We derived the fault isolation strategies used in WRAPLE from a knowledge-based information-theoretic approach that incorporates fixed experience. This approach contrasts with fault isolation strategies, which are developed from estimates and remain fixed. A fault isolation strategy that "learned" would adapt to field conditions and change on the basis of actual failures and use of maintenance resources, permitting more efficient maintenance and reducing mean time to repair. In this article, we describe WRAPLE and the learning algorithms by which it modifies its output. We also present an example of a typical system to illustrate the technique.