gebhart/patrepeval huggingface dataset:
DNA damage resulting from the oxidation of hydroquinone by copper: role for a Cu(II)/Cu(I) redox cycle and reactive oxygen generation (1993)

The myelotoxicity, including leukemia, associated with benzene exposure has been attributed to the further activation of benzene-derived metabolites. In a previous study, we observed that (Cu(II) strongly mediates the oxidation of hydroquinone (HQ) producing benzoquinone (BQ) and H2O2 through Cu(II)/Cu(I) redox mechanism. Since copper exists in the nucleus and is closely associated with chromosomes and DNA, in this study we investigated whether this chemical--metal redox system induces strand breaks in phi X-174 RFI plasmid DNA. In the presence of micromolar concentrations of Cu(II) and HQ, both single and double strand breaks were induced, whereas HQ, Cu(II), H2O2 or BQ alone at the employed concentrations elicited no significant damage to DNA. The HQ/Cu(II) system was at least twice as efficient as a H2O2/Cu(II) system at inducing DNA strand breaks. Of Cu(II), Fe(III), Mn(II), Cd(II) and Zn(II), only HQ/Cu(II) induced extensive DNA strand breaks. Among HQ, 1,2,4-benzenetriol (BT), catechol and phenol, HQ/Cu(II) and BT/Cu(II) were the two most efficient DNA cleaving systems. The presence of bathocuproinedisulfonic acid (BCS) or catalase prevented the HQ/Cu(II)-induced DNA strand breaks. In addition, the HQ/Cu(II)-induced DNA strand breaks could be completely blocked by reduced glutathione and dithiothreitol, but not by L-cysteine. The interaction of L-cysteine with copper in the absence of HQ induced significant DNA strand breaks with the same pattern of DNA strand breaks as that of HQ/Cu(II) plus L-cysteine. In contrast to the HQ/Cu(II) system, a HQ/myeloperoxidase (MPO)/H2O2 system did not induce any DNA strand breaks, and furthermore, the presence of MPO inhibited the HQ/Cu(II)-induced DNA strand breaks. When DNA pretreated with Cu(II) was exposed to HQ, DNA strand breaks were formed that could be prevented by BCS or catalase, indicating that DNA-bound copper can undergo redox cycling in the presence of HQ, generating H2O2. Similar to the H2O2/Cu(II) system, the HQ/Cu(II)-induced DNA strand breaks could not be efficiently inhibited by hydroxyl radical scavengers but could be protected by singlet oxygen scavengers, indicating that the localized generation of singlet oxygen or a singlet oxygen-like entity, possibly a copper-peroxide complex, rather than free hydroxyl radical probably plays a role in the HQ/Cu(II)-induced DNA strand breaks. The above results suggest that macromolecule-associated copper and reactive oxygen generation may be important factors in the mechanism of HQ-induced DNA damage in target cells.
A retrovirus‐based system to stably silence GDF‐8 expression and enhance myogenic differentiation in human rhabdomyosarcoma cells (2008)

The results demonstrate that deactivation of myostatin by using retrovirus-based RNAi thus may be useful for therapy in rhabdomyosarcomas.
The role of purinergic signaling in the liver and in transplantation: effects of extracellular nucleotides on hepatic graft vascular injury, rejection and metabolism (2007)

Extracellular nucleotides (e.g. ATP, UTP, ADP) are released by activated endothelium, leukocytes and platelets within the injured vasculature and bind specific cell-surface type-2 purinergic (P2) receptors. This process drives vascular inflammation and thrombosis within grafted organs. Importantly, there are also vascular ectonucleotidases i.e. ectoenzymes that hydrolyze extracellular nucleotides in the blood to generate nucleosides (viz. adenosine). Endothelial cell NTPDase1/CD39 has been shown to critically modulate levels of circulating nucleotides. This process tends to limit the activation of platelet and leukocyte expressed P2 receptors and also generates adenosine to reverse inflammatory events. This vascular protective CD39 activity is rapidly inhibited by oxidative reactions, such as is observed with liver ischemia reperfusion injury. In this review, we chiefly address the impact of these signaling cascades following liver transplantation. Interestingly, the hepatic vasculature, hepatocytes and all non-parenchymal cell types express several components co-ordinating the purinergic signaling response. With hepatic and vascular dysfunction, we note heightened P2- expression and alterations in ectonucleotidase expression and function that may predispose to progression of disease. In addition to documented impacts upon the vasculature during engraftment, extracellular nucleotides also have direct influences upon liver function and bile flow (both under physiological and pathological states). We have recently shown that alterations in purinergic signaling mediated by altered CD39 expression have major impacts upon hepatic metabolism, repair mechanisms, regeneration and associated immune responses. Future clinical applications in transplantation might involve new therapeutic modalities using soluble recombinant forms of CD39, altering expression of this ectonucleotidase by drugs and/or using small molecules to inhibit deleterious P2-mediated signaling while augmenting beneficial adenosine-mediated effects within the transplanted liver.
Slow transit constipation: a model of human gut dysmotility. Review of possible aetiologies (2000)

Slow transit constipation is a severe condition of gut dysmotility that predominantly affects young women and may result in surgical intervention. Current medical treatments for STC are often ineffective, and the outcome of surgery is unpredictable. STC was first described almost a century ago. Since this time, progress in improving therapy for this condition has been complicated by a lack of understanding of the aetiology, and great variation in the methods and criteria used for the study of patients with this debilitating disorder. It is difficult to find unequivocal data, and harder still to give a definitive picture of the cause or causes of STC. Here we consider the evidence for various aetiologies of STC, in the light of the physiological and pathological findings.
Cardiovascular Effects of New Oral Glucose-Lowering Agents (2018)

Cardiovascular disease (CVD) is a major challenge in the management of type 2 diabetes mellitus. Glucose-lowering agents that reduce the risk of major cardiovascular events would be considered a major advance, as recently reported with liraglutide and semaglutide, 2 glucagon-like peptide-1 receptor agonists, and with empagliflozin and canagliflozin, 2 SGLT-2 (sodium-glucose cotransporter type 2) inhibitors, but not with DPP-4 (dipeptidyl peptidase-4) inhibitors. The present review is devoted to CV effects of new oral glucose-lowering agents. DPP-4 inhibitors (gliptins) showed some positive cardiac and vascular effects in preliminary studies, and initial data from phase 2 to 3 clinical trials suggested a reduction in major cardiovascular events. However, subsequent CV outcome trials with alogliptin, saxagliptin, and sitagliptin showed noninferiority but failed to demonstrate any superiority compared with placebo in patients with type 2 diabetes mellitus and high CV risk. An unexpected higher risk of hospitalization for heart failure was reported with saxagliptin. SGLT-2 inhibitors (gliflozins) promote glucosuria, thus reducing glucose toxicity and body weight, and enhance natriuresis, thus lowering blood pressure. Two CV outcome trials in type 2 diabetes mellitus patients mainly in secondary prevention showed remarkable positive results. Empagliflozin in EMPA-REG-OUTCOME (EMPAgliflozin Cardiovascular OUTCOME Events in Type 2 Diabetes Mellitus Patients) reduced major cardiovascular events, CV mortality, all-cause mortality, and hospitalization for heart failure. In CANVAS (Canagliflozin Cardiovascular Assessment Study), the reduction in CV mortality with canagliflozin failed to reach statistical significance despite a similar reduction in major cardiovascular events. The underlying protective mechanisms of SGLT-2 inhibitors remain unknown and both hemodynamic and metabolic explanations have been proposed. CVD-REAL studies (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors; with the limitation of an observational approach) suggested that these favorable results may be considered as a class effect shared by all SGLT-2 inhibitors (including dapagliflozin) and be extrapolated to a larger population of patients with type 2 diabetes mellitus in primary prevention. Ongoing CV outcome trials with other DPP-4 (linagliptin) and SGLT-2 (dapagliflozin, ertugliflozin) inhibitors should provide additional information about CV effects of both pharmacological classes.
Does content relevance lead to positive attitude toward websites? exploring the role of flow and goal specificity (2009)

It is common practice to have Websites interact with consumers by delivering personalized services, among which content relevance is most widely adopted on Internet advertising. However, little is known about the impact of relevance on consumersâ psychological states and the underlying mechanism of relationship between relevance and attitude toward Websites. Building upon flow theory and Hoffman and Novakâs (1996) conceptual model, this study investigates the role of flow and relevance in influencing attitude toward Websites. The findings show that the link between content relevance and attitude toward Web sites is mediated by consumersâ flow experience. In addition, goal specificity moderates the effect of relevance on flow experience. Under the conditions of high goal specificity, the relevance effect on flow is magnified. Theoretical and practical implications of this study are discussed.
The Modern First Lady and Public Policy: From Edith Wilson through Hillary Rodham Clinton (2001)

The Modern First Lady and Public Policy: From Edith Wilson through Hillary Rodham Clinton Get access Allida M. Black Allida M. Black Allida M. Black is a research professor of history and international affairs at The George Washington University and project director and editor of the Eleanor Roosevelt Papers, an annotated collection of Eleanor Roosevelt's writings and discussions of human rights and democratic politics. Her publications include three books: Casting Her Own Shadow: Eleanor Roosevelt and the Shaping of Postwar Liberalism (1996); What I Hope to Leave Behind: The Essential Essays of Eleanor Roosevelt (1995); and Courage in a Dangerous World: The Political Writings of Eleanor Roosevelt (1999), as well as a variety of articles discussing First Ladies and politics. She is working on First Women: Power, Image, and Politics from Betty Ford through Hillary Rodham Clinton, which will be published by Columbia University Press. Search for other works by this author on: Oxford Academic Google Scholar OAH Magazine of History, Volume 15, Issue 3, Spring 2001, Pages 15–21, https://doi.org/10.1093/maghis/15.3.15 Published: 01 March 2001
Immunobiology of Dendritic Cells (2000)

Dendritic cells (DCs) are antigen-presenting cells with a unique ability to induce primary immune responses. DCs capture and transfer information from the outside world to the cells of the adaptive immune system. DCs are not only critical for the induction of primary immune responses, but may also be important for the induction of immunological tolerance, as well as for the regulation of the type of T cell-mediated immune response. Although our understanding of DC biology is still in its infancy, we are now beginning to use DC-based immunotherapy protocols to elicit immunity against cancer and infectious diseases.
The Development of Autoimmune Encephalomyelitis Provoked by Myelin Oligodendrocyte Glycoprotein Is Associated with an Upregulation of Both Proinflammatory and Immunoregulatory Cytokines in the Central Nervous System (1998)

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the central nervous system (CNS). We previously reported upregulation of gene expression for a number of proinflammatory cytokines, interleukin-1beta (IL-1beta), IL-2, IL-6, tumor necrosis factor-alpha (TNF-alpha), TNF-beta, and interferon-gamma (IFN-gamma), in the CNS of mice with myelin basic protein (MBP)-induced relapsing EAE by using semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). However, in these mice there was no significant increase of gene expression for immunoregulatory cytokines (IL-4, IL-10, transforming growth factor-beta [TGF-beta]). We report here that gene expression for both proinflammatory and immunoregulatory cytokines increased during the course of disease in the CNS of mice with myelin oligodendrocyte glycoprotein (MOG)-induced nonrelapsing EAE. These results indicate that the gene expression pattern of immunoregulatory cytokines in the CNS may be different between MBP-induced and MOG-induced EAE and that it may influence the type of disease. Accordingly, the course of the disease may be influenced by the interplay between the proinflammatory and immunoregulatory cytokines.
Expression of the Angiogenic Protein, Platelet-Derived Endothelial Cell Growth Factor, in Coronary Atherosclerotic Plaques (1999)

Recent information indicates that platelet-derived endothelial cell growth factor (PD-ECGF), a 45-kDa angiogenic protein, is expressed in the endothelium of various tissues and that its level of expression is correlated with the number of microvessels in human tumors. Because the formation of neovessels is also thought to play a role in atherosclerotic vascular remodeling, we analyzed PD-ECGF expression in fresh, coronary plaque tissues obtained by directional coronary atherectomy. Specimens from 31 patients were collected and analyzed by reverse transcription-polymerase chain reaction, histochemical staining, immunohistochemistry, and in situ hybridization with the use of PD-ECGF-specific primers and probes. Lesional vascular remodeling was assessed by intravascular ultrasound. PD-ECGF immunoreactivity and mRNA were found in plaque macrophages, endothelial cells of plaque neovessels, and stellate smooth muscle cells of 20 atherectomy specimens (64.5%). PD-ECGF immunoreactivity was correlated with the number of lesional microvessels and mast cells. Double-staining experiments revealed a close spatial proximity of PD-ECGF-positive cells and mast cells. Furthermore, the numbers of microvessels and mast cells were significantly higher in lesions lacking compensatory enlargement. The data indicate that PD-ECGF is expressed within cells of the atherosclerotic plaque and may be involved in driving angiogenesis in concert with mast cells.
Identification of additional genes on transposon Tn10: tetC and tetD (1984)

Two genes (tetC and tetD) were identified and located on transposon Tn10 between gene tetA and insertion sequence IS10R. Genes tetC and tetD encode proteins of apparent subunit molecular weights of 23,000 and 18,000, respectively. The TetD protein was found to be membrane associated. Tetracycline resistance levels promoted by transposon Tn10 were found to be unaffected in Escherichia coli K-12 when mutants lacking tetC or tetC and tetD were tested. The nucleotide sequence of genes tetC and tetD is reported in the accompanying article (K. Schollmeier and W. Hillen, J. Bacteriol. 160:499-503, 1984).
Priority-Scaled Preemption of Radio Resources for 3GPPLTE Networks (2011)

The preemption technique plays an important role in the radio resource management (RRM) of 3GPP Long Term Evolution (LTE) networks. In preemption handling methods, the resource allocation to high priority bearer requests is done by preempting the resources either partially or fully from the low priority preemptable active bearers (LP PABs). The paper proposes the priority-scaled (PS) preemption technique using Allocation and Retention Priority (ARP). The proposed technique suggests the priority-scaled (PS) preemption of resources up to minimum quality of service (QoS) level from all LP PABs. This is in contrast with conventional preemption technique, wherein high priority bearer requests preempt resources completely up to minimum QoS level, with PABs selected in sequence from lowest priority onwards. The paper investigates performance of the proposed technique in terms of number of active bearers dropped and blocked to accommodate higher priority bearer requests. The PS preemption technique reduces the dropping of LP PABs compared to conventional technique for subsequent arrivals of new low priority radio access bearer (RAB) requests, at the cost of QoS by higher priority bearer services. However, the QoS sacrifice made by the high priority PABs is limited to minimum QoS level.
Processing map for hot working of stainless steel type AISI 316L (1993)

Processing and instability maps using a dynamic materials model have been developed for stainless steel type AISI 316L in the temperature range 600–1250°C and strain rate range 0·001–100 s−l with a view to optimising its hot workability. Stainless steel type AISI 316L undergoes dynamic recrystallisation, with a peak efficiency of 35% at 1250°C and 0·05 s−1, which are the optimum parameters for hot working this material. The material undergoes dynamic recovery at 900°C and 0·001 s−1. The increase in the dynamic recrystallisation and dynamic recovery temperatures in comparison with stainless steel type AISI 304L is attributed to the presence of a backstress caused by the molybdenum additions. These results are in general agreement with those reported elsewhere on stainless steel type 316 deformed in hot extrusion and hot torsion. At temperatures <850°C and strain rates >10 s −1, the material exhibits flow localisation owing to adiabatic shear band formation, whereas at higher temperatures (>850°C) and strain rates (>10 s−1) mechanical twinning and wavy slip bands are observed.MST/1769
Low-power equalizer architectures for high speed modems (1998)

In many DSP-based high-speed modem applications, such as broadband modems for high-speed Internet access to the home or gigabit Ethernet transceivers, channel equalization requires processing power so high that power consumption and clock speed become major design challenges. This article describes techniques to implement low-cost adaptive equalizers for ASIC implementations of broadband modems. Power consumption can be reduced using a careful selection of architectural, algorithmic, and VLSI circuit techniques. The derivation of a hybrid FIR filter structure is given that enables the designer to adjust both the speed and power consumption to suit an application. Furthermore, the architecture can be made programmable to target multiple applications in one piece of silicon while maintaining or even improving the efficiency of the architecture. Run-time techniques are shown that can minimize the power consumption for a given application or operating environment. In all cases, the power reduction techniques are supported by simulations and measurements made on a test integrated circuit.
Exome Sequencing to Predict Neoantigens in Melanoma (2015)

The ability to use circulating peripheral blood cells and matched tumor sequencing data as a basis for neoantigen prediction has exciting possibilities for application in the personalized treatment of cancer patients. We have used a high-throughput screening approach, combining whole-exome sequence data, mRNA microarrays, and publicly available epitope prediction algorithm output to identify mutated proteins processed and displayed by patient tumors and recognized by circulating immune cells. Matched autologous melanoma cell lines and peripheral blood mononuclear cells were used to create mixed lymphocyte tumor cell cultures, resulting in an expansion of tumor-reactive T cells to use for mutated peptide screening. Five patients were investigated, three of whom had a durable complete response (CR; 15+ years) in an autologous melanoma-pulsed dendritic cell clinical trial. We identified seven mutated antigens in total that stimulated T-effector memory cells in two of the five patients. While the procedure did not result in clinically applicable neoantigens for all patients, those identified were likely important in tumor clearance, leading to durable CR. The nature of the screening process allows results to be obtained rapidly and is easily applicable to a wide variety of different tumor types.
Enhanced Photocatalytic Activity of α-Methylstyrene Oligomerization through Effective Metal-to-Ligand Charge-Transfer Localization on the Bridging Ligand (2011)

A series of Pd complexes containing a visible-light harvesting moiety with various combination of substituents (R, X) were synthesized. The variation of the substituents resulted in significant change in the electrochemical and photophysical properties of the complexes. Additionally, photocatalytic activity drastically increased through the introduction of an electron-donating group on R and an electron-withdrawing group on X, respectively. The molecular orbital analysis based on density functional theory (DFT) calculation suggested that the enhancement of the catalytic activity is due to the effective Metal-to-Ligand Charge-Transfer (MLCT) localization on the bridging ligand.
Could Heat Shock Transcription Factors Function as Hydrogen Peroxide Sensors in Plants? (2006)

In this review, we summarize recent studies on Hsf function in Arabidopsis and tomato and present evidence obtained from microarray expression studies in Arabidopsis that the Hsf gene network is highly flexible and specialized, with specific members and/or member combinations controlling the response of plants to particular stress conditions. In addition, we describe recent studies that support the hypothesis that certain Hsfs function as molecular sensors that directly sense reactive oxygen species (ROS) and control the expression of oxidative stress response genes during oxidative stress.
Mutations affect storage and use of memory differentially in Drosophila (1983)

The behavior of normal Drosophila and of X-linked olfactory conditioning mutants was analyzed by using an olfactory memory choice task. Memory in normal flies was optimal at 5-12 min after training and then decayed slowly. Memory in the mutants was 40-80% of normal when tested 30 sec after training but it decayed rapidly and was very low after 7 min. Successive conditioning experiments indicated that some types of mutants can behave as though they store information for a longer period than that revealed by straightforward memory tests, but this information reveals itself only by interaction with newly acquired information in a conflict situation. It thus seems that the mutations can either prevent the formation of normal memory or prevent memory from evoking a normal behavioral response.
Horseradish peroxidase immobilized in macroporous hydrogel for acrylamide polymerization (2008)

Abstract Thermosensitive hydrogel made up of poly( N ‐isopropylacrylamide) (PNIPA)‐chitosan semi‐interpenetrating network (semi‐IPN) with ultrarapid responding rate was synthesized. Horseradish peroxidase (HRP) was then immobilized on this hydrogel that acted as an enzyme‐carrier by glutaraldehyde bridge. Polymerization of acrylamide was initiated by a redox system (hydrogen peroxide/acetylacetone (Acac)) and was catalyzed by the immobilized enzyme at room temperature. The attention was focused on the properties of the carrier‐enzyme systems. The hydrogel was proofed to be macroporous by environmental scanning electron microscope images. Swelling properties of the hydrogel such as swelling ratio and deswelling–reswelling kinetics were measured. The properties of the immobilized enzyme such as enzyme activity, storage stability, and thermostability were also studied. The immobilized enzyme could be used repeatedly. Gel permeation chromatography measurement of the resulted polyacrylamide (PAAm) showed that the molecular weight reduced as the repeated times of the immobilized enzyme catalysis increased. In conclusion, the macroporous hydrogel would be a suitable enzyme carrier for practical applications in future. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2222–2232, 2008