gebhart/patrepeval huggingface dataset:
Electrochemical and IR Spectroelectrochemical Studies of the Electrocatalytic Reduction of Carbon Dioxide by [Ir2(dimen)4]2+(dimen = 1,8-Diisocyanomenthane) (1996)

The electrocatalytic reactions of carbon dioxide that are catalyzed by [Ir2(dimen)4]2+ (dimen = 1,8-diisocyanomenthane) were studied with cyclic voltammetry and infrared spectroelectrochemistry. The hexafluorophosphate (PF6-) salt and the tetraphenylborate (B(C6H5)4-) salt are electrocatalysts for carbon dioxide reduction. Infrared spectroelectrochemistry allowed the identification of the carbon dioxide reduction products and provided information about the mechanism(s) of the reduction. Bicarbonate and formate were identified as the electrocatalytic carbon dioxide reaction products by comparing the infrared bands observed by spectroelectrochemistry with authentic samples of tetrabutylammonium formate, tetrabutylammonium oxalate, and tetrabutylammonium bicarbonate. Formate arises from a net two-electron reduction of carbon dioxide that produces free formate and a formate complex of [Ir2(dimen)4]2+. Bicarbonate results from the reaction of hydroxide (produced when residual water is reduced to hydrogen) with carbon dioxide.
Prediction of Sensitivity of Rectal Cancer Cells in Response to Preoperative Radiotherapy by DNA Microarray Analysis of Gene Expression Profiles (2006)

Preoperative radiotherapy has been widely used to improve local control of disease and to improve survival in the treatment of rectal cancer. However, the response to radiotherapy differs among individual tumors. Our objective here was to identify a set of discriminating genes that can be used for characterization and prediction of response to radiotherapy in rectal cancer. Fifty-two rectal cancer patients who underwent preoperative radiotherapy were studied. Biopsy specimens were obtained from rectal cancer before preoperative radiotherapy. Response to radiotherapy was determined by histopathologic examination of surgically resected specimens and classified as responders or nonresponders. By determining gene expression profiles using human U95Av2 Gene Chip, we identified 33 novel discriminating genes of which the expression differed significantly between responders and nonresponders. Using this gene set, we were able to establish a new model to predict response to radiotherapy in rectal cancer with an accuracy of 82.4%. The list of discriminating genes included growth factor, apoptosis, cell proliferation, signal transduction, or cell adhesion-related genes. Among 33 discriminating genes, apoptosis inducers (lumican, thrombospondin 2, and galectin-1) showed higher expression in responders whereas apoptosis inhibitors (cyclophilin 40 and glutathione peroxidase) showed higher expression in nonresponders. The present study suggested the possibility that gene expression profiling may be useful in predicting response to radiotherapy to establish an individualized tailored therapy for rectal cancer. Global expression profiles of responders and nonresponders may provide insights into the development of novel therapeutic targets.
Altered Nitric Oxide System in Patients With Open-Angle Glaucoma (2007)

This is the first in vivo study providing evidence for an altered ocular L-arginine/nitric oxide system in patients with glaucoma. Normalization of the ocular nitric oxide production may be beneficial in terms of normalization of ocular blood flow and neuroprotection of retinal ganglion cells.
Investigation of the Local Structure of the LiNi[sub 0.5]Mn[sub 0.5]O[sub 2] Cathode Material during Electrochemical Cycling by X-Ray Absorption and NMR Spectroscopy (2002)

In situ X-ray absorption spectroscopy (XAS) of the Mn and Ni K-edges and magic angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy have been carried out during the first charging and discharging process for the layered cathode material. The Ni K-edge structure in the X-ray absorption near-edge structure (XANES) spectrum exhibits a rigid positive energy shift with increased Li deintercalation level, while the Mn XANES spectra do not show any substantial energy changes. The Ni edge shifts back reversibly during discharge. Further Li-ion intercalation at (vs. Li) could be accomplished by reduction of the ions. The MAS NMR results showed the presence of Li in the layers, in addition to the expected sites for Li in the lithium layers. All the Li ions in the transition metal layers are removed on the first charge, leaving residual lithium ions in the lithium layers. © 2002 The Electrochemical Society. All rights reserved.
Cyclooxygenase-2 Inhibition Increases Mortality, Enhances Left Ventricular Remodeling, and Impairs Systolic Function After Myocardial Infarction in the Pig (2007)

In pigs, COX-2 inhibition after MI is associated with increased mortality, enhanced left ventricular remodeling, and impaired systolic function, probably due to decreased infarct collagen fiber density.
Oral Niacin Prevents Photocarcinogenesis and Photoimmunosuppression in Mice (1999)

Topical nicotinamide (niacinamide) has demonstrable preventive activity against photocarcinogenesis in mice. To better understand how this vitamin prevents ultraviolet (UV) carcinogenesis, we tested systemic administration of another form of the vitamin, niacin, and its capacity to elevate cutaneous nicotinamide-adenine dinucleotide (NAD) content as well as to decrease photoimmunosuppression and photocarcinogenesis. BALB/cAnNTacfBR mice were fed the AIN-76A diet supplemented with 0%, 0.1%, 0.5%, or 1.0% niacin throughout the experiment. UV irradiation consisted of five 30-minute exposures per week to banks of six FS40 Westinghouse sunlamps for 22 weeks in the carcinogenesis experiments, yielding a total cumulative dose of approximately 1.41 x 10(6) Jm-2 of UV-B radiation. Dietary supplementation with 0.1%, 0.5%, or 1.0% niacin reduced the control incidence of skin cancer from 68% to 60%, 48%, and 28%, respectively, at 26.5 weeks after the first UV treatment. Two potential mechanisms by which niacin prevents tumor formation were identified. Photoimmunosuppression, critical for photocarcinogenesis, is measured by a passive transfer assay. Syngeneic, antigenic tumor challenges grew to an average of 91.6 +/- 19.7, 79.8 +/- 11.5, 41.9 +/- 11.7, or 13.2 +/- 4.1 mm2 in naive recipients of splenocytes from UV-irradiated mice treated with 0%, 0.1%, 0.5%, or 1.0% niacin supplementation, respectively, demonstrating niacin prevention of immunosuppression. Niacin supplementation elevated skin NAD content, which is known to modulate the function of DNA strand scission surveillance proteins p53 and poly(ADP-ribose) polymerase, two proteins critical in cellular responses to UV-induced DNA damage. These results clearly demonstrate a dose-dependent preventive effect of oral niacin on photocarcinogenesis and photoimmunosuppression and establish the capacity of oral niacin to elevate skin NAD levels.
Human killer cell activatory receptors for MHC class I molecules are included in a multimeric complex expressed by natural killer cells (1997)

Engagement of killer cell inhibitory receptors (KIRs) with their MHC class I ligands inhibits T and NK lymphocyte activation. In humans, killer cell activatory receptors (KARs) are highly homologous to KIRs, interact with an identical set of MHC class I molecules, and are encoded by individual genes belonging to the Ig-like superfamily. In contrast to KIRs, engagement of KARs leads to T and NK cell activation. We identified a set of disulfide-linked dimers selectively associated with KARs. KAR-associated polypeptides (KARAPs) are phosphorylated on tyrosine and serine residues. Reconstitution of KAR cell surface expression in the absence of KARAPs correlates with the failure of KAR to transduce any detectable activation signals. These results indicate that KARs are included in a multimeric complex with phosphorylated KARAPs and define a novel set of polypeptides that are likely to be involved in the control of lymphocyte activation upon MHC class I recognition.
GRASSLAND MANAGEMENT AND CONVERSION INTO GRASSLAND: EFFECTS ON SOIL CARBON (2001)

Grasslands are heavily relied upon for food and forage production. A key component for sustaining production in grassland ecosystems is the maintenance of soil organic matter (SOM), which can be strongly influenced by management. Many management techniques intended to increase forage production may potentially increase SOM, thus sequestering atmospheric carbon (C). Further, conversion from either cultivation or native vegetation into grassland could also sequester atmospheric carbon. We reviewed studies examining the influence of improved grassland management practices and conversion into grasslands on soil C worldwide to assess the potential for C sequestration. Results from 115 studies containing over 300 data points were analyzed. Management improvements included fertilization (39%), improved grazing management (24%), conversion from cultivation (15%) and native vegetation (15%), sowing of legumes (4%) and grasses (2%), earthworm introduction (1%), and irrigation (1%). Soil C content and concentration increased with improved management in 74% of the studies, and mean soil C increased with all types of improvement. Carbon sequestration rates were highest during the first 40 yr after treatments began and tended to be greatest in the top 10 cm of soil. Impacts were greater in woodland and grassland biomes than in forest, desert, rain forest, or shrubland biomes. Conversion from cultivation, the introduction of earthworms, and irrigation resulted in the largest increases. Rates of C sequestration by type of improvement ranged from 0.11 to 3.04 Mg C·ha−1 yr−1, with a mean of 0.54 Mg C·ha−1·yr−1, and were highly influenced by biome type and climate. We conclude that grasslands can act as a significant carbon sink with the implementation of improved management.
Association of MITF and other melanosome-related proteins with chemoresistance in melanoma tumors and cell lines (2013)

Previous studies in cell lines have suggested a role for melanosomes and related protein trafficking pathways in melanoma drug response. We have investigated the expression of six proteins related to melanosomes and melanogenesis (MITF, GPR143, gp100/PMEL, MLANA, TYRP1, and RAB27A) in pretreatment metastases from melanoma patients (n = 52) with different response to dacarbazine/temozolomide. Microphthalmia-associated transcription factor (MITF) and G-protein coupled receptor 143 (GPR143) showed significantly higher expression in nonresponders compared with responders. The premelanosome protein (gp100/PMEL) has been indicated previously in resistance to cisplatin in melanoma cells, but the expression levels of gp100/PMEL showed no association with response to dacarbazine/temozolomide in our clinical material. We also investigated the effects on chemosensitivity of siRNA inhibition of gp100/PMEL in the MNT-1 melanoma cell line. As expected from the study of the tumor material, no effect was detected with respect to response to temozolomide. However, knockdown of gp100/PMEL sensitized the cells to both paclitaxel and cisplatin. Overall, our results suggest that MITF, and several MITF-regulated factors, are associated with resistance to chemotherapy in melanoma and that different MITF targets can be of importance for different drugs.
Endocrine Treatment of Advanced Breast Cancer (1996)

Endocrine treatment is the preferred first-line therapy for advanced breast cancer because of its good tolerability. There are several groups of agents which differ in their mode of action but almost all in some way reduce stimulation by oestrogen. Over recent years, there has been a substantial increase in the number of medical agents in clinical trial. New antioestrogens with reduced or no agonist activity, and potent, more specific, aromatase inhibitors are now reaching the clinic. In most cases, the clinical effectiveness of these agents remains to be fully established and their optimal therapeutic application is yet to be determined.
Different effect of desipramine on protein kinase C in platelets between bipolar and major depressive disorders (1999)

Protein kinase C (PKC) activity was investigated in platelets from affective disorder subjects and healthy volunteers. The PKC activity of platelets incubated with desipramine was determined in vitro. The PKC activity of the major depressive disorder subjects and healthy volunteers was inhibited by desipramine, whereas that of the bipolar disorder subjects showed both inhibition and activation. In addition, the base PKC activity incubation with antidepressants of the major depressive disorder patients was significantly higher than of the bipolar disorder patients. These preliminary results suggest that the function of PKC may, at least in part, be associated with the mechanism of affective disorder.
Integration of bacterial lytic polysaccharide monooxygenases into designer cellulosomes promotes enhanced cellulose degradation (2014)

Efficient conversion of cellulose into soluble sugars is a key technological bottleneck limiting efficient production of plant-derived biofuels and chemicals. In nature, the process is achieved by the action of a wide range of cellulases and associated enzymes. In aerobic microrganisms, cellulases are secreted as free enzymes. Alternatively, in certain anaerobic microbes, cellulases are assembled into large multienzymes complexes, termed "cellulosomes," which allow for efficient hydrolysis of cellulose. Recently, it has been shown that enzymes classified as lytic polysaccharide monooxygenases (LPMOs) were able to strongly enhance the activity of cellulases. However, LPMOs are exclusively found in aerobic organisms and, thus, cannot benefit from the advantages offered by the cellulosomal system. In this study, we designed several dockerin-fused LPMOs based on enzymes from the bacterium Thermobifida fusca. The resulting chimeras exhibited activity levels on microcrystalline cellulose similar to that of the wild-type enzymes. The dockerin moieties of the chimeras were demonstrated to be functional and to specifically bind to their corresponding cohesin partner. The chimeric LPMOs were able to self-assemble in designer cellulosomes alongside an endo- and an exo-cellulase also converted to the cellulosomal mode. The resulting complexes showed a 1.7-fold increase in the release of soluble sugars from cellulose, compared with the free enzymes, and a 2.6-fold enhancement compared with free cellulases without LPMO enhancement. These results highlight the feasibility of the conversion of LPMOs to the cellulosomal mode, and that these enzymes can benefit from the proximity effects generated by the cellulosome architecture.
Novel adoptive T-cell immunotherapy using a WT1-specific TCR vector encoding silencers for endogenous TCRs shows marked antileukemia reactivity and safety (2011)

Adoptive T-cell therapy for malignancies using redirected T cells genetically engineered by tumor antigen-specific T-cell receptor (TCR) gene transfer is associated with mispairing between introduced and endogenous TCR chains with unknown specificity. Therefore, deterioration of antitumor reactivity and serious autoimmune reactivity are major concerns. To address this problem, we have recently established a novel retroviral vector system encoding siRNAs for endogenous TCR genes (siTCR vector). In this study, to test the clinical application of siTCR gene therapy for human leukemia, we examined in detail the efficacy and safety of WT1-siTCR-transduced T cells. Compared with conventional WT1-TCR (WT1-coTCR) gene-transduced T cells, these cells showed significant enhancement of antileukemia reactivity resulting from stronger expression of the introduced WT1-specific TCR with inhibition of endogenous TCRs. Notably, WT1-siTCR gene-transduced T cells were remarkably expandable after repetitive stimulation with WT1 peptide in vitro, without any deterioration of antigen specificity. WT1-siTCR gene-transduced T cells from leukemia patients successfully lysed autologous leukemia cells, but not normal hematopoietic progenitor cells. In a mouse xenograft model, adoptively transferred WT1-siTCR gene-transduced T cells exerted distinct antileukemia efficacy but did not inhibit human hematopoiesis. Our results suggest that gene-immunotherapy for leukemia using this WT1-siTCR system holds considerable promise.
PD-1 Blockade in Renal Cell Carcinoma: To Equilibrium and Beyond (2014)

The past several years have witnessed a resurgence of interest in cancer immunotherapy. The development of blocking antibodies against the inhibitory programmed death-1 (PD-1) pathway represents a clinical breakthrough in the treatment of solid tumors such as melanoma, and these agents show great promise in renal cell carcinoma (RCC). The early data have been surprising in that they demonstrate that blockade of a single immune checkpoint can elicit objective responses in patients with RCC, despite the recognized complexity of the immunosuppressive tumor microenvironment. Reinvigorating the patient's own immune cells to reactivate and to target the tumor has the potential advantages of more selective killing and thus decreased toxicity. In addition, checkpoint blockade immunotherapy has the advantage of inducing a memory response that is unattainable with our current cytotoxic and targeted therapies. This Crossroads overview will highlight the emerging investigation of PD-1 blockade in RCC and how this T cell-targeted strategy may thwart the tumor's escape mechanisms and shift the immune system/tumor balance back to a state of equilibrium and even to tumor elimination.
Light-Field Demultiplexing and Disparity Estimation (2014)

In this paper we study the post-processing pipeline to recover the views (light-field) from the raw data of a plenoptic camera such as Lytro. First, the microlens centers are estimated and then the raw image is demultiplexed without demosaicing it beforehand. This avoids image artifacts due to view cross-talk. Furthermore, we present a new blockmatching algorithm to estimate disparities for plenoptic views that have not been demosaiced. Our algorithm enforces the coherence through the views thanks to the view configuration given by the plenoptic camera: (i) the views are horizontally and vertically rectified and have the same baseline, and therefore (ii) at each point, the vertical and horizontal disparities are the same. Finally, we show that disparity estimation is more accurate when the raw image is demultiplexed without demosaicing the raw image. In particular, we show that our algorithm outperforms the disparity estimation method in [17].
Single amino acid substitutions at conserved residues of human interferon-alpha can effect antiviral specific activity. (1985)

Site-specific in vitro mutagenesis was used to direct various amino acid substitutions at conserved positions within the sequence of human interferon-alpha 1 (IFN-alpha 1). The antiviral specific activity of IFN-alpha 1, expressed in M13 as a fusion protein [IFN-alpha 1 (phi WT)], could be altered by single amino acid substitutions. The substitution of glycine for tyrosine at position 123 results in a loss of more than 99% of the antiviral specific activity on human cells, but causes no significant change in the antiviral specific activity on primary bovine cells. The tyrosine at position 123 is thus implicated in determining human cell specificity. Based on analysis of IFN-alpha 2, IFN-alpha 1 contains two dulsulphide bridges between cysteine residues 29 and 139 and cysteine residues 1 and 99. IFN-alpha 1 also contains a fifth cysteine residue at position 86. IFN-alpha 1 (phi WT) carrying three serine for cysteine substitutions at positions 1, 86 and 99 retains 23% of the antiviral specific activity of IFN-alpha 1 (phi WT) on human cells. However, the antiviral activity on bovine cells is not significantly affected by this modification. The presence of the disulphide bridge between residues 1 and 99 thus appears to be required for full antiviral activity on human but not bovine cells. A single serine for cysteine substitution at position 29 reduces the antiviral specific activity on both human and bovine cells by some 95%. This data shows that the disulphide bridge between residues 29 and 139 is critical for the antiviral activity of IFN-alpha's.
Triplex Formation by Oligonucleotides Containing 5-(1-Propynyl)-2‘-deoxyuridine:  Decreased Magnesium Dependence and Improved Intracellular Gene Targeting (1999)

Oligonucleotides capable of sequence-specific triple helix formation have been proposed as DNA binding ligands useful for modulation of gene expression and for directed genome modification. However, the effectiveness of such triplex-forming oligonucleotides (TFOs) depends on their ability to bind to their target sites within cells, and this can be limited under physiologic conditions. In particular, triplex formation in the pyrimidine motif is favored by unphysiologically low pH and high magnesium concentrations. To address these limitations, a series of pyrimidine TFOs were tested for third-strand binding under a variety of conditions. Those containing 5-(1-propynyl)-2'-deoxyuridine (pdU) and 5-methyl-2'-deoxycytidine (5meC) showed superior binding characteristics at neutral pH and at low magnesium concentrations, as determined by gel mobility shift assays and thermal dissociation profiles. Over a range of Mg2+ concentrations, pdU-modified TFOs formed more stable triplexes than did TFOs containing 2'-deoxythymidine. At 1 mM Mg2+, a DeltaTm of 30 degreesC was observed for pdU- versus T-containing 15-mers (of generic sequence 5' TTTTCTTTTTTCTTTTCT 3') binding to the cognate A:T bp rich site, indicating that pdU-containing TFOs are capable of substantial binding even at physiologically low Mg2+ concentrations. In addition, the pdU-containing TFOs were superior in gene targeting experiments in mammalian cells, yielding 4-fold higher mutation frequencies in a shuttle vector-based mutagenesis assay designed to detect mutations induced by third-strand-directed psoralen adducts. These results suggest the utility of the pdU substitution in the pyrimidine motif for triplex-based gene targeting experiments.
Chronic, Multiple Tics of Gilles de la Tourette's Disease (1978)

Central nervous system metabolism in six children and one adult with the syndrome of chronic multiple tics was studied by measuring the accumulation of acid metabolites of dopamine and serotonin (homovanillic acid [HVA] and 5-hydroxyindole-acetic acid [5-HIAA], respectively) in the CSF following probenecid administration. The accumulation of 5-HIAA was reduced in patients with multiple tics in contrast with other pediatric patients (N = 27). The degree of reduction in 5-HIAA relative to HVA appeared to be associated with the severity of the tic disorder. With dextroamphetamine, tic symptoms worsened, CSF HVA level decreased, and CSF 5-HIAA concentration increased. These findings suggest an association in Gilles de la Tourette's disease of reduced functioning of inhibitory serotonergic mechanisms and functional dopaminergic overactivity.