gebhart/patrepeval huggingface dataset:
ARDB--Antibiotic Resistance Genes Database (2008)

The treatment of infections is increasingly compromised by the ability of bacteria to develop resistance to antibiotics through mutations or through the acquisition of resistance genes. Antibiotic resistance genes also have the potential to be used for bio-terror purposes through genetically modified organisms. In order to facilitate the identification and characterization of these genes, we have created a manually curated database--the Antibiotic Resistance Genes Database (ARDB)--unifying most of the publicly available information on antibiotic resistance. Each gene and resistance type is annotated with rich information, including resistance profile, mechanism of action, ontology, COG and CDD annotations, as well as external links to sequence and protein databases. Our database also supports sequence similarity searches and implements an initial version of a tool for characterizing common mutations that confer antibiotic resistance. The information we provide can be used as compendium of antibiotic resistance factors as well as to identify the resistance genes of newly sequenced genes, genomes, or metagenomes. Currently, ARDB contains resistance information for 13,293 genes, 377 types, 257 antibiotics, 632 genomes, 933 species and 124 genera. ARDB is available at http://ardb.cbcb.umd.edu/.
Dupilumab Treatment in Adults with Moderate-to-Severe Atopic Dermatitis (2014)

Patients treated with dupilumab had marked and rapid improvement in all the evaluated measures of atopic dermatitis disease activity. Side-effect profiles were not dose-limiting. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov numbers, NCT01259323, NCT01385657, NCT01639040, and NCT01548404.).
Clinical safety, pharmacokinetics, and efficacy of ambrisentan therapy in children with pulmonary arterial hypertension (2012)

Recent trials in adult PAH revealed the efficacy of ambrisentan. However, in children with PAH, the clinical safety and pharmacokinetics of ambrisentan has not been well studied. Our aim was to investigate the clinical safety, pharmacokinetics, tolerability, and efficacy of endothelin receptor antagonist therapy with ambrisentan in children with pulmonary arterial hypertension (PAH). This retrospective cohort study provides clinical data from pediatric patients with PAH receiving ambrisentan as add-on therapy or transition from bosentan. Safety included evaluation of adverse events including aminotransferase abnormalities. The clinical impact was evaluated by improvement from baseline in clinical variables. A total of 38 pediatric patients with PAH received ambrisentan. Fifteen of 38 patients were switched from bosentan to ambrisentan. The remaining 23 children were treated with ambrisentan as an add-on therapy due to disease progression. In both transition and add-on cases, mean pulmonary artery pressure significantly improved (transition; 55 ± 18 vs. 45 ± 20 mmHg, n = 13, P = 0.04, add-on; 52 ± 17 vs. 45 ± 19 mmHg, n = 13, P = 0.03) during the follow-up. World Health Organization functional class improved in 31% of patients, but one patient required an atrial septostomy due to disease progression during the follow-up period (median, range; 20, 4-44 months). Five patients (13%) discontinued ambrisentan due to severe headache, lack of clinical efficacy, or near syncope. Ten patients (26%) had side effects associated with ambrisentan treatment, including nasal congestion, headache, and flushing. However, no patients had aminotransferase abnormalities and there were no deaths after initiation of ambrisentan during follow-up. Pharmacokinetics were evaluated in sixteen children treated with ambrisentan from 2.5 mg to 10.0 mg; the mean peak plasma concentration was 738 ± 452 ng/ml, mean time to peak plasma concentration was 3.2 ± 2.1 hours, and mean area under the curve plasma concentration was 6657 ± 4246 ng·hour/ml. In conclusion, initial experience with ambrisentan in children suggests that treatment is safe with similar pharmacokinetics to those in adults and may improve PAH in some children.
Where Is the Semantic System? A Critical Review and Meta-Analysis of 120 Functional Neuroimaging Studies (2009)

Semantic memory refers to knowledge about people, objects, actions, relations, self, and culture acquired through experience. The neural systems that store and retrieve this information have been studied for many years, but a consensus regarding their identity has not been reached. Using strict inclusion criteria, we analyzed 120 functional neuroimaging studies focusing on semantic processing. Reliable areas of activation in these studies were identified using the activation likelihood estimate (ALE) technique. These activations formed a distinct, left-lateralized network comprised of 7 regions: posterior inferior parietal lobe, middle temporal gyrus, fusiform and parahippocampal gyri, dorsomedial prefrontal cortex, inferior frontal gyrus, ventromedial prefrontal cortex, and posterior cingulate gyrus. Secondary analyses showed specific subregions of this network associated with knowledge of actions, manipulable artifacts, abstract concepts, and concrete concepts. The cortical regions involved in semantic processing can be grouped into 3 broad categories: posterior multimodal and heteromodal association cortex, heteromodal prefrontal cortex, and medial limbic regions. The expansion of these regions in the human relative to the nonhuman primate brain may explain uniquely human capacities to use language productively, plan, solve problems, and create cultural and technological artifacts, all of which depend on the fluid and efficient retrieval and manipulation of semantic knowledge.
Improved Thermal Stability of LiCoO2 by Cyclotriphosphazene Additives in Lithium-ion Batteries (2005)

Abstract Fluorinated cyclotriphosphazene is selected as a novel flame-retarding additive in the electrolyte for lithium-ion batteries. The effect of the phosphazenes on the thermal stability of LiCoO2 cathode has been investigated by the thermal analyses on charged LiCoO2 electrodes in the presence of the electrolyte with or without the additives. Possible mechanism for the influence of the additive on the thermal stability of LiCoO2 has been proposed.
Current status of poly(ADP-ribose) polymerase inhibitors and future directions (2017)

Inhibitors of poly(ADP-ribose) polymerases (PARPs), which play a key role in DNA damage/repair pathways, have been developed as antitumor agents based on the concept of synthetic lethality. Synthetic lethality is the idea that cell death would be efficiently induced by simultaneous loss of function of plural key molecules, for example, by exposing tumor cells with inactivating gene mutation of BRCA-mediated DNA repair to chemically induced inhibition of PARPs. Indeed, three PARP inhibitors, olaparib, rucaparib and niraparib have already been approved in the US or Europe, mainly for the treatment of <i>BRCA</i>-mutant ovarian cancer. Clinical trials of various combinations of PARP inhibitors with cytotoxic or molecular-targeted agents are also underway. In particular, expanded applications of PARP inhibitors are anticipated following recent reports that defects in homologous recombination repair (HRR) are associated with mutations in repair genes other than <i>BRCA1/BRCA2</i>, such as <i>ATM</i>, <i>ATR</i>, <i>PALB2</i>, <i>RAD51</i>, <i>CHEK1</i> and <i>CHEK2</i>, as well as with epigenetic loss of <i>BRCA1</i> function through promoter methylation or overexpression of the BRCA2-interacting transcriptional repressor EMSY. Current topics of interest include selection of the best agent in each clinical context, identification of new treatment targets for HRR-proficient cases, and development of PARP inhibitor-based regimens that are less toxic and that prolong overall survival as well as progression-free survival. In addition, potential long-term side effects and suitable biomarkers for predicting efficacy and mechanisms of clinical resistance are in discussion. This review summarizes representative preclinical and clinical data for PARP inhibitors and discusses their potential for future applications to treat various malignancies.
Immunotherapy of equine sarcoid: dose-escalation trial for the use of chimeric papillomavirus-like particles (2007)

Equine sarcoids are fibrosarcoma-like skin tumours with a prevalence of approximately 1-2 %. Strong evidence exists for a causative role of bovine papillomavirus (BPV) type 1 or type 2 in the development of sarcoids. No effective treatment of equine sarcoid is available and after surgical excision relapse of the tumours is very frequent. We developed chimeric virus-like particles (CVLPs) of BPV 1 L1-E7 for the immunotherapy of equine sarcoid. In a phase I clinical trial 12 horses suffering from equine sarcoid with an average number of more than 22 tumours per animal were vaccinated in a dose-escalation setting. The animals were followed-up for 63 days, eight of the twelve horses were followed-up for more than a year and side-effects, humoral immune responses and tumour appearance were recorded. BPV DNA was detected in tumours of 11 cases. CVLPs were well tolerated in all dose groups, a robust anti-L1 antibody response was induced in all but one of the horses. Anti-E7 antibodies were detected in five of the 12 animals at low titres. Two animals showed a clear improvement of the clinical status after treatment, i.e. the number of the tumours per horse was reduced. In another horse regression of five sarcoids was observed; three of them relapsed during the study. Two animals showed tumour regression as well as growth of new sarcoids. In two horses the clinical status remained unchanged, in another two horses growth of existing tumours or growth of additional tumours was observed. The remaining three animals showed simultaneously regression and growth of existing tumours. Neither the humoral immune responses nor the observed effects on the tumours was correlated with the dose group.
Significant expression of vascular endothelial growth factor/vascular permeability factor in mouse ascites tumors. (1998)

Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, is believed to be a potent mediator of peritoneal fluid accumulation and angiogenesis and of tumor growth in ascites tumor. Such roles, however, have not been generally established because of insufficient quantitative and systemic analyses. To address this, we examined the expression of VEGF in 13 mouse ascites tumors (5 sarcomas, 3 carcinomas, 2 lymphomas, 1 leukemia, 1 mastocytoma, and 1 plasmacytoma). Using a newly developed sensitive and specific radioreceptor binding assay and functional assays, we found that active VEGF was significantly accumulated (6-850 ng/ml) in the ascites fluids of all 13 tumors. VEGF concentrations are higher in the tumors of sarcoma and carcinoma origin (430.4 +/- 234.2 ng/ml) than in those of lymphoma and hematological tumor origin (19.2 +/- 10.45 ng/ml). VEGF that accumulated in the peritoneal fluids or expressed in the ascites tumor cells was easily visualized with immunoprecipitation Western blot analysis with a rough correlation to the expression levels of VEGF gene in these tumor cells, suggesting that the tumor cells, at least in part, contributed to the production of the VEGF that accumulated in the ascites fluid. Most ascites tumors expressed VEGF; the 164-amino acid isoform was predominant, the 120-amino acid isoform was less abundant, and the 188-amino acid isoform was least abundant. Several representative ascites tumors expressed similar, if not higher, levels of VEGF when they were cultured at normoxic states, suggesting that they expressed VEGF at high levels in a constitutive manner. The microvessel densities in the peritoneal walls of tumor-bearing mice, which are significantly higher than those in normal mice, basically correlated to but did not parallel the VEGF concentrations in their respective ascites fluids. Thus, a complicated relationship may exist between the VEGF production and angiogenesis associated with ascites tumor in vivo. Taken together, our observations suggest that VEGF plays a fundamental role in ascites tumor formation; however, its importance may vary according to tumor origin.
A high-throughput hybridization method for titer determination of viruses and gene therapy vectors (1998)

One of the challenges facing researchers working with viruses and gene therapy vectors is the need to rapidly assay for infectious virus. Current methods used to titer many viruses are cumbersome and are not amenable to handling large numbers of samples. Here we describe the development of an assay that can rapidly quantify infectious viruses and gene therapy vectors. The assay relies on biological amplification of viral sequences and hybridization of labeled probes to immobilized nucleic acid from infected cells. The amplification of the viral genome makes this a highly sensitive method. The assay is configured in a high-throughput format that has been used to detect recombinant adeno-associated virus (AAV), wild-type AAV and infectious adenovirus. The assay is quantitative, and can be used to titer virus preparations with or without a known standard.
The Physiological Factor: The “Seventh” Advantage to Games and Its Use in Treatment Planning (1997)

Eric Berne (1964) identified six reasons for games: biological, existential, internal psychological, external psychological, internal social, and external social. Bary and Hufford (1990) elaborated on these six factors, describing them as the basis for comprehensive diagnosis and treatment planning. They explained how each factor must be resolved to achieve a complete homeostatic rebalancing that allows for autonomy, awareness, spontaneity, and freedom from previous script limitations. This article suggests that a seventh factor should be added: the physiological advantage to games. Through early conditioning, a person adopts body armoring that influences the content of the six psychosocial factors. In turn, these psychosocial factors reinforce and maintain the body armoring, thus creating a closed system with strong resistance to change. With some clients this body armor will soften, adjust, shift, and change as work is done on the other factors. However, with some clients, specific bodywork must be adde...
[Impairment of lipid metabolism in the liver and its correction after exposure to ethanol and antitubercular agents]. (1986)

Impairments in the lipid spectrum of rat liver tissue, developed as a result of long-term simultaneous effect of ethanol and antituberculosis drugs isoniazid ann rifampycin, were effectively corrected by means of phospholipid preparations as well as by legalone (sylimarine). Pyridoxine, tocopherol and ATP did not normalize the lipid metabolism under these conditions.
T‐cell receptor binding affinities and kinetics: impact on T‐cell activity and specificity (2008)

The interaction between the T-cell receptor (TCR) and its peptide-major histocompatibility complex (pepMHC) ligand plays a critical role in determining the activity and specificity of the T cell. The binding properties associated with these interactions have now been studied in many systems, providing a framework for a mechanistic understanding of the initial events that govern T-cell function. There have been various other reviews that have described the structural and biochemical features of TCR : pepMHC interactions. Here we provide an overview of four areas that directly impact our understanding of T-cell function, as viewed from the perspective of the TCR : pepMHC interaction: (1) relationships between T-cell activity and TCR : pepMHC binding parameters, (2) TCR affinity, avidity and clustering, (3) influence of coreceptors on pepMHC binding by TCRs and T-cell activity, and (4) impact of TCR binding affinity on antigenic peptide specificity.
Occlusive and reperfused myocardial infarcts: differentiation with Mn-DPDP--enhanced MR imaging. (1989)

To assess whether the administration of manganese N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid (DPDP) permits differentiation between occlusive and reperfused infarcts, the authors subjected rats to either 6 hours of left coronary artery occlusion (n = 13) or 2 hours of occlusion followed by 4 hours of reperfusion (n = 10) before magnetic resonance (MR) imaging. Electrocardiographic-gated T1-weighted images were obtained before and for 1 hour after injection of 400 mumol/kg of Mn-DPDP. On T1-weighted images obtained before injection of Mn-DPDP. no significant differences in signal intensity were observed between normal and infarcted regions. Use of Mn-DPDP permitted delineation of the area of infarction. The pattern of enhancement in the injured zone was different for occlusive and reperfused myocardial infarcts. In rats with occlusive infarcts, In rats with occlusive infarcts, three well-defined zones were seen. Epicardium and endocardium were enhanced, while the midmyocardial zone was hypointense. The midmyocardial signal intensity gradually increased during the 60 minutes after injection. In rats with reperfused infarcts, the injured area was uniformly and intensely enhanced. Histologic examination confirmed the presence and location of myocardial infarct. Mn-DPDP may improve the detection and delineation of acute myocardial infarcts, demonstrate perfusion of the infarct, and permit discrimination between reperfused and occlusive infarcts.
On‐chip silicon 8‐channel hybrid (de)multiplexer enabling simultaneous mode‐ and polarization‐division‐multiplexing (2014)

Abstract An 8‐channel hybrid (de)multiplexer to simultaneously achieve mode‐ and polarization‐division‐(de)multiplexing is proposed and demonstrated experimentally on a silicon‐on‐insulator platform to improve the link capacity of an on‐chip optical interconnect. The present hybrid (de)multiplexer has four channels for each polarization. A polarization beam splitter based on a three‐waveguide coupler is used to combine/separate the fundamental modes of TE‐ and TM‐polarizations (TE 0 and TM 0 ). Six asymmetric directional couplers are cascaded for (de)multiplexing the high‐order modes (TE 1 , TE 2 , TE 3 , TM 1 , TM 2 , and TM 3 ). The experimental results show all eight channels have low loss and low crosstalk (&lt;−10 dB) over a ∼ 30 nm wavelength range.
Influence of Drying and Storage on Lipid and Carotenoid Stability of the Microalga Phaeodactylum tricornutum (2011)

The influence of short-term storage and spray- and freeze-drying of fresh microalgal paste on the stability of lipids and carotenoids of Phaeodactylum tricornutum was investigated. Furthermore, the effects of storage time (14 and 35 days) and condition (vacuum packed vs non vacuum packed, -20 °C vs 4 °C vs 20 °C) after spray- and freeze-drying were studied. Total lipid content, free fatty acid content, carotenoid content and degree of lipid oxidation were measured. No effects of spray- and freeze-drying and subsequent storage were found on total lipid content, except for short-term storage of the fresh microalgal paste, which led to pronounced lipolysis and therefore a lower total lipid content. Freeze-dried microalgae were found to be more susceptible to lipolysis upon storage than spray-dried microalgae. On the other hand, spray-dried microalgae were more susceptible to oxidation than freeze-dried microalgae, possibly due to breakdown of protecting carotenoids upon spray-drying. Hardly any effect of storage condition was observed for any of the parameters tested.
Comparison of transport pathways of catechol-substituted cephalosporins, BO-1236 and BO-1341, through the outer membrane of Escherichia coli. (1990)

The penetration of /Mactam antibiotics through the outer membraneis a prerequisite for exhibiting the antibacterial activity against Gram-negative bacteria. The elucidation of penetration routes has been the subject of many papers, and our
Structural basis for recognition of the nonclassical MHC molecule HLA-G by the leukocyte Ig-like receptor B2 (LILRB2/LIR2/ILT4/CD85d) (2006)

HLA-G is a nonclassical MHC class I (MHCI) molecule that can suppress a wide range of immune responses in the maternal-fetal interface. The human inhibitory immune receptors leukocyte Ig-like receptor (LILR) B1 [also called LIR1, Ig-like transcript 2 (ILT2), or CD85j] and LILRB2 (LIR2/ILT4/CD85d) preferentially recognize HLA-G. HLA-G inherently exhibits various forms, including beta(2)-microglobulin (beta(2)m)-free and disulfide-linked dimer forms. Notably, LILRB1 cannot recognize the beta(2)m-free form of HLA-G or HLA-B27, but LILRB2 can recognize the beta(2)m-free form of HLA-B27. To date, the structural basis for HLA-G/LILR recognition remains to be examined. Here, we report the 2.5-A resolution crystal structure of the LILRB2/HLA-G complex. LILRB2 exhibits an overlapping but distinct MHCI recognition mode compared with LILRB1 and dominantly recognizes the hydrophobic site of the HLA-G alpha3 domain. NMR binding studies also confirmed these LILR recognition differences on both conformed (heavy chain/peptide/beta(2)m) and free forms of beta(2)m. Binding studies using beta(2)m-free MHCIs revealed differential beta(2)m-dependent LILR-binding specificities. These results suggest that subtle structural differences between LILRB family members cause the distinct binding specificities to various forms of HLA-G and other MHCIs, which may in turn regulate immune suppression.
Requirements for gene silencing mediated by U1 snRNA binding to a target sequence (2008)

U1 interference (U1i) is a novel method to block gene expression. U1i requires expression of a 5'-end-mutated U1 snRNA designed to base pair to the 3'-terminal exon of the target gene's pre-mRNA that leads to inhibition of polyadenylation. Here, we show U1i is robust (> or =95%) and a 10-nt target length is sufficient for good silencing. Surprisingly, longer U1 snRNAs, which could increase annealing to the target, fail to improve silencing. Extensive mutagenesis of the 10-bp U1 snRNA:target duplex shows that any single mismatch different from GU at positions 3-8, destroys silencing. However, mismatches within the other positions give partial silencing, suggesting that off-target inhibition could occur. The specificity of U1i may be enhanced, however, by the fact that silencing is impaired by RNA secondary structure or by splicing factors binding nearby, the latter mediated by Arginine-Serine (RS) domains. U1i inhibition can be reconstituted in vivo by tethering of RS domains of U1-70K and U2AF65. These results help to: (i) define good target sites for U1i; (ii) identify and understand natural cellular examples of U1i; (iii) clarify the contribution of hydrogen bonding to U1i and to U1 snRNP binding to 5' splice sites and (iv) understand the mechanism of U1i.