gebhart/patrepeval huggingface dataset:
Host-Range Restriction of Vaccinia Virus E3L Deletion Mutant Can Be Overcome In Vitro, but Not In Vivo, by Expression of the Influenza Virus NS1 Protein (2011)

During the last decades, research focused on vaccinia virus (VACV) pathogenesis has been intensified prompted by its potential beneficial application as a vector for vaccine development and anti-cancer therapies, but also due to the fear of its potential use as a bio-terrorism threat. Recombinant viruses lacking a type I interferon (IFN) antagonist are attenuated and hence good vaccine candidates. However, vaccine virus growth requires production in IFN-deficient systems, and thus viral IFN antagonists that are active in vitro, yet not in vivo, are of great value. The VACV E3 and influenza virus NS1 proteins are distinct double-stranded RNA-binding proteins that play an important role in pathogenesis by inhibiting the mammalian IFN-regulated innate antiviral response. Based on the functional similarities between E3 and NS1, we investigated the ability of NS1 to replace the biological functions of E3 of VACV in both in vitro and in vivo systems. For this, we generated a VACV recombinant virus lacking the E3L gene, yet expressing NS1 (VVΔE3L/NS1). Our study revealed that NS1 can functionally replace E3 in cultured cells, rescuing the protein synthesis blockade, and preventing apoptosis and RNA breakdown. In contrast, in vivo the VVΔE3L/NS1 virus was highly attenuated after intranasal inoculation, as it was unable to spread to the lungs and other organs. These results indicate that there are commonalities but also functional differences in the roles of NS1 and E3 as inhibitors of the innate antiviral response, which could potentially be utilized for vaccine production purposes in the future.
Real-Time subspace integration for St. Venant-Kirchhoff deformable models (2005)

In this paper, we present an approach for fast subspace integration of reduced-coordinate nonlinear deformable models that is suitable for interactive applications in computer graphics and haptics. Our approach exploits dimensional model reduction to build reduced-coordinate deformable models for objects with complex geometry. We exploit the fact that model reduction on large deformation models with linear materials (as commonly used in graphics) result in internal force models that are simply cubic polynomials in reduced coordinates. Coefficients of these polynomials can be precomputed, for efficient runtime evaluation. This allows simulation of nonlinear dynamics using fast implicit Newmark subspace integrators, with subspace integration costs independent of geometric complexity. We present two useful approaches for generating low-dimensional subspace bases: modal derivatives and an interactive sketching technique. Mass-scaled principal component analysis (mass-PCA) is suggested for dimensionality reduction. Finally, several examples are given from computer animation to illustrate high performance, including force-feedback haptic rendering of a complicated object undergoing large deformations.
New peroxisome proliferator-activated receptor agonists: potential treatments for atherogenic dyslipidemia and non-alcoholic fatty liver disease (2014)

ABT-335 is a new formulation of fenofibrate that has been approved for concomitant use with statins. K-877, a SPPARM-α with encouraging preliminary results in modulating atherogenic dyslipidemia, and INT131, a SPPARM-γ with predominantly insulin-sensitizing actions, may also have favorable lipid-modifying effects. Although the development of dual PPAR-α/γ agonists (glitazars) and the SPPARM-δ GW501516 has been abandoned because of safety issues, another SPPARM-δ (MBX-8025) and a dual PPAR-α/δ agonist (GFT-505) have shown promising efficacy in decreasing plasma triglyceride and increasing high-density lipoprotein cholesterol concentrations, as well as improving insulin sensitivity and liver function. The beneficial effects of GFT-505 are complemented by preclinical findings that indicate reduction of hepatic fat accumulation, inflammation and fibrosis, making it a promising candidate for the treatment of NAFLD/nonalcoholic steatohepatitis (NASH). Long-term trials are required to test the efficacy and safety of these new PPAR agonists in reducing cardiovascular outcomes and treating NAFLD/NASH.
Feasibility of using carboxylic-rich polymeric surfaces for the covalent binding of oligonucleotides for microPCR applications (2002)

The chemical binding of oligonucleotide/DNA on polystyrene-related polymeric surfaces has been investigated using contact angle measurements, x-ray photoelectron spectroscopy and gravimetric analysis. The results of the covalent attachment of the phosphorylated oligonucleotides using the hetero-bifunctional cross linker 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride to polystyrene-co-maleic anhydride (PSMAA) and polystyrene-co-maleic acid (PSMA) are described. The immobilization efficiency of covalently coupled 26-mer oligonucleotides to polymeric surfaces was estimated as 0.3 × 1010 and 0.1 × 109 molecules mm-2 for PSMA and PSMAA, respectively. The results suggest that, although the covalent binding on PSMAA per se is not capable of the high density of DNA required by micro-PCR applications, the method has the potential to be used as a cheap alternative for other low-cost, less DNA-sensitive applications such as disposable biosensors.
Regional brain electrical asymmetries discriminate between previously depressed and healthy control subjects. (1990)

Baseline resting electroencephalogram (EEG) activity was recorded from 6 normothymic depressives and 8 controls using three different reference montages. Power in all frequency bands was extracted by Fourier transformation. Significant Group X Region X Hemisphere interactions were found consistently for alpha band power only. Previously depressed subjects had less left-sided anterior and less right-sided posterior activation (i.e., more alpha activity) than did never depressed subjects. Previously depressed subjects had no history of pharmacological treatment and did not differ from controls in emotional state at the time of testing. The pattern of anterior and posterior asymmetry in the previously depressed subjects is similar to that found in acutely depressed subjects and suggests that this may be a state-independent marker for depression.
Membrane permeability of coelenterazine analogues measured with fish eggs (1997)

To determine the suitability of various coelenterazine analogues for the regeneration of aequorin in living cells, the membrane permeabilities of 11 analogues were measured using the eggs of the killifish Fundulus grandis by soaking the eggs in solutions containing the analogues. The results indicated that e-coelenterazine, which has an exceptionally high rate of in vitro regeneration of aequorin, not only permeated poorly into the eggs but also was highly unstable. All other analogues tested permeated sufficiently into the eggs. The highest permeability was found with f-coelenterazine; the concentration of f-coelenterazine in the eggs was about five times that in the surrounding medium, assuming that the distribution of the compound in the egg is uniform.
Chiral synthesis via organoboranes. 15. Selective reductions. 42. Asymmetric reduction of representative prochiral ketones with potassium 9-O-(1,2:5,6-di-O-isopropylidene-.alpha.-D-glucofuranosyl)-9-boratabicyclo[3.3.1]nonane (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChiral synthesis via organoboranes. 15. Selective reductions. 42. Asymmetric reduction of representative prochiral ketones with potassium 9-O-(1,2:5,6-di-O-isopropylidene-.alpha.-D-glucofuranosyl)-9-boratabicyclo[3.3.1]nonaneHerbert C. Brown, Byung Tae Cho, and Won Suh ParkCite this: J. Org. Chem. 1988, 53, 6, 1231–1238Publication Date (Print):March 1, 1988Publication History Published online1 May 2002Published inissue 1 March 1988https://pubs.acs.org/doi/10.1021/jo00241a021https://doi.org/10.1021/jo00241a021research-articleACS PublicationsRequest reuse permissionsArticle Views809Altmetric-Citations69LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Studies on the incidence of coniferous needle endophytes in the Pacific Northwest (1978)

The incidence of internal fungal infections has been scored in coniferous needles from 19 hosts sampled in over 200 sites dispersed throughout western Oregon and southern Washington. Abies grandis, A. magnifica, Picea sitchensis, Pseudotsuga menziesii, and Sequoia sempervirens have proved congenial hosts for needle blade endophytes; petiole fungi are common in all species of Picea and Tsuga sampled. An undescribed taxon in the Hemiphacidiaceae, Chloroscypha spp., Cryptocline spp., Leptostroma spp., Naemacyclus spp., Phomopsis spp., Phyllosticta sp., and several unidentified Coelomycetes with Phoma-like spores were the dominant fungal taxa in the coniferous hosts sampled. The observed patterns of species dominance and diversity suggest that the true population of endophytes has been inadequately sampled in the present study and that an order of magnitude more intensive sampling might be required for real patterns of dominance and diversity to emerge. Many endophytes are restricted to a single coniferous host or to a restricted group of hosts. When similarity coefficients between coniferous species are computed on the basis of their internal needle microfloras, the resultant taxonomic groupings appear similar to those derived from consideration of conventional morphological criteria. Comparison of endophyte incidence with host distribution patterns for Pseudotsuga menziesii reveals that infection rates decrease at high elevations and dry sites.
Targeted proteins for diagnostic imaging: does chemistry make a difference? (1992)

The Oyen et al. study is valuable in that it systematically evaluates several of the factors involved in radiolabeled protein uptake and retention in infectious foci. The role of particular proteins and their receptor specific interactions seems to be inconsequential in agreement with the findings of other. However, the role of the radiolabel was shown to be important and significant differences were delineated from comparisons of the radionuclides and their associated chemistries. The conclusion implicating radionuclide chemistry and associated linkages underscores the need to optimize the attachment and labeling chemical modifications of protein carriers. Evaluation criteria should include serum stability, determination and assessment of the effect of molar substitution ratio, and potential for improving blood clearance without reducing the target-to-non-target ratio. Important areas for future study include characterization of radioactive metabolites and the design and synthesis of new ligands which direct the disposition of metabolites reducing retention in normal organs or accelerating renal excretion. Additionally, intracellular processing of radiolabel, compartmental distribution and strategies for augmenting internalization and retention within the target cell merit detailed exploration. For each radionuclide of interest, 111In, radioiodines, 99mTc and others, improved chemical moieties exist for controlling radiolabel fate. When carrying out mechanistic and evaluative studies, clear-cut conclusions will only be reached when defined and controlled chemistry is used. Having established a "gold standard," simplifications in radiolabeling and other chemical refinements can then be pursued with a quantitative understanding of the trade-offs in targeting agent performance versus other considerations such as cost reduction, simplicity, and convenience.
Trivalent CAR T cells overcome interpatient antigenic variability in glioblastoma (2017)

UCAR T cells can overcome antigenic heterogeneity in GBM and lead to improved treatment outcomes.
Collagen-Induced Arthritis in Rats Assessment by Serial Magnification Radiography (1985)

Serial whole body and lateral hindpaw magnification radiographs were obtained on 15 rats with collagen-induced arthritis. The radiographs were evaluated for findings of inflammatory arthritis. Soft tissue swelling and juxta-articular osteopenia usually developed two weeks after immunization. The swelling remained stable for the remaining seven weeks of the study, but the osteopenia apparently improved. Three weeks after immunization, erosions and periostitis began to develop in ten of the rats. These latter radiographic changes rapidly worsened over the next three weeks and then stabilized. The most frequent and severe changes were seen in the intertarsal, tibiotalar, and metatarsophalangeal joints. The toes, forepaws, and knees were infrequently involved. Other peripheral joints and the axial skeleton were spared. Five rats developed soft tissue swelling but had no articular erosions or periostitis. Serial radiography has potential usefulness for monitoring the effects of treatment in this experimental model for inflammatory arthritis.
Docosahexaenoic Acid and Smoking-Related Chronic Obstructive Pulmonary Disease (1999)

If the inflammatory response to inhalation of cigarette smoke causes chronic obstructive pulmonary disease (COPD), suppression of that natural response might be beneficial. We hypothesized that a smoker's risk of developing COPD is inversely related to physiologic levels of two fatty acids that have antiinflammatory properties: eicosapentaenoic acid (EPA, C20:5) and docosahexaenoic acid (DHA, C22:6). The proportion of each fatty acid in plasma lipids was measured in 2,349 current or former smokers. COPD was identified and defined by clinical symptoms and/or spirometry. After adjustment for smoking exposure and other possible confounders, the prevalence odds of COPD were inversely related to the DHA (but not to the EPA) content of plasma lipid components in most of the models. For example, as compared with the first quartile of the DHA distribution, the prevalence odds ratios (ORs) for chronic bronchitis were 0.98, 0.88, and 0.69 for the second, third, and fourth quartiles, respectively (p for linear trend = 0.09). The corresponding ORs for COPD as defined spirometrically, were 0.65, 0.51, and 0.48 (p < 0. 001). Among 543 current heavy smokers, adjusted mean values of FEV1 (lowest to highest DHA quartile) were 2,706, 2,785, 2,801, and 2,854 ml. DHA may have a role in preventing or treating COPD and other chronic inflammatory conditions of the lung. Pilot testing of that hypothesis in experimental models seems warranted.
Risk factors for contamination of domestic hot water systems by legionellae (1991)

To assess risk factors associated with the contamination of the domestic environment by legionellae, 211 houses in the Quebec City area were randomly selected and water samples were collected from the hot water tank, the shower heads, and the most frequently used faucet. After centrifugation, concentrated samples were seeded in triplicate on BCYE and GPV media. Data on the characteristics of the hot water system and plumbing in the house and on the personal habits of the occupants were collected for each house. Among these 211 houses, hot water was provided by either an oil or gas heater in 33 and by an electric heater in 178. Legionellae were isolated from none of the samples from houses with oil or gas heaters and from 39% (69 of 178) of those with electric water heaters (P less than 0.0001). This association remained highly significant after control for water temperature and other variables in a stratified analysis. In the 178 houses with an electric heater, 12% of the faucets, 15% of the shower heads, and 37% of the water heaters were contaminated. Legionella pneumophila serogroups 2 and 4 were the most frequently isolated strains. Logistic regression showed that factors associated with electric water heater contamination were (i) location of the house in older districts of the city (P less than 0.0001), (ii) old age of the water heater (P = 0.003), and (iii) low water temperature (P = 0.05). Contamination of the water heater was the only factor significantly associated with the contamination of peripheral outlets (P less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
Physical and functional link of the leukemia-associated factors AML1 and PML (2004)

The AML1-CBFbeta transcription factor complex is the most frequent target of specific chromosome translocations in acute myeloid leukemia (AML). The promyelocytic leukemia (PML) gene is also frequently involved in AML-associated translocation. Here we report that a specific isoform PML I forms a complex with AML1. PML I was able to recruit AML1 and coactivator p300 in PML nuclear bodies and enhance the AML1-mediated transcription in the presence of p300. A specific C-terminal region of PML I and a C-terminal region of AML1 were found to be required for both their association and colocalization in the nuclear bodies. Overexpression of PML I stimulates myeloid cells to differentiate. These results suggest that PML I could act as a mediator for AML1 and its coactivator p300/CBP to assemble into functional complexes and, consequently, activate AML1-dependent transcription and myeloid cell differentiation.
Actionable Diagnosis of Neuroleptospirosis by Next-Generation Sequencing (2014)

A 14-year-old boy with severe combined immunodeficiency presented three times to a medical facility over a period of 4 months with fever and headache that progressed to hydrocephalus and status epilepticus necessitating a medically induced coma. Diagnostic workup including brain biopsy was unrevealing. Unbiased next-generation sequencing of the cerebrospinal fluid identified 475 of 3,063,784 sequence reads (0.016%) corresponding to leptospira infection. Clinical assays for leptospirosis were negative. Targeted antimicrobial agents were administered, and the patient was discharged home 32 days later with a status close to his premorbid condition. Polymerase-chain-reaction (PCR) and serologic testing at the Centers for Disease Control and Prevention (CDC) subsequently confirmed evidence of Leptospira santarosai infection.
Geostatistical analysis of ground‐penetrating radar data: A means of describing spatial variation in the subsurface (1998)

We have investigated the use of ground‐penetrating radar (GFR) as a means of characterizing the heterogeneity of the subsurface. Radar data were collected at several sites in southwestern British Columbia underlain by glaciodeltaic sediments. A cliff face study was conducted in which geostatistical analysis of a digitized photograph of the face and the radar image of the face showed excellent agreement in the maximum correlation direction and the correlation length determined from these two data sets. Other two‐dimensional (2‐D) sections of radar data were divided into sedimentary architectural elements on the basis of the distinct radar appearance of these sedimentary units. Examples of four sedimentary units were used to obtain semivariograms from the radar data and resulted in maximum correlation lengths between 0.5 and 4.8 m. A 3‐D radar survey, collected over a package of gravel and sand foresets, was analyzed to determine the paleoflow direction; a correlation length of 4 m was found in that direction.
Heat Shock Factor 1 Attenuates 4-Hydroxynonenal-mediated Apoptosis (2007)

Lipid peroxidation is a consequence of both normal physiology and oxidative stress that generates various reactive metabolites, a principal end product being 4-hydroxynonenal (HNE). As a diffusible electrophile, HNE reacts extensively with cellular nucleophiles. Consequently, HNE alters cellular signaling and activates the intrinsic apoptotic cascade. We have previously demonstrated that in addition to promoting apoptosis, HNE activates stress response pathways, including the antioxidant, endoplasmic reticulum stress, DNA damage, and heat shock responses. Here we demonstrate that activation of the heat shock response by HNE is dependent on the expression and nuclear translocation of heat shock factor 1 (HSF1), which promotes the expression of heat shock protein 40 (Hsp40) and Hsp70-1. Ectopic expression and immunoprecipitation of c-Myc-tagged Hsp70-1 indicates that HNE disrupts the inhibitory interaction between Hsp70-1 and HSF1, leading to the activation heat shock gene expression. Using siRNA to silence HSF1 expression, we observe that HSF1 is necessary for the induction of Hsp40 and Hsp70-1 by HNE, and the lack of Hsp expression is correlated with an increase in apoptosis. Nrf2, the transcription factor that mediates the antioxidant response, was also silenced using siRNA. Silencing Nrf2 also enhanced the cytotoxicity of HNE, but not as effectively as HSF1. Silencing HSF1 expression facilitates the activation of JNK pro-apoptotic signaling and selectively decreases expression of the anti-apoptotic Bcl-2 family member Bcl-X(L). Overexpression of Bcl-X(L) attenuates HNE-mediated apoptosis in HSF1-silenced cells. Overall, activation of HSF1 and stabilization of Bcl-X(L) mediate a protective response that may contribute significantly to the cellular biology of lipid peroxidation.
Risk of Tardive Dyskinesia in Older Patients (1995)

Use of higher amounts of neuroleptics, particularly high-potency ones, should be avoided in older patients, patients with alcohol abuse/dependence, or patients with a subtle movement disorder at baseline; these patients are at a higher risk of developing TD.
RBFOX and PTBP1 proteins regulate the alternative splicing of micro-exons in human brain transcripts (2014)

Ninety-four percent of mammalian protein-coding exons exceed 51 nucleotides (nt) in length. The paucity of micro-exons (≤ 51 nt) suggests that their recognition and correct processing by the splicing machinery present greater challenges than for longer exons. Yet, because thousands of human genes harbor processed micro-exons, specialized mechanisms may be in place to promote their splicing. Here, we survey deep genomic data sets to define 13,085 micro-exons and to study their splicing mechanisms and molecular functions. More than 60% of annotated human micro-exons exhibit a high level of sequence conservation, an indicator of functionality. While most human micro-exons require splicing-enhancing genomic features to be processed, the splicing of hundreds of micro-exons is enhanced by the adjacent binding of splice factors in the introns of pre-messenger RNAs. Notably, splicing of a significant number of micro-exons was found to be facilitated by the binding of RBFOX proteins, which promote their inclusion in the brain, muscle, and heart. Our analyses suggest that accurate regulation of micro-exon inclusion by RBFOX proteins and PTBP1 plays an important role in the maintenance of tissue-specific protein-protein interactions.
Saccharomyces Genome Database: the genomics resource of budding yeast (2011)

The Saccharomyces Genome Database (SGD, http:// www.yeastgenome.org) is the community resource for the budding yeast Saccharomyces cerevisiae.