gebhart/patrepeval huggingface dataset:
In vivo Antigen Expression by Pasteurella multocida (1991)

Pasteurella multocida was purified from the blood of turkeys affected with acute fowl cholera, and membrane preparations from those bacteria were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and visualized on immunoblots. Antigens were detected in the membranes of these in vivo-propagated bacteria that were not detected in membrane preparations of the same P. multocida strain grown in vitro. The unique antigens were detected in the detergent-insoluble phase and were enriched to various degrees by different detergents.
Emerging Roles of Claudins in Human Cancer (2013)

Claudins are major integral membrane proteins of tight junctions. Altered expression of several claudin proteins, in particular claudin-1, -3, -4 and -7, has been linked to the development of various cancers. Although their dysregulation in cancer suggests that claudins play a role in tumorigenesis, the exact underlying mechanism remains unclear. The involvement of claudins in tumor progression was suggested by their important role in the migration, invasion and metastasis of cancer cells in a tissue-dependent manner. Recent studies have shown that they play a role in epithelial to mesenchymal transition (EMT), the formation of cancer stem cells or tumor-initiating cells (CSCs/TICs), and chemoresistance, suggesting that claudins are promising targets for the treatment of chemoresistant and recurrent tumors. A recently identified claudin-low breast cancer subtype that is characterized by the enrichment of EMT and stem cell-like features is significantly associated with disease recurrence, underscoring the importance of claudins as predictors of tumor recurrence. The critical role of epigenetic mechanisms in the regulation of claudin expression indicates the possible application of epigenetic therapy to target claudins. A better understanding of the emerging role of claudins in CSC/TICs and chemoresistance may help to develop therapies against recurrent cancers.
Serotonin transporter deficient mice are vulnerable to escape deficits following inescapable shocks (2010)

Modulation of serotonin transporter (5-HTT) function causes changes in affective behavior, both in humans and rodents. Stressful life events likewise affect emotional behavior. In humans, a low-expressing genetic 5-htt variant, the s allele of the 5-htt linked promoter region, has been associated with increased risk for depression only where there was a history of stressful life events. To investigate this gene by environment interaction in mice, we compared the effects of inescapable shocks on the behavior of wild-type (5-htt+/+), heterozygote (5-htt+/-) and serotonin transporter deficient (5-htt-/-) mice. Inescapable shocks induce behavioral changes including a shock escape deficit, in a subsequent test when escape is possible. Confirming a gene by environment interaction, we found that stress increases escape latencies in a gene-dose dependent manner (5-htt-/->5-htt+/->5-htt +/+), where as there were no differences among the genotypes in the unstressed condition. The vulnerability to increased escape latency could not be accounted for by enhanced fear learning, as 5-htt-/- mice did not show heightened fear conditioning. The interaction of 5-htt genotype and stress appeared to produce a selective behavioral vulnerability, because no interaction of 5-htt genotype and stress was observed in other measures of anxiety and depression-linked behavior, including the open field, novelty suppressed feeding, and forced swim tests. We replicated prior findings that the 5-htt-/- displays heightened anxiety and depression-like behavior at baseline (unstressed condition). In conclusion, our data offer the possibility for future investigation of the neural basis underlying 5-htt genotype-by-stress interaction shown here.
Dominant inhibitory adipocyte-specific secretory factor (ADSF)/resistin enhances adipogenesis and improves insulin sensitivity (2004)

Adipocyte-specific secretory factor (ADSF)/resistin is a small cysteine-rich protein secreted from adipose tissue that belongs to a gene family found in inflammatory zone (FIZZ) or found in resistin-like molecule (RELM). ADSF has been implicated in modulating adipogenesis and insulin resistance. To examine the long-term function of ADSF in adipogenesis and glucose homeostasis, we constructed an expression vector for a dominant inhibitory form of ADSF by fusing it to the human IgGgamma constant region (hFc). ADSF-hFc not only homodimerizes but heterooligomerizes with ADSF/resistin and prevents ADSF/resistin inhibition of adipocyte differentiation of 3T3-L1 cells in a dominant negative manner. Transgenic mice overexpressing ADSF-hFc in adipose tissue show increased adiposity with elevated expression of adipocyte markers as well as enlarged adipocyte size. This finding clearly demonstrates in vivo the inhibitory role of ADSF in adipogenesis. ADSF-hFc transgenic mice with impaired ADSF function exhibit improved glucose tolerance and insulin sensitivity either on chow or high-fat diets. Because of the enhanced adipocyte differentiation, the ADSF-hFc transgenic mice show increased expression of leptin and adiponectin in adipose tissue. The elevated circulating levels for these adipocyte-derived hormones with decreased plasma triglyceride and free fatty acid levels may account for the improved glucose and insulin tolerance in these transgenic mice.
Quantitative analysis of the CD4+ T cell response to therapeutic antibodies in healthy donors using a novel T cell:PBMC assay (2017)

Many biopharmaceuticals (BPs) are known to be immunogenic in the clinic, which can result in modified pharmacokinetics, reduced efficacy, allergic reactions and anaphylaxis. During recent years, several technologies to predict immunogenicity have been introduced, but the predictive value is still considered low. Thus, there is an unmet medical need for optimization of such technologies. The generation of T cell dependent high affinity anti-drug antibodies plays a key role in clinical immunogenicity. This study aimed at developing and evaluating a novel in vitro T cell:PBMC assay for prediction of the immunogenicity potential of BPs. To this end, we assessed the ability of infliximab (anti-TNF-α), rituximab (anti-CD20), adalimumab (anti-TNF-α) and natalizumab (anti-α4-integrin), all showing immunogenicity in the clinic, to induce a CD4+ T cells response. Keyhole limpet hemocyanin (KLH) and cytomegalovirus pp65 protein (CMV) were included as neo-antigen and recall antigen positive controls, respectively. By analyzing 26 healthy donors having HLA-DRB1 alleles matching the European population, we calculated the frequency of responding donors, the magnitude of the response, and the frequency of BP-specific T cells, as measured by 3[H]-thymidine incorporation and ELISpot IL-2 secretion. KLH and CMV demonstrated a strong T cell response in all the donors analyzed. The frequency of responding donors to the BPs was 4% for infliximab, 8% for adalimumab, 19% for rituximab and 27% for natalizumab, which is compared to and discussed with their respective observed clinical immunogenicity. This study further complements predictive immunogenicity testing by quantifying the in vitro CD4+ T cell responses to different BPs. Even though the data generated using this modified method does not directly translate to the clinical situation, a high sensitivity and immunogenic potential of most BPs is demonstrated.
A 2-poisson model for probabilistic coreference of named entities for improved text retrieval (2009)

Text retrieval queries frequently contain named entities. The standard approach of term frequency weighting does not work well when estimating the term frequency of a named entity, since anaphoric expressions (like he, she, the movie, etc) are frequently used to refer to named entities in a document, and the use of anaphoric expressions causes the term frequency of named entities to be underestimated. In this paper, we propose a novel 2-Poisson model to estimate the frequency of anaphoric expressions of a named entity, without explicitly resolving the anaphoric expressions. Our key assumption is that the frequency of anaphoric expressions is distributed over named entities in a document according to the probabilities of whether the document is elite for the named entities. This assumption leads us to formulate our proposed Co-referentially Enhanced Entity Frequency (CEEF). Experimental results on the text collection of TREC Blog Track show that CEEF achieves significant and consistent improvements over state-of-the-art retrieval methods using standard term frequency estimation. In particular, we achieve a 3% increase of MAP over the best performing run of TREC 2008 Blog Track.
Vascular Endothelial Growth Factor Mediates Corneal Nerve Repair (2008)

In addition to providing new information on the regeneration of murine corneal nerves, this study presents evidence that VEGF signaling influences the repair of corneal nerves by demonstrating that VEGF and VEGF receptors are present in the trigeminal ganglia and that abrogation of VEGF signaling reduces nerve growth in vitro and in vivo.
Enantioselective and Diastereoselective Mukaiyama−Michael Reactions Catalyzed by Bis(oxazoline) Copper(II) Complexes (2001)

The scope of highly enantioselective and diastereoselective Michael additions of enolsilanes to unsaturated imide derivatives has been developed with use of [Cu((S,S)-t-Bu-box)](SbF6)2 (1a) as a Lewis acid catalyst. The products of these additions are useful synthons that contain termini capable of differentiation under mild conditions. Michael acceptor pi-facial selectivity is consistent with two-point binding of the imide substrate and can be viewed as an extension of substrate enantioselection in the corresponding Diels-Alder reactions. A model analogous to the one employed to describe the hetero Diels-Alder reaction is proposed to account for the observed relation between enolsilane geometry and product absolute diastereocontrol. Insights into modes of catalyst inactivation are given, including spectroscopic evidence for inhibition of the catalyst by a dihydropyran intermediate that evolves during the course of the reaction. A procedure is disclosed in which an alcohol additive is used to hydrolyze the inhibiting dihydropyran and afford the desilylated Michael adduct in significantly shortened reaction time.
Perfect reconstruction formulas and bounds on aliasing error in sub-Nyquist nonuniform sampling of multiband signals (2000)

We examine the problem of periodic nonuniform sampling of a multiband signal and its reconstruction from the samples. This sampling scheme, which has been studied previously, has an interesting optimality property that uniform sampling lacks: one can sample and reconstruct the class /spl Bscr/(/spl Fscr/) of multiband signals with spectral support /spl Fscr/, at rates arbitrarily close to the Landau (1969) minimum rate equal to the Lebesgue measure of /spl Fscr/, even when /spl Fscr/ does not tile R under translation. Using the conditions for exact reconstruction, we derive an explicit reconstruction formula. We compute bounds on the peak value and the energy of the aliasing error in the event that the input signal is band-limited to the "span of /spl Fscr/" (the smallest interval containing /spl Fscr/) which is a bigger class than the valid signals /spl Bscr/(/spl Fscr/), band-limited to /spl Fscr/. We also examine the performance of the reconstruction system when the input contains additive sample noise.
Telomere instability in the male germline (2005)

Telomeres play a key role in upholding the integrity of the genome, and telomerase expression in spermatogonial stem cells is responsible for the maintenance of telomere length in the human male germline. We have previously described extensive allelic variation in somatic cell telomere length that is set in the zygote, the ultimate source of which may be the germline. This implies that despite telomerase activity, substantial telomere length variation can be generated and tolerated in the germline; in order to investigate this further, we have examined the nature of telomere length variation in the human male germline. Here, we describe an analysis of both genome-wide telomere length and single molecule analysis of specific chromosome ends in human sperm. We observed individual specific differences in genome-wide telomere length. This variation may result from genetic differences within the components that determine the telomere length setting of each individual. Superimposed on the genome wide telomere length setting was a stochastic component of variation that generates germ-cells containing severely truncated telomeres. If not re-lengthened during early embryogenesis, such telomeres may limit the replicative capacity of cells derived from the zygote and have the potential to create fusagenic chromosomes, unbalanced translocations and terminal micro-deletions. These data may have implications for the genetic determination of ageing, genetic disease and fertility.
A novel integrated biological process for cellulosic ethanol production featuring high ethanol productivity, enzyme recycling and yeast cells reuse (2012)

High enzyme loading requirements, slow xylose fermentation and low ethanol productivity are three of the major issues impeding commercial biochemical production of cellulosic ethanol. We report here a novel integrated biological process to overcome these problems. Enzymatic hydrolysis was performed for only 24 h to avoid the slow rate period which begins at about that time. Unhydrolyzed recalcitrant solids with adsorbed enzymes were recycled to the subsequent cycles. By this approach, easily digestible biomass was processed first and recalcitrant biomass was given enough residence time to get hydrolyzed during subsequent processing steps. Fermentation was conducted using a high yeast inoculation level and was also completed in 24 h. The yeast cells were then recycled. With this novel processing approach, the enzyme loading was reduced from 36 to 22.3 and 25.8 mg protein per gram glucan, respectively, for separate hydrolysis and fermentation (SHF) and for simultaneous saccharification and co-fermentation (SSCF) on AFEX™ pretreated corn stover. The process ethanol productivity was enhanced by 2 to 3 fold due to both fast enzymatic hydrolysis and fast fermentation.
Progress in modeling ignition implosion experiments on the National Ignition Facility (2013)

Abstract not provided
Mechanisms of Increased Vascular Superoxide Production in Human Diabetes Mellitus (2002)

These observations suggest important roles for NAD(P)H oxidases, endothelial NO synthase uncoupling, and protein kinase C signaling in mediating increased vascular superoxide production and endothelial dysfunction in human diabetes mellitus.
HIV-1 Env DNA Vaccine plus Protein Boost Delivered by EP Expands B- and T-Cell Responses and Neutralizing Phenotype In Vivo (2013)

An effective HIV vaccine will most likely require the induction of strong T-cell responses, broadly neutralizing antibodies (bNAbs), and the elicitation of antibody-dependent cellular cytotoxicity (ADCC). Previously, we demonstrated the induction of strong HIV/SIV cellular immune responses in macaques and humans using synthetic consensus DNA immunogens delivered via adaptive electroporation (EP). However, the ability of this improved DNA approach to prime for relevant antibody responses has not been previously studied. Here, we investigate the immunogenicity of consensus DNA constructs encoding gp140 sequences from HIV-1 subtypes A, B, C and D in a DNA prime-protein boost vaccine regimen. Mice and guinea pigs were primed with single- and multi-clade DNA via EP and boosted with recombinant gp120 protein. Sera were analyzed for gp120 binding and induction of neutralizing antibody activity. Immunization with recombinant Env protein alone induced low-titer binding antibodies with limited neutralization breath. In contrast, the synthetic DNA prime-protein boost protocol induced significantly higher antibody binding titers. Furthermore, sera from DNA prime-protein boost groups were able to neutralize a broader range of viruses in a panel of tier 1 clade B viruses as well as multiple tier 1 clade A and clade C viruses. Further investigation of synthetic DNA prime plus adaptive EP plus protein boost appears warranted.
Drug delivery strategies to enhance the&nbsp;permeability of the blood&ndash;brain barrier for&nbsp;treatment of glioma (2015)

Gliomas are amongst the most insidious and destructive types of brain cancer and are associated with a poor prognosis, frequent recurrences, and extremely high lethality despite combination treatment of surgery, radiotherapy, and chemotherapy. The existence of the blood-brain barrier (BBB) restricts the delivery of therapeutic molecules into the brain and offers the clinical efficacy of many pharmaceuticals that have been demonstrated to be effective for other kinds of tumors. This challenge emphasizes the need to be able to deliver drugs effectively across the BBB to reach the brain parenchyma. Enhancement of the permeability of the BBB and being able to transport drugs across it has been shown to be a promising strategy to improve drug absorption and treatment efficacy. This review highlights the innovative technologies that have been introduced to enhance the permeability of the BBB and to obtain an optimal distribution and concentration of drugs in the brain to treat gliomas, such as nanotechniques, hyperthermia techniques, receptor-mediated transport, cell-penetrating peptides, and cell-mediated delivery.
Monovalent derivatives of concanavalin A. (1976)

Monovalent dimers of concanavalin A (Con A) have been prepared by a combination of succinylation and photoaffinity labeling. Partial derivatization of native Con A using the photoaffinity label, p-azidophenyl-alpha-D-mannopyranoside, followed by affinity chromatography yielded a fraction that consisted of dimers with a single saccharide-binding site at pH 5. These monovalent dimers formed divalent tetramers at pH 7. In order to achieve a monovalent dimer at this pH, the divalent tetramers were succinylated by previously developed methods. Ultracentrifugation, equilibrium dialysis, and chromatographic experiments indicated that the resultant preparations consisted mainly of monovalent dimers which showed subunit exchange to yield about 15% divalent dimers after 12 hr at physiological pH. Freshly prepared material failed to agglutinate sheep erythrocytes at concentrations 500-fold higher than native tetravalent Con A. In addition, they showed saturating dose-response curves of mitogenic stimulation of mouse splenic lymphocytes. These curves resembled those of divalent succinyl-Con A but not those of the native molecule. Further development of methods for preparing stable monovalent derivatives of Con A should allow a refined analysis of the effects of lectin valence at the cell surface.
Acute Effects of Continuous Positive Airway Pressure on Cardiac Sympathetic Tone in Congestive Heart Failure (2001)

The short-term application of CPAP results in an inhibition of cardiac sympathetic nervous activity. Further investigation into the potential value of long-term CPAP in CHF patients is warranted.
Rings and filaments of β protein from bacteriophage λ suggest a superfamily of recombination proteins (1999)

The beta protein of bacteriophage lambda acts in homologous genetic recombination by catalyzing the annealing of complementary single-stranded DNA produced by the lambda exonuclease. It has been shown that the beta protein binds to the products of the annealing reaction more tightly than to the initial substrates. We find that beta protein exists in three structural states. In the absence of DNA, beta protein forms inactive rings with approximately 12 subunits. The active form of the beta protein in the presence of oligonucleotides or single-stranded DNA is a ring, composed of approximately 15-18 subunits. The double-stranded products of the annealing reaction catalyzed by the rings are bound by beta protein in a left-handed helical structure, which protects the products from nucleolytic degradation. These observations suggest structural homology for a family of proteins, including the phage P22 erf, the bacterial RecT, and the eukaryotic Rad52 proteins, all of which are involved in homologous recombination.
Pharmacokinetics and Safety of a 7-Day Administration of Intravenous Itraconazole followed by a 14-Day Administration of Itraconazole Oral Solution in Patients with Hematologic Malignancy (2001)

ABSTRACT The pharmacokinetics and safety of an intravenous hydroxypropyl-β-cyclodextrin solution of itraconazole administered for 7 days followed by itraconazole oral solution administered at 200 mg once or twice daily for 14 days were assessed in 17 patients with hematologic malignancies. Steady-state plasma itraconazole concentrations were reached by 48 h after the start of intravenous treatment. The mean trough plasma itraconazole concentration at the end of the intravenous treatment was 0.54 ± 0.20 μg/ml. This concentration was not maintained during once-daily oral treatment but increased further in the twice-daily treatment group, with a trough itraconazole concentration of 1.12 ± 0.73 μg/ml at the end of oral treatment. As expected in the patient population studied, all patients experienced some adverse events (mainly gastrointestinal). Biochemical and hematologic abnormalities were frequent, but no consistent changes occurred. In conclusion, 7 days of intravenous treatment followed by 14 days of twice-daily oral treatment with itraconazole solution enables plasma itraconazole concentrations of at least 0.5 μg/ml to be reached rapidly and to be maintained. The regimen is well tolerated and has a good safety profile.
Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia (2006)

Epigenetic therapy with hypomethylating drugs is now the standard of care in myelodysplastic syndrome (MDS). Response rates remain low, and mechanism-based dose optimization has not been reported. We investigated the clinical and pharmacodynamic results of different dose schedules of decitabine. Adults with advanced MDS or chronic myelomonocytic leukemia (CMML) were randomized to 1 of 3 decitabine schedules: (1) 20 mg/m2 intravenously daily for 5 days; (2) 20 mg/m2 subcutaneously daily for 5 days; and (3) 10 mg/m2 intravenously daily for 10 days. Randomization followed a Bayesian adaptive design. Ninety-five patients were treated (77 with MDS, and 18 with CMML). Overall, 32 patients (34%) achieved a complete response (CR), and 69 (73%) had an objective response by the new modified International Working Group criteria. The 5-day intravenous schedule, which had the highest dose-intensity, was selected as optimal; the CR rate in that arm was 39%, compared with 21% in the 5-day subcutaneous arm and 24% in the 10-day intravenous arm (P < .05). The high dose-intensity arm was also superior at inducing hypomethylation at day 5 and at activating P15 expression at days 12 or 28 after therapy. We conclude that a low-dose, dose-intensity schedule of decitabine optimizes epigenetic modulation and clinical responses in MDS.
Microemulsion System as a Steel Corrosion Inhibitor (2002)

Abstract The inhibition effect of surfactant systems on the corrosion of carbon steel (AISI 1010) by 0.1 M hydrochloric acid (HCl) was investigated by polarization measurement techniques. Dodecylammonium bromide (DDAB) surfactant was used as a micellar solution in aqueous 0.1 M HCl and as an active component of a microemulsified oil-in-water system, containing n-butanol, n-hexane, and aqueous 0.1 M HCl. The adsorption of DDAB followed the Langmuir isotherm equation for both interfaces studied, and the largest βc was observed, in the cathodic range, when the concentration of the inhibitor was increased. The results obtained from electrochemical measurements were discussed, and it was observed that the microemulsion had a better inhibition effect than the pure surfactant solution.