gebhart/patrepeval huggingface dataset:
Structure-Based Design of Human TLR8-Specific Agonists with Augmented Potency and Adjuvanticity (2015)

Human Toll-like receptor 8 (hTLR8) is expressed in myeloid dendritic cells, monocytes, and monocyte-derived dendritic cells. Engagement by TLR8 agonists evokes a distinct cytokine profile which favors the development of type 1 helper T cells. Crystal structures of the ectodomain of hTLR8 cocrystallized with two regioisomers of a dual TLR7/8-agonistic N1-substituted imidazoquinolines showed subtle differences in their interactions in the binding site of hTLR8. We hypothesized that the potency of a previously reported best-in-class pure TLR8 agonist, 3-pentylquinoline-2-amine, could be further enhanced by "designing in" functional groups that would mimic key intermolecular interactions that we had observed in the crystal structures. We performed a focused exploration of decorating the quinoline core with alkylamino groups at all possible positions. These studies have led to the identification of a novel TLR8 agonist that was ∼ 20-fold more potent than the parent compound and displays prominent adjuvantic activity in a rabbit model of immunization.
Inhibition of the cytotoxic effect of Clostridium difficile in vitro by Clostridium butyricum MIYAIRI 588 strain (2011)

In contrast to most modern pharmaceuticals, probiotics are used in many parts of the world with little or no research data on the complex system of interactions that each strain may elicit in the human body. Research on probiotics has recently become more significant, as probiotics have begun to be prescribed by clinicians as an alternative for some gut infections, especially when antibiotics are contraindicated. This study attempted to elucidate the inhibitory interaction between the Japanese probiotic strain Clostridium butyricum MIYAIRI 588 (CBM588) and the hospital pathogen Clostridium difficile, which is responsible for a large proportion of antibiotic-associated diarrhoea and colitis. CBM588 has previously shown effectiveness against C. difficile in vivo, and here it was found that the toxicity of C. difficile in in vitro co-culture with CBM588 was greatly decreased or absent. This was dependent on the inoculation ratio and was not accounted for by the small degree of growth and mRNA inhibition observed. CBM588 and its cell-free supernatant also had no effect on toxin already secreted into the culture medium, and culture of the two strains separated by a semi-permeable membrane resulted in loss of the inhibition. Therefore, it was concluded that the detoxification probably occurred by the inhibition of toxin protein production and that this required close proximity or contact between the two species. The low-pH conditions caused by organic acid secretion were also observed to have inhibitory effects on C. difficile growth, metabolism and toxicity.
Tripling to 250 GHz with Planar, Multiple Barrier Heterostructure Barrier Varactors (1996)

We report on the design, simulation, fabrication, and testing of four-barrier, planar, heterostructure barrier varactor (HBV) triplers. For direct tripling, HBVs are an ideal device since the C-V characteristic is symmetric and only odd-harmonic generation occurs under large signal excitation. However, the optimal design of HBVs for specific applications is more complex than for conventional Schottky Barrier Devices. This is a direct result of the complex nature of the heterostructure, as well as the nearly infinite number of variations in heterostructure materials and the number of barriers to be considered. The fabrication process is similar to that used at the University of Virginia for the fabrication of multiple-anode Schottky Barrier Varactors. An overview of the fabrication process and the DC and RF testing results are discussed. Specific results demonstrating 2.5 mW of output power at 252 GHz (80 mW input) are reported for this direct tripler.
Characterization of allergens from Penicillium oxalicum and P. notatum by immunoblotting and N‐terminal amino acid sequence analysis (1999)

Results obtained suggest that the 34 kDa major allergen of P. oxalicum may be a vacuolar serine proteinase. The 34 and the 32 kDa major allergens of P. notatum may be the alkaline and the vacuolar serine proteinases of P. notatum, respectively. The 30 and 16 kDa IgE-binding components of P. oxalicum and the 28 kDa IgE-binding component of P. notatum may be breakdown products of the 34 and the 32 kDa major vacuolar serine proteinase allergens of P. oxalicum and P. notatum, respectively.
Translational fusion of heat labile enterotoxin chain B and β‐subunit of human chorionic gonadotropin: periplasmic expression in Escherichia coli and its immunogenicity (1996)

A fusion gene was constructed consisting of heat labile enterotoxin chain B (LTB) of E. coli genetically linked at its C-terminus to the beta-subunit of human chorionic gonadotropin in translational fusion, under the control of tac promoter and LTB signal sequence. Expression of the fusion gene (about 5 microgram/ml) in E. coli was confirmed by immunoblot analysis using both anti-LTB and anti-betahCG polyclonal antibodies. The fusion protein was efficiently processed and exported to the periplasmic space. LTB in the fusion protein retained its ability to bind to GM1 ganglioside receptor. Mice immunized with the fusion protein produce antibodies that recognize recombinant betahCG and the native hCG suggesting its potential use as a contraceptive vaccine.
Enzyme-Friendly, Mass Spectrometry-Compatible Surfactant for In-Solution Enzymatic Digestion of Proteins (2003)

Improved in-solution tryptic digestion of proteins in terms of speed and peptide coverage was achieved with the aid of a novel acid-labile anionic surfactant (ALS). Unlike SDS, ALS solubilizes proteins without inhibiting trypsin or other common endopeptidases activity. Trypsin activity was evaluated in the presence of various denaturants; little or no decrease in proteolytic activity was observed in 0.1-1% ALS solutions (w/v). Sample preparation prior to mass spectrometry and liquid chromatography analysis consists of sample acidification. ALS degrades rapidly at low-pH conditions, which eliminates surfactant-caused interference with analysis. Described methodology combines the advantages of protein solubilization, rapid digestion, high peptide coverages, and easy sample preparation for mass spectrometry and liquid chromatography analyses.
Partial characterization of a lymphoid cell line (Reh) product with leukocyte inhibitory factor (LIF) activity. (1981)

Abstract An LIF-like activity spontaneously produced by a “non-T, non-B leukemia” cell line (Reh) was partially characterized. Reh cells were grown in RPMI 1640 in 10% fetal calf serum to a density of 1.6 × 106 cells/ml. The cells were then transferred to serum-free medium (RPMI 1640) and cultured for varying periods of time up to 48 hr. The cellfree supernatants from these cultures were then tested for LIF activity using human polymorphonuclear leukocytes as indicator cells under agarose. It was found that a 48-hr incubation time yielded the greatest LIF-like activity in the supernatant. Although the Reh cell line spontaneously elaborated this LIF-like activity, pulsing the cells with PHA for 1 hr induced approximately 4 times more activity in the supernatant. Compared with lymphocyte-derived LIF, the Reh-LIF activity was relatively unstable. Maximum activity was detected between pH 6.0 and 7.5; the factor was inactivated by incubation for 30 min at 56°C and lost considerable activity if stored at 4°C for more than 3 days, although the molecule was stable at 20°C and 70°C for several weeks. The apparent m.w. of the Reh cell line factor was estimated to be 68,000 by gel filtration on Sephadex G-100. The Reh-LIF activity was resistant to enzymatic treatment with trypsin and papain but was inactivated by chymotrypsin and phenylmethyl-sulfonylfluoride. Furthermore, Reh-LIF activity was partially destroyed by treatment with NalO4 but not neuraminidase. Denaturing and reducing agents alone or in combination did not affect Reh-LIF activity, but reduction followed by alkylation did result in a considerable loss of activity. These findings suggest that Reh-LIF has the properties of a glycoprotein with a serine group(s) in its active site and contains disulfide bonds within its structure. These data also indicate that the Reh cell line-derived LIF-like activity has a number of physicochemical properties in common with those of LIF derived from stimulated human lymphocytes. Therefore, this cell line may provide a practical source for obtaining large amounts of LIF for the purpose of purification.
Towards a next generation data center architecture (2008)

Applications hosted in today's data centers suffer from internal fragmentation of resources, rigidity, and bandwidth constraints imposed by the architecture of the network connecting the data center's servers. Conventional architectures statically map web services to Ethernet VLANs, each constrained in size to a few hundred servers owing to control plane overheads. The IP routers used to span traffic across VLANs and the load balancers used to spray requests within a VLAN across servers are realized via expensive customized hardware and proprietary software. Bisection bandwidth is low, severly constraining distributed computation Further, the conventional architecture concentrates traffic in a few pieces of hardware that must be frequently upgraded and replaced to keep pace with demand - an approach that directly contradicts the prevailing philosophy in the rest of the data center, which is to scale out (adding more cheap components) rather than scale up (adding more power and complexity to a small number of expensive components).
Wafer Bonding of GaN and ZnSSe for Optoelectronic Applications (2004)

We report on the wafer bonding of an InGaN/GaN LED structure on sapphire to a p-type ZnSSe layer grown by molecular beam epitaxy on GaAs as a first step in fabricating III–N resonant cavity structures with II–VI distributed Bragg reflectors. The ZnSSe surface was prepared using thermal and polishing processes to insure a smooth and flat surface. Wafers were successfully bonded in nitrogen at 270°C. The GaAs substrate was then removed and contacts were made to p-type GaAs/ZnSSe and n-type GaN layers. This wafer bonded GaN based LED was evaluated with current-voltage (I–V) measurements and electroluminescence (EL) measurements.
Kinetics of  O 2 Reduction on a Pt Electrode Covered with a Thin Film of Solid Polymer Electrolyte (1997)

The kinetics of O-2 reduction on both oxidized and reduced Pt rotating disk surfaces covered with thin films (1 to 15 mu m) of recast polybenzimidazole (PBI) or Nafion have been examined in 0.1 M aqueous solutions of H3PO4, H2SO4, and HClO4 at 25.0 degrees C. Polymer films were deposited on a Pt disk electrode by a spin-coating technique. Experiments were performed formed at different rotation rates and potential scan rates. This investigation was undertaken to establish to what extent the solid polymer electrolyte influences the mechanism and kinetics of O-2 reduction. The number of electrons exchanged per O-2 molecule and kinetic parameters for O-2 reduction (reaction order with respect to O-2, Tafel slope/transfer coefficient, and exchange current density) are not changed in the presence of the polymer films, indicating that the reaction path and kinetics are not altered in the presence of recast PBI and Nafion films. The diffusion coefficient (D) and concentration
Effect of addition of a detoxifying agent to laying hen diets containing uncontaminated or Fusarium toxin-contaminated maize on performance of hens and on carryover of zearalenone (2002)

16-wk experiment with laying hens was carried out to examine the effects of feeding of mycotoxin-contaminated maize (CM) on performance, nutrient digestibility, weight of organs, serum chemical parameters, and antibody titers to Newcastle disease virus (NDV) in serum. Also tested were fimbrien antigen K88 in egg yolk and zearalenone (ZON) residues in eggs and tissues. The Fusarium-toxin-contaminated maize contained 17,630 microg deoxynivalenol and 1,580 microg ZON/kg. Moreover, Mycofix Plus (MP), a so-called detoxifying agent, was added to both the uncontaminated control (UCM) and to the CM diet (70% dietary maize inclusion). Each of the four resulting diets (UCM, UCM-MP, CM, CM-MP) was tested on 25 laying hybrids (Lohmann Brown). Feeding of the CM diets significantly depressed feed intake compared to the control groups by approximately 5%. This was mainly due to the effects observed at the beginning of the experiment. Daily egg mass production/hen was 56.6, 58.4, 53.9, and 55.2 g in groups UCM, UCM-MP, CM and CM-MP, respectively. Nutrient digestibility and metabolizability of gross energy were slightly depressed by feeding the CM diets and improved by MP addition. Feeding of the CM diets resulted in a significant decrease in serum titers to NDV and to an increase in yolk titers to antigen K88. No residues of ZON or of its metabolites were found in yolk, albumen, abdominal fat, breast meat, follicles greater than 1 cm in diameter, ovaries including follicles smaller than 1 cm in diameter, magnum, and serum. ZON and alpha-zearalenol (alpha-ZOL) were detected in livers of hens fed the CM diets at mean concentrations of 2.1 and 3.7 microg/kg, respectively. It was concluded that feeding maize which was highly contaminated with Fusarium mycotoxins adversely influenced performance of hens and modulated immune response. At the given level of zearalenone and at the indicated detection limits, no residues of ZON and its metabolites were found in eggs. The effects of the tested detoxifying agent were quite mycotoxin-independent.
Synthesis via RAFT Polymerization of Tadpole-Shaped Organic/Inorganic Hybrid Poly(acrylic acid) Containing Polyhedral Oligomeric Silsesquioxane (POSS) and Their Self-assembly in Water (2009)

Tadpole-shaped inorganic/organic hybrid poly(tert-butyl acrylate) was prepared by RAFT polymerization of tert-butyl acrylate (tBA) using a POSS-containing chain transfer agent (CTA). The polymerization kinetics showed a pseudofirst-order behavior with a short induction period; the number-average molecular weights linearly increase with conversion. In conjunction with low polydispersity (PDI < 1.3), this confirms a controlled polymerization. POSS-PtBA was further hydrolyzed into amphiphilic, tadpole-shaped poly(acrylic acid) (POSS-PAA). The self-assembly behavior of POSS-PAA in aqueous solution at pH = 8.5 was investigated by transmission electron microscopy (TEM) as well as static and dynamic light scattering (SLS and DLS). The results show that POSS-PAA self-assembles in water into rather large aggregates where the POSS moieties are dispersed in the particle. The size (average radius ≈ 60 nm by DLS) is nearly independent of the chain length of PAA. The aggregates are pH-responsive, contracting when decreasing pH from 8.5 to 4.
Design, Immune Responses and Anti-Tumor Potential of an HPV16 E6E7 Multi-Epitope Vaccine (2015)

Cervical cancer is a common type of cancer among women worldwide and infection with high-risk human papillomavirus (HPVs) types represents the major risk factor for the etiopathogenesis of the disease. HPV-16 is the most frequently identified HPV type in cervical lesions and expression of E6 and E7 oncoproteins is required for the uncontrolled cellular proliferation. In the present study we report the design and experimental testing of a recombinant multi-epitope protein containing immunogenic epitopes of HPV-16 E6 and E7. Tumor preventive assays, based on the engraftment of TC-1 cells in mice, showed that the E6E7 multi-epitope protein induced a full preventive anti-tumor protection in wild-type mice, as well as in mice deficient in expression of CD4+ T cells and TLR4 receptor. Nonetheless, no anti-tumor protection was observed in mice deficient in CD8+ T cells. Also, the vaccine promoted high activation of E6/E7-specific T cells and in a therapeutic-approach, E6E7 protein conferred full anti-tumor protection in mice. These results show a potential use of this E6E7 multi-epitope antigen as a new and promising antigen for the development of a therapeutic vaccine against tumors induced by HPV.
Ex vivo Expansion of Highly Purified NK Cells for Immunotherapy after Haploidentical Stem Cell Transplantation in Children (2005)

Clinical scale enrichment and activation of allogeneic donor NK cells is feasible. High dose NK cell application may be a new treatment option for pediatric patients with leukemia or solid tumors in case of minimal residual disease or unbalanced chimerism post haplo-SCT as we could show for the first three patients .
DESIGN OPTIMIZATION OF THE ELECTRICALLY PEAKING HYBRID (ELPH) VEHICLE (1998)

Electrically Peaking Hybrid (ELPH) is a parallel hybrid electric vehicle propulsion concept that was invented at Texas A&M University, by the advanced vehicle systems research group. Over the past six years, design methodologies, component development, and system optimization work has been going on for this invention. This project was a first attempt in integrating the above developments into an optimized design of an ELPH passenger car. Design specifications were chosen for a full size passenger car, performing as well as any conventional car, over the EPA-FTP-75 combined city/highway drive cycles. The results of this design project were two propulsion systems. Both were appropriate for commercial production, from the point of view of cost, availability of the technologies, and components. One utilized regenerative braking and the other did not. Substantial fuel savings and emissions reductions resulted from simulating these designs on the FTP-75 drive cycle. For example, our ELPH full size car, with regenerative braking, was capable of delivering over 50 miles per gallon in city driving, with corresponding reductions in its emissions. This project established the viability of the ELPH concept and the design methodologies, in computer simulations. More work remains to be done on investigating more advanced power plants, such as fuel cells, and more advanced components, such as switched reluctance motor drives, for the designs. Furthermore, the design optimization can be carried out to more detailed levels, for prototyping and production.
Regioselective deuteriation kinetics of 2‐, 4‐, and 6‐methyl groups in D2O solutions of pyrylium and N‐methylpyridinium perchlorates possessing also 3‐methyl or 3‐phenyl groups (1982)

Abstract By 1 H‐NMR it was found that 2, 3, 4, 6‐tetramethylpyrylium perchlorate (I) in D 2 O undergoes isotopic exchange at the 2, 4, and 6‐methyl groups with relative rates 5 : 40 : 1, respectively (assignments of α‐methyl NMR signals were substantiated by unambiguous synthesis). If the 3‐methyl group is replaced by a 3‐phenyl group, the relative rates for the pyrylium salt III are 2.5 : 49 : 1, respectively (in D 2 O + CD 3 OD). On the other hand, the relative rates for the 2, 4, and 6‐methyls in 1,2,4,6‐tetramethyl‐3‐phenylpyridinium perchlorate are 12 : 1 : 4, respectively (in D 2 O + CD 3 OD + NaOD). These rate differences allow the preparation of selectively deuteriated pyrylium or pyridinium salts, and of other aromatic or heterocyclic compounds starting from pyrylium salts with selectively deuteriated side‐chains.
The Conserved Helix C Region in the Superfamily of Interferon-γ/Interleukin-10-related Cytokines Corresponds to a High-affinity Binding Site for the HSP70 Chaperone DnaK (2002)

HSP70 chaperones mediate protein folding by ATP-dependent interaction with short linear peptide segments that are exposed on unfolded proteins. The mode of action of the Escherichia coli homolog DnaK is representative of all HSP70 chaperones, including the endoplasmic reticulum variant BiP/GRP78. DnaK has been shown to be effective in assisting refolding of a wide variety of prokaryotic and eukaryotic proteins, including the alpha-helical homodimeric secretory cytokine interferon-gamma (IFN-gamma). We screened solid-phase peptide libraries from human and mouse IFN-gamma to identify DnaK-binding sites. Conserved DnaK-binding sites were identified in the N-terminal half of helix B and in the C-terminal half of helix C, both of which are located at the IFN-gamma dimer interface. Soluble peptides derived from helices B and C bound DnaK with high affinity in competition assays. No DnaK-binding sites were found in the loops connecting the alpha-helices. The helix C DnaK-binding site appears to be conserved in most members of the superfamily of interleukin (IL)-10-related cytokines that comprises, apart from IL-10 and IFN-gamma, a series of recently discovered small secretory proteins, including IL-19, IL-20, IL-22/IL-TIF, IL-24/MDA-7 (melanoma differentiation-associated gene), IL-26/AK155, and a number of viral IL-10 homologs. These cytokines belong to a relatively small group of homodimeric proteins with highly interdigitated interfaces that exhibit the strongly hydrophobic character of the interior core of a single-chain folded domain. We propose that binding of DnaK to helix C in the superfamily of IL-10-related cytokines may constitute the hallmark of a novel conserved regulatory mechanism in which HSP70-like chaperones assist in the formation of a hydrophobic dimeric "folding" interface.
Safety and Immunogenicity of Adenovirus-Vectored Near-Consensus HIV Type 1 Clade B gag Vaccines in Healthy Adults (2008)

Vaccines inducing pathogen-specific cell-mediated immunity are being developed using attenuated adenoviral (Ad) vectors. We report the results of two independent Phase I trials of similar replication-deficient Ad5 vaccines containing a near-consensus HIV-1 clade B gag transgene. Healthy HIV-uninfected adults were enrolled in two separate, multicenter, dose-escalating, blinded, placebo-controlled studies to assess the safety and immunogenicity of a three-dose homologous regimen of Ad5 and MRKAd5 HIV-1 gag vaccines given on day 1, week 4, and week 26. Adverse events were collected for 29 days following each intradeltoid injection. The primary immunogenicity endpoint was the proportion of subjects with a positive unfractionated Gag-specific IFN-gamma ELISPOT response measured 4 weeks after the last dose (week 30). Analyses were performed after combining data for each dose group from both protocols, stratifying by baseline Ad5 titers. Overall, 252 subjects were randomized to receive either vaccine or placebo, including 229 subjects (91%) who completed the study through week 30. Tolerability and immunogenicity did not appear to differ between the Ad5 and MRKAd5 vaccines. The frequency of injection-site reactions was dose dependent. Systemic adverse events were also dose dependent and more frequent in subjects with baseline Ad5 titers <200 versus > or =200, especially after the first dose. The percent of ELISPOT responders and the ELISPOT geometric means overall were significantly higher for all four vaccine doses studied compared to placebo, and were generally higher in vaccine recipients with baseline Ad5 titers <200 versus > or = 200. Ad5 titers increased after vaccination in a dose-dependent fashion. Both Ad5-vectored HIV-1 vaccines were generally well tolerated and induced cell-mediated immune responses against HIV Gag-peptides in the majority of healthy adults with baseline Ad5 titers <200. Preexistent and/or vaccine-induced immunity to the Ad5 vector may dampen the CMI response to HIV Gag.
Comparison of Intranasal Dexmedetomidine and Oral Pentobarbital Sedation for Transthoracic Echocardiography in Infants and Toddlers: A Prospective, Randomized, Double-Blind Trial (2018)

Intranasal dexmedetomidine was comparable to oral pentobarbital sedation for TTEcho sedation in infants and did not increase the risk of clinically important adverse events. Intranasal dexmedetomidine appears to be an effective "rescue" sedative for both failed pentobarbital and dexmedetomidine sedation. Dexmedetomidine could be a safer option for repeated sedation in children, but further studies are needed to assess long-term consequence of repeated sedation in this high-risk population.