gebhart/patrepeval huggingface dataset:
Presence of maternal antibodies to human immunodeficiency virus 1 envelope glycoprotein gp120 epitopes correlates with the uninfected status of children born to seropositive mothers. (1989)

The present study demonstrates that maternal antibodies to certain epitopes of human immunodeficiency virus 1 (HIV-1) proteins are associated with a defined outcome for at-risk pregnancies of HIV-infected women. An initial retrospective analysis of antibodies to synthetic peptides and recombinant proteins representing env, pol, and gag regions of HIV-1 was carried out. Sera studied were from 33 children who were born to HIV-infected mothers and whose clinical outcome was known at the time of analysis. Sera, collected within the first 6 months of life, of uninfected at-risk children were found to selectively contain maternal antibodies to certain peptides containing epitopes of the HIV envelope glycoprotein gp120. To confirm the predictive role of maternal antibodies to defined HIV-1 epitopes, a prospective analysis was then performed on sera from 21 HIV-seropositive mothers and their infants, whose clinical and immunological status was then followed up for a period of at least 15 months. As expected, antibodies to the same envelope protein peptides were detected almost exclusively in sera from mothers of uninfected children. Our data suggest that antibodies against select epitopes of HIV envelope protein gp120 might play an important role in preventing mother-to-child transmission of HIV-1 infection. Accordingly, site-directed serology might be used to predict the outcome of an at-risk pregnancy of an HIV-infected woman.
Improving wideband speech recognition using mixed-bandwidth training data in CD-DNN-HMM (2012)

Context-dependent deep neural network hidden Markov model (CD-DNN-HMM) is a recently proposed acoustic model that significantly outperformed Gaussian mixture model (GMM)-HMM systems in many large vocabulary speech recognition (LVSR) tasks. In this paper we present our strategy of using mixed-bandwidth training data to improve wideband speech recognition accuracy in the CD-DNN-HMM framework. We show that DNNs provide the flexibility of using arbitrary features. By using the Mel-scale log-filter bank features we not only achieve higher recognition accuracy than using MFCCs, but also can formulate the mixed-bandwidth training problem as a missing feature problem, in which several feature dimensions have no value when narrowband speech is presented. This treatment makes training CD-DNN-HMMs with mixed-bandwidth data an easy task since no bandwidth extension is needed. Our experiments on voice search data indicate that the proposed solution not only provides higher recognition accuracy for the wideband speech but also allows the same CD-DNN-HMM to recognize mixed-bandwidth speech. By exploiting mixed-bandwidth training data CD-DNN-HMM outperforms fMPE+BMMI trained GMM-HMM, which cannot benefit from using narrowband data, by 18.4%.
A Comprehensive Review on Cyclodextrin-Based Carriers for Delivery of Chemotherapeutic Cytotoxic Anticancer Drugs (2015)

Most of the cytotoxic chemotherapeutic agents have poor aqueous solubility. These molecules are associated with poor physicochemical and biopharmaceutical properties, which makes the formulation difficult. An important approach in this regard is the use of combination of cyclodextrin and nanotechnology in delivery system. This paper provides an overview of limitations associated with anticancer drugs, their complexation with cyclodextrins, loading/encapsulating the complexed drugs into carriers, and various approaches used for the delivery. The present review article aims to assess the utility of cyclodextrin-based carriers like liposomes, niosomes, nanoparticles, micelles, millirods, and siRNA for delivery of antineoplastic agents. These systems based on cyclodextrin complexation and nanotechnology will camouflage the undesirable properties of drug and lead to synergistic or additive effect. Cyclodextrin-based nanotechnology seems to provide better therapeutic effect and sustain long life of healthy and recovered cells. Still, considerable study on delivery system and administration routes of cyclodextrin-based carriers is necessary with respect to their pharmacokinetics and toxicology to substantiate their safety and efficiency. In future, it would be possible to resolve the conventional and current issues associated with the development and commercialization of antineoplastic agents.
Progress in xenotransplantation following the introduction of gene-knockout technology (2006)

The production of alpha1,3-galactosyltransferase gene-knockout (GT-KO) pigs has overcome the barrier of preformed anti-Galalpha1,3Gal (Gal) antibodies that has inhibited progress in pig-to-primate organ xenotransplantation for many years. Survival of GT-KO pig organs in nonhuman primates is currently limited by the development of a thrombotic microangiopathy that results in increasing ischemic injury of the transplanted organ over weeks or months. Potential causative factors include vascular endothelial activation from preformed anti-nonGal antibodies or cells of the innate immune system that recognize nonGal pig antigens directly, and coagulation dysregulation associated with molecular incompatibilities between pig and primate. Carefully isolated pancreatic islets from wild-type (genetically unmodified) adult pigs express minimal Gal epitopes, allowing survival sometimes for weeks or months after transplantation into nonhuman primates receiving immunosuppression directed only at T-cell function. However, there is a considerable immediate loss of islets, probably related to activation of coagulation and complement cascades. Further genetic manipulation of organ-source pigs is therefore required to overcome these problems. GT-KO pigs expressing a human complement-regulatory protein, e.g. decay-accelerating factor, and/or an 'anti-coagulant' gene, e.g. human tissue factor pathway inhibitor, might prevent the change in vascular endothelium from an anti-coagulant to a procoagulant phenotype, and protect the islets from early loss.
The study of clostridial and related toxins. The search for unique mechanisms and common denominators. (1990)

Experiments have been conducted that deal with the structure and biological activity of clostridial toxins. Studies have dealt mainly with botulinum neurotoxin, but work has also been done with tetanus toxin and with the binary toxin. Structural studies indicate that proteolytic processing of botulinum neurotoxin induces two major outcomes: activation and aging. The first is associated with a marked increase in toxicity and with conversion from a single chain to a dichain structure. The second is associated with nominal changes in toxicity and with molecular rearrangements in the dichain structure. Immunological studies have resulted in isolation and characterization of a monoclonal antibody that neutralizes tetanus toxin. Monoclonal antibodies have also been raised against botulinum neurotoxin, and these antibodies have been used to demonstrate that: i) activation is not due to marked conformational changes in the relevant epitopes, ii) binding of the toxin to cholinergic nerve endings does not produce detectable conformational changes, and iii) all functional domains of the toxin appear to be internalized simultaneously. Immunological studies done in vivo and in vitro suggest that certain antibodies may enter cholinergic nerves and neutralize subsequently internalized toxin. Additional work on clostridial toxins has produced the following results: i) the ligand binding assay typically used with tetanus toxin (i.e., low pH and ionic strength) is of questionable biological significance, ii) the binary toxin, like the clostridial neurotoxins, enters cells by receptor-mediated endocytosis, and iii) tetanus toxin can alter the disposition of protein kinase C in one neuroblastoma cell line.
Identification of related proteins with weak sequence identity using secondary structure information (2001)

Molecular modeling of proteins is confronted with the problem of finding homologous proteins, especially when few identities remain after the process of molecular evolution. Using even the most recent methods based on sequence identity detection, structural relationships are still difficult to establish with high reliability. As protein structures are more conserved than sequences, we investigated the possibility of using protein secondary structure comparison (observed or predicted structures) to discriminate between related and unrelated proteins sequences in the range of 10%-30% sequence identity. Pairwise comparison of secondary structures have been measured using the structural overlap (Sov) parameter. In this article, we show that if the secondary structures likeness is >50%, most of the pairs are structurally related. Taking into account the secondary structures of proteins that have been detected by BLAST, FASTA, or SSEARCH in the noisy region (with high E: value), we show that distantly related protein sequences (even with <20% identity) can be still identified. This strategy can be used to identify three-dimensional templates in homology modeling by finding unexpected related proteins and to select proteins for experimental investigation in a structural genomic approach, as well as for genome annotation.
Plug-and-Display: decoration of Virus-Like Particles via isopeptide bonds for modular immunization (2016)

Virus-like particles (VLPs) are non-infectious self-assembling nanoparticles, useful in medicine and nanotechnology. Their repetitive molecularly-defined architecture is attractive for engineering multivalency, notably for vaccination. However, decorating VLPs with target-antigens by genetic fusion or chemical modification is time-consuming and often leads to capsid misassembly or antigen misfolding, hindering generation of protective immunity. Here we establish a platform for irreversibly decorating VLPs simply by mixing with protein antigen. SpyCatcher is a genetically-encoded protein designed to spontaneously form a covalent bond to its peptide-partner SpyTag. We expressed in E. coli VLPs from the bacteriophage AP205 genetically fused to SpyCatcher. We demonstrated quantitative covalent coupling to SpyCatcher-VLPs after mixing with SpyTag-linked to malaria antigens, including CIDR and Pfs25. In addition, we showed coupling to the VLPs for peptides relevant to cancer from epidermal growth factor receptor and telomerase. Injecting SpyCatcher-VLPs decorated with a malarial antigen efficiently induced antibody responses after only a single immunization. This simple, efficient and modular decoration of nanoparticles should accelerate vaccine development, as well as other applications of nanoparticle devices.
Nano-SnSb alloy deposited on MCMB as an anode material for lithium ion batteries (2001)

Nanosized SnSb alloy has been deposited and dispersed uniformly on the surface of mesophase carbon microbeads (MCMB) by a co-precipitation method in glycerin solution. As an active anode material for lithium ion batteries these composites show improved cycling performance. This improvement is due to the dispersion of the nano-sized alloy particles on the carbon surface that can alleviate the aggregation of nano-sized alloy particles during Li insertion and extraction. Furthermore, as both SnSb alloy and MCMB are active materials for Li-storage, a higher reversible capacity of 420 mA h g−1 has been achieved for the composite containing 26 wt% of SnSb alloy deposited on MCMB.
Role of hydrogen-bonding and its interplay with octahedral tilting in CH3NH3PbI3 (2015)

First principles calculations on the hybrid perovskite CH3NH3PbI3 predict strong hydrogen-bonding which influences the structure and dynamics of the methylammonium cation and reveal its interaction with the tilting of the PbI6 octahedra. The calculated atomic coordinates are in excellent agreement with neutron diffraction results.
Alleviating Cancer Drug Toxicity by Inhibiting a Bacterial Enzyme (2010)

The dose-limiting side effect of the common colon cancer chemotherapeutic CPT-11 is severe diarrhea caused by symbiotic bacterial β-glucuronidases that reactivate the drug in the gut. We sought to target these enzymes without killing the commensal bacteria essential for human health. Potent bacterial β-glucuronidase inhibitors were identified by high-throughput screening and shown to have no effect on the orthologous mammalian enzyme. Crystal structures established that selectivity was based on a loop unique to bacterial β-glucuronidases. Inhibitors were highly effective against the enzyme target in living aerobic and anaerobic bacteria, but did not kill the bacteria or harm mammalian cells. Finally, oral administration of an inhibitor protected mice from CPT-11-induced toxicity. Thus, drugs may be designed to inhibit undesirable enzyme activities in essential microbial symbiotes to enhance chemotherapeutic efficacy.
Large oncosomes mediate intercellular transfer of functional microRNA (2013)

Prostate cancer cells release atypically large extracellular vesicles (EVs), termed large oncosomes, which may play a role in the tumor microenvironment by transporting bioactive molecules across tissue spaces and through the blood stream. In this study, we applied a novel method for selective isolation of large oncosomes applicable to human platelet-poor plasma, where the presence of caveolin-1-positive large oncosomes identified patients with metastatic disease. This procedure was also used to validate results of a miRNA array performed on heterogeneous populations of EVs isolated from tumorigenic RWPE-2 prostate cells and from isogenic non-tumorigenic RWPE-1 cells. The results showed that distinct classes of miRNAs are expressed at higher levels in EVs derived from the tumorigenic cells in comparison to their non-tumorigenic counterpart. Large oncosomes enhanced migration of cancer-associated fibroblasts (CAFs), an effect that was increased by miR-1227, a miRNA abundant in large oncosomes produced by RWPE-2 cells. Our findings suggest that large oncosomes in the circulation report metastatic disease in patients with prostate cancer, and that this class of EV harbors functional molecules that may play a role in conditioning the tumor microenvironment.
Diverse cell stresses induce unique patterns of tRNA up- and down-regulation: tRNA-seq for quantifying changes in tRNA copy number (2014)

Emerging evidence points to roles for tRNA modifications and tRNA abundance in cellular stress responses. While isolated instances of stress-induced tRNA degradation have been reported, we sought to assess the effects of stress on tRNA levels at a systems level. To this end, we developed a next-generation sequencing method that exploits the paucity of ribonucleoside modifications at the 3'-end of tRNAs to quantify changes in all cellular tRNA molecules. Application of this tRNA-seq method to Saccharomyces cerevisiae identified all 76 expressed unique tRNA species out of 295 coded in the yeast genome, including all isoacceptor variants, with highly precise relative (fold-change) quantification of tRNAs. In studies of stress-induced changes in tRNA levels, we found that oxidation (H2O2) and alkylation (methylmethane sulfonate, MMS) stresses induced nearly identical patterns of up- and down-regulation for 58 tRNAs. However, 18 tRNAs showed opposing changes for the stresses, which parallels our observation of signature reprogramming of tRNA modifications caused by H2O2 and MMS. Further, stress-induced degradation was limited to only a small proportion of a few tRNA species. With tRNA-seq applicable to any organism, these results suggest that translational control of stress response involves a contribution from tRNA abundance.
Chinese hamster ovary cells contain transcriptionally active full-length type C proviruses (1994)

We have isolated a genomic locus from Chinese hamster ovary (CHO) cells that contains a full-length provirus. Nucleotide sequence analysis indicates that it is a defective member of the rodent type C retrovirus family with an env region that is similar to those of mouse amphotropic retrovirus and subgroup B feline leukemia virus. We were able to demonstrate that this provirus is a member of a closely related family of full-length proviruses in CHO cells and Chinese hamster liver. Hybridization probes generated from this genomic clone were used to characterize type C retrovirus RNA expression in CHO cells. Full-length genomic RNA and subgenomic envelope mRNA were detected in CHO cell lines but not in the human-derived 293 cell line. Interestingly, we discovered that the site of retrovirus integration lies within a G repeat sequence belonging to the short interspersed element family of retroposons.
Neutrophils lacking phosphoinositide 3-kinase γ show loss of directionality during N -formyl-Met-Leu-Phe-induced chemotaxis (2002)

Confocal imaging and time-lapsed videomicroscopy were used to study the directionality, motility, rate of cell movement, and morphologies of phosphoinositide 3-kinase gamma (PI3K)gamma(-/-) neutrophils undergoing chemotaxis in Zigmond chambers containing N-formyl-Met-Leu-Phe gradients. Most of the PI3Kgamma(-/-) neutrophils failed to translocate up the chemotactic gradient. A partial reduction in cell motility and abnormal morphologies were also observed. In the wild-type neutrophils, the pleckstrin homology domain-containing protein kinase B (AKT) and F-actin colocalize to the leading edge of polarized neutrophils oriented toward the gradient, which was not observed in PI3Kgamma(-/-) neutrophils. In PI3Kgamma(-/-) neutrophils, AKT staining consistently failed to perfectly overlap with the F-actin. This failure was observed as an F-actin-filled region of 2.3 +/- 0.5 microm between AKT and the cell membrane. These data suggest that PI3Kgamma regulates neutrophil chemotaxis primarily by controlling the direction of cell migration and the intracellular colocalization of AKT and F-actin to the leading edge.
Two-Dimensional Electrophoresis for Analysis ofMycobacterium tuberculosisCulture Filtrate and Purification and Characterization of Six Novel Proteins (1998)

Culture filtrate from Mycobacterium tuberculosis contains molecules which promote high levels of protective immunity in animal models of subunit vaccination against tuberculosis. We have used two-dimensional electrophoresis for analysis and purification of six novel M. tuberculosis culture filtrate proteins (CFPs): CFP17, CFP20, CFP21, CFP22, CFP25, and CFP28. The proteins were tested for recognition by M. tuberculosis-reactive memory cells from different strains of inbred mice and for their capacity to induce a skin test response in M. tuberculosis-infected guinea pigs. CFP17, CFP20, CFP21 and CFP25 induced both a high gamma interferon release and a strong delayed-type hypersensitivity response, and CFP21 was broadly recognized by different strains of inbred mice. N-terminal sequences were obtained for the six proteins, and the corresponding genes were identified in the Sanger M. tuberculosis genome database. In parallel we established a two-dimensional electrophoresis reference map of short-term culture filtrate components and mapped novel proteins as well as already-known CFP.
Population bottlenecks and patterns of human polymorphism (1999)

Fay and Wu (1999) examine a historical model in which a population quickly shrinks, stays small for some time, and then suddenly recovers its original population size, at which it stays until samples are drawn from it. This is a bottleneck model of the kind traditionally used in population genetics That model is one of population size expansion, and it pervades the literature on analysis of mitochondrial DNA (e.g., Rogers and Harpending 1992), as well as the more recent literature on microsatellites (e.g., However, Hey's paper explored only models of constant population size and models of expansion. Both of these models are considerably simpler than a bottleneck model, and they were the models that had received most of the attention in the literature. However, Hey's (1997) paper may have contributed to a confusion over models, for the final sentence did mention ''bottleneck. This means that the polymorphism patterns of genes with inherently different population sizes (e.g., mtDNA and nuclear genes) may be out of phase with one another if the period of population size fluctuation is sufficiently short and the fluctuation has been recent. Fay and Wu's letter is also timely in light of the increasing amount of nuclear gene data that are emerging. Since Hey's (1997) paper, which focused mostly on a few small data sets, larger data sets from PDHA1 (Harris and Hey 1999), -globin Also recently, small samples from a series of X-linked loci revealed that five out of six loci had positive values of D (although three were just slightly positive) Thus, the overall im-
Dependence of McrBC cleavage on distance between recognition elements. (1998)

DNA cleavage by the modification-dependent restriction enzyme McrBC requires the presence of two suitably modified recognition elements appropriately spaced in the substrate. To characterize the spacing requirement in more detail, we have constructed a plasmid with a single McrBC cleavage site, in which the distance between recognition elements could be systematically varied while preserving the local sequence surrounding the recognition elements. Optimal separation between elements was 55-103 basepairs, with detectable cleavage observed at spacing of 32 bp to 2 kb; no cleavage was seen with spacing of 22 bp or less or with 3 kb between elements. Changing the spacing by 4 basepairs within the optimal range had little effect on the efficiency of cleavage, suggesting that the recognition elements need not lie on the same face of the DNA helix.
The Reaction of Electron Excess Aromatic Heterocycle, 1,4-Dihydropyrrolo[3,2-b]pyrrole and Some Related Compounds with Chlorosulfonyl Isocyanate (CSI) (1996)

The reaction of 3,6-di-t~-butyl-l,4-dihydropyrrolo[3,2-b]pyole and its N,N'-dimethoxycarbonyl derivative with chlorosulfonyl isocyanate (CSI) was investigated.f i e higher reactivity for the electrophilic reaction and a remarkable electron excessiveness of the system were demonstrated by comparing with those of indole and pyrrole derivatives.The 1,4-dihydropyrrolo[3,2-blpyrrole (1) is a recently occurred hicyclic hetero-aromatic compo~nd'.~and its chemical behaviors may he analogized by indole (2) or pyrrole (3).Despite the intrinsic capability of I for electrophilic reaction on the ground of its highly electron excess character expected: little is yet known concerned with the reactivity of this molecule.For instance, Vilsmeier formylation is the only reported electrophilic substitution reaction for 1, to our knowledge.4We report here the reaction of 3,6-di-tert-butyl-1,4-dihydropyrrolo[3,2-blpyrrole (4),' and dimethyl 3,6-di-tert-butyl-l,4-dihydropyrrolo[3,2-b]pyrrole-l,4dicarboxylate (6)' with chlorosulfonyl isocyanete (CSI).Additionally, the reaction of N-methoxycarbonyl derivatives of indole (12, 13) and pyrrole (15) was also examined with the intention of comparing the reactivities.