gebhart/patrepeval huggingface dataset:
Virus-Vectored Influenza Virus Vaccines (2014)

Despite the availability of an inactivated vaccine that has been licensed for >50 years, the influenza virus continues to cause morbidity and mortality worldwide. Constant evolution of circulating influenza virus strains and the emergence of new strains diminishes the effectiveness of annual vaccines that rely on a match with circulating influenza strains. Thus, there is a continued need for new, efficacious vaccines conferring cross-clade protection to avoid the need for biannual reformulation of seasonal influenza vaccines. Recombinant virus-vectored vaccines are an appealing alternative to classical inactivated vaccines because virus vectors enable native expression of influenza antigens, even from virulent influenza viruses, while expressed in the context of the vector that can improve immunogenicity. In addition, a vectored vaccine often enables delivery of the vaccine to sites of inductive immunity such as the respiratory tract enabling protection from influenza virus infection. Moreover, the ability to readily manipulate virus vectors to produce novel influenza vaccines may provide the quickest path toward a universal vaccine protecting against all influenza viruses. This review will discuss experimental virus-vectored vaccines for use in humans, comparing them to licensed vaccines and the hurdles faced for licensure of these next-generation influenza virus vaccines.
Design of Antitumor Prodrugs: Substrates for Antibody Targeted Enzymes (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDesign of Antitumor Prodrugs: Substrates for Antibody Targeted EnzymesLouis N. Jungheim and Timothy A. ShepherdCite this: Chem. Rev. 1994, 94, 6, 1553–1566Publication Date (Print):September 1, 1994Publication History Published online1 May 2002Published inissue 1 September 1994https://pubs.acs.org/doi/10.1021/cr00030a004https://doi.org/10.1021/cr00030a004research-articleACS PublicationsRequest reuse permissionsArticle Views806Altmetric-Citations79LEARN 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
Genotype C hepatitis B virus infection is associated with an increased risk of hepatocellular carcinoma (2004)

Genotype C HBV infection is an independent risk factor for HCC development in addition to liver cirrhosis.
Validation of Molecular Docking Calculations Involving FGF-1 and FGF-2 (2004)

A predictive relationship between calculated and observed binding affinities for the complexation of ligands to the fibroblast growth factors FGF-1 and FGF-2 based on molecular docking calculations is described. The majority of the ligands examined in this study have high conformational flexibility, and to account for this, multiple conformers were generated for each and subsequently used in flexible docking calculations. Two scoring functions, Gscore and Emodel, were used to quantify the protein:ligand interaction of which the Emodel score showed the best correlation with experimental binding energies. Both scoring functions, however, predicted similar locations for the ligand sulfate groups in the binding site. The van der Waals radii of nonpolar atoms of both the protein and ligand, which modify the effective sizes of both the protein binding site and the ligand, were also systematically altered by factors of 1.0, 0.9, and 0.8 in order to optimize the conditions for predictive docking. Least squares analyses of the Emodel scores against experimental binding energies yielded best r(2) values of 0.91 and 0.83 for FGF-1 and FGF-2, respectively, with slightly lower q(2) values. Optimized scale factor combinations in conjunction with the least squares lines of best fit based on the Emodel function were used to define a predictive model that was tested against ligands not included in the original set. Acceptable predictions of binding affinity were obtained for use in the initial screening of potential leadlike molecules for both FGF-1 and FGF-2.
The nature and effects of cortical microvascular pathology in aging and Alzheimer's disease (2004)

Age-related and amyloid-induced pathology of the cerebral microvasculature have been implicated as potential contributing factors to the pathogenesis of Alzheimer's disease (AD). The microvasculature plays a crucial role in maintaining brain homeostasis and deterioration of its integrity may have deleterious effects on brain function in AD, possibly leading to neurofibrillary degeneration, plaque formation, and cell loss. Brain vessels possess peculiar anatomical and physiological properties owing to their role in the exchange processes of various substances between blood and brain, which are highly regulated for the maintenance of ionic homeostasis of the neuronal environment. Here we review neuropathological aspects of cortical microvessels in aging and AD in relationship to known cardiovascular risk factors and their possible impact on the cognitive decline seen in late-onset dementia.
Microbiological Characterization of Everninomicins B and D (1974)

Everninomicins B and D are components of a complex of antibiotic substances produced by Micromonospora. Both were shown to be highly active inhibitors of growth of all gram-positive bacteria, Neisseria, and Bacteroides studied in vitro. Potency of activity appeared to be greater than that of chloramphenicol, but less than that of penicillin G, when assayed against strains susceptible to each of the drugs. The everninomicins were bacteriostatic for all strains tested, except group A streptococci. No facultatively anaerobic gram-negative bacilli were susceptible. Resistant mutants were selected with difficulty from susceptible staphylococci in the laboratory, and these demonstrated no cross-resistance to available antimicrobial agents. Most variations in media, growth conditions, or procedure of assay had little or no effect on antimicrobial activity. Only addition of serum or increase in inoculum size reduced antibacterial activity. Significant differences in activity of the two components were encountered infrequently; the B component was four- to sixfold more active against gonococci and group A streptococci, whereas the D component was fourfold more active against enterococci. Because of the high degree of in vitro activity and lack of resistance among susceptible genera of bacteria, the everninomicins clearly merit further careful study as potential therapeutic agents.
Mode Coupling and Dynamical Heterogeneity in Colloidal Gelation:  A Simulation Study (2005)

We present simulation results addressing the dynamics of a colloidal system with attractive interactions close to gelation. Our interaction also has a soft, long-range repulsive barrier that suppresses liquid-gas type phase separation at long wavelengths. The new results presented here lend further weight to an intriguing picture emerging from our previous simulation work on the same system. Whereas mode coupling theory (MCT) offers quantitatively good results for the decay of correlators, closer inspection of the dynamics reveals a bimodal population of fast and slow particles with a very long exchange time scale. This population split represents a particular form of dynamic heterogeneity (DH). Although DH is usually associated with activated hopping and/or facilitated dynamics in glasses, the form of DH observed here may be more collective in character and associated with static (i.e., structural) heterogeneity.
The cerebrospinal-fluid soluble form of Alzheimer's amyloid β is complexed to SP-40,40 (apolipoprotein J), an inhibitor of the complement membrane-attack complex (1993)

The amyloid fibrils deposited in Alzheimer's neuritic plaque cores and cerebral blood vessels are mainly composed of aggregated forms of a unique peptide, 39-42 amino acids long, named amyloid beta (A beta). A similar, although soluble, A beta ('sA beta') has been identified in cerebrospinal fluid, plasma and cell supernatants, indicating that it is normally produced by proteolytic processing of its precursor protein, amyloid precursor protein (APP). Using direct binding experiments we have isolated and characterized an 80 kDa circulating protein that specifically interacts with a synthetic peptide identical with A beta. The protein was unmistakably identified as SP-40,40 or ApoJ, a cytolytic inhibitor and lipid carrier, by means of amino acid sequence and immunoreactivity with specific antibodies. Immunoprecipitation with anti-SP-40,40 retrieved soluble A beta from cerebrospinal fluid, indicating that the interaction occurs in vivo.
Multispectral Color Imaging for Dermatology: Application in Inflammatory and Immunologic Diseases (2005)

This paper presents an experimental investigation of the application of multispectral imaging in dermatology. The focus areas of this work are as follows: a) the improving the color reproduction accuracy of skin lesions, b) exploring the spectral feature of skin disease using the multispectral color enhancement technique, and c) multispectral image analysis aiming at supporting quantitative diagnosis. The experiment focused on inflammatory and immunologic diseases; the color of skin lesions associated with these diseases is believed to be difficult to reproduce by conventional imaging devices. In view of this fact, we demonstrate the effectiveness of using spectral information for the color reproduction and quantitative analysis of skin disorders.
It's a Small RNA World, After All (2005)

Small RNAs (sRNAs) can regulate transcript and protein abundance. Previously, they have been identified using traditional cloning approaches, which has limited how many could be characterized. Now, the Meyers and Green laboratories have used massively parallel signature sequencing technology to find over 1.5 million sRNAs in Arabidopsis thaliana. These new sRNAs reveal a greater-than-expected potential role for sRNAs in gene regulation, preferential expression or usage of sRNAs in flowers, and the prospect of targeted sRNA-mediated regulation of pseudogenes. In addition, new plant microRNAs have been identified, some of which may be unique to Arabidopsis.
Influenza viral (A/WSN/33) hemagglutinin is expressed and glycosylated in the yeast Saccharomyces cerevisiae. (1985)

Recombinant plasmids were constructed in which genes coding for either the entire or the signal-minus (amino acid residues 2-17 deleted) hemagglutinin (HA) of WSN influenza virus were placed under the control of the alcohol dehydrogenase I gene promoter of Saccharomyces cerevisiae. Both recombinant plasmids were shown to direct the synthesis of HA-specific polypeptides that were detected by immunoprecipitation with antiviral antibodies. The complete HA produced in yeast had an approximate Mr of 70,000 and was glycosylated, as determined by the endoglycosidase H sensitivity, and was bound to membrane. Therefore, the complete HA polypeptide possessing the signal sequence probably traversed the yeast secretory pathways. Signal-minus HA, on the other hand, had a lower molecular weight and was nonglycosylated. The specific binding of yeast HA with antiviral antibodies could be competitively inhibited by influenza viral HA, demonstrating that the HA produced in yeast contained antigenic determinants of the native viral HA.
Fine Particulate Air Pollution and Mortality in 20 U.S. Cities, 1987–1994 (2000)

There is consistent evidence that the levels of fine particulate matter in the air are associated with the risk of death from all causes and from cardiovascular and respiratory illnesses. These findings strengthen the rationale for controlling the levels of respirable particles in outdoor air.
Proteomic Analyses of the Two Mucus Layers of the Colon Barrier Reveal That Their Main Component, the Muc2 Mucin, Is Strongly Bound to the Fcgbp Protein (2009)

The colon epithelium is protected from the luminal microbes as recently revealed by an inner firmly attached mucus layer impervious to bacteria and an outer loose mucus layer that is the habitat of bacteria. For an additional understanding of these layers, we analyzed the protein composition of these two mucus layers from the mouse colon. Proteomics using nano-LC-MS and MS/MS revealed more than 1000 protein entries. As the mucus layers contain detached cells, a majority of the proteins had an intracellular origin. However, at least 44 entries were described as secreted proteins and predicted to be mucus constituents together with extracellular/plasma and bacterial proteins, the latter largely in the loose mucus layer. A major protein was the Muc2 mucin that by its net-like disulfide-bonded polymer structure builds the mucus. When guanidinium chloride insoluble Muc2 units were analyzed, N-terminal parts of the Fc-gamma binding protein (Fcgbp) was found to be covalently attached in mouse and human colon, whereas its C-terminus was lost by reducing the disulfide bonds. In conclusion, the Fcgbp protein is probably cleaved at GD/PH and covalently attached to Muc2 via one or several of its von Willebrand D domains.
The Extra Domain A from Fibronectin Targets Antigens to TLR4-Expressing Cells and Induces Cytotoxic T Cell Responses In Vivo (2007)

Vaccination strategies based on the in vivo targeting of Ags to dendritic cells (DCs) are needed to improve the induction of specific T cell immunity against tumors and infectious agents. In this study, we have used a recombinant protein encompassing the extra domain A from fibronectin (EDA), an endogenous ligand for TLR4, to deliver Ags to TLR4-expressing DC. The purified EDA protein was shown to bind to TLR4-expressing HEK293 cells and to activate the TLR4 signaling pathway. EDA also stimulated the production by DC of proinflammatory cytokines such as IL-12 or TNF-alpha and induced their maturation in vitro and in vivo. A fusion protein between EDA and a cytotoxic T cell epitope from OVA efficiently presented this epitope to specific T cells and induced the in vivo activation of a strong and specific CTL response. Moreover, a fusion protein containing EDA and the full OVA also improved OVA presentation by DC and induced CTL responses in vivo. These EDA recombinant proteins protected mice from a challenge with tumor cells expressing OVA. These results strongly suggest that the fibronectin extra domain A may serve as a suitable Ag carrier for the development of antiviral or antitumoral vaccines.
Therapeutic potential of an anti-CD79b antibody–drug conjugate, anti–CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma (2009)

Here we describe the generation of an antibody-drug conjugate (ADC) consisting of a humanized anti-CD79b antibody that is conjugated to monomethylauristatin E (MMAE) through engineered cysteines (THIOMABs) by a protease cleavable linker. By using flow cytometry, we detected the surface expression of CD79b in almost all non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia patients, suggesting that anti-CD79b-vcMMAE could be widely used in these malignancies. By using NHL cell lines to simulate a patient population we discovered that a minimal cell-surface expression level of CD79b was required for in vitro activity. Within the subpopulation of cell lines above this minimal threshold, we found that sensitivity to free MMAE, mutation of cancer genes, and cell doubling time were poorly correlated with in vitro activity; however, the expression level of BCL-XL was correlated with reduced sensitivity to anti-CD79b-vcMMAE. This observation was supported by in vivo data showing that a Bcl-2 family inhibitor, ABT-263, strikingly enhanced the activity of anti-CD79b-vcMMAE. Furthermore, anti-CD79b-vcMMAE was significantly more effective than a standard-of-care regimen, R-CHOP (ie, rituximab with a single intravenous injection of 30 mg/kg cyclophosphamide, 2.475 mg/kg doxorubicin, 0.375 mg/kg vincristine, and oral dosing of 0.15 mg/kg prednisone once a day for 5 days), in 3 xenograft models of NHL. Together, these data suggest that anti-CD79b-vcMMAE could be broadly efficacious for the treatment of NHL.
Structure of human MIP-3α chemokine (2006)

The structure of the human macrophage inflammatory protein-3alpha (MIP-3alpha) has been determined at 1.81 angstroms resolution by X-ray crystallography. The dimer crystallized in the tetragonal space group I4, with unit-cell parameters a = b = 83.99, c = 57.20 angstroms. The crystals exhibit two molecules in the asymmetric unit. The structure was solved by the molecular-replacement method and the model was refined to a conventional R value of 20.6% (R(free) = 25.7%). MIP-3alpha possesses the same monomeric structure as previously described for other chemokines. However, in addition to limited structural changes in the beta1-beta2 hairpin of monomer B, the electron density is fully defined for a few extra residues at the N- and C-termini of monomer A and the C-terminus of monomer B compared with MIP-3alpha in space group P6(1). As the N-terminal and loop regions have been shown to be critical for receptor binding and signaling, this additional structural information may help in determining the basis of the CCR6 selectivity of MIP-3alpha.
Detection of drugs of abuse in exhaled breath using a device for rapid collection: comparison with plasma, urine and self-reporting in 47 drug users (2013)

Exhaled breath has recently been identified as a matrix for the detection of drugs of abuse. This work aims to further document this application using a new and simple collection device in patients following recovery from acute intoxication. Breath, plasma and urine samples were collected from 47 patients (38 males, age range 25-74) together with interview data. Analysis of breath and plasma samples was done by liquid chromatography-mass spectrometry methods. Urine was screened using immunochemical reagents and positive findings confirmed with liquid chromatography-mass spectrometry methods. The 12 analytes investigated were: methadone, amphetamine, methamphetamine, 6-acetylmorphine, morphine, benzoylecgonine, cocaine, diazepam, oxazepam, alprazolam, buprenorphine and tetrahydrocannabinol. In all 47 cases, recent intake of an abused substance prior to admission was reported, but in one case the substance (ketobemidone) was not investigated. In 40 of the remaining cases (87%) breath analysis gave a positive finding of any of the substances that were part of the analytical investigation. Identifications were based on correct chromatographic retention time and product ion ratios obtained in selected reaction monitoring mode. In general, data from breath, plasma, urine and self-reporting were in good agreement, but in 23% of the cases substances were detected that had not been self-reported. All substances covered were detected in a number of breath samples. Considering that breath sampling was often done about 24 h after intake, the detection rate was considered to be high for most substances. Analytes with low detection rates were benzodiazepines, and a further increase in analytical sensitivity is needed to overcome this. This study further supports use of exhaled breath as a new matrix in clinical toxicology.
Characterization of recombinant human single chain urokinase-type plasminogen activator mutants produced by site-specific mutagenesis of lysine 158. (1987)

The cDNA encoding full-length single chain urokinase-type plasminogen activator (scu-PA) was cloned and sequenced, and the recombinant scu-PA (rscu-PA) was expressed in Chinese hamster ovary cells. Two mutants, constructed by in vitro site-specific mutagenesis of Lys158 in rscu-PA to Gly158 (rscu-PA-Gly158) or to Glu158 (rscu-PA-Glu158), were also expressed in Chinese hamster ovary cells. Wild type and mutant rscu-PAs were purified to homogeneity by immunoadsorption on an insolubilized monoclonal antibody raised against natural scu-PA (nscu-PA), followed by gel filtration. The specific activity of the mutant scu-PAs on fibrin plates is very low (less than 1,000 IU/mg) compared to that of the wild type rscu-PA (44,000 IU/mg). The mutants, in contrast to the wild type rscu-PA, are not converted to amidolytically active two chain u-PA (tcu-PA) by plasmin and do not cause lysis of a 125I-fibrin-labeled plasma clot immersed in citrated plasma. However, in a purified system, both rscu-PA-Gly158 and rscu-PA-Glu158 activate plasminogen following Michaelis-Menten kinetics, with a much lower affinity (Km = 60-80 microM) but with a higher turnover rate constant (k2 = 0.01 s-1) as compared to the wild type rscu-PA (Km = 1.0 microM, k2 = 0.002 s-1). We conclude that conversion of scu-PA to tcu-PA is not a prerequisite for the activation of plasminogen. Substitution of Lys158 by Gly158 or Glu158 does, however, markedly decrease the stability of the Michaelis complex.
Antitumor effects of specific telomerase inhibitor GRN163 in humanglioblastoma xenografts (2004)

Telomerase is a ribonucleoprotein complex that elongates telomeric DNA and appears to play an important role in cellular immortalization of cancers. Because telomerase is expressed in the vast majority of malignant gliomas but not in normal brain tissues, it is a logical target for gliomaspecific therapy. The telomerase inhibitor GRN163, a 13-mer oligonucleotide N3'-->P5' thio-phosphoramidate (Geron Corporation, Menlo Park, Calif.), is complementary to the template region of the human telomerase RNA subunit hTR. When athymic mice bearing U-251 MG human brain tumor xenografts in their flanks were treated intratumorally with GRN163, a significant growth delay in tumor size was observed (P < 0.01 in all groups) as compared to the tumor size in mice receiving a mismatched oligonucleotide or the carrier alone. We also investigated biodistribution of the drug in vivo in an intracerebral rat brain-tumor model. Fluorescein-labeled GRN163 was loaded into an osmotic minipump and infused directly into U-251 MG brain tumors over 7 days. Examination of the brains revealed that GRN163 was present in tumor cells at all time points studied. When GRN163 was infused into intracerebral U-251 MG tumors shortly after their implantation, it prevented their establishment and growth. Lastly, when rats with larger intracerebral tumors were treated with the inhibitor, GRN163 increased animal survival times. Our results demonstrate that the antitelomerase agent GRN163 inhibits growth of glioblastoma in vivo, exhibits favorable intracerebral tumor uptake properties, and prevents the growth of intracerebral tumors. These findings support further development of this compound as a potential anticancer agent.
Application of Histamine-Induced Conjunctivitis to the Assessment of a Topical Antihistamine, Levocabastine (1987)

In an animal model, topical application of levocabastine to the eye inhibits the inflammatory conjunctival response to topically applied histamine. This is so even at one-fourth the concentration at which levocabastine is normally dispensed. Total blocking of histamine response continues for 24 h and is then irregularly observable for an additional 72 h. Levocabastine may be absorbed through the conjunctiva to give systemically transmitted protection to the contralateral eye. Levocabastine is a potent competitor against histamine for conjunctival H1 receptors and should prove a useful, possibly long-acting drug for the reversal of inflammatory conjunctivitis and inhibition of its recurrence.