gebhart/patrepeval huggingface dataset:
Activation of NF-κB by nontypeable Hemophilus influenzae is mediated by toll-like receptor 2-TAK1-dependent NIK–IKKα/β–IκBα and MKK3/6–p38 MAP kinase signaling pathways in epithelial cells (2001)

Nontypeable Hemophilus influenzae (NTHi) is an important human pathogen in both children and adults. In children, it causes otitis media, the most common childhood infection and the leading cause of conductive hearing loss in the United States. In adults, it causes lower respiratory tract infections in the setting of chronic obstructive pulmonary disease, the fourth leading cause of death in the United States. The molecular mechanisms underlying the pathogenesis of NTHi-induced infections remain undefined, but they may involve activation of NF-kappa B, a transcriptional activator of multiple host defense genes involved in immune and inflammatory responses. Here, we show that NTHi strongly activates NF-kappa B in human epithelial cells via two distinct signaling pathways, NF-kappa B translocation-dependent and -independent pathways. The NF-kappa B translocation-dependent pathway involves activation of NF-kappa B inducing kinase (NIK)--IKK alpha/beta complex leading to I kappa B alpha phosphorylation and degradation, whereas the NF-kappa B translocation-independent pathway involves activation of MKK3/6--p38 mitogen-activated protein (MAP) kinase pathway. Bifurcation of NTHi-induced NIK-IKK alpha/beta-I kappa B alpha and MKK3/6--p38 MAP kinase pathways may occur at transforming growth factor-beta activated kinase 1 (TAK1). Furthermore, we show that toll-like receptor 2 (TLR2) is required for NTHi-induced NF-kappa B activation. In addition, several key inflammatory mediators including IL-1 beta, IL-8, and tumor necrosis factor-alpha are up-regulated by NTHi. Finally, P6, a 16-kDa lipoprotein highly conserved in the outer membrane of all NTHi and H. influenzae type b strains, appears to also activate NF-kappa B via similar signaling pathways. Taken together, our results demonstrate that NTHi activates NF-kappa B via TLR2-TAK1-dependent NIK--IKK alpha/beta-I kappa B alpha and MKK3/6--p38 MAP kinase signaling pathways. These studies may bring new insights into molecular pathogenesis of NTHi-induced infections and open up new therapeutic targets for these diseases.
Multifunctional Roles for Serum Protein Fetuin-A in Inhibition of Human Vascular Smooth Muscle Cell Calcification (2005)

Vascular calcification predicts an increased risk for cardiovascular events/mortality in atherosclerosis, diabetes, and ESRD. Serum concentrations of alpha(2)-Heremens-Schmid glycoprotein, commonly referred to as fetuin-A, are reduced in ESRD, a condition associated with an elevated circulating calcium x phosphate product. Mice that lack fetuin-A exhibit extensive soft tissue calcification, which is accelerated on a mineral-rich diet, suggesting that fetuin-A acts to inhibit calcification systemically. Western blot and immunohistochemistry demonstrated that serum-derived fetuin-A co-localized with calcified human vascular smooth muscle cells (VSMC) in vitro and in calcified arteries in vivo. Fetuin-A inhibited in vitro VSMC calcification, induced by elevated concentrations of extracellular mineral ions, in a concentration-dependent manner. This was achieved in part through inhibition of apoptosis and caspase cleavage. Confocal microscopy and electron microscopy-immunogold demonstrated that fetuin-A was internalized by VSMC and concentrated in intracellular vesicles. Subsequently, fetuin-A was secreted via vesicle release from apoptotic and viable VSMC. Vesicles have previously been identified as the nidus for mineral nucleation. The presence of fetuin-A in vesicles abrogated their ability to nucleate basic calcium phosphate. In addition, fetuin-A enhanced phagocytosis of vesicles by VSMC. These observations provide evidence that the uptake of the serum protein fetuin-A by VSMC is a key event in the inhibition of vesicle-mediated VSMC calcification. Strategies aimed at maintaining normal circulating levels of fetuin-A may prove beneficial in patients with ESRD.
Identification of Three HLA-A*0201-Restricted Cytotoxic T Cell Epitopes in the Cytomegalovirus Protein pp65 That Are Conserved Between Eight Strains of the Virus (1999)

The Ag specificity of the CTL response against CMV is directed almost entirely to a single CMV tegument protein, the phosphoprotein pp65. We report the identification of three peptides derived from the protein pp65 that displayed a high or intermediate binding to HLA-A*0201 molecules, which were also able to induce an in vitro CTL response in peripheral blood lymphocytes from CMV seropositive individuals. The peptide-specific CTLs generated were capable of recognizing the naturally processed pp65 either presented by CMV-infected cells or by cells infected with an adenovirus construct expressing pp65 in an HLA-A*0201-restricted manner. Thus, we were able to demonstrate responses to subdominant CTL epitopes in CMV-pp65 that were not detected in polyclonal cultures obtained by conventional stimulations. We also found that the amino acid sequences of the three peptides identified as HLA-A*0201-restricted CTL epitopes were conserved among different wild-type strains of CMV obtained from renal transplant patients, an AIDS patient, and a congenitally infected infant, as well as three laboratory strains of the virus (AD169, Towne and Davis). These observations suggest that these pp65 CTL peptide epitopes could potentially be used as synthetic peptide vaccines or for other therapeutic strategies aimed at HLA-A*0201-positive individuals, who represent approximately 40% of the European Caucasoid population. However, strain variation must be taken in consideration when the search for CTL epitopes is extended to other HLA class I alleles, because these mutations may span potential CTL epitopes for other HLA molecules, as it is described in this study.
Essential requirement of toll-like receptor 4 expression on CD11c+ cells for locoregional immunotherapy of malignant ascites using a streptococcal preparation OK-432. (2006)

Toll-like receptors (TLRs) are important molecules that stimulate the innate immunity in order to eradicate microbial pathogens, after which the adaptive immunity emerges. The involvement of TLRs in the action mechanism of OK-432, a bacterial preparation, was investigated in the locoregional treatment of malignant ascites from gastric cancer. The expression of TLRs in ascites cells was analyzed using reverse-transcription polymerase chain reaction specific for TLRs and by flow cytometry using anti-TLR2, -TLR4, -CD4, -CD8, and -CD11c antibodies. These measurements were compared with the locoregional response of OK-432 immunotherapy for malignant ascites, as well as TNF-alpha producing potential, which was measured by ELISA, of ascites cells stimulated in vitro with OK-432. It was observed that OK-432 immunotherapy for malignant ascites showed 8 positive (67%) and 4 negative responses with the tolerable adverse effects of fever elevation and abdominal pain. The TNF-alpha production of ascites cells by in vitro OK-432 stimulation was significantly higher in responder patients than in non-responders. The clinical responses were correlated with the expression of the TLR4 gene of ascites cells. The TNF-alpha-producing potential of ascites cells by in vitro OK-432 stimulation was dependent on the existence of a CD11c + TLR-4+ cell population in ascites cells. OK-432 was highly stimulatory for TNF-alpha production of ascites cells compared with other biological response modifiers of PSK and LEM. These results suggest that TLR-4 expression on ascites cells of a macrophage lineage is essential for ascites cells to produce TNF-alpha in relation to OK-432 stimulation and for subsequent positive clinical responses in locoregional immunotherapy using OK-432 for malignant ascites from gastric cancer.
Über Pyridinium‐N‐phenol‐betaine und ihre Verwendung zur Charakterisierung der Polarität von Lösungsmitteln (1963)

Abstract Aus Pyryliumsalzen und Aminophenolen entstehen zunächst N ‐[Hydroxyphenyl]‐pyridiniumsalze, die mit starken Basen in die tieffarbigen, kristallinen Pyridinium‐ N ‐phenol‐betaine übergehen. Diese zeichnen sich durch die größte bisher bekannte, fast das gesamte sichtbare Spektrum umfassende Solvatochromie aus. Dem vorwiegend polaren Grundzustand entsprechend, wandert die solvatochrome Absorptionsbande mit zunehmender Polarität des Lösungsmittels nach kürzeren Wellen („negative Solvatochromie”︁). Die Lage des Absorptionsmaximums liefert ein Maß für die polarisierende Kraft des Lösungsmittels. Durch konstitutionelle änderungen an der Betainmolekel lassen sich Farbstoffe aufbauen, die eine geringere Neigung besitzen, mit dem Lösungsmittels H‐Brücken zu bilden. Die gesamte polarisierende Wirkung der verschiedenen Lösungsmittel kann dadurch auf einen allgemein polarisierenden und auf einen durch H‐Brückenbildung hervorgerufenen Effekt zurückgeführt werden. Für 44 verschiedene Lösungsmittel werden die charakteristischen Maßzahlen ihrer Polarisationskraft angegeben, die in naher Beziehung zu den aus kinetischen Daten stammenden Y‐Werten von Winstein und den optisch ermittelten Z‐Werten von Kosower stehen. — Pyridinium‐ N ‐phenol‐betaine zeigen auch eine durch Mesomerie bedingte Thermochromie. Steigende Temperatur führt zu einer Verschiebung der Solvatochromiebande nach längeren Wellen, N ‐Dimethylanilin‐pyridiniumsalze, als „vorwiegend unpolare”︁ Farbstoffe, verhalten sich bezüglich der Thermochromie wie auch bezüglich der Solvatochromie entgegengesetzt.
Vaccine Adjuvants (1980)

Nonreplicating, purified subunit or synthetic viral vaccines of the future are likely to be weak immunogens that will require immunopotentiation if they are to be effective. These marginal vaccines could be improved by combination with potent and safe immunologic adjuvants. The use of adjuvants should also reduce the amount of purified antigen required for successful immunization, thus making vaccine production more economical and more feasible. It may be possible to combine the recently developed relatively nontoxic synthetic immunoregulators of low molecular weight with antigens in order to modulate preselected compartments of the immune system. To date, the question of adjuvant safety has not been resolved and represents the major obstacle to the orderly development of adjuvanted vaccines. The fear of inducing cancer and other immediate or long-term perturbations of the immune system must be patently and rationally overcome by basic and applied experimentation and by the development of appropriate guidelines for studies in humans.
Enantioselective Total Syntheses of Communesins A and B (2011)

As easy as A, B: The first total syntheses of (−)-communesins A and B (see picture) were achieved, which featured the formation of their spiro-fused indoline part through an intramolecular oxidative coupling and of their A ring through a cascade reaction.
Steroids. LXXXI.1 Transformation of Sapogenins to Androgens and Estrogens. Beckmann Rearrangement of ▵16-20-Ketosteroids (1956)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSteroids. LXXXI.1 Transformation of Sapogenins to Androgens and Estrogens. Beckmann Rearrangement of ▵16-20-KetosteroidsG. ROSENKRANZ, O. MANCERA, FRANZ SONDHEIMER, and CARL DJERASSICite this: J. Org. Chem. 1956, 21, 5, 520–522Publication Date (Print):May 1, 1956Publication History Published online1 May 2002Published inissue 1 May 1956https://pubs.acs.org/doi/10.1021/jo01111a009https://doi.org/10.1021/jo01111a009research-articleACS PublicationsRequest reuse permissionsArticle Views381Altmetric-Citations57LEARN 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
Recombinant human butyrylcholinesterase from milk of transgenic animals to protect against organophosphate poisoning (2007)

Dangerous organophosphorus (OP) compounds have been used as insecticides in agriculture and in chemical warfare. Because exposure to OP could create a danger for humans in the future, butyrylcholinesterase (BChE) has been developed for prophylaxis to these chemicals. Because it is impractical to obtain sufficient quantities of plasma BChE to treat humans exposed to OP agents, the production of recombinant BChE (rBChE) in milk of transgenic animals was investigated. Transgenic mice and goats were generated with human BChE cDNA under control of the goat beta-casein promoter. Milk from transgenic animals contained 0.1-5 g/liter of active rBChE. The plasma half-life of PEGylated, goat-derived, purified rBChE in guinea pigs was 7-fold longer than non-PEGylated dimers. The rBChE from transgenic mice was inhibited by nerve agents at a 1:1 molar ratio. Transgenic goats produced active rBChE in milk sufficient for prophylaxis of humans at risk for exposure to OP agents.
Invasiveness of Yersinia enterocolitica lacking the virulence plasmid: an in-vivo study (1987)

Rabbits were given, by the intra-gastric route, two isogenic strains of Yersinia enterocolitica that differed only in the presence or absence of the virulence plasmid. Clinical illness and characteristic morphological lesions of Y. enterocolitica infection were seen only in rabbits infected with the plasmid-bearing strain (MCH700S). Although rabbits infected with a strain lacking the plasmid (MCH700L) remained healthy, mild histological changes in the small intestine, consisting of epithelial-cell damage, dilatation of lymphatics and a slight increase in neutrophil polymorphonuclear leukocytes in lamina propria, were seen in the first 12 h after inoculation. Bacteria, which were identified as Y. enterocolitica by indirect fluorescent antibody staining, were seen in dilated lymphatics. These early lesions tended to abate quickly and were no longer detectable at 24 h. Strain MCH700L was recovered from the mesenteric lymph nodes in increasing numbers until 24 h after inoculation; the number then began to decrease rapidly. In contrast, the early lesions in rabbits given strain MCH700S progressed to micro-abscesses, focal destruction of villi, and ulcerations beginning 24 h after inoculation; the number of bacteria recovered from the lymph nodes continued to increase beyond 24 h after inoculation. Bacteria were also recovered from the liver and spleen. These results suggest that both plasmid-bearing and non-bearing strains of Y. enterocolitica are capable of penetrating the intestinal mucosa. However, the virulence plasmid is required for invading bacteria to proliferate in the host tissue and to establish infection.
Ring-opening copolymerization of optically active .beta.-butyrolactone with several lactones catalyzed by distannoxane complexes: synthesis of new biodegradable polyesters (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleRing-opening copolymerization of optically active .beta.-butyrolactone with several lactones catalyzed by distannoxane complexes: synthesis of new biodegradable polyestersYoji Hori, Yoko Takahashi, Akio Yamaguchi, and Takao NishishitaCite this: Macromolecules 1993, 26, 16, 4388–4390Publication Date (Print):August 1, 1993Publication History Published online1 May 2002Published inissue 1 August 1993https://pubs.acs.org/doi/10.1021/ma00068a053https://doi.org/10.1021/ma00068a053research-articleACS PublicationsRequest reuse permissionsArticle Views369Altmetric-Citations56LEARN 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
Vascular endothelial growth factor (VEGF) is an autocrine growth factor for VEGF receptor–positive human tumors (2001)

Angiogenesis is required for the progression of tumors from a benign to a malignant phenotype and for metastasis. Malignant tumor cells secrete factors such as vascular endothelial growth factor (VEGF), which bind to their cognate receptors on endothelial cells to induce angiogenesis. Here it is shown that several tumor types express VEGF receptors (VEGFRs) and that inhibition of VEGF (VEGF antisense oligonucleotide AS-3) or VEGFRs (neutralizing antibodies) inhibited the proliferation of these cell lines in vitro. Furthermore, this effect was abrogated by exogenous VEGF. Thus, VEGF is an autocrine growth factor for tumor cell lines that express VEGFRs. A modified form of VEGF AS-3 (AS-3m), in which flanking 4 nucleotides were substituted with 2-O-methylnucleosides (mixed backbone oligonucleotides), retained specificity and was active when given orally or systemically in vitro and in murine tumor models. In VEGFR-2-expressing tumors, VEGF inhibition may have dual functions: direct inhibition of tumor cell growth and inhibition of angiogenesis.
Automobile Accidents Involving Patients with Obstructive Sleep Apnea (1988)

Although patients with obstructive sleep apnea often report falling asleep while driving, the frequency of auto accidents involving these patients has not been rigorously studied. Therefore, we compared the driving records of 29 patients with obstructive sleep apnea with those of 35 subjects without sleep apnea. The patients with sleep apnea had a sevenfold greater rate of automobile accidents than did the subjects without apnea (p less than 0.01). The percentage of persons with one or more accidents was also greater in the patients with apnea than in the control subjects without apnea (31% versus 6%, p less than 0.01). The percentage of persons having one or more accidents in which they were at fault was also greater in the patients with apnea than in the control subjects (24% versus 3%, p less than 0.02). The automobile accident rate of the patients with sleep apnea was 2.6 times the accident rate of all licensed drivers in the state of Virginia (p less than 0.02). In addition, 24% of patients with sleep apnea reported falling asleep at least once per week while driving. We conclude that patients with obstructive sleep apnea have a significantly higher frequency of auto accidents than do subjects without apnea. Impaired drivers with sleep apnea may cause many preventable auto accidents.
Functional, Biophysical, and Structural Characterization of Human IgG1 and IgG4 Fc Variants with Ablated Immune Functionality (2017)

Engineering of fragment crystallizable (Fc) domains of therapeutic immunoglobulin (IgG) antibodies to eliminate their immune effector functions while retaining other Fc characteristics has numerous applications, including blocking antigens on Fc gamma (Fcγ) receptor-expressing immune cells. We previously reported on a human IgG2 variant termed IgG2σ with barely detectable activity in antibody-dependent cellular cytotoxicity, phagocytosis, complement activity, and Fcγ receptor binding assays. Here, we extend that work to IgG1 and IgG4 antibodies, alternative subtypes which may offer advantages over IgG2 antibodies. In several in vitro and in vivo assays, the IgG1σ and IgG4σ variants showed equal or even lower Fc-related activities than the corresponding IgG2σ variant. In particular, IgG1σ and IgG4σ variants demonstrate complete lack of effector function as measured by antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, antibody-dependent cellular phagocytosis, and in vivo T-cell activation. The IgG1σ and IgG4σ variants showed acceptable solubility and stability, and typical human IgG1 pharmacokinetic profiles in human FcRn-transgenic mice and cynomolgus monkeys. In silico T-cell epitope analyses predict a lack of immunogenicity in humans. Finally, crystal structures and simulations of the IgG1σ and IgG4σ Fc domains can explain the lack of Fc-mediated immune functions. These variants show promise for use in those therapeutic antibodies and Fc fusions for which the Fc domain should be immunologically "silent".
Photochemistry and Radiation Chemistry of Colloidal Semiconductors 34. Properties of Q‐PbS (1989)

Abstract Precipitation of lead ions by hydrogen sulfide in the presence of poly(vinyl alcohol) in aqueous or methanolic solution yields Q‐PbS particles (quantized particles) which have a structured absorption spectrum. The particles have a rod‐like or spherical shape (size quantization mainly in two or three dimensions, respectively). PbS with a structured absorption can also be made in acetonitrile using poly(ethylene oxide) as stabilizer. PbS stabilized by sodium polyphosphate has a structureless absorption spectrum. — Depending on the method of preparation and surface modification after preparation PbS samples fluorescing in the red or/and infrared are obtained. Methyl viologen generally quenches but can in certain cases promote the fluorescence when it is present in low concentration. Oxygen quenches when the colloid is stabilized by polyphosphate. — The rate of the photoanodic dissolution in the presence of air is increased by methyl viologen. Half reduced methyl viologen does not transfer an electron to Q‐PbS but can do so in the case of larger particles. — Illumination under argon leads to increased Ostwald ripening of the particles. However, when sulfite is present in the deaerated solution, photoanodic dissolution takes place. — Attack by hydroxyl radicals generated radiolytically leads to Pb 2+ + SO 2− 4 . The fluorescence of a Q‐PbS particle is efficiently decreased after the attack by a single OH radical (i.e. after injection of one positive hole). — Single electron transfer from 1‐hydroxy methyl ethyl radicals, (CH 3 ) 2 COH, to Q‐PbS also leads to a decrease in fluorescence. These effects are attributed to interactions of the charge carriers deposited by the radicals on the colloidal particles with the exitonic state produced by light absorption. — Accumulated electron transfer to PbS‐particles from organic radicals yields lead metal and organic sulfur compounds. In the beginning of this process, the fluorescence strongly increases (10% quantum yield) which is explained by destruction of surface defect states.
Improving VoD server efficiency with bittorrent (2007)

This paper presents and evaluates Toast, a scalable Video-on-Demand (VoD)streaming system that combines the popular BitTorrent peer-to-peer (P2P)file-transfer technology with a simple dedicated streaming server to decrease server load and increase client transfer speed. Toast includes a modified version of BitTorrent that supports streaming data delivery and that communicates with a VoD server when the desired data cannot be delivered in real-time by other peers.