gebhart/patrepeval huggingface dataset:
Helper T cell subsets for immunoglobulin A responses: oral immunization with tetanus toxoid and cholera toxin as adjuvant selectively induces Th2 cells in mucosa associated tissues. (1993)

Antigen-specific B cell responses to mucosally delivered proteins are dependent upon CD4-positive T helper (Th) cells, and the frequency of Th1 and Th2 cell responses after oral immunization may determine the level and isotype of mucosal antibody responses. We have used a protein-based vaccine, tetanus toxoid (TT), together with the mucosal adjuvant cholera toxin (CT), for oral immunization of mice to study the nature of antigen-specific Th cell subsets induced in Peyer's patches (PP) of the gastrointestinal (GI) tract and in the spleen (SP) during peak antibody responses. Mice orally immunized with TT and CT responded with antigen-specific secretory immunoglobulin A (S-IgA) antibodies in the GI tract, and with both IgG and IgA antibody responses in serum. PP and SP CD4+ T cells from mice orally immunized with TT plus CT were cultured with antigen-coated latex microspheres for induction of proliferative responses and for enumeration of cytokine producing CD4+ T cells. Interestingly, both PP and SP CD4+ T cell cultures showed increased numbers of IL-4- and IL-5 (Th2-type)-producing, spot-forming cells (SFCs) after 21 d of immunization, while essentially no interferon-gamma (IFN-gamma) or IL-2 (Th1-type) SFCs were noted. Cytokine-specific Northern blots and RT-PCR also revealed that significant IL-4 and IL-5 mRNA levels, but not IFN-gamma or IL-2 mRNA, were present in CD4+ T cells isolated from antigen-stimulated cultures. However, systemic immunization with TT and CT induced antigen-specific IgG and IgM but not IgA antibodies in serum. Further, both IL-2 and IFN-gamma-producing Th1-type cells as well as IL-4- and IL-5-secreting Th2-type cells were generated in SP. Our results show that oral immunization with TT and the mucosal adjuvant CT selectively induced antigen-specific Th2-type responses which may represent the major helper cell phenotype involved in mucosal IgA responses in the GI tract.
Targeted disruption of the apolipoprotein C-III gene in mice results in hypotriglyceridemia and protection from postprandial hypertriglyceridemia. (1994)

Using gene targeting in embryonic stem cells, we have generated mice lacking apolipoprotein C-III (ApoC-III). Homozygous mutant animals show absence of ApoC-III protein and no expression of ApoC-III mRNA in the liver or in the intestine. Expression of the neighboring genes, coding for apolipoprotein A-I and apolipoprotein A-IV, are not altered in the liver but are reduced in the intestine. This suggests that these three genes share a tissue-specific element for intestinal expression and that insertion of an additional promoter for the neomycin-resistant gene into the locus affects interaction between the tissue-specific element and the promoter of the individual gene. Fasted plasma triglyceride levels in the homozygous mutants are reduced to about 70% of normal, while heterozygotes have values intermediate between those of the homozygous mutants and wild types. Plasma levels of total cholesterol and of high density lipoprotein cholesterol in homozygotes are consistently lower than those in normal mices but the reduction does not reach statistical significance. A fat meal test showed that postprandial hypertriglyceridemia is abolished in homozygotes lacking ApoC-III. The homozygous mutants also clear chylomicrons faster than wild type controls. These data indicate that ApoC-III modulates the catabolism of triglyceride-rich lipoproteins and plays a role in the postprandial management of triglycerides.
Keratin 5 expression in squamocellular carcinoma of the head and neck (2014)

Keratin 5 (K5) is present in the basal layer of a stratified squamous keratinized and non-keratinized epithelium. K5 and K14 have been demonstrated in the mucosa and tumors of the oral cavity, oropharynx, hypopharynx and larynx, and in the mitotic active basal cells of a stratified squamous epithelium. The aim of the present study was to assess K5 expression in squamocellular carcinoma with various localizations in the head and neck. A total of 13 biopsy fragments were included from patients diagnosed with squamocellular carcinoma of the larynx area (n=2), pharynx (n=2), hard palate (n=1), tongue (n=2), submandibular (n=1), lip (n=1), gingival sulcus (n=1), nasal pyramid (n=1), maxilla (n=1) and zygomatic (n=1). The immunohistochemical staining for K5 was evaluated according to the following score criteria: 0 (0% positive cells); 1 (<10% positive cells); 2 (10-30% positive cells); and 3 (>30% positive cells). K5 expression was observed in all squamocellular carcinomas included in the present study with scores between 1 and 3. For well- and moderately-differentiated histopathological types, a maximum score of 3 was recorded for all of the cases, not including the laryngeal area, which presented a score of 2. The following scores were identified in the regions of the poorly differentiated carcinomas: Jaw, 3; gingival sulcus, 2; and tongue and submandibular area, 1. These observations may aid with an improved stratification of head and neck squamocellular carcinoma, thus improving the diagnosis and treatment strategies for this type of cancer.
Retroviral insertional mutagenesis of a target allele in a heterozygous murine cell line. (1985)

A clonal murine cell line that is heterozygous at the beta 2-microglobulin locus (B2m) was obtained by Abelson murine leukemia virus (Ab-MuLV) transformation of liver cells from (C57BL/6 X BALB/c) F1 fetuses. To obtain proviral insertional mutants, we superinfected a subclone of these cells, which does not express the env surface protein of the Moloney leukemia virus (Mo-MuLV, the helper virus that was used to transmit the defective Ab-MuLV genome during transformation), with Mo-MuLV. Mutant clones that fail to express the C57BL/6 allele of B2m (B2mb) were then immunoselected by using a monoclonal antibody that specifically recognizes the B2mb gene product and not that of the B2ma allele. Of 22 independent clones obtained, one contains a proviral insertion that is near or in the first exon of the B2mb gene. Surprisingly, the insertion is of the Ab-MuLV genome and not of replication-competent Mo-MuLV. This indicates that superinfection with Mo-MuLV "rescued" the defective Ab-MuLV genome, which then inserted into the B2mb gene. We conclude that when an allele-specific selection procedure exists, proviral insertion is a potential method for obtaining mutations in heterozygous mammalian cells. This approach may thereby provide a method for molecular cloning of such selectable genes, using a retroviral hybridization probe.
Immortalized and tumorigenic adult human prostatic epithelial cell lines: Characteristics and applications part 2. Tumorigenic cell lines (1997)

This is Part 2 of a three-part review and deals with tumorigenic cell lines. Several immortalized and malignant adult human prostatic epithelial cell lines have been recently developed. The three most widely used carcinoma cell lines-DU-145, PC-3, and LNCaP-developed between 1977 and 1980, have greatly contributed to our current understanding of prostate cancer. Before a cell line can be accepted as having prostatic epithelial origin, some basic characteristics must be established. Expression of specific cytokeratins but absence of desmin and factor VIII should be first determined to establish epithelial origin. Responsiveness to androgens and expression of androgen receptor and prostate-specific antigen should be examined under stringent culture conditions to establish prostatic epithelial origin. Response to growth factors and expression of their receptors facilitates further characterization of cell behavior. Cell lines immortalized by human papillomaviruses (HPVs) are of special interest because HPVs are involved in a variety of anogenital cancers and may also play a role in prostate carcinogenesis. Malignant transformation of HPV-18 immortalized cells with the ras oncogene provides cell systems for investigating the multistep process of carcinogenesis. Each cell line has some unique characteristics, whether it arose directly from a carcinoma or resulted from immortalization with Simian virus 40 (SV40) or HPV, or was transformed in vitro by oncogenes. Comparisons of these characteristics should facilitate elucidation of the mechanisms involved in the initiation, promotion, and progression of prostate cancer. These cell lines will further serve as useful models for investigating tumor progression, invasion, metastasis, new therapeutic strategies, drug resistance, and its reversal and chemoprevention. The nontumorigenic cell lines were discussed in Part 1 [1]. This review summarizes the characteristics of several currently available tumorigenic, adult human prostatic epithelial cell lines.
Enhanced Carotenoid Biosynthesis by Oxidative Stress in Acetate-Induced Cyst Cells of a Green Unicellular Alga, Haematococcus pluvialis (1993)

In a green alga, Haematococcus pluvialis, a morphological change of vegetative cells into cyst cells was rapidly induced by the addition of acetate or acetate plus Fe to the vegetative growth phase. Accompanied by cyst formation, algal astaxanthin formation was more enhanced by the addition of acetate plus Fe than by the addition of acetate alone. Encystment and enhanced carotenoid biosynthesis were inhibited by either actinomycin D or cycloheximide. However, after cyst formation was induced by the addition of acetate alone, carotenoid formation could be enhanced with the subsequent addition of Fe even in the presence of the inhibitors. The Fe -enhanced carotenogenesis was inhibited by potassium iodide, a scavenger for hydroxyl radical, suggesting that hydroxyl radical formed by an iron-catalyzed Fenton reaction may be required for enhanced carotenoid biosynthesis. Moreover, it was demonstrated that four active oxygen species, singlet oxygen, superoxide anion radical, hydrogen peroxide, and peroxy radical, were capable of replacing Fe in its role in the enhanced carotenoid formation in the acetate-induced cyst. From these results, it was concluded that oxidative stress is involved in the posttranslational activation of carotenoid biosynthesis in acetate-induced cyst cells.
Electrochemically Assisted Covalent Modification of Carbon Electrodes (2000)

A comprehensive review of the methods, scope and applications of electrochemically assisted covalently modified carbon electrodes is presented. Methods involve the oxidation of amines or arylacetates or the reduction of aryl diazonium cations. For these species it is proposed that a radical formed in solution at the carbon surface couples with the surface via a covalent bond to a surface C. In an alternative strategy, oxidation of GC electrodes in anhydrous alcohols is assumed to produce a surface-based radical which reacts with alcohols giving an ether link with the surface. Some less characterized and/or related methods are also described. A wide range of groups has been covalently linked to carbon surfaces using these methods and further modifications of initially formed monolayers have also been successful. Applications of covalently modified electrodes are reviewed; these range from formation of improved carbon composite materials to preparation of new sensing surfaces and formation of carbon surfaces with controlled structure for studies of electron transfer activity.
Argonaute2 Is the Catalytic Engine of Mammalian RNAi (2004)

Gene silencing through RNA interference (RNAi) is carried out by RISC, the RNA-induced silencing complex. RISC contains two signature components, small interfering RNAs (siRNAs) and Argonaute family proteins. Here, we show that the multiple Argonaute proteins present in mammals are both biologically and biochemically distinct, with a single mammalian family member, Argonaute2, being responsible for messenger RNA cleavage activity. This protein is essential for mouse development, and cells lacking Argonaute2 are unable to mount an experimental response to siRNAs. Mutations within a cryptic ribonuclease H domain within Argonaute2, as identified by comparison with the structure of an archeal Argonaute protein, inactivate RISC. Thus, our evidence supports a model in which Argonaute contributes "Slicer" activity to RISC, providing the catalytic engine for RNAi.
Rejection of large HPV-16 expressing tumors in aged mice by a single immunization of VacciMax® encapsulated CTL/T helper peptides (2007)

The incidence of cancer increases significantly in later life, yet few pre-clinical studies of cancer immunotherapy use mice of advanced age. A novel vaccine delivery platform (VacciMax,VM) is described that encapsulates antigens and adjuvants in multilamellar liposomes in a water-in-oil emulsion. The therapeutic potential of VM-based vaccines administered as a single dose was tested in HLA-A2 transgenic mice of advanced age (48-58 weeks old) bearing large palpable TC1/A2 tumors. The VM-based vaccines contained one or more peptides having human CTL epitopes derived from HPV 16 E6 and E7. VM formulations contained a single peptide, a mixture of four peptides or the same four peptides linked together in a single long peptide. All VM formulations contained PADRE and CpG as adjuvants and ISA51 as the hydrophobic component of the water-in-oil emulsion. VM-formulated vaccines containing the four peptides as a mixture or linked together in one long peptide eradicated 19-day old established tumors within 21 days of immunization. Peptide-specific cytotoxic cellular responses were confirmed by ELISPOT and intracellular staining for IFN-gamma producing CD8+ T cells. Mice rendered tumor-free by vaccination were re-challenged in the opposite flank with 10 million HLF-16 tumor cells, another HLA-A2/E6/E7 expressing tumor cell line. None of these mice developed tumors following the re-challenge. In summary, this report describes a VM-formulated therapeutic vaccine with the following unprecedented outcome: a) eradication of large tumors (> 700 mm3) b) in mice of advanced age c) in less than three weeks post-immunization d) following a single vaccination.
THE ORAL EFFICACY OF VARDENAFIL HYDROCHLORIDE FOR INDUCING PENILE ERECTION IN A CONSCIOUS RABBIT MODEL (2001)

The effect of vardenafil on penile erection after oral administration was clearly demonstrated in the conscious rabbit model. The time course and early onset of activity indicate that it may be useful for treating erectile dysfunction. Potentiation of the effect by the nitric oxide donor sodium nitroprusside implies that it would have enhanced activity during sexual arousal, when nitric oxide is produced endogenously. The clinical development of this product for erectile dysfunction is proceeding.
Using Include Files to Streamline Web Site Management (2004)

ABSTRACT The article introduces the concepts and practices of using Server Side Includes (SSI) and Hypertext Preprocessor (PHP) include function to streamline Web site management by separating content from structure. Examples are given with details. Comparison is made in terms of ease of use and functionality. Alternative practices such as using Dream-weaver templates and creating database-driven Web pages are also discussed and compared with SSI and PHP include. Recommendations are made in terms of when to use which method.
Caveolin Interaction with Protein Kinase C (1997)

Caveolar localization of protein kinase C and the regulation of caveolar function by protein kinase C are well known. This study was undertaken to examine whether caveolin subtypes interact with various protein kinase C isoenzymes using the caveolin scaffolding domain peptide. When protein kinase C-alpha, -epsilon, and -zeta were overexpressed in COS cells followed by subcellular fractionation using the sucrose gradient method, all the isoenzymes (alpha, epsilon, and zeta) were detected in the same fraction as caveolin. The scaffolding domain peptide of caveolin-1 and -3, but not -2, inhibited the kinase activity and autophosphorylation of protein kinase C-alpha and -zeta, but not of protein kinase C-epsilon, overexpressed in insect cells. Truncation mutation studies of the caveolin-1 and -3 peptides demonstrated that a minimum of 16 or 14 amino acid residues of the peptide were required for the inhibition or direct binding of protein kinase C. Thus, the caveolin peptide physically interacted with protein kinase C and regulated its function. Further, this regulation occurred in a protein kinase C isoenzyme-dependent manner. Our results may provide a new mechanism regarding the regulation of protein kinase C isoenzyme activity and the molecular interaction of protein kinase C with its putative binding proteins.
Mechanism of Divergent Growth Factor Effects in Mesenchymal Stem Cell Differentiation (2005)

Closely related signals often lead to very different cellular outcomes. We found that the differentiation of human mesenchymal stem cells into bone-forming cells is stimulated by epidermal growth factor (EGF) but not platelet-derived growth factor (PDGF). We used mass spectrometry-based proteomics to comprehensively compare proteins that were tyrosine phosphorylated in response to EGF and PDGF and their associated partners. More than 90% of these signaling proteins were used by both ligands, whereas the phosphatidylinositol 3-kinase (PI3K) pathway was exclusively activated by PDGF, implicating it as a possible control point. Indeed, chemical inhibition of PI3K in PDGF-stimulated cells removed the differential effect of the two growth factors, bestowing full differentiation effect onto PDGF. Thus, quantitative proteomics can directly compare entire signaling networks and discover critical differences capable of changing cell fate.
Structure of the Extracellular Region of HER3 Reveals an Interdomain Tether (2002)

We have determined the 2.6 angstrom crystal structure of the entire extracellular region of human HER3 (ErbB3), a member of the epidermal growth factor receptor (EGFR) family. The structure consists of four domains with structural homology to domains found in the type I insulin-like growth factor receptor. The HER3 structure reveals a contact between domains II and IV that constrains the relative orientations of ligand-binding domains and provides a structural basis for understanding both multiple-affinity forms of EGFRs and conformational changes induced in the receptor by ligand binding during signaling. These results also suggest new therapeutic approaches to modulating the behavior of members of the EGFR family.
The Neuropeptide Y Y5 Receptor Mediates the Blockade of “Photic-Like” NMDA-Induced Phase Shifts in the Golden Hamster (2001)

Circadian or daily rhythms generated from the mammalian suprachiasmatic nuclei (SCN) of the hypothalamus can be synchronized by light and nonphotic stimuli. Whereas glutamate mediates photic information, nonphotic information can in some cases be mediated by neuropeptide Y (NPY) or serotonin. NPY or serotonin can reduce the phase-resetting effect of light or glutamate; however, the mechanisms and level of interaction of these two kinds of stimuli are unknown. Here we investigate the effect of NPY on the NMDA-induced phase shift of the hamster SCN circadian neural activity rhythm by means of single-unit recording techniques. NMDA (10-100 microm) applied in the early subjective night induced phase delays in the time of peak firing, whereas doses in the millimolar range disrupted firing patterns. The NMDA-induced phase delay was blocked by coapplication of NPY (0.02-200 microm). NPY Y1/Y5 and Y5 receptor agonists, but not the Y2 receptor agonist, blocked the NMDA-induced phase delay in a similar manner as NPY. The coapplication of a Y5 but not Y1 receptor antagonist eliminated NPY blockade of NMDA-induced phase delays, suggesting that the Y5 receptor is capable of mediating the inhibitory effect of NPY on photic responses. These results indicate that nonphotic and photic stimuli may interact at a level at or beyond NMDA receptor response and indicate that the Y5 receptor is involved in this interaction. Alteration of Y5 receptor function may therefore be expected to alter synchronization of circadian rhythms to light.
Reinforcement Learning Based Graph-to-Sequence Model for Natural Question Generation (2020)

Natural question generation (QG) aims to generate questions from a passage and an answer. Previous works on QG either (i) ignore the rich structure information hidden in text, (ii) solely rely on cross-entropy loss that leads to issues like exposure bias and inconsistency between train/test measurement, or (iii) fail to fully exploit the answer information. To address these limitations, in this paper, we propose a reinforcement learning (RL) based graph-to sequence (Graph2Seq) model for QG. Our model consists of a Graph2Seq generator with a novel Bidirectional Gated Graph Neural Network based encoder to embed the passage, and a hybrid evaluator with a mixed objective function that combines both the cross-entropy and RL loss to ensure the generation of syntactically and semantically valid text. We also introduce an effective Deep Alignment Network for incorporating the answer information into the passage at both the word and contextual level. Our model is end-to-end trainable and achieves new state-of-the-art scores, outperforming existing methods by a significant margin on the standard SQuAD benchmark for QG.
The role of glucagon on type 2 diabetes at a glance (2014)

The opposite effects of insulin and glucagon in fuel homeostasis, the paracrine/endocrine inhibitory effects of insulin on glucagon secretion and the hyperglucagonemia in the pathogenesis of type 2 diabetes (T2D) have long been recognized. Inappropriately increased alpha-cell function importantly contributes to hyperglycemia and reflects the loss of tonic restraint normally exerted by high local concentrations of insulin on alpha-cells, possibly as a result of beta-cell failure and alpha-cell insulin resistance, but additional mechanisms, such as the participation of incretin hormones in this response, have also been suggested. Three classes of drugs already available for clinical use address the abnormalities of glucagon secretion in T2D, namely, the GLP-1 receptor agonists (GLP-1RA), the inhibitors of dipeptidyl peptidase-4 (DPP-4i) and the amylin agonist pramlintide; it has been proposed that the glucagonostatic and insulinotropic effects of GLP-1RA equally contribute to their hypoglycemic efficacy. In this review, the control of glucagon secretion and its participation in T2D pathogenesis are summarized.