gebhart/patrepeval huggingface dataset:
Blood CD33(+)HLA-DR(−) myeloid-derived suppressor cells are increased with age and a history of cancer (2013)

As we age, the composition of our peripheral leukocytes changes dramatically. Many of these alterations contribute to the general immune dysfunction that burdens the elderly, which in turn, contributes to increased susceptibility to disease. MDSCs represent a heterogeneous population of immunosuppressive leukocytes that are elevated in the peripheral blood of cancer patients. Given the relation between cancer incidence and age, this study examined the frequency of peripheral blood CD33(+)HLA-DR(-) MDSCs across three cohorts: healthy adults (19-59 years old), community-dwelling seniors (61-76 years old), and frail elderly (67-99 years old). This analysis is the first to demonstrate that MDSCs and specifically the CD11b(+)CD15(+) MDSC subset are increased with age. Proinflammatory cytokines that are required for the differentiation of MDSCs (e.g., TNF-α, IL-6, and IL-1β) were similarly found to be increased in the serum of the frail elderly. Furthermore, the proportion of MDSCs and the CD11b(+)CD15(+) subset were found to be elevated significantly in elderly donors with a history of cancer. This age-related elevation in the frequency of MDSCs may contribute to the increased cancer incidence that occurs with age. Further investigation into the functional consequences of elevated MDSCs will provide valuable insight into the progression of age-related pathologies.
Trends in multimedia applications and the network models to support them (2002)

Leading corporations and federal agencies are beginning to recognize the great potential of multimedia applications. IBM and Apple have announced major commitments to develop equipment and software for multimedia applications. Current trends in multimedia applications are examined. A summary of the network implications in view of broadband ISDN (B-ISDN) is included. Multimedia database systems; audio, video, and graphics multimedia mail; teleconferencing; video extension to the X window (VEX); and an audio server under development at Olivetti Research Center (VOX) are outlined. Handling multimedia requests, distributed computing and shared resources, media conversion, and issues of network design are discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Deletion of Interleukin-6 in Mice With the Dominant Negative Form of Transforming Growth Factor β Receptor II Improves Colitis but Exacerbates Autoimmune Cholangitis (2010)

The data from these observations emphasize that there are distinct mechanisms involved in inducing pathology in inflammatory bowel disease compared to autoimmune cholangitis. These data also suggest that patients with inflammatory bowel disease may not be the best candidates for treatment with anti-IL-6R if they have accompanying autoimmune liver disease and emphasize caution for therapeutic use of anti-IL-6R antibody.
24-Hour Urine Composition of Sri Lankan Adults and Their Response to 100 mg Dihydrochlorothiazide (1980)

In the present study, 205 'normal hospitalised subjects' in the age group 16-60 years were included in a clinical trial to estimate the 24-hour urinary composition. Their response to 100 mg dihydrochlorothiazide was also determined. The study revealed that there is a marked difference in the 24-hour urine volume and composition between that observed in the present study and that presented in the modern literature; 100 mg dihydrochlorothiazide was found to produce a significant diuretic and natriuretic effect in normal Sri Lankan adults. There is a very high correlation between the volume of urine and the cations in the basal excretion as well as with the standard diuretic. The coefficient of regression of volume on cations in the basal excretion was found to be less than that with the standard diuretic.
Proteomic investigation of 5‐fluorouracil resistance in a human hepatocellular carcinoma cell line (2011)

Multi-drug resistance (MDR) is a major obstacle towards a successful treatment of hepatocellular carcinoma (HCC). The mechanisms of MDR are intricate and have not been fully understood. Therefore, we employed a cell-line model consisting of the 5-fluorouracil (5-FU) resistant BEL7402/5-FU cell line and its parental BEL7402 cell line. Using relative and absolute quantification (iTRAQ)-coupled 2D LC-MS/MS, a successfully exploited high-throughput proteomic technology, in total, 660 unique proteins were identified and 52 proteins showed to be differentially expressed in BEL7402/5-FU compared with BEL7402. Several differentially expressed proteins were further validated by Western blot and real-time quantitative RT-PCR analysis. Furthermore, the association of MDR with ANXA3, one of the highly expressed proteins in BEL7402/5-FU, was verified. Our study represents the first successful application of iTRAQ technology for MDR mechanisms analysis in HCC. Many of the differentially expressed proteins identified had not been linked to MDR in HCC before, which provide valuable information for further understanding of MDR.
Heat Stress (2012)

Abstract This chapter's goal is to provide useful information about the way people respond to acute and chronic heat stress and heat strain, the man's physiological response to heat stress. The chapter provides detailed information about the physiological aspects of heat stress. It also presents some groundwork about biological control systems, how heat is produced and stored in the body, and how it is exchanged with the environment. This background is necessary to understand the many complex and interactive phenomena associated with heat stress and with the challenges of heat strain. It is important to recognize the uniqueness of heat as a form of energy to understand issues of heat stress and strain and to see its special role in human welfare. No other potentially endangering energy, for example, is produced by the body itself, none other is so essential for life, and none other is the thermodynamic destiny in entropy for all other forms of energy.
Inhibition of human colon cancer malignant cell behavior and growth by antisense epidermal growth factor receptor expression vector. (1998)

Human colon cancer cells utilize the epidermal growth factor (EGF) family of growth factors and the receptor for these growth factors (EGFR) in sustaining their malignant phenotype. Disrupting EGFR expression by expressing antisense EGFR RNA (through transfection with an appropriate antisense EGFR expression vector under metallothionein promoter control) downregulated the malignant behavior of human colon cancer Moser cells and blocked the ability of exogenous EGF in stimulating malignant cell behavior. The antiproliferative effect of antisense EGFR expression vector was determined in three human colon cancer cell lines (Moser, HCT116 and HT29 possessing different biological properties and rate of proliferation) in an in vitro therapeutic setting using an antisense EGFR expression vector under the control of a viral promoter. Different degree of inhibition was achieved for each cell line after one dose of antisense treatment. The differences in the antiproliferative effect observed may be due to differences in the rate of proliferation and/or recovery from antisense effect, and the differences in transfection efficiency among the cell lines.
Fiber-optic organic vapor sensor (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFiber-optic organic vapor sensorSteven M. Barnard and David R. WaltCite this: Environ. Sci. Technol. 1991, 25, 7, 1301–1304Publication Date (Print):July 1, 1991Publication History Published online1 May 2002Published inissue 1 July 1991https://doi.org/10.1021/es00019a012Request reuse permissionsArticle Views299Altmetric-Citations50LEARN 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 InReddit PDF (1 MB) Get e-Alertsclose Get e-Alerts
Vitamin A deficient mice exhibit increased viral antigens and enhanced cytokine/chemokine production in nasal tissues following respiratory virus infection despite the presence of FoxP3 + T cells (2015)

The World Health Organization (WHO) estimates that 250 million children under the age of five suffer from vitamin A deficiencies (VAD). Individuals with VAD experience higher rates of mortality and increased morbidity during enteric and respiratory infections compared with those who are vitamin A sufficient. Previously, our laboratory has demonstrated that VAD mice have significantly impaired virus-specific IgA and CD8(+) T-cell responses in the airways. Here, we demonstrate that VAD mice experience enhanced cytokine/chemokine gene expression and release in the respiratory tract 10 days following virus infection compared with control vitamin A sufficient animals. Cytokines/chemokines that are reproducibly up-regulated at the gene expression and protein levels include IFNγ and IL-6. Despite previous indications that cytokine dysregulation in VAD animals might reflect low forkhead box P3 (FoxP3)-positive regulatory T-cell frequencies, we found no reduction in FoxP3(+) T cells in VAD respiratory tissues. As an alternative explanation for the high cytokine levels, we found that the extent of virus infection and the persistence of viral antigens were increased on day 10 post-infection in VAD animals compared with controls, and consequently that respiratory tract tissues had an increased potential to activate virus-specific T cells. Results encourage cautious management of viral infections in patients with VAD, as efforts to enhance FoxP3(+) T cell frequencies and quell immune effectors could potentially exacerbate disease if the virus has not been cleared.
Assessment of amyloid beta-protein precursor gene mutations in a large set of familial and sporadic Alzheimer disease cases. (1992)

A genetic locus associated with familial Alzheimer disease (FAD) and a candidate gene, APP, encoding the amyloid protein precursor have both been assigned previously to chromosome 21, and, in a few FAD families, mutations of APP have been detected. However, obligate crossovers between APP and FAD have also been reported in several FAD pedigrees, including FAD4, a large kindred showing highly suggestive evidence for linkage of the disorder to chromosome 21. In case the apparent APP crossover in FAD4 actually represented an intragenic recombination event or segregation of different mutations in different family branches, we have performed a more detailed assessment of APP as a candidate gene in this family. The entire coding region of the APP gene was sequenced for FAD4 and for FAD1, a second large kindred. No mutations were found, indicating that, in at least one chromosome 21-linked FAD pedigree, the gene defect is not accounted for by a mutation in the known coding region of the APP gene. A total of 25 well-characterized early- and late-onset FAD pedigrees were typed for genetic linkage to APP, to assess the percentage of FAD families predicted to carry mutations in the APP gene. None of the FAD families yielded positive lod scores at a recombination fraction of 0.0. To estimate the overall prevalence of FAD-associated mutations in the beta A4 domain of APP, we sequenced exons 16 and 17 in 30 (20 early- and 10 late-onset) FAD kindreds and in 11 sporadic AD cases, and we screened 56 FAD kindreds and 81 cases of sporadic AD for the presence of the originally reported FAD-associated mutation, APP717 Val----Ile (by BclI digestion). No APP gene mutations were found in any of the FAD families or sporadic-AD samples examined in this study, suggesting that the mutations in exons 16 and 17 are a rare cause of FAD. Overall, these data suggest that APP gene mutations account for a very small portion of FAD.
Regioselective Synthesis of 1,2-Dihydropyridines by Rhodium-Catalyzed Hydroboration of Pyridines (2012)

Pyridine undergoes addition of pinacolborane at 50 °C in the presence of a rhodium catalyst, giving N-boryl-1,2-dihydropyridine in a high yield. The selective 1,2-hydroboration also takes place in the reactions of substituted pyridines. In the reaction of 3-substituted pyridines, 3-substituted N-boryl-1,2-dihydropyridines are formed regioselectively.
Novel Protein Kinase C .DELTA. Isoform Insensitive to Caspase-3. (2001)

Protein kinase C delta (PKC delta) plays a key regulatory role in a variety of cellular functions, including apoptosis, as well as cell growth and differentiation. We previously reported that apoptosis was induced by pretreatment with 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), an inhibitor of PKC, in mouse thymocytes. In the present study, we showed that a novel PKC delta isoform (PKC deltaII) was transiently expressed when thymocytes were pretreated with H-7. The analysis of the cDNA encoding PKC deltaII indicated that a 78 bp fragment was inserted into the caspase-3 sensitive site of the original PKC delta (PKC deltaI), presumably by alternative splicing. The PKC deltaII expressed in COS-1 cells was one product with a molecular mass of 81 kDa and with kinase activity similar to that of PKC deltaI. The expressed PKC deltaI protein (78 kDa) was in part cleaved into a 38 kDa fragment in vivo and in vitro, but the PKC deltaII protein was not. Cleavage of the PKC deltaI protein was inhibited by a specific inhibitor of caspase-3, indicating that PKC deltaII is insensitive to caspase-3. The PKC deltaII was highly expressed in the testis and ovary, and at a lower level in the thymocytes, brain and kidney, whereas PKC deltaI was detected in most tissues, suggesting that the function of PKC deltaII is different from that of PKC deltaI.
Mutation Analysis of Oculopharyngeal Muscular Dystrophy in Hispanic American Families (1999)

These results support and extend our study of haplotype analysis and suggest that a founder effect may have occurred for OPMD in this Hispanic American population.
Sequential effects of interleukin 2-diphtheria toxin fusion protein on T-cell activation. (1989)

The interleukin 2-diphtheria toxin-related fusion protein (IL-2-toxin) rapidly inhibits protein synthesis in IL-2 receptor (IL-2R)-bearing phytohemagglutinin-activated T cells but transiently stimulates DNA synthesis. At 7 hr after interaction with IL-2R+ phytohemagglutinin-activated T cells, IL-2-toxin-treated cells bear augmented steady-state levels of c-myc, interferon gamma, and IL-2R mRNA; these effects are indistinguishable from those produced by recombinant IL-2. Amplification of IL-2 sequences by the polymerase chain reaction reveals an increased level of IL-2 mRNA in cell cultures treated with recombinant IL-2, IL-2-toxin, and cycloheximide. These results suggest that IL-2-toxin can affect de novo IL-2 gene transcription/mRNA stabilization through independent mechanisms exerted by both the IL-2R binding domain and ADP-ribosyltransferase activity of the fusion protein. After 20 hr of culture, IL-2R mRNA was markedly decreased in both IL-2-toxin- and cycloheximide-treated phytohemagglutinin-activated T cells. Although interaction of IL-2-toxin with IL-2R+ T cells initially mimics the stimulatory effects of IL-2 upon c-myc, interferon gamma, IL-2R, and IL-2 gene expression, the consequences of inhibition of protein synthesis mediated by the ADP-ribosyltransferase activity of the toxin dominate after 7 hr and are indistinguishable from those effects mediated by cycloheximide.
Sertoli cell synthesizes and secretes a protease inhibitor, .alpha.2-macroglobulin (1990)

The mechanism by which the seminiferous epithelium limits the damaging effects of proteases that are released from degenerating late spermatids does not depend upon protease inhibitors in the systemic circulation since these proteins are excluded from the seminiferous tubule by the blood-testis barrier. The purpose of this study was to identify the major protease inhibitor of the testis and determine its cellular origin. Sertoli cells, the major epithelial component of the seminiferous epithelium, release a protease inhibitor, testicular alpha 2-macroglobulin, in vitro. Immunoprecipitation using [35S]methionine and a monospecific polyclonal antibody prepared against purified testicular alpha 2-macroglobulin establishes that this protein is actively synthesized and secreted by Sertoli cells. Measurements of immunoreactive protease inhibitors in tubular and rete testis fluids collected by micropuncture suggest that alpha 2-macroglobulin rather than alpha 1-antitrypsin is the major protease inhibitor in the seminiferous tubules in vivo. The ability of alpha 2-macroglobulin to inactivate proteases and growth factors such as TGF-beta by a common mechanism suggests that this protein may have a dual function in the testis.
Structural mechanism of high affinity FcγRI recognition of immunoglobulin G (2015)

Antibody-based immunotherapies are becoming powerful means of modern medicine for treating cancers and autoimmune diseases. The increasing popularity of antibody-based treatment demands a better understanding of antibody functions and in particular, their interaction with Fc receptors as effectiveness of antibodies often depends on their ability to activate or avoid effector cell functions through Fc receptors. Until recently, our understanding of antibody recognition by Fc receptors is based on the structures of low affinity Fc receptor in complex with Fc. These structural studies provided significant insights to our understanding of how an IgG antibody generally docks on Fcγ receptor and the requirement of immune complex formation for effector cell activations. They are less informative, however, to the molecular forces underlying the vast different affinities between antibodies and their Fcγ receptors. Recently, the structure of the high affinity FcγRI in complex with IgG-Fc has been determined. This review will focus on the knowledge learned from the high affinity complex structural work and a potential receptor-glycan interaction as an important contribution to the receptor affinity.
Nonphosphorylatable substrate analogs selectively block autophosphorylation and activation of the insulin receptor, epidermal growth factor receptor, and pp60 kinases (1989)

The receptors for insulin and epidermal growth factor undergo tyrosine autophosphorylation in response to ligand stimulation, while pp60v-src is an unregulated tyrosine kinase. In this report we show that each of the kinases phosphorylates an exogenous peptide that corresponds to the insulin proreceptor sequence 1142-1153. When the kinases were pre-phosphorylated, saturable Michaelis-Menten kinetics were observed. However, when the kinases had not been pre-phosphorylated biphasic kinetics were observed; at progressively higher substrate concentrations (greater than Km) less substrate phosphorylation was seen. Furthermore, when the kinases had not been pre-phosphorylated kinase autophosphorylation was inhibited at high substrate concentrations. On this basis we postulated that the substrate inhibition of substrate phosphorylation resulted directly from substrate inhibition of kinase autophosphorylation. To test this we designed additional peptides to function specifically as inhibitors of the kinases. Each of the 3 tyrosine residues within the substrate sequence were replaced either by 4-methoxyphenylalanine or phenylalanine, residues structurally similar to tyrosine but unable to accept phosphoryl transfer. Both analogs inhibited insulin and epidermal growth factor receptor autophosphorylation, whereas only the Phe-substituted analog inhibited pp60v-src phosphorylation. These data suggest that autophosphorylation of tyrosine residues near the kinase active site is a generalized mechanism for tyrosine kinase activation and that activation can be selectively blocked by substrates and nonphosphorylatable analogs.
Localized surface antigens of guinea pig sperm migrate to new regions prior to fertilization. (1984)

We have previously defined distinct localizations of antigens on the surface of the guinea pig sperm using monoclonal antibodies. In the present study we have demonstrated that these antigen localizations are dynamic and can be altered during changes in the functional state of the sperm. Before the sperm is capable of fertilizing the egg, it must undergo capacitation and an exocytic event, the acrosome reaction. Prior to capacitation, the antigen recognized by the monoclonal antibody, PT-1, was restricted to the posterior tail region (principle piece and end piece). After incubation in capacitating media at 37 degrees C for 1 h, 100% of the sperm population showed migration of the PT-1 antigen onto the anterior tail. This redistribution of surface antigen resulted from a migration of the surface molecules originally present on the posterior tail. It did not occur in the presence of metabolic poisons or when tail-beating was prevented. It was temperature-dependent, and did not require exogenous Ca2+. Since the PT-1 antigen is freely diffusing on the posterior tail before migration, the mechanism of redistribution could involve the alteration of a presumptive membrane barrier. In addition, we observed the redistribution of a second surface antigen after the acrosome reaction. The antigen recognized by the monoclonal antibody, PH-20, was localized exclusively in the posterior head region of acrosome-intact sperm. Within 7-10 min of induction of the acrosome reaction with Ca2+ and A23187, 90-100% of the acrosome-reacted sperm population no longer demonstrated binding of the PH-20 antibody on the posterior head, but showed binding instead on the inner acrosomal membrane. This redistribution of the PH-20 antigen also resulted from the migration of pre-existing surface molecules, but did not appear to require energy. The migration of PH-20 antigen was a selective process; other antigens localized to the posterior head region did not leave the posterior head after the acrosome reaction. These rearrangements of cell surface molecules may act to regulate cell surface function during fertilization.
DNA sequence analysis: a general, simple and rapid method for sequencing large oligodeoxyribonucleotide fragments by mapping (1974)

Several electrophoretic and chromatographic systems have been investigated and compared for sequence analysis of oligodeoxyribonucleotides. Three systems were found to be useful for the separation of a series of sequential degradation products resulting from a labeled oligonucleotide: (I) 2-D electrophoresisdagger; (II) 2-D PEI-cellulose; and (III) 2-D homochromatography. System (III) proved generally most informative regardless of base composition and sequence. Furthermore, only in this system will the omission of an oligonucleotide in a series of oligonucleotides be self-evident from the two-dimensional map. The sequence of up to fifteen nucleotides can be determined solely by the characteristic mobility shifts of its sequential degradation products distributed on the two-dimensional map. With this method, ten nucleotides from the double-stranded region adjacent to the left-hand 3'-terminus and seven from the right-hand 3'-terminus of bacteriophage lambda DNA have been sequenced. Similarly, nine nucleotides from the double-stranded region adjacent to the left-hand 3'-terminus and five nucleotides from the right-hand terminus of bacteriophage phi80 DNA have also been sequenced. The advantages and disadvantages of each separation system with respect to sequence analysis are discussed.