gebhart/patrepeval huggingface dataset:
Effective tumor immunotherapy directed against an oncogene-encoded product using a vaccinia virus vector. (1987)

We have constructed a vaccinia virus recombinant that expresses the extracellular domain of the rat neu oncogene-encoded protein, a 185-kDa transmembrane glycoprotein termed p185. Strain NFS mice immunized with this recombinant virus developed a strong antibody response against the neu oncogene product and were fully protected against subsequent tumor challenge with neu-transformed NIH 3T3 cells. No tumor immunoprotection was found when recombinant virus-immunized mice were challenged with Ha-ras-transformed NIH 3T3 cells. These data indicate that immunization with a single oncogene-encoded antigen can fully and specifically protect animals against tumor cells bearing this antigen.
Identification of mixed HIV-1/HIV-2 infections in Brazil by polymerase chain reaction (1991)

Analysis of sera from hospitalized Brazilian patients by whole-virus lysate-based enzyme immunoassay and Western blot indicated that 0.4% were reactive to HIV-2 alone while 4% were reactive to both HIV-1 and HIV-2. When these sera were tested for HIV antibody by type-specific peptide enzyme immunoassays, dual seropositivity was confirmed in only 0.4% of patients. To define genetically the HIV strains within the population, we analyzed peripheral blood mononuclear cells from selected seropositive patients for the presence of HIV-1 and HIV-2 proviral DNA using the polymerase chain reaction (PCR). Independent primers/probes sets were used for the amplification and detection of viral sequences from the long terminal repeat (LTR), gag, and protease (prt) gene regions. Our findings confirmed the serologic evidence of HIV-2 in Brazil and determined the extent of mixed HIV-1 and HIV-2 infections. Detailed evaluation of the amplified viral protease sequences by endonuclease restriction analysis and DNA sequencing independently confirmed mixed HIV-1 and HIV-2 infections in the two patients seropositive for HIV-1 and HIV-2. The data further indicated that these isolates are distinct from the HIV laboratory standards. We interpret the combination of culture and PCR findings to demonstrate the presence of both HIV-1 and HIV-2 in Brazil.
Development of a complete human anti‐human transferrin receptor C antibody as a novel marker of oral dysplasia and oral cancer (2014)

Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide. Up to 20% of oral dysplasia cases have been suggested to undergo malignant transformation to OSCC; however, there are no methods to predict OSCC development. In this study, to identify the genes associated with oral dysplasia progression, we performed genomic copy number analyses of genomic DNA samples isolated from primary oral dysplasia and OSCC via the microdissection method and found elevated expression of transferrin receptor C (TfR1/TFRC) with genomic amplification in oral dysplasia and OSCC. The expression rate of TFRC in OSCC was significantly higher than that in dysplasia, suggesting that OSCC disease progression might be related to TFRC expression. Additionally, we investigated the in vitro and in vivo impacts of a newly established anti-human TFRC monoclonal antibody, which was isolated from a human cDNA library using the phage-display method, on cell proliferation and survival. The anti-TFRC antibody blocked the interaction between transferrin and TFRC and consequently inhibited iron uptake, leading to the iron deprivation-mediated suppression of cell growth and induction of apoptosis. Moreover, we demonstrated that the anti-TFRC antibody efficiently inhibited tumor growth in a murine xenograft OSCC model. Therefore, we suggest our developed complete human anti-human TFRC antibody as a useful, novel treatment for oral dysplasia and OSCC.
Phase Transformation and Microstructural Changes during Ageing Process of an Ag-Pd-Cu-Au Alloy (2007)

Abstract Age-hardening behaviour and the related phase transformation and microstructural changes during isothermal ageing process were studied to elucidate the age-hardening mechanism of an Ag-based dental casting alloy composed of Ag–Pd–Cu–Au–Zn, Ir and In by means of hardness test, X-ray diffraction (XRD), scanning electron microscopic (SEM) observations and energy dispersive spectroscopic microanalysis (EDS). In the hardness test at 350 and 400 °C, the hardness of the solution-treated specimen began to increase and reached a maximum value with increasing ageing time, and subsequently the hardness decreased gradually. By considering XRD results and SEM observations together, the solution-treated specimen consisted of three phases, the Ag-rich α1 phase as a matrix, the Cu–Pd α2 phase and the CuPd β phase with a CsCl-type as particle-like structures. By ageing the solution-treated specimen, the Ag-rich α1 and Cu–Pd α2 phases were transformed into the Ag-rich α ′ 1 and Cu3Pd α ′ 2 phases, respectively. The CuPd β phase with a CsCl-type was not changed apparently during the ageing process. From the results of the hardness test, XRD study, SEM observations and EDS analysis, it could be derived that the hardness increased by the diffusion and precipitation of the Cu-rich phase from the Ag-rich matrix during the early stage of phase transformation of α1 into α ′ 1 and that the progress of coarsening of the Cu-rich precipitates with an entanglement structure caused the hardness decrease during the later stage of phase transformation of α1 into α ′ 1 . The particle-like structures composed of the Cu–Pd α2 and the CuPd β phase with a CsCl-type contributed little to the hardness increase which occurred in the early stage of aging process.
MPTP Toxicity: Implications for Research in Parkinson's Disease (1988)

In summary, the parkinsonism induced by MPTP in man closely resembles time-telescoped Parkinson's disease. Parkinsonian symptoms can be duplicated in all aspects under controlled conditions in subhuman primates; the biochemical changes are replicated in mice, dogs, and to varying degrees in other species. Mechanisms of bioactivation by MAO-B of MPTP to MPP+, concentration of MPP+ in neurons with a catecholamine uptake system, and vulnerability to cellular toxic effects of MPP+ are the basis for the specificity of MPTP targeting of nigrostriatal dopaminergic neurons. It is hoped that an understanding of the mechanism of species specificity and cellular toxicity will in time explain the pathogenesis of idiopathic Parkinson's disease and suggest new opportunities for effective therapy.
Synergic interaction between ascorbic acid and antibiotics against Pseudomonas aeruginosa (2005)

Studies were carried out on in vitro combination of ascorbic acid (AA) with six antibiotics against 12 multi-resistant Pseudomonas aeruginosa isolates. Synergic activity was detected with AA chloramphenicol, kanamycin, streptomycin and tetracycline. Indifference was observed to any antibiotics and antagonism only for chloramphenicol. Results indicated that multiresistant P. aeruginosa was affected by combination of AA and antibiotics. Future research on ascorbic acid-antimicrobial interactions may find new methods to control strains of multiresistant P. aeruginosa.
An implementation of GEM (1984)

This paper presents a simple approach for extending the relational system INGRES into one supporting a semantic data model it describe a DBMS consisting of (i) a user-friendly front-end, supporting the GEM semantic data model and query language under the UNIX time-sharing system, and (ii) a dedicated back-end processor providing efficient support for database transactions, concurrency control and recovery GEM extends the relational model to support the notions of entities with surrogates, the relationships of aggregation and generalization, null values and set-valued attributes, and provides simple extensions of QUEL to handle these new constructs in this proposed implementation of GEM, the relational database processor IDM 500 by Britton-Lee is used as the back-end machine
Effective Enhancement of Short-Chain-Length−Medium-Chain-Length Polyhydroxyalkanoate Copolymer Production by Coexpression of Genetically Engineered 3-Ketoacyl-Acyl-Carrier-Protein Synthase III (fabH) and Polyhydroxyalkanoate Synthesis Genes (2004)

Polyhydroxyalkanoates (PHAs) are biodegradable polyesters that have a wide variety of physical properties dependent on the lengths of the pendant groups of the monomer units in the polymer. PHAs composed of mostly short-chain-length (SCL) monomers are often stiff and brittle, whereas PHAs composed of mostly medium-chain-length (MCL) monomers are elastomeric in nature. SCL-MCL PHA copolymers can have properties between the two states, dependent on the ratio of SCL and MCL monomers in the copolymer. It is desirable to elucidate new and low cost ways to produce PHA composed of mostly SCL monomer units with a small mol % of MCL monomers from renewable resources, since this type of SCL-MCL PHA copolymer has superior qualities compared to SCL homopolymer. To address this issue, we have created strains of recombinant E. coli capable of producing beta-ketothiolase (PhbA) and acetoacetyl-CoA synthase (PhbB) from Ralstonia eutropha, genetically engineered 3-ketoacyl-ACP synthase III (FabH) from Escherichia coli, and genetically engineered PHA synthases (PhaC) from Pseudomonas sp. 61-3 to enhance the production of SCL-MCL PHA copolymers from glucose. The cumulative effect of having two monomer-supplying pathways and genetically engineered PHA synthases resulted in higher accumulated amounts of SCL-MCL PHA copolymer from glucose. Polymers were isolated from two recombinant E. coli strains, the first harboring the phbAB, fabH(F87T), and phaC1(SCQM) genes and the second harboring the phbAB, fabH(F87W), and phaC1(SCQM) genes. The thermal and physical properties of the isolated polymers were characterized. It was found that even a very low mol % of MCL monomer in a SCL-MCL PHA copolymer had dramatic effects on the thermal properties of the copolymers.
Artificial combination of two cis-regulatory elements generates a unique pattern of expression in transgenic plants. (1987)

We show that a 36-base-pair-long upstream fragment from the soybean hsp17.3-B gene comprising two partly overlapping heat-shock element (HSE)-like sequences can confer heat inducibility to a reporter gene in transgenic tobacco. The heat-shock response does not display organ specificity and is not affected by light. Insertion of these HSE-like elements into the pea rbcS-3A 5' flanking fragment (position -410 to +15) either at position -410 (5' to the enhancer) or at position -49 (between the enhancer and the "TATA" box) renders the transcript level of the reporter gene light-inducible and organ-specific under heat-shock conditions. These results demonstrate the possibility of generating a unique pattern of expression (e.g., light-dependent and organ-specific heat-shock response) by artificial combination of appropriate cis-acting regulatory elements. Moreover, by using the HSE-like sequences as a weak heat-inducible enhancer in the chimeric regulatory regions we uncover the function of negative elements within the pea rbcS-3A upstream region. These negative elements are responsible for a repressed transcript level in roots as well as in dark-adapted leaves. Therefore, the upstream fragment containing two HSE-like elements can be considered a useful tool to test the function of other cis-acting elements.
The Chemistry of 1,2,4-Triazoles. (1961)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Chemistry of 1,2,4-Triazoles.K. T. PottsCite this: Chem. Rev. 1961, 61, 2, 87–127Publication Date (Print):April 1, 1961Publication History Published online1 May 2002Published inissue 1 April 1961https://pubs.acs.org/doi/10.1021/cr60210a001https://doi.org/10.1021/cr60210a001research-articleACS PublicationsRequest reuse permissionsArticle Views6766Altmetric-Citations314LEARN 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
Establishment of Gastrointestinal Epithelial Organoids (2013)

The intestinal epithelium constitutes a system of constant and rapid renewal triggered by proliferation of intestinal stem cells (ISCs), and is an ideal system for studying cell proliferation, migration, and differentiation. Primary cell cultures have proven to be promising for unraveling the mechanisms involved in epithelium homeostasis. In 2009, Sato et al. established a long-term primary culture to generate epithelial organoids (enteroids) with crypt- and villus-like epithelial domains representing the complete census of progenitors and differentiated cells. Similarly, isolated ISCs expressing Lgr5 (leucine-rich repeat-containing G protein-coupled receptor) can generate enteroids. Here, we describe methods to establish gastric, small intestinal, and colonic epithelial organoids and generate Lgr5(+ve) single cell-derived epithelial organoids. We also describe the imaging techniques used to characterize those organoids. This in vitro model constitutes a powerful tool for studying stem cell biology and intestinal epithelial cell physiology throughout the digestive tract. Curr. Protoc. Mouse Biol. 3:217-240 © 2013 by John Wiley & Sons, Inc.
Mode of action of SDZ NIM 811, a nonimmunosuppressive cyclosporin A analog with activity against human immunodeficiency virus (HIV) type 1: interference with HIV protein-cyclophilin A interactions (1995)

Cyclosporins, in particular the nonimmunosuppressive derivative SDZ NIM 811, exhibit potent anti-human immunodeficiency virus type 1 (HIV-1) activity in vitro. SDZ NIM 811 interferes at two stages of the viral replication cycle: (i) translocation of the preintegration complex to the nucleus and (ii) production of infectious virus particles. Immunosuppressive activity is not correlated with anti-HIV-1 activity of cyclosporins. However, binding to cyclophilin A, the major cellular receptor protein of cyclosporins, is a prerequisite for HIV inhibition: all structural changes of the cyclosporin A molecule leading to loss of affinity to cyclophilin abolished the antiviral effect. Cyclosporin derivatives did not interact directly with HIV-1 proteins; cyclophilin was the only detectable receptor protein for antivirally active cyclosporins. There is no evidence that inhibition of HIV occurs via a gain of function of cyclophilin in the presence of cyclosporins: the complex of cyclophilin A with SDZ NIM 811 does not bind to calcineurin or to any other viral or cellular proteins under conditions in which calcineurin binding to the cyclophilin A-cyclosporin A complex is easily detectable. Thus, the loss of function caused by binding of cyclosporins to cyclophilin seems to be sufficient for the anti-HIV effect. Cyclophilin A was demonstrated to bind to HIV-1 p24gag, and the formation of complexes was blocked by cyclosporins with 50% inhibitory concentrations of about 0.7 microM. HIV-2 and simian immunodeficiency virus are only weakly or not at all inhibited by cyclosporins. For gag-encoded proteins derived from HIV-1, HIV-2, or simian immunodeficiency virus particles, cyclophilin-binding capacity correlated with sensitivity of the viruses to inhibition by cyclosporins. Cyclophilin A also binds to HIV-1 proteins other than gag-encoded proteins, namely, p17gag, Nef, Vif, and gp120env; the biological significance of these interactions is questionable. We conclude that HIV-1 Gag-cyclophilin A interaction may be essential in HIV-1 replication, and interference with this interaction may be the molecular basis for the antiviral activity of cyclosporins.
Effects of Endurance Training on the Breathing Pattern of Professional Cyclists. (2001)

The aim of this longitudinal study was to clarify the changes induced by endurance training on the breathing pattern of 13 professional cyclists (age+/-SD: 24+/-2 years; VO(2 max) approximately 75 ml x kg(-1) x min(-1)) during the three periods (rest, precompetition, and competition) of a sports season. Both the volume and the intensity of training were quantified during these periods. In each session (corresponding to each of the three periods) all subjects performed (1) a pulmonary function test (to measure forced vital capacity [FVC], peak expiratory flow [PEF], and maximal voluntary ventilation [MVV]), and (2) a ramp test until exhaustion on a cycle ergometer (workload increases of 25 W x min(-1)). The following variables were recorded every 100 W until the end of the tests: pulmonary ventilation (VE, in l x min(-1) BTPS), tidal volume (VT, inl BTPS), breathing frequency (f(b), in breaths x min(-1)), ventilatory equivalents for oxygen (VE x VO(2)(-1)) and carbon dioxide (VE x VCO(2)(-1)), inspiratory (TI) and expiratory (TE) times (s), ratio of TI to total respiratory duration or inspiratory "duty cycle" (TI/TTOT, and mean inspiratory flow rate (VT)/TI), in l x s(-1)). The results showed no changes in any of these variables (p>0.05) between the three periods of study, despite significant changes in training loads (i.e., increases in the volume and/or intensity of training throughout the season). These findings suggest that endurance conditioning does not alter the breathing pattern of professional cyclists during an incremental exercise test.
Direct On-Wafer Non-Invasive Thermal Monitoring of AlGaN/GaN Power HFETs Under Microwave Large Signal Conditions (2005)

For the first time, we report direct on-wafer noninvasive temperature distribution measurements of AlGaN/GaN HFETs grown on Si substrates under microwave large-signal conditions. An infrared camera and a load-pull measurement system coupled to a probe station enable us to produce surface temperature maps with micronic resolution. Results include the impact of the RF drive, differences between RF and DC drive, as well as impact of reduced power added efficiency on the surface temperature of the device.
Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy (2017)

In patients with SMA1, a single intravenous infusion of adeno-associated viral vector containing DNA coding for SMN resulted in longer survival, superior achievement of motor milestones, and better motor function than in historical cohorts. Further studies are necessary to confirm the safety and efficacy of this gene therapy. (Funded by AveXis and others; ClinicalTrials.gov number, NCT02122952 .).
Immunosuppressive role of semaphorin‐3A on T cell proliferation is mediated by inhibition of actin cytoskeleton reorganization (2006)

Timely negative regulation of the immune system is critical to allow it to perform its duty while maintaining it under tight control to avoid overactivation. We previously reported that the neuronal receptor neuropilin-1 (NP-1) is expressed in human lymph nodes. However, the role of NP-1 interaction with its physiological ligand semaphorin-3A (Sema-3A) on immune cells remains elusive. Here we show that Sema-3A is expressed by activated DC and T cells, and that its secretion in DC/T cell cocultures is delayed. Sema-3A/NP-1 interaction down-modulated T cell activation since addition of Sema-3A in DC/T cell cocultures dramatically inhibited allogeneic T cell proliferation. More importantly, neutralization by blocking antibodies or by antagonist peptide of endogenous Sema-3A produced by DC/T cell cocultures resulted in a 130% increase in T cell proliferation. Sema-3A acted directly on T cells, since it could block anti-CD3/CD28-stimulated proliferation of T cells. Finally, immunomodulatory functions of Sema-3A relied on the blockage of actin cytoskeleton reorganization, affecting TCR polarization and interfering with early TCR signal transduction events such as ZAP-70 or focal adhesion kinase phosphorylation. Therefore, we propose that Sema-3A secretion and the resulting NP-1/Sema-3A interaction are involved in a late negative feedback loop controlling DC-induced T cell proliferation.
Lipid levels are associated with a regulatory polymorphism of the monoamine oxidase-A gene promoter (MAOA-uVNTR). (2008)

The present findings suggest that MAOA-uVNTR may influence lipid levels and individuals with less active alleles are at increased health risk.
Frequent Intrapatient Recombination between Human Immunodeficiency Virus Type 1 R5 and X4 Envelopes: Implications for Coreceptor Switch (2007)

Emergence of human immunodeficiency virus type 1 (HIV-1) populations that switch or broaden coreceptor usage from CCR5 to CXCR4 is intimately coupled to CD4+ cell depletion and disease progression toward AIDS. To better understand the molecular mechanisms involved in the coreceptor switch, we determined the nucleotide sequences of 253 V1 to V3 env clones from 27 sequential HIV-1 subtype B isolates from four patients with virus populations that switch coreceptor usage. Coreceptor usage of clones from dualtropic R5X4 isolates was characterized experimentally. Sequence analysis revealed that 9% of the clones from CXCR4-using isolates had originated by recombination events between R5 and X4 viruses. The majority (73%) of the recombinants used CXCR4. Furthermore, coreceptor usage of the recombinants was determined by a small region of the envelope, including V3. This is the first report demonstrating that intrapatient recombination between viruses with distinct coreceptor usage occurs frequently. It has been proposed that X4 viruses are more easily suppressed by the immune system than R5 viruses. We hypothesize that recombination between circulating R5 viruses and X4 viruses can result in chimeric viruses with the potential to both evade the immune system and infect CXCR4-expressing cells. The broadening in cell tropism of the viral population to include CXCR4-expressing cells would gradually impair the immune system and eventually allow the X4 population to expand. In conclusion, intrapatient recombination between viruses with distinct coreceptor usage may contribute to the emergence of X4 viruses in later stages of infection.