gebhart/patrepeval huggingface dataset:
Safety and Enhanced Immunogenicity of a Hepatitis B Core ParticlePlasmodium falciparumMalaria Vaccine Formulated in Adjuvant Montanide ISA 720 in a Phase I Trial (2005)

Highly purified subunit vaccines require potent adjuvants in order to elicit optimal immune responses. In a previous phase I trial, an alum formulation of ICC-1132, a malaria vaccine candidate comprising hepatitis B core (HBc) virus-like particle containing Plasmodium falciparum circumsporozoite (CS) protein epitopes, was shown to elicit Plasmodium falciparum-specific antibody and cellular responses. The present study was designed as a single-blind, escalating-dose phase I trial to evaluate the safety and immunogenicity of single intramuscular doses of ICC-1132 formulated in the more potent water-in-oil adjuvant Montanide ISA 720 (ICC-1132/ISA 720). The vaccine was safe and well tolerated, with transient injection site pain as the most frequent complaint. All vaccinees that received either 20 mug or 50 mug of ICC-1132/ISA 720 developed antiimmunogen and anti-HBc antibodies. The majority of volunteers in these two groups developed sporozoite-specific antibodies, predominantly of opsonizing immunoglobulin G subtypes. Peak titers and persistence of parasite-specific antibody following a single injection of the ISA 720 formulated vaccine were comparable to those obtained following two to three immunizations with alum-adsorbed ICC-1132. Peripheral blood mononuclear cells of ICC-1132/ISA 720 vaccinees proliferated and released cytokines (interleukin 2 and gamma interferon) when stimulated with recombinant P. falciparum CS protein, and CS-specific CD4(+) T-cell lines were established from volunteers with high levels of antibodies to the repeat region. The promising results obtained with a single dose of ICC-1132 formulated in Montanide ISA 720 encourage further clinical development of this malaria vaccine candidate.
The Catalytic Activity of Ruthenates ARuO3 (A= Ca, Sr or Ba) for the Hydrogen Evolution Reaction in Acidic Medium (2012)

Ruthenate perovskites ARuO3, (A= Ca, Sr or Ba) were prepared by coprecipitation method. The electrocatalytic activity of the prepared perovskites was investigated toward the hydrogen evolution reaction (HER). X-ray diffraction analysis suggested successful incorporation of Ru4+ at the Ca2+, Sr2+ and Ba2+ cations sites confirming the formation of the orthorhombic perovskite phases of CaRuO3 and SrRuO3 and the hexagonal perovskite phase of BaRuO3. The average particle size for the prepared perovskites was 39.0, 42.2 and 101.4 nm for Ca, Sr and BaRuO3, respectively. Scanning electron micrographs showed a well-defined hexagonal crystal structure in case of BaRuO3, while CaRuO3 and SrRuO3 composed of agglomerations of nearly spherical grains. CaRuO3 showed smaller agglomerations and more cavities than SrRuO3. The influence of the type of A-cation on the catalytic activity for HER was studied by Tafel linear polarization. The order of the electrocatalytic activity was BaRuO3>CaRuO3>SrRuO3. This was shown from the values of the exchange current density, -60.7, -13.1 and -884.6 μA.cm-2 for Ca, Sr and BaRuO3, respectively. This suggested that the A-site metal ion not only has a strong effect on the stability of the whole crystal configuration but also provides the possibility to improve catalyst performance by synergetic interactions with the B-site metal ion. The activation energy, reaction order and reaction mechanism have been investigated using the electrochemical techniques, Tafel linear polarization and impedance. Again, the calculated values of the activation energy gave similar trend for catalytic activity; 42.6, 86.3 and 17.7 kJ/mol for Ca, Sr and BaRuO3respectively. Both Tafel and the impedance data showed that the volmer step is the rate determining step. In addition, the effect of the partial substitution at the A-site in Sr1-xCaxRuO3 was also studied. The catalytic activity of ternary perovskites was about twice higher than that of binary ones. The catalytic activity of ternary oxides increased with increasing the fraction of Ca-doped.
Fibrin Formed in Plasma is Composed of Fibers More Massive than those Formed from Purified Fibrinogen (1988)

Reports of altered fibrin resulting from interactions with plasma proteins and cellular release products have raised the possibility that plasma fibrin may differ from purified fibrin. To investigate this possibility, the structures of thrombin-induced gels formed from platelet poor plasma and from purified fibrinogen were compared using turbidity and gel perfusion techniques. Plasma gels formed more slowly and were composed of fibers two to four times more massive than gels formed from purified fibrinogen. Increasing calcium concentration, decreasing ionic strength, decreasing thrombin concentration, or increasing fibrinogen concentration resulted in increasing fiber size. Addition of excess thrombin accelerated plasma gel formation and decreased gel fiber size, but did not totally eliminate the structural differences between the two systems. Thus, antithrombin activity, while possibly contributory, is not solely responsible for the altered gel structure. Penetration of plasma gels by fibrinolytic agents, egress to areas of injury by inflammatory cells, and gel removal by plasmin are processes at least partially dependent on gel fiber and pore size.
A novel lipopolysaccharide-induced transcription factor regulating tumor necrosis factor α gene expression: Molecular cloning, sequencing, characterization, and chromosomal assignment (1999)

Lipopolysaccharide (LPS) is a potent stimulator of monocytes and macrophages, causing secretion of tumor necrosis factor alpha (TNF-alpha) and other inflammatory mediators. Given the deleterious effects to the host of TNF-alpha, it has been postulated that TNF-alpha gene expression must be tightly regulated. The nature of the nuclear factor(s) that control TNF-alpha gene transcription in humans remains obscure, although NF-kappaB has been suggested. Our previous studies pertaining to macrophage response to LPS identified a novel DNA-binding domain located from -550 to -487 in the human TNF-alpha promoter that contains transcriptional activity, but lacks any known NF-kappaB-binding sites. We have used this DNA fragment to isolate and purify a 60-kDa protein binding to this fragment and obtained its amino-terminal sequence, which was used to design degenerate probes to screen a cDNA library from THP-1 cells. A novel cDNA clone (1.8 kb) was isolated and fully sequenced. Characterization of this cDNA clone revealed that its induction was dependent on LPS activation of THP-1 cells; hence, the name LPS-induced TNF-alpha factor (LITAF). Inhibition of LITAF mRNA expression in THP-1 cells resulted in a reduction of TNF-alpha transcripts. In addition, high level of expression of LITAF mRNA was observed predominantly in the placenta, peripheral blood leukocytes, lymph nodes, and the spleen. Finally, chromosomal localization using fluorescence in situ hybridization revealed that LITAF mapped to chromosome 16p12-16p13.3. Together, these findings suggest that LITAF plays an important role in the activation of the human TNF-alpha gene and proposes a new mechanism to control TNF-alpha gene expression.
Neural control of computer cursor velocity by decoding motor cortical spiking activity in humans with tetraplegia (2008)

Computer-mediated connections between human motor cortical neurons and assistive devices promise to improve or restore lost function in people with paralysis. Recently, a pilot clinical study of an intracortical neural interface system demonstrated that a tetraplegic human was able to obtain continuous two-dimensional control of a computer cursor using neural activity recorded from his motor cortex. This control, however, was not sufficiently accurate for reliable use in many common computer control tasks. Here, we studied several central design choices for such a system including the kinematic representation for cursor movement, the decoding method that translates neuronal ensemble spiking activity into a control signal and the cursor control task used during training for optimizing the parameters of the decoding method. In two tetraplegic participants, we found that controlling a cursor's velocity resulted in more accurate closed-loop control than controlling its position directly and that cursor velocity control was achieved more rapidly than position control. Control quality was further improved over conventional linear filters by using a probabilistic method, the Kalman filter, to decode human motor cortical activity. Performance assessment based on standard metrics used for the evaluation of a wide range of pointing devices demonstrated significantly improved cursor control with velocity rather than position decoding.
Conformational and dynamic considerations in the design of peptide hormone analogs (1983)

Abstract Efforts to understand the chemical‐physical basis for peptide hormone and neurotransmitter action requires integration of conformational parameters and biological properties. Since most peptide hormones are conformationally flexible, the question arises as to which of the manifold of conformations is of biological significance. In molecular terms, it is necessary to carefully distinguish chemical‐physical features important to binding (the binding message) from those involved in transduction (the biological activity message). One approach to this involves the design, synthesis, and conformational analysis of semirigid hormone analogs. The distinction between binding and transduction can best be examined by evaluation of full biological profiles of partial agonists, antagonists, and analogs with prolonged biological activity. Using this multidisciplinary approach, we have prepared several semirigid [Pen 1 ]‐oxytocin antagonist analogs and evaluated their conformational properties and biological activities. Specific conformational features can be related to inhibitory activities in several cases. On the basis of structure–activity relationships and conformational considerations, we have designed a series of conformationally restricted cyclic and acyclic analogs of the linear peptide α‐melanotropin. Some of these peptides have exceptionally prolonged in vivo activity (weeks), and others exhibit superagonist potency (10,000 times the native hormone). We have evidence that potency and prolonged activity have different structural and conformational requirements. It is suggested that potency is primarily a function of receptor recognition (the binding message), whereas prolonged activity is related to transduction (the biological activity message).
Neutralizing Antibodies Against HIV Determined by Amplification of Viral Long Terminal Repeat Sequences From Cells Infected in Vitro by Nonneutralized Virions (1998)

Based on the earliest intracellular synthesis of nascent HIV-1 long terminal repeat (LTR) fragments, we have established a heminested polymerase chain reaction (HNPCR) amplification of the 5' LTR sequences (LTR-HNPCR) for molecular assay of virus-neutralizing antibodies (VNAb). We incubated HIV antibodies with virus isolates for an hour, followed by addition of lymphoid cells (H9 or peripheral blood mononuclear cells [PBMC]) and further incubation for an hour. After washing the cells three times for thorough removal of free virions and antibodies, LTR-HNPCR consistently revealed HIV DNA in H9 cells after 15 minutes, in PBMC after 4 hours, and corresponding virion expression after 7 days in culture. Replication-competent HIV detected by LTR-HNPCR following overnight culture of infected PBMC for 16 to 18 hours was comparable with tissue culture infectivity measured by p24 antigen expression at 7 days. After establishing a molecular assay for in vitro HIV neutralization by HIV Ig, a panel of five HIV isolates tested with 6 monoclonal antibodies and HIV Ig revealed that LTR-HNPCR was comparable with other VNAb assays. These preliminary data indicate that the molecular assay for HIV neutralization has a clear-cut end point, is specific, reliable, and more rapid than other VNAb assays. Therefore, it offers potential utility in evaluating immune response to candidate vaccines.
Analysis of theEscherichia coligenome. IV. DNA sequence of the region from 89.2 to 92.8 minutes (1993)

We present the sequence of 176 kilobases of the Escherichia coli K-12 genome, from katG at 89.2 to an open reading frame (ORF) of unknown function at 92.8 minutes on the genetic map. This brings the total of contiguous sequence from the E. coli genome project to 500 kb (81.5 to 92.8 minutes). This segment contains 134 putative coding genes (ORFs) of which 66 genes were previously identified. Eight new genes--acs, pepE, and nrfB-G--were identified as well as the previously mapped gldA and alr genes. Still, 58 ORFs remain unidentified despite literature and similarity searches. The arrangement of proposed genes relative to possible promoters and terminators suggests 55 potential transcription units. Other features include 13 REP elements, one IRU (ERIC) repeat, 59 computer-predicted bends, 42 Chi sites and one new grey hole. Sixteen signal peptides were found, including those of lamB, btuB, and malE. Two ribosomal RNA loci, rrnB and rrnE, are located in this segment, so we have now sequenced four of the seven E. coli rRNA loci. Comparison of the rRNA loci reveals some differences in the ribosomal structural RNAs which are generally compatible with the proposed secondary structures.
Cyclooxygenase 2—implications on maintenance of gastric mucosal integrity and ulcer healing: controversial issues and perspectives (2001)

Cyclooxygenase (COX), the key enzyme for synthesis of prostaglandins, exists in two isoforms (COX-1 and COX-2). COX-1 is constitutively expressed in the gastrointestinal tract in large quantities and has been suggested to maintain mucosal integrity through continuous generation of prostaglandins. COX-2 is induced predominantly during inflammation. On this premise selective COX-2 inhibitors not affecting COX-1 in the gastrointestinal tract mucosa have been developed as gastrointestinal sparing anti-inflammatory drugs. They appear to be well tolerated by experimental animals and humans following acute and chronic (three or more months) administration. However, there is increasing evidence that COX-2 has a greater physiological role than merely mediating pain and inflammation. Thus gastric and intestinal lesions do not develop when COX-1 is inhibited but only when the activity of both COX-1 and COX-2 is suppressed. Selective COX-2 inhibitors delay the healing of experimental gastric ulcers to the same extent as non-COX-2 specific non-steroidal anti-inflammatory drugs (NSAIDs). Moreover, when given chronically to experimental animals, they can activate experimental colitis and cause intestinal perforation. The direct involvement of COX-2 in ulcer healing has been supported by observations that expression of COX-2 mRNA and protein is upregulated at the ulcer margin in a temporal and spatial relation to enhanced epithelial cell proliferation and increased expression of growth factors. Moreover, there is increasing evidence that upregulation of COX-2 mRNA and protein occurs during exposure of the gastric mucosa to noxious agents or to ischaemia-reperfusion. These observations support the concept that COX-2 represents (in addition to COX-1) a further line of defence for the gastrointestinal mucosa necessary for maintenance of mucosal integrity and ulcer healing.
The synthesis of aracemic 4-substituted pyrrolidinones and 3-substituted pyrrolidines. An asymmetric synthesis of (-)-rolipram (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe synthesis of aracemic 4-substituted pyrrolidinones and 3-substituted pyrrolidines. An asymmetric synthesis of (-)-rolipramA. I. Meyers and Lawrence SnyderCite this: J. Org. Chem. 1993, 58, 1, 36–42Publication Date (Print):January 1, 1993Publication History Published online1 May 2002Published inissue 1 January 1993https://doi.org/10.1021/jo00053a012RIGHTS & PERMISSIONSArticle Views1031Altmetric-Citations92LEARN 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 (896 KB) Get e-Alerts Get e-Alerts
Erythroid response to treatment with G‐CSF plus erythropoietin for the anaemia of patients with myelodysplastic syndromes: proposal for a predictive model (1997)

Previous studies have shown that approximately 40% of patients with myelodysplastic syndrome (MDS) and anaemia respond to treatment with human recombinant granulocyte-CSF (G-CSF) plus erythropoietin (epo). The present study was designed to investigate pre-treatment variables for their ability to predict erythroid responses to this treatment. 98 patients with MDS (30 RA, 31 RARS, 32 RAEB, five RAEB-t) were treated with a combination of G-CSF (0.3-3.0 microg/kg/d, s.c.) and epo (60-300 U/kg/d, s.c.) for at least 10 weeks. Minimum criteria for erythroid response was a 100% reduction of red blood cell (RBC) transfusion need or an increase in haemoglobin level of > or = 1.5 g/dl. 35 patients (36%) showed responses to treatment. Medium duration of response was 11-24 months. In multivariate analysis, serum erythropoietin levels and initial RBC-transfusion need retained high statistical significance (P < 0.01). Using pre-treatment serum epo levels as a ternary variable (< 100, 100-500 or > 500 U/l) and RBC transfusion need as a binary variable (< 2 or > or = 2 units per month), the analysis provided a predictive score for erythroid response. This score divided patients into three groups: one group with a high probability of erythroid responses (74%), one intermediate group (23%) and one group with poor responses to treatment (7%). This predictive scoring system could be used in decisions regarding use of these cytokines for treating the anaemia of MDS, both for defining patients who should not be given the treatment and for selecting patients for inclusion in prospective trials.
Transcriptional Regulation of the MDR1 Gene by Histone Acetyltransferase and Deacetylase Is Mediated by NF-Y (1998)

Recent studies have shown that the histone-modifying enzymes histone acetyltransferase (HAT) and histone deacetylase (HDAC) are involved in transcriptional activation and repression, respectively. However, little is known about the endogenous genes that are regulated by these enzymes or how specificity is achieved. In the present report, we demonstrate that HAT and HDAC activities modulate transcription of the P-glycoprotein-encoding gene, MDR1. Incubation of human colon carcinoma SW620 cells in 100-ng/ml trichostatin A (TSA), a specific HDAC inhibitor, increased the steady-state level of MDR1 mRNA 20-fold. Furthermore, TSA treatment of cells transfected with a wild-type MDR1 promoter/luciferase construct resulted in a 10- to 15-fold induction of promoter activity. Deletion and point mutation analysis determined that an inverted CCAAT box was essential for this activation. Consistent with this observation, overexpression of p300/CREB binding protein-associated factor (P/CAF), a transcriptional coactivator with intrinsic HAT activity, activated the wild-type MDR1 promoter but not a promoter containing a mutation in the CCAAT box; deletion of the P/CAF HAT domain abolished activation. Gel shift and supershift analyses identified NF-Y as the CCAAT-box binding protein in these cells, and cotransfection of a dominant negative NF-Y expression vector decreased the activation of the MDR1 promoter by TSA. Moreover, NF-YA and P/CAF were shown to interact in vitro. This is the first report of a natural promoter that is modulated by HAT and HDAC activities in which the transcription factor mediating this regulation has been identified.
Gas phase polysulfide passivation of InP for MISFET fabrication (2002)

Gas phase polysulfide passivation of InP was studied and used to improve the electrical properties of metal-insulator-semiconductor structures and metal-insulator-semiconductor field effect transistors (MISFETs). The gas phase polysulfide treatment was used successfully to reduce the interface state density of silicon nitride/InP. MISFETs with a slow drain current drift were fabricated. The results indicate that both depletion mode and accumulation-depletion mode InP MISFETs can be fabricated with a useful drain current.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Scleroderma and autoimmune thrombocytopenia associated with ingestion of l-tryptophan (1993)

We report the occurrence of scleroderma and autoimmune thrombocytopenia in a patient who took L-tryptophan as a muscle-building adjuvant. This is the first time such an association has been reported.
Parallel models of associative memory (1981)

This update of the 1981 classic on neural networks includes new commentaries by the authors that show how the original ideas are related to subsequent developments. As researchers continue to uncover ways of applying the complex information processing abilities of neural networks, they give these models an exciting future which may well involve revolutionary developments in understanding the brain and the mind -- developments that may allow researchers to build adaptive intelligent machines. The original chapters show where the ideas came from and the new commentaries show where they are going
Identification of Polo-like Kinase 1 as a Potential Therapeutic Target in Anaplastic Thyroid Carcinoma (2009)

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive and chemoresistant cancers. The serine/threonine kinase Polo-like kinase 1 (PLK1), a key regulator of multiple steps during mitotic progression, is highly expressed in ATC. Here, we used the BI 2536 PLK1 inhibitor on ATC and nontransformed thyroid follicular cell lines. Our data show that ATC cells are addicted to high levels of PLK1 activity for proliferation, survival, anchorage-independent growth, and tumorigenicity. On treatment with nanomolar doses of BI 2536, ATC cells progressed normally through S phase but died thereafter, directly from mitotic arrest. Immunofluorescence microscopy, immunoblot, and flow cytometry analysis showed that, on PLK1 blockade, ATC cells arrested in prometaphase with a 4N DNA content. Treated ATC cells accumulated phosphohistone H3 and displayed characteristic mitotic (Polo) spindle aberrations. Nontransformed thyroid cells were 3.2- to 18.4-fold less susceptible to BI 2536-induced cell cycle effects compared with ATC cells. These findings identify PLK1 as a promising target for the molecular therapy of ATC.