gebhart/patrepeval huggingface dataset:
Protection against cerebral malaria by the low-molecular-weight thiol pantethine (2008)

We report that administration of the low-molecular-weight thiol pantethine prevented the cerebral syndrome in Plasmodium berghei ANKA-infected mice. The protection was associated with an impairment of the host response to the infection, with in particular a decrease of circulating microparticles and preservation of the blood-brain barrier integrity. Parasite development was unaffected. Pantethine modulated one of the early steps of the inflammation-coagulation cascade, i.e., the transbilayer translocation of phosphatidylserine at the cell surface that we demonstrated on red blood cells and platelets. In this, pantethine mimicked the inactivation of the ATP-binding-cassette transporter A1 (ABCA1), which also prevents the cerebral syndrome in this malaria model. However, pantethine acts through a different pathway, because ABCA1 activity was unaffected by the treatment. The mechanisms of pantethine action were investigated, using the intact molecule and its constituents. The disulfide group (oxidized form) is necessary to lower the platelet response to activation by thrombin and collagen. Thio-sensitive mechanisms are also involved in the impairment of microparticle release by TNF-activated endothelial cells. In isolated cells, the effects were obtained by cystamine that lacks the pantothenic moiety of the molecule; however, the complete molecule is necessary to protect against cerebral malaria. Pantethine is well tolerated, and it has already been administered in other contexts to man with limited side effects. Therefore, trials of pantethine treatment in adjunctive therapy for severe malaria are warranted.
Blood pressure variability. Importance in research and in clinical hypertension. (1996)

mean value, but also 24h blood pressure variability seems to be independently related to the end organ damage of hypertension. This is illustrated in figure 1, which is taken from a study where 108 hypertensive patients underwent a 24h intra-arterial blood pressure monitoring in ambulatory conditions by Oxford technique 16. A score based on clinical and laboratory examinations was used to quantify the severity and the rate of end organ damage related to hypertension. The 108 patients were subdivided into five groups with progressively higher 24h mean blood pressure levels. In each group, the hypertensive patients with greater blood pressure variability (evaluated as the standard deviation of the 24h mean blood pressure) showed more severe and more frequent end organ damage than the patients with similar 24h mean values but less pronounced 24h blood pressure variability.
Differentiation-induced gene expression in 3T3-L1 preadipocytes. Characterization of a differentially expressed gene encoding stearoyl-CoA desaturase. (1988)

Previous studies have shown that differentiation of 3T3-L1 preadipocytes leads to the activation of transcription of an unidentified gene which encodes a 4.9-kilobase (kb) mRNA. Several cDNAs that include the complete sequence of this mRNA were obtained and used to isolate and characterize the gene. Analysis of the nucleotide and amino acid sequences of both cDNA and genomic clones revealed that the gene encodes the mouse stearoyl-CoA desaturase (SCD), an enzyme known to be expressed upon differentiation of 3T3-L1 preadipocytes. The predicted amino acid sequence (355 residues) of the mouse 3T3-L1 adipocyte SCD exhibits 92% identity to that of the rat liver SCD. There is also a high degree of nucleotide sequence identity between the mouse and rat mRNAs in their unusually long approximately 3.5-kb 3'-untranslated regions. Mice fed a diet containing unsaturated triacylglycerides express SCD mRNA only in adipose tissue, whereas mice starved and refed a fat-free diet, express SCD mRNA in both liver and adipose tissue. The mouse gene for the desaturase spans approximately 15 kb and contains 6 exons and 5 introns with all intron-exon junctions conforming to the GT/AG splicing rule. As determined by S1 nuclease mapping and primer extension analysis, the transcriptional initiation site maps 152 nucleotides upstream from the initiation methionine codon. A canonical promoter "TATA" box is located 30 base pairs upstream of the Cap site. A typical "CCAAT" box sequence is not present in the adjacent 5'-flanking region; however, there is a GC-rich sequence (at nucleotide -215) similar to the binding site for the nuclear transcription factor Sp1. Upstream from the transcriptional initiation site are elements with homology (approximately 75%) to the putative fat-specific transcriptional element FSE2 and core consensus sequences for cAMP and glucocorticoid regulatory elements. A chimeric construct, containing 363 base pairs of 5'-flanking sequence and 30 nucleotides of 5'-untranslated sequence of the mouse SCD gene ligated to the bacterial chloramphenicol acetyltransferase gene, was transfected into 3T3-L1 cells. When cells were induced to differentiate into adipocytes, expression of the SCD chloramphenicol acetyltransferase gene increased approximately 63-fold, suggesting that the SCD promoter region contains elements that mediate the response to adipogenic agents which induce differentiation.
Identification of heavy chain residues in a humanized anti-CD3 antibody important for efficient antigen binding and T cell activation (1995)

A previously identified humanized anti-CD3 Ab variant, v9, binds T cells with > 100-fold higher efficiency than the original variant, v1, and almost as efficiently as a chimeric molecule containing corresponding murine variable domains. Variants v1 and v9 differ at six positions in the H chain second CDR. Here a mutational analysis was used to identify which of these six replacements are primarily responsible for the difference in binding efficiency. These anti-CD3 variants were used to probe the relationship between Ag binding efficiency and potency in stimulating T cell proliferation. The human to mouse mutations T57S and V63F increase the binding efficiency of variant v1 for T cells by 8- and 12-fold, respectively, and together in variant M18 enhance binding by 26-fold to within 4-fold of variant v9. A framework mutation, 169L, was identified that enhances the binding of variants v1 and M18 by 14- and 3-fold, respectively. The Ag binding efficiencies of anti-CD3 variants correlate directly with their potencies in stimulating the proliferative activity of both resting human PBMC and IL-2-activated human T lymphocytes. Humanized variant v9 is equipotent to the murine parent Ab in stimulating ATL activity. PBMC activated by variants v1 and v9 IgG in a short term culture are equally cytotoxic against human breast carcinoma cells. Thus, high efficiency Ag binding by anti-CD3 variants is important for stimulating efficient T cell proliferation, but not cytotoxicity, in vitro.
Whole-Genome Random Sequencing and Assembly of Haemophilus influenzae Rd (1995)

An approach for genome analysis based on sequencing and assembly of unselected pieces of DNA from the whole chromosome has been applied to obtain the complete nucleotide sequence (1,830,137 base pairs) of the genome from the bacterium Haemophilus influenzae Rd. This approach eliminates the need for initial mapping efforts and is therefore applicable to the vast array of microbial species for which genome maps are unavailable. The H. influenzae Rd genome sequence (Genome Sequence DataBase accession number L42023) represents the only complete genome sequence from a free-living organism.
[Studies on synthesis, anticonvulsant activity and the structure--activity relationships of 6-(substituted phenyl)-3 (2H) pyridazinones]. (1991)

In searching for effective anticonvulsant agent fourteen 6-(substituted-phenyl)-4,5-dihydro-3 (2H) pyridazinones and fifteen 6-(substitutedphenyl)-3 (2H) pyridazinones have been synthesized and screened in mice for their ability to antagonize maximal electroshock seizure (MES). The ED50 values showed that 6-(2',4'-dichlorophenyl)-3 (2H) pyridazinone was the most potent anticonvulsant in these compounds. The structure--activity relationships in these two series were examined. We came to the conclusion that the higher is the hydrophobic parameter pi of the substituent on phenyl ring, the more potent anticonvulsant is the compound. And also, only the compounds with an electronwithdrawing substituent on the phenyl ring exhibited appreciable anticonvulsant activity.
PARTICLE MIGRATION AFTER TRANSURETHRAL INJECTION OF CARBON COATED BEADS FOR STRESS URINARY INCONTINENCE (2001)

Due to limited success and proved particle migration, carbon coated beads do not show any improvement over existing bulking materials. The clinical effect of bead migration must be determined before extended use of this substance.
Mean and variance of the Gibbs free energy of oligonucleotides in the nearest neighbor model under varying conditions (2004)

We derive analytic results about the distribution of nearest neighbor DeltaG values for a Bernoulli random sequence model (specified by oligonucleotide length and average GC-content) under given experimental conditions. We find that the distribution of DeltaG values is approximately Gaussian and provide exact formulas for expectation and variance.
Propionate metabolism in Saccharomyces cerevisiae: implications for the metabolon hypothesis (1994)

Aerobic, glucose-limited chemostat of Saccharomyces cerevisiae CBS 8066 co-metabolized propionate when this compound was added to the reservoir medium. Co-metabolism of propionate led to an increase of the biomass and protein yields. Attempts to grow S. cerevisiae on propionate as a sole source of carbon and energy were not successful. Activities of propionyl-CoA synthetase in cell-free extracts were sufficient to account for the rates of propionate consumption observed in the chemostat cultures. Activities of propionyl-CoA carboxylase, a key enzyme of the methylmalonyl-CoA pathway of propionate metabolism, were negligible. In contrast, activities of 2-methylcitrate synthase, a key enzyme activity of the 2-methylcitrate pathway of propionate metabolism, increased substantially with increasing propionate-to-glucose ratios in the reservoir media, and were sufficient to account for the propionate consumption rates observed in the chemostat cultures. This suggested that the 2-methylcitrate pathway is the major pathway of propionate metabolism in S. cerevisiae. In the literature, labelling patterns observed after incubation of this yeast with [3-13C]propionate have been interpreted as evidence for channelling of tricarboxylic acid (TCA) cycle intermediates, possibly as a consequence of the organization of TCA cycle enzymes in a metabolon. However, this interpretation of 13C-labelling patterns rested on the assumption that propionate metabolism in S. cerevisiae occurs via the methylmalonyl-CoA pathway. Since the distribution of 13C in alanine reported in the literature is fully compatible with a major role of the 2-methylcitrate pathway in propionate metabolism, it cannot be interpreted as evidence for the existence of a TCA cycle metabolon in S. cerevisiae.
B7.2 expressed by T cells does not induce CD28-mediated costimulatory activity but retains CTLA4 binding: implications for induction of antitumor immunity to T cell tumors (1997)

The B7 family of costimulatory molecules provides the second signal necessary for activation of T cells. In the absence of the second signal, responding T cells become anergic. Although predominantly expressed on professional APCs, recent evidence shows that the B7 molecules are also expressed on T cells. To study the functions of B7 molecules on T cells, we transfected murine B7.1 (CD80) and B7.2 (CD86) cDNAs into the EL4 T cell thymoma cell line and examined the transfectants for their ability to costimulate T cell proliferation in vitro and to induce antitumor immunity in vivo. Here we show that although EL4-B7.1 cells costimulate T cells and induce tumor regression, EL4-B7.2 transfectants failed to costimulate T cell proliferation or induce tumor regression. To understand the cellular basis for this difference, we examined the binding of EL4-B7.1 and EL4-B7.2 to CTLA4 and CD28. Whereas EL4-B7.1 cells bound both CTLA4-Ig and CD28-Ig, EL4-B7.2 transfectants preferentially bound CTLA4-Ig, but not CD28-Ig. Similar binding data were obtained with freshly isolated murine T cells, which have been shown to constitutively express B7.2. Our data suggest, therefore, that B7.2 expressed on T cells may not costimulate but instead inhibit the T cell response by preferential binding to CTLA4.
Band-Limited Volterra Series-Based Digital Predistortion for Wideband RF Power Amplifiers (2012)

The continuously increasing demand for wide bandwidth creates great difficulties in employing digital predistortion (DPD) for radio frequency (RF) power amplifiers (PAs) in future ultra-wideband systems because the existing DPD system requires multiple times the input signal bandwidth in the transmitter and receiver chain, which is sometimes almost impossible to implement in practice. In this paper, we present a novel band-limited digital predistortion technique in which a band-limiting function is inserted into the general Volterra operators in the DPD model to control the signal bandwidth under modeling, which logically transforms the general Volterra series-based model into a band-limited version. This new approach eliminates the system bandwidth constraints of the conventional DPD techniques, and it allows users to arbitrarily choose the bandwidth to be linearized in the PA output according to the system requirement without sacrificing performance, which makes the DPD system design much more flexible and feasible. In order to validate this idea, a high-power LDMOS Doherty PA excited by various wideband signals, including 100-MHz long-term evolution advanced signals, was tested. Experimental results showed that excellent linearization performance can be obtained by employing the proposed approach. Furthermore, this technique can be applied to other linear-in-parameter models. In future ultra-wideband systems, this new technique can significantly improve system performance and reduce DPD implementation cost.
Epidermal growth factor receptor (EGFR)-targeted immunoliposomes mediate specific and efficient drug delivery to EGFR- and EGFRvIII-overexpressing tumor cells (2004)

(2004). Epidermal growth factor receptor (EGFR)-targeted immunoliposomes mediate specific and efficient drug delivery to EGFR- and EGFRvIII-overexpressing tumor cells. The Women's Oncology Review: Vol. 4, No. 2, pp. 99-101.
CpG Blocks Immunosuppression by Myeloid-Derived Suppressor Cells in Tumor-Bearing Mice (2011)

We show here for the first time that TLR9 activation inhibits the regulatory function of MDSC in tumor-bearing mice and define a role for the antitumoral cytokine IFN-α in this process.
Isocyanide Addition to Pyridinium Salts. Efficient Entry into Substituted Nicotinonitrile Derivatives (2006)

The addition of isocyanides to pyridinium salts is studied. The process takes place efficiently when a carboxamido group is present in the 3 position of the pyridine ring. The outcome of the reaction involves the stabilization of the nitrilium intermediate by the amide, which suffers a mild dehydration, leading regioselectively to β-cyano-γ-carbamoyl-1,4-dihydropyridines. In this way, a variety of nicotinamide derivatives were carbamoylated. Extension to quinolinium, isoquinolinium, and N-acylpyridinium salts is also reported.
New Families of Photocurable Oligomeric Fluoromonomers for Use in Dental Composites (1996)

Photopolymerizable methacrylate-based resins with moderate-to-high organofluorine contents may improve the hydrophobicity, durability, and toughness of composites used in aesthetic dental filling applications. A variety of multifunctional oligomeric fluorinated monomers were developed and evaluated with the goal of identifying polymer systems that combine high strength, low water sorption, and minimal polymerization shrinkage. Certain fluorooligomer resin compositions prepared here appear capable of successfully meeting these challenges.
Detection of soluble Legionella pneumophila antigens in serum and urine specimens by enzyme-linked immunosorbent assay with monoclonal and polyclonal antibodies (1984)

Urine and serum specimens from three patients with pneumonia caused by Legionella pneumophila serogroup 1 (Lp1) were tested by enzyme-linked immunosorbent assay (ELISA) for Lp1-soluble antigen. A three-layer direct ELISA with polyclonal antibodies and a four-layer indirect ELISA with both polyclonal and monoclonal antibodies were used. Lp1 antigen was detected in both urine and serum from the three patients. As determined by ELISA, the concentration of antigen was 30- to 100-fold less in serum than in urine collected on the same day. In some instances the indirect ELISA was more sensitive than the direct ELISA, but in others it was less sensitive, depending on the monoclonal antibody used. The subgroup of the infecting Lp1 organism was determined based on antigenic determinants expressed in the urine. This study illustrates the use of serum as well as urine as an antigen reservoir in the laboratory diagnosis of legionellosis by ELISA and the potential for developing more sensitive antigen detection systems by the judicious use of monoclonal antibodies.
Telomerase as a novel and potentially selective target for cancer chemotherapy (2003)

Telomeres are the structures that protect eukaryotic chromosomes from recognition by DNA damage surveillance mechanisms and are maintained in the germ line of multicellular animals by telomerase. In most human somatic cells telomerase is silenced during development and after extensive cell division telomeres shorten to trigger growth arrest. Around 80% of human cancers escape from this growth arrest by re-activating telomerase but at diagnosis many cancers still have very short telomeres making them very vulnerable to the inhibition of telomerase. As normal cells have a considerable telomere reserve, even in elderly humans, this makes telomerase an attractive and potentially selective anti-cancer drug target. Proof-of-principle experiments are reviewed which show that this optimism may be justified at least for the subset of human cancers with short telomeres. I also address many of the commonly raised concerns that surround telomerase as a target for anti-cancer drug design.
Vibration in phase-shifting interferometry (1995)

Unexpected mechanical vibrations can significantly degrade the otherwise high accuracy of phase-shifting interferometry. Fourier analysis of phase-shift algorithms is shown to provide the analytical means of predicting measurement errors as a function of the frequency, the phase, and the amplitude of vibrations. The results of this analysis are concisely represented by a phase-error transfer function, which may be multiplied by the noise spectrum to predict the response of an interferometer to various forms of vibration. Analytical forms for the phase error are derived for several well-known algorithms, and the results are supported by numerical simulations and experiments with an interference microscope.
The Absolute Configuration of Homocitric Acid (2-Hydroxy-1,2,4-butanetricarboxylic Acid), an Intermediate in Lysine Biosynthesis* (1966)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Absolute Configuration of Homocitric Acid (2-Hydroxy-1,2,4-butanetricarboxylic Acid), an Intermediate in Lysine Biosynthesis*Ursula Thomas, M. G. Kalyanpur, and C. M. StevensCite this: Biochemistry 1966, 5, 8, 2513–2516Publication Date (Print):August 1, 1966Publication History Published online1 May 2002Published inissue 1 August 1966https://doi.org/10.1021/bi00872a004RIGHTS & PERMISSIONSArticle Views91Altmetric-Citations24LEARN 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 (335 KB) Get e-Alerts Get e-Alerts
DNA Probe Method for the Detection of Specific Microorganisms in the Soil Bacterial Community (1988)

We developed a protocol which yields purified bacterial DNA from the soil bacterial community. The bacteria were first dispersed and separated from soil particles in the presence of polyvinylpolypyrrolidone, which removes humic acid contaminants by adsorption to this insoluble polymer. The soil bacteria were then collected by centrifugation and lysed by using a comprehensive protocol designed to maximize disruption of the various types of bacteria present. Total bacterial DNA was purified from the cell lysate and remaining soil contaminants by using equilibrium density gradients. The isolated DNA was essentially pure as determined by UV spectral analysis, was at least 48 kilobases long, and was not subject to degradation, which indicated that there was no contaminating nuclease activity. The isolated DNA was readily digested by exogenously added restriction endonucleases and successfully analyzed by slot blot and Southern blot hybridizations. Using single-stranded, P-labeled DNA probes, we could detect and quantitate the presence of a specific microbial population in the natural soil community on the basis of the presence of a DNA sequence unique to that organism. The sensitivity of our methodology was sufficient to detect Bradyrhizobium japonicum at densities as low as 4.3 x 10 cells per g (dry weight) of soil, which corresponds to about 0.2 pg of hybridizable DNA in a 1-mug DNA sample.
Selection of solid dosage form composition through drug–excipient compatibility testing (1999)

A drug-excipient compatibility screening model was developed by which potential stability problems due to interactions of drug substances with excipients in solid dosage forms can be predicted. The model involved storing drug-excipient blends with 20% added water in closed glass vials at 50 degrees C and analyzing them after 1 and 3 weeks for chemical and physical stability. The total weight of drug-excipient blend in a vial was usually kept at about 200 mg. The amount of drug substance in a blend was determined on the basis of the expected drug-to-excipient ratio in the final formulation. Potential roles of several key factors, such as the chemical nature of the excipient, drug-to-excipient ratio, moisture, microenvironmental pH of the drug-excipient mixture, temperature, and light, on dosage form stability could be identified by using the model. Certain physical changes, such as polymorphic conversion or change from crystalline to amorphous form, that could occur in drug-excipient mixtures were also studied. Selection of dosage form composition by using this model at the outset of a drug development program would lead to reduction of "surprise" problems during long-term stability testing of drug products.