gebhart/patrepeval huggingface dataset:
Antifungal serum concentration monitoring: an update (2007)

Invasive fungal infections (IFIs) are occurring with increasing incidence and are associated with significant morbidity and mortality. Understanding the relationship between the pharmacokinetic and pharmacodynamic properties of antifungals is essential to optimize the potential for favourable clinical and microbiological outcomes while minimizing risks of treatment-related toxicity. Antifungal serum concentrations may aid in the determination of appropriate dosing in select circumstances. The polyene and echinocandin classes of antifungals lack sufficient data to justify serum concentration monitoring in routine clinical practice. In contrast, serum concentration monitoring of flucytosine may help to reduce the risk of treatment-related haematological toxicity. Determination of itraconazole serum concentrations is advised in situations where the drug is used for prolonged periods to treat serious IFIs (such as invasive aspergillosis or histoplasmosis) because of variability in absorption following oral administration (most notable for the capsule formulation). The use of serum concentration monitoring during therapy with the extended-spectrum triazoles (i.e. voriconazole and posaconazole) is still evolving, due primarily to inter-patient variability in drug exposure combined with sparse data regarding relationships with efficacy (posaconazole) and both safety and efficacy (voriconazole).
OX40 (CD134) and OX40 ligand interaction plays an adjuvant role during in vivo Th2 responses (2003)

The role of OX40-OX40 ligand (OX40L) interaction in Th cell differentiation remains contentious. In vitro studies have revealed a Th2-biased effect by OX40 signals in T cells. However, in vivo studies demonstrated that OX40-OX40L interaction is involved in responses either Th1 or Th2, or both, which appears to be dependent on the experimental conditions used. We document in our report Th cell differentiation in OX40L-deficient and OX40L-transgenic (Tg) mice in response to protein antigens (Ag) and to Leishmania major (L. major) infection. Upon immunization with protein Ag, we demonstrate the adjuvant effect of OX40 signals during in vivo Th2 responses. However, adjuvant treatment to mice ameliorates the Th2-specific effect of OX40-OX40L interaction and rather induces concurrent promotion of both Th1 and Th2 responses via OX40 signals. Thus, previous reports showing promotion of Th1 response by OX40-OX40L interaction may in actual fact be affected by the adjuvant effects mediated by the various experimental conditions. Indeed, constitutive OX40-OX40L interactions in OX40L-Tg mice converted the normally resistant C57BL/6 strain, into a susceptible status following L. major infection due to an extraordinary elevated Th2 response. These results provide convincing evidence demonstrating that the OX40-OX40L interaction is paramount in the development of Th2 responses in vivo.
A simple framework for filtering queued SMTP mail (cyberwar countermeasures) (2002)

Pre-information age military battlefields are based on the traditional land, sea, air, and space paradigm. Global internetworking is causal to the creation of a dangerously real 5th dimension of warfare-cyberspace. This paper describes an Internet based assault, commonly referred to as e-mail spam, on the Langley AFB internetworking infrastructure. We discuss the cyber-attack, a framework for defending against the attack, and the results of the campaign. The countermeasure was accomplished by running the MTA in a mode which accepts and queues SMTP mail; processes the messages with a rules-based filter; and then forwards mail after filtering. The filtering framework is simple and effective for a large subset of e-mail bombs. The prototype filter scripts may be obtained from the authors.
Simian rotavirus SA11 replication in cell cultures (1979)

Understanding the basic virology of rotavirus infections has been hampered by the fastidiousness of most isolates and by the lack of a rapid quantitative assay method. The growth characteristics of the simian rotavirus SA11 were studied because it grows to high titers in tissue culture and infectivity can be quantitated by plaque assay. SA11 replication was analyzed in a variety of primary cell cultures or continuous cell lines derived from both homologous and heterologous hosts. Viral replication was observed in each of the cell cultured examined. The individual cell cultures demonstrated marked variability in their susceptibility to rotavirus infection. The highest titers were obtained with MA104, BSC-1, CV-1, and BGM cells. Observable cytopathic effect was found to correlate with the percentage of infected cells in the culture. This study presents growth curves of the simian rotavirus in a variety of cell cultures.
Lysosomal targeting of Limp II membrane glycoprotein requires a novel Leu-Ile motif at a particular position in its cytoplasmic tail. (1994)

A class of integral membrane glycoproteins specific to lysosomes has been identified, and they are classified into two separate groups depending on whether or not their cytoplasmic sequence contains a tyrosine residue. Lamp-1 and lamp-2 have a tyrosine-containing motif in their cytoplasmic segments, and this motif was found to direct the glycoproteins to lysosomes. Limp II glycoprotein, on the other hand, lacks a tyrosine in its cytoplasmic segment and it must be directed to lysosomes by a different signal (Fukuda, M. (1991) J. Biol. Chem. 266, 21327-21330). In order to elucidate the targeting signal of Limp II, a cDNA encoding its cytoplasmic segment was fused with a reporter molecule, a chimeric protein of human gonadotropin alpha chain-vesicular stomatitis G-protein transmembrane. After various mutations its expression was examined by immunofluorescence. First it was shown that a chimeric protein with a Limp II wild-type tail is transported to lysosomes. Deletion of the three amino acids of the cytoplasmic tail at the carboxyl terminus abolished this sorting to lysosomes. Substitution of individual amino acids revealed that the Leu-Ile motif in the Leu-Ile-Arg-Thr sequence at the carboxyl terminus is crucial to the sorting signal. When this motif was brought closer to the transmembrane domain by deletion of nine amino acids next to the transmembrane domain, this sorting function was abolished. In addition, substitution of alanine for the serine, which is at 5 residues from the transmembrane also abolished the sorting capacity, although there was no evidence that the phosphorylation of serine is involved in sorting. Altered proteins that were not transported to lysosomes were found to accumulate at the cell surface and, unlike proteins with a wild-type cytoplasmic tail, were unable to undergo endocytosis. These results indicate that the carboxyl-terminal amino acid sequence, including the Leu-Ile motif and the sequence that connects the motif to the transmembrane domain, is critical for the sorting of Limp II to lysosomes.
Amine-Based CO2 Capture Technology Development from the Beginning of 2013—A Review (2015)

It is generally accepted by the scientific community that anthropogenic CO2 emissions are leading to global climate change, notably an increase in global temperatures commonly referred to as global warming. The primary source of anthropogenic CO2 emissions is the combustion of fossil fuels for energy. As society's demand for energy increases and more CO2 is produced, it becomes imperative to decrease the amount emitted to the atmosphere. One promising approach to do this is to capture CO2 at the effluent of the combustion site, namely, power plants, in a process called postcombustion CO2 capture. Technologies to achieve this are heavily researched due in large part to the intuitive nature of removing CO2 from the stack gas and the ease in retrofitting existing CO2 sources with these technologies. As such, several reviews have been written on postcombustion CO2 capture. However, it is a fast-developing field, and the most recent review papers already do not include the state-of-the-art research. Notable among CO2 capture technologies are amine-based technologies. Amines are well-known for their reversible reactions with CO2, which make them ideal for the separation of CO2 from many CO2-containing gases, including flue gas. For this reason, this review will cover amine-based technology developed and published in and after the year 2013.
The structure of the human βII-tryptase tetramer: Fo(u)r better or worse (1999)

Tryptases, the predominant serine proteinases of human mast cells, have recently been implicated as mediators in the pathogenesis of allergic and inflammatory conditions, most notably asthma. Their distinguishing features, their activity as a heparin-stabilized tetramer and resistance to most proteinaceous inhibitors, are perfectly explained by the 3-A crystal structure of human betaII-tryptase in complex with 4-amidinophenylpyruvic acid. The tetramer consists of four quasiequivalent monomers arranged in a flat frame-like structure. The active centers are directed toward a central pore whose narrow openings of approximately 40 A x 15 A govern the interaction with macromolecular substrates and inhibitors. The tryptase monomer exhibits the overall fold of trypsin-like serine proteinases but differs considerably in the conformation of six surface loops arranged around the active site. These loops border and shape the active site cleft to a large extent and form all contacts with neighboring monomers via two distinct interfaces. The smaller of these interfaces, which is exclusively hydrophobic, can be stabilized by the binding of heparin chains to elongated patches of positively charged residues on adjacent monomers or, alternatively, by high salt concentrations in vitro. On tetramer dissociation, the monomers are likely to undergo transformation into a zymogen-like conformation that is favored and stabilized by intramonomer interactions. The structure thus provides an improved understanding of the unique properties of the biologically active tryptase tetramer in solution and will be an incentive for the rational design of mono- and multifunctional tryptase inhibitors.
Positive Effects of Combined Antiretroviral Therapy on CD4 + T Cell Homeostasis and Function in Advanced HIV Disease (1997)

Highly active antiretroviral therapy (HAART) increases CD4(+) cell numbers, but its ability to correct the human immunodeficiency virus (HIV)-induced immune deficiency remains unknown. A three-phase T cell reconstitution was demonstrated after HAART, with: (i) an early rise of memory CD4(+) cells, (ii) a reduction in T cell activation correlated to the decreasing retroviral activity together with an improved CD4(+) T cell reactivity to recall antigens, and (iii) a late rise of "naïve" CD4(+) lymphocytes while CD8(+) T cells declined, however, without complete normalization of these parameters. Thus, decreasing the HIV load can reverse HIV-driven activation and CD4(+) T cell defects in advanced HIV-infected patients.
A comparison of the efficacy of different disinfection methods in eliminating Salmonella contamination from turkey houses (2010)

This study shows that disinfectants containing a mixture of formaldehyde, glutaraldehyde and QAC perform significantly better under field conditions than oxidising products and should therefore be the first choice for disinfection of turkey premises where Salmonella is present.
Expanding the Chemistry of DNA for in Vitro Selection (2010)

Six new 5-position modified dUTP derivatives connected by a unique amide linkage were synthesized and tested for compatibility with the enzymatic steps of in vitro selection. Six commercially available DNA polymerases were tested for their ability to efficiently incorporate each of these dUTP derivatives during PCR. It was not possible to perform PCR under standard conditions using any of the modified dUTP derivatives studied. In contrast, primer extension reactions of random templates, as well as defined sequence templates, were successful. KOD XL and D. Vent DNA polymerases were found to be the most efficient at synthesizing full-length primer extension product, with all of the dUTP derivatives tested giving yields similar to those obtained with TTP. Several of these modified dUTPs were then used in an in vitro selection experiment comparing the use of modified dUTP derivatives with TTP for selecting aptamers to a protein target (necrosis factor receptor superfamily member 9, TNFRSF9) that had previously been found to be refractory to in vitro selection using DNA. Remarkably, selections employing modified DNA libraries resulted in the first successful isolation of DNA aptamers able to bind TNFRSF9 with high affinity.
Target Detection Assay (TDA): a versatile procedure to determine DNA blinding sites as demonstrated on SP1 protein (1990)

We developed a rapid method designated Target Detection Assay (TDA) to determine DNA binding sites for putative DNA binding proteins. A purified, functionally active DNA binding protein and a pool of random double-stranded oligonucleotides harbouring PCR primer sites at each end are included the TDA cycle which consists of four separate steps: a DNA protein incubation step, a protein DNA complex separation step, a DNA elution step and a polymerase chain reaction (PCR) DNA amplification step. The stringency of selection can be increased in consecutive TDA cycles. Since tiny amounts of retained DNA can be rescued by PCR, buffer systems, salt concentrations and competitor DNA contents can be varied in order to determine high affinity binding sites for the protein of choice. To test the efficiency of the TDA procedure potential DNA binding sites were selected by the DNA binding protein SP1 from a pool of oligonucleotides with random nucleotides at 12 positions. Target sites selected by recombinant SP1 closely matched the SP1 consensus site. If DNA recognition sites have to be determined for known, mutated or putative DNA binding proteins, the Target Detection Assay (TDA) is a versatile and rapid technique for consideration.
Partial Nitrification/Denitrification Can Be Attributed to the Slow Response of Nitrite Oxidizing Bacteria to Periodic Anoxic Disturbances (2010)

This work aims to assess and model the behavior of both ammonium (AOB) and nitrite (NOB) oxidizing bacteria during the transition from completely anoxic to aerobic conditions. An enhanced aerobically grown culture containing AOB and NOB was subjected to anoxic conditions of varying durations from 1.5 to 12 h before its exposure to aerobic conditions. Experiments were carried out in both continuously stirred tank reactor (CSTR) and batch type reactors. Although the AOB did not exhibit any impact in their performance following the anoxic disturbance, the NOB were seriously inhibited presenting a period of reduced growth rate, which was proportional to the duration of the disturbance. This finding proves the previously postulated mechanism (NOB inhibition under periodic aerobic/anoxic operation) for achieving nitrogen removal via the partial nitrification/denitrification (PND) process as demonstrated in lab- and pilot-scale operating conditions. A mathematical model was developed to describe with sufficient accuracy the performance of AOB and NOB under aerobic, anoxic, and transient conditions in both CSTR and batch type systems. The model is able to describe the inhibitory effect of anoxic exposure to NOB by assuming enzyme deactivation (under anoxic conditions) and reactivation (adjustment of the NOB enzymatic mechanism) under aerobic conditions. The presented kinetic model is quite simple and general and therefore may be used for predicting the performance of mixed growth biological systems operating via the PND process.
Identification and Transgenic Analysis of a Murine Promoter that Targets Cholinergic Neuron Expression (1999)

Choline acetyltransferase (ChAT) is a specific phenotypic marker of cholinergic neurons. Previous reports showed that different upstream regions of the ChAT gene are necessary for cell type-specific expression of reporter genes in cholinergic cell lines. The identity of the mouse ChAT promoter region controlling the establishment, maintenance, and plasticity of the cholinergic phenotype in vivo is not known. We characterized a promoter region of the mouse ChAT gene in transgenic mice, using beta-galactosidase (LacZ) as a reporter gene. A 3,402-bp segment from the 5'-untranslated region of the mouse ChAT gene (from -3,356 to +46, +1 being the translation initiation site) was sufficient to direct the expression of LacZ to selected neurons of the nervous system; however, it did not provide complete cholinergic specificity. A larger fragment (6,417 bp, from -6,371 to +46) of this region contains the requisite regulatory elements that restrict expression of the LacZ reporter gene only in cholinergic neurons of transgenic mice. This 6.4-kb DNA fragment encompasses 633 bp of the 5'-flanking region of the mouse vesicular acetylcholine transporter (VAChT), the entire open reading frame of the VAChT gene, contained within the first intron of the ChAT gene, and sequences upstream of the start coding sequences of the ChAT gene. This promoter will allow targeting of specific gene products to cholinergic neurons to evaluate the mechanisms of diseases characterized by dysfunction of cholinergic neurons and will be valuable in design strategies to correct those disorders.
A novel and convenient route to 3'-carbonates from unprotected 2'-deoxy nucleosides through an enzymic reaction (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA novel and convenient route to 3'-carbonates from unprotected 2'-deoxy nucleosides through an enzymic reactionFranciso Moris and Vicente GotorCite this: J. Org. Chem. 1992, 57, 8, 2490–2492Publication Date (Print):April 1, 1992Publication History Published online1 May 2002Published inissue 1 April 1992https://doi.org/10.1021/jo00034a056RIGHTS & PERMISSIONSArticle Views196Altmetric-Citations49LEARN 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 (405 KB) Get e-Alerts Get e-Alerts
MONITORED HIGH-DOSE AZATHIOPRINE TREATMENT REDUCES ACUTE REJECTION EPISODES AFTER RENAL TRANSPLANTATION (1998)

High-dose AZA therapy in a triple-drug regimen, monitored by 6-TGN, will keep myelotoxicity within acceptable limits with the benefit of a reduction in acute rejection episodes.
Glycosylation at Asn-184 inhibits the conversion of single-chain to two-chain tissue-type plasminogen activator by plasmin (1990)

Tissue-type plasminogen activator (tPA) is a glycosylated serine protease which is an effective thrombolytic agent. Native single-chain tPA (sc-tPA) is converted to two-chain tPA (tc-tPA) by plasmin, the product of the reaction of plasminogen with tPA. Native sc-tPA occurs as two glycoforms. Type I sc-tPA is fully glycosylated, while type II lacks glycosylation at Asn-184. The rates at which type I and type II human melanoma sc-tPA were converted to type I and type II tc-tPA by plasmin were determined by two different methods. In each case, the second-order rate constant (kcat/Km) for type II sc-tPA (approximately 8 microM-1 s-1) was about twice that for type I sc-tPA (approximately 4 microM-1 s-1). These results indicate that glycosylation at Asn-184 hinders the conversion of sc-tPA to tc-tPA and suggest that under physiological conditions type I sc-tPA may persist in the single-chain form longer than type II sc-tPA. Previous studies have shown that type I tc-tPA has a lower activity than type II tc-tPA and that sc-tPA has a lower activity and susceptibility to inhibition when compared to tc-tPA. The present work provides further evidence that tPA glycosylation serves to modulate activity. The two major glycoforms may represent more persistent but slow acting (type I) and less persistent but faster acting (type II) variants of tPA.
Formulation, release characteristics, and bioavailability study of gastroretentive floating matrix tablet and floating raft system of Mebeverine HCl (2017)

To prolong the residence time of dosage forms within the gastrointestinal tract until all drug is released at the desired rate is one of the real challenges for oral controlled-release drug delivery systems. This study was designed to develop a controlled-release floating matrix tablet and floating raft system of Mebeverine HCl (MbH) and evaluate different excipients for their floating behavior and in vitro controlled-release profiles. Oral pharmacokinetics of the optimum matrix tablet, raft system formula, and marketed Duspatalin<sup>®</sup> 200 mg retard as reference were studied in beagle dogs. The optimized tablet formula (FT-10) and raft system formula (FRS-11) were found to float within 34±5 sec and 15±7 sec, respectively, and both remain buoyant over a period of 12 h in simulated gastric fluid. FT-10 (Compritol/HPMC K100M 1:1) showed the slowest drug release among all prepared tablet formulations, releasing about 80.2% of MbH over 8 h. In contrast, FRS-11 (Sodium alginate 3%/HPMC K100M 1%/Precirol 2%) had the greatest retardation, providing sustained release of 82.1% within 8 h. Compared with the marketed MbH product, the C<sub>max</sub> of FT-10 was almost the same, while FRS-11 maximum concentration was higher. The t<sub>max</sub> was 3.33, 2.167, and 3.0 h for marketed MbH product, FT-10, and FRS-11, respectively. In addition, the oral bioavailability experiment showed that the relative bioavailability of the MbH was 104.76 and 116.01% after oral administration of FT-10 and FRS-11, respectively, compared to marketed product. These results demonstrated that both controlled-released floating matrix tablet and raft system would be promising gastroretentive delivery systems for prolonging drug action.