gebhart/patrepeval huggingface dataset:
Acrolein Mercapturates: Synthesis, Characterization, and Assessment of Their Role in the Bladder Toxicity of Cyclophosphamide (1995)

Acrolein is the metabolite of cyclophosphamide (CP) believed to be involved in the bladder toxicity associated with this anticancer drug. The mechanism by which this extremely reactive intermediate is delivered to the bladder is not known. Glutathione (GSH) readily conjugates with acrolein, and the acrolein mercapturate S-(3-hydroxypropyl)-N-acetylcysteine (3-hydroxy-PrMCA) has been found in the urine of animals and man given CP. The objectives of this study were to prepare and characterize synthetic standards of the GSH acrolein adduct (3-oxopropyl)glutathione (3-oxoPrGSH), the acrolein mercapturates S-(3-oxopropyl)-N-acetylcysteine (3-oxoPrMCA) and 3-hydroxyPrMCA, and the S-oxidation product of 3-oxoPrMCA (3-oxoPrMCA S-oxide). In addition, the release of acrolein from, and the bladder toxicity of, these conjugates was determined. 3-OxoPrGSH and 3-oxoPrMCA were prepared with a 99% yield by condensing acrolein with GSH and N-acetylcysteine, respectively. 3-HydroxyPrMCA was prepared with a 63% yield by refluxing 3-chloropropanol and N-acetylcysteine in a basic medium. Oxidation of 3-oxoPrMCA with H2O2 was used to prepare 3-oxoPrMCA S-oxide. By decreasing the reaction time to 1 h, and adjusting the ratio of 3-oxoPrMCA to H2O2, the yield of 3-oxoPrMCA S-oxide was increased to 96%. The anhydrous aldehyde, 3-oxoPrMCA, afforded characteristic aldehydic proton resonances (1H NMR) in deuterated dimethyl sulfoxide. New resonances were observed in deuterated water, indicating a 75% hydration of the aldehyde to the corresponding geminal diol. This phenomenon was enhanced with 3-oxoPrMCA S-oxide where approximately 100% hydration of the aldehyde to the corresponding geminal diol was observed. When incubated at 25 degrees C in 100 mM potassium phosphate buffer containing 1 M KCl, pH 8.0, 3-oxoPrMCA released approximately 6% and 3-oxoPrMCA S-oxide released approximately 16-18% of the theoretical maximum yield of acrolein after 30 min, as indicated by an increase in absorbance at 210 nm and confirmed by trapping this aldehyde as a semicarbazone. There was less than a 2% yield of acrolein from 3-hydroxyPrMCA or 3-oxoPrGSH under similar conditions. At pH 7.4 the release of acrolein from 3-oxoPrMCA and 3-oxoPrMCA S-oxide was decreased by 50%. An assay where aldehydes are reacted with m-aminophenol in acid media produced fluorescence consistent with 72%, 46%, 23%, and 1% yields of acrolein from 3-oxoPrMCA S-oxide, 3-oxoPrMCA, 3-oxoPrGSH, and 3-hydroxyPrMCA, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
Oligonucleotide-Mediated Survival of Motor Neuron Protein Expression in CNS Improves Phenotype in a Mouse Model of Spinal Muscular Atrophy (2009)

Spinal muscular atrophy (SMA) is caused by homozygous mutation or deletion of the <i>SMN1</i> gene encoding survival of motor neuron (SMN) protein, resulting in the selective loss of α-motor neurons. Humans typically have one or more copies of the <i>SMN2</i> gene, the coding region of which is nearly identical to <i>SMN1</i>, except that a point mutation causes splicing out of exon 7 and production of a largely nonfunctional SMNΔ7 protein. The development of drugs that mitigate aberrant <i>SMN2</i> splicing is an attractive therapeutic approach for SMA. A steric block antisense oligonucleotide (AO) has recently been developed that blocked an intronic splice suppressor element, and enhanced <i>SMN2</i> exon 7 inclusion in SMA patient fibroblasts. Here, we show that periodic intracerebroventricular (ICV) delivery of this AO resulted in increased SMN expression in brain and spinal cord to as much as 50% of the level of healthy littermates. Real-time PCR of <i>SMN2</i> transcripts confirmed the AO-mediated increase in full-length SMN. The AO-derived increase in SMN expression led to a concomitant improvement in bodyweight throughout the lifespan of the SMA animals. Treatment of SMA mice with AO also provided partial correction of motor deficits, manifest as improved righting response. Injections of a scrambled oligonucleotide had no effect on SMN expression or phenotype in the SMA mice. Our results validate that AOs that abrogate aberrant splicing of <i>SMN2</i> are promising compounds for treating SMA.
Chemical Composition of Satureja boissieri Hausskn. ex Boiss. Species From Adıyaman (Turkey) (2013)

The genus Satureja L. (Lamiaceae) includes about 200 species of herbs and shrubs, often aromatic, widely distributed in the Mediterranean area, Asia and boreal America (Rustaiyan et al., 2004). Satureja is rep- resented by sixteen taxa in Turkey (Davis, 1982; Tumen, 2000) and the endemism ratio is 33% in Turkey, where Satureja species are grown mainly in south and west Anatolia (Davis, 1982). The essential oil components of aerial parts of Satureja boissieri Hausskn. ex Boiss. was investigated by GC and GC-MS. The yield of plant is ca. 0.20 g L -1 . Thirty five component were identified representing 95.4% oil. Carvacrol (30.1%), thymol (21.8%), p -cymene (12.5%) and g-terpinene (6.5%) were found as main constituents. The results were discussed in terms of natural products, renewable resources and chemotaxonomy.
Additional member of the protein-tyrosine kinase family: the src- and lck-related protooncogene c-tkl. (1987)

We report the isolation and nucleotide sequence of a 3.7-kilobase (kb) cDNA clone from chicken spleen corresponding to a previously undescribed member of the src family of protooncogenes. It encodes a protein with a C-terminal domain related to the src family of protein-tyrosine kinases (EC 2.7.1.112) and, among these, has most significant homology to the lck gene isolated from a murine leukemia virus-induced thymoma cell line. The gene is therefore referred to as c-tkl for cellular tyrosine kinase related to lck. Analysis of genomic DNA reveals that c-tkl is a chromosomal locus distinct from c-src and c-lck. Furthermore, the size of c-tkl mRNA as well as its pattern of expression indicates that it is not the chicken homologue of lck but a different gene. A 3.8-kb transcript of the c-tkl gene, identical to the size determined for c-src mRNA, was observed in cultured chicken embryo fibroblasts and in chicken spleen and brain. In contrast, detection of a definite c-src mRNA signal with mRNA from spleen was not possible under the hybridization conditions employed when the 5' end of v-src was used as the probe, and none of the 11 clones obtained from the cDNA library corresponded to a c-src transcript. Thus previous studies of c-src mRNA expression in spleen may have actually detected c-tkl transcripts.
Immunological Differences between the Envelope Glycoproteins of Two Strains of Human Respiratory Syncytial Virus (1987)

The envelope glycoproteins of two distinct strains of respiratory syncytial virus (RSV) (Long and 18537 strains) were purified by affinity chromatography and characterized by immunological methods. The fusion (F) proteins from the two strains were similar in molecular weight by gel electrophoresis and were very closely related immunologically. Rabbit antisera to either F protein reacted with near equivalent titres with the heterologous F protein by Western blot, enzyme-linked immunoassay (EIA), neutralization and fusion inhibition assays. In contrast to the similarity of the F proteins, the attachment proteins (G) differed significantly. The 18537 G protein had a molecular weight of 78K compared to 84K for the Long G protein. Rabbit antisera to the G proteins clearly reacted preferentially with the homologous protein, although some cross-reactivity was noted by Western blot and EIA. Anti-G serum neutralized the homologous strain of RSV in the presence or absence of complement to much higher titre than the heterologous virus strain. The implications for vaccine development are discussed.
Increased number of micronuclei and nuclear anomalies in buccal mucosa cells from people exposed to alcohol-containing mouthwash (2012)

The aim of this study was to evaluate the effects of alcohol-containing mouthwash on the induction of micronuclei and nuclear anomalies in exfoliated buccal cells, including binucleated cells, cells with nuclear buds, and karyolitic, karyorrhectic, condensed chromatin, and pyknotic cells. Buccal mucosa cells were collected from 107 healthy participants who were divided into three groups: control subjects who did not use mouthwash (n = 33), subjects who were exposed for 30 days and two times rinsing with 30 seconds each time to alcohol-containing mouthwash (n = 38; 26% ethanol concentration); and subjects exposed to a non-alcohol-containing mouthwash (n = 36). A slide was used to collect cells from the oral mucosa from the inner lining of both cheeks. Samples were spread directly onto two separate, precleaned and precoded slides. Smears were air-dried, fixed, stained, and analyzed by microscopy for micronuclei and nuclear anomalies. Frequency of micronuclei, nuclear buds, and karyolitic, karyorrhectic, and condensed chromatin cells increased significantly (P < 0.05) in the alcohol-containing mouthwash group after mouthwash exposition, compared with both the control and the non-alcohol-containing mouthwash groups. Our results suggest that subjects exposed to alcohol-containing mouthwash exhibited an increase in frequency of micronuclei and nuclear anomalies in oral mucosal cells, which is directly related to DNA damage.
Criteria for the Evaluation of Library Networks (1987)

The relatively recent growth of library networks has focused on establishing, organizing, and maintaining systems for facilitating resource sharing. This paper samples some evaluation measures found in the literature regarding evaluating various types of networks: large-scale multi-type library networks (bibliographic utilities), regional networks, single-type and local systems. The paper concludes with a discussion of proposed criteria which may be useful for all types of library networks.
Staurosporine, a Novel Protein Kinase C Inhibitor, Prevents Postischemic Neuronal Damage in the Gerbil and Rat (1990)

The protective effects of protein kinase inhibitors and a calmodulin kinase inhibitor (W-7) against ischemic neuronal damage were examined in the CA1 subfield of the hippocampus. Staurosporine, KT5720, and KT5822 were used as inhibitors of protein kinase C (PKC), cyclic AMP-dependent protein kinase, and cyclic GMP-dependent protein kinase, respectively. All test compounds were injected topically into the CA1 subfield of the hippocampus. In the gerbil ischemia model, staurosporine (0.1-10 ng) administered 30 min before ischemia prevented neuronal damage in a dose-dependent manner. However, KT5720, KT5822, and W-7 were ineffective, even at a dose of 10 ng. In the rat ischemia model, staurosporine (10 ng) also prevented neuronal damage when administered before ischemic insult, although staurosporine administered 10 or 180 min after recirculation was ineffective. These results suggest the involvement of PKC in CA1 pyramidal cell death after ischemia and that the fate of vulnerable CA1 pyramidal cells through PKC-mediated processes could be determined during the early recirculation period.
New Substituted 1-(2,3-Dihydrobenzo[1,4]dioxin-2-ylmethyl)piperidin-4-yl Derivatives with α2-Adrenoceptor Antagonist Activity (2000)

The emergence of a novel theory concerning the role of noradrenaline in the progression and the treatment of neurodegenerative diseases such as Parkinson's and Alzheimer's diseases has provided a new impetus toward the discovery of novel compounds acting at alpha(2)-adrenoceptors. A series of substituted 1-(2, 3-dihydrobenzo[1,4]dioxin-2-ylmethyl)piperidin-4-yl derivatives bearing an amide, urea, or imidazolidinone moiety was studied. Some members of this series of compounds proved to be potent alpha(2)-adrenoceptor antagonists with good selectivity versus alpha(1)-adrenergic and D(2)-dopamine receptors. Particular emphasis is given to compound 33g which displays potent alpha(2)-adrenoceptor binding affinity in vitro and central effects in vivo following oral administration.
Chemical and Physical Properties of Freezing Point-depressing Glycoproteins from Antarctic Fishes (1970)

Glycoproteins were isolated from the blood sera of the Antarctic fishes Trematomus borchgrevinki and Dissostichus mawsoni. Some of these glycoproteins have the unique property of depressing the freezing point of water more than expected on the basis of the number of particles present in solution and are termed active glycoproteins. These freezing point-depressing glycoproteins depress the freezing point of water to the same extent as NaCl on a weight basis. They are composed primarily of threonine (16%), alanine (23%), N-acetylgalactosamine (29%), and galactose (28%). Compared with the active glycoproteins, the inactive ones (which form ideal solutions) have approximately the same composition except that proline is present. The active glycoproteins have been separated into three distinct groups, based on results from ion exchange chromatography and acrylamide gel electrophoresis. The three active glycoproteins occur in equal amounts in the blood sera, have identical compositions on a weight basis, but differ in molecular weights (10,500,17,000 and 21,500 g). Studies of viscosity and circular dichroism and dialysis experiments indicate that the active glycoproteins are expanded molecules, a property which undoubtedly is of importance to their function.
Glucagon Gene 3′-Flanking Sequences Direct Formation of Proglucagon Messenger RNA 3′-Ends in Islet and Nonislet Cells Lines (1990)

Glucagon and the glucagon-like peptides are encoded within a larger precursor, proglucagon. Transcription of the glucagon gene in pancreas, intestine, and brain gives rise to identical proglucagon mRNA transcripts, after which tissue-specific posttranslational processing produces different profiles of proglucagon-derived peptides in each tissue. The importance of glucagon gene 3′-untranslated and 3′-flanking sequences in the control of glucagon mRNA production was studied by transfecting a series of 3′-deleted glucagon genes into fibroblast and islet cell lines. Glucagon genes containing 2 kilobases of 3′-flanking sequences gave rise to accurately processed mRNA transcripts in both baby hamster kidney fibroblasts and lnR1-G9 islet cell lines. Deletion of all but 50 basepairs of 3′-flanking sequence had no effect on glucagon mRNA 3′-end formation. In contrast, additional deletion of 3′-flanking and 3′-untranslated sequences resulted in the production of read-through mRNA transcripts with aberrant 3′-ends. The results of these studies define a 50-basepair region in the 3′-flanking sequence of the glucagon gene important for the accurate processing of proglucagon mRNA transcripts.
Identification and Characterization of a Family of Mammalian Methyl-CpG Binding Proteins (1998)

Methylation at the DNA sequence 5'-CpG is required for mouse development. MeCP2 and MBD1 (formerly PCM1) are two known proteins that bind specifically to methylated DNA via a related amino acid motif and that can repress transcription. We describe here three novel human and mouse proteins (MBD2, MBD3, and MBD4) that contain the methyl-CpG binding domain. MBD2 and MBD4 bind specifically to methylated DNA in vitro. Expression of MBD2 and MBD4 tagged with green fluorescent protein in mouse cells shows that both proteins colocalize with foci of heavily methylated satellite DNA. Localization is disrupted in cells that have greatly reduced levels of CpG methylation. MBD3 does not bind methylated DNA in vivo or in vitro. MBD1, MBD2, MBD3, and MBD4 are expressed in somatic tissues, but MBD1 and MBD2 expression is reduced or absent in embryonic stem cells which are known to be deficient in MeCP1 activity. The data demonstrate that MBD2 and MBD4 bind specifically to methyl-CpG in vitro and in vivo and are therefore likely to be mediators of the biological consequences of the methylation signal.
Multifunctional, self-assembling anionic peptide-lipid nanocomplexes for targeted siRNA delivery (2014)

Formulations of cationic liposomes and polymers readily self-assemble by electrostatic interactions with siRNA to form cationic nanoparticles which achieve efficient transfection and silencing in vitro. However, the utility of cationic formulations in vivo is limited due to rapid clearance from the circulation, due to their association with serum proteins, as well as systemic and cellular toxicity. These problems may be overcome with anionic formulations but they provide challenges of self-assembly and transfection efficiency. We have developed anionic, siRNA nanocomplexes utilizing anionic PEGylated liposomes and cationic targeting peptides that overcome these problems. Biophysical measurements indicated that at optimal ratios of components, anionic PEGylated nanocomplexes formed spherical particles and that, unlike cationic nanocomplexes, were resistant to aggregation in the presence of serum, and achieved significant gene silencing although their non-PEGylated anionic counterparts were less efficient. We have evaluated the utility of anionic nanoparticles for the treatment of neuronal diseases by administration to rat brains of siRNA to BACE1, a key enzyme involved in the formation of amyloid plaques. Silencing of BACE1 was achieved in vivo following a single injection of anionic nanoparticles by convection enhanced delivery and specificity of RNA interference verified by 5' RACE-PCR and Western blot analysis of protein.
Reproductive tract infections including sexually transmitted infections: a population-based study of women of reproductive age in a rural district of Vietnam (2007)

RTI/STI were prevalent among married women in a rural population of Vietnam. Syndromic algorithms should be consistently supplemented by risk assessment in order to reduce under and overtreatment. Microscopic diagnosis could be applied in primary care settings to achieve more accurate diagnoses. The promotion of health education aimed at reducing RTI/STI prevalences is an important tool in STI/HIV control programmes. Vaccination to prevent hepatitis B for migrants should be considered.
Ku DNA end-binding protein modulates homologous repair of double-strand breaks in mammalian cells (2001)

Chromosomal double-strand breaks (DSBs) in mammalian cells are repaired by either homology-directed repair (HDR), using a homologous sequence as a repair template, or nonhomologous end-joining (NHEJ), which often involves sequence alterations at the DSB site. To characterize the interrelationship of these two pathways, we analyzed HDR of a DSB in cells deficient for NHEJ components. We find that the HDR frequency is enhanced in Ku70(-/-), XRCC4(-/-), and DNA-PKcs(-/-) cells, with the increase being particularly striking in Ku70(-/-) cells. Neither sister-chromatid exchange nor gene-targeting frequencies show a dependence on these NHEJ proteins. A Ku-modulated two-ended versus one-ended chromosome break model is presented to explain these results.
[Prevention in the pregnancy-puerperium cycle: a model of interdisciplinary action at the Hospital Universitário Regional do Norte do Paraná]. (1991)

This paper shows a systematic approach adapted by an interdisciplinary team in the assistance to pregnant women through joint actions, which also promoted a special environment for professional development. This work is part of an extension project.
A Multicenter Trial Defining a Serum Protein Signature Associated with Pancreatic Ductal Adenocarcinoma (2015)

Background. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with rapid tumor progression and poor prognosis. This study was motivated by the lack of sensitive and specific PDAC biomarkers and aimed to identify a diagnostic, serum protein signature for PDAC. Methods. To mimic a real life test situation, a multicenter trial comprising a serum sample cohort, including 338 patients with either PDAC or other pancreatic diseases (OPD) and controls with nonpancreatic conditions (NPC), was analyzed on 293-plex recombinant antibody microarrays targeting immunoregulatory and cancer-associated antigens. Results. Serum samples collected from different hospitals were analyzed and showed that (i) sampling from five different hospitals could not be identified as a preanalytical variable and (ii) a multiplexed biomarker signature could be identified, utilizing up to 10 serum markers that could discriminate PDAC from controls, with sensitivities and specificities in the 91-100% range. The first protein profiles associated with the location of the primary tumor in the pancreas could also be identified. Conclusions. The results demonstrate that robust enough serum signatures could be identified in a multicenter trial, potentially contributing to the development of a multiplexed biomarker immunoassay for improved PDAC diagnosis.
Semantics-based context-aware dynamic service composition (2009)

This article presents a semantics-based context-aware dynamic service composition framework that composes an application through combining distributed components based on the semantics of components and contexts of users. The proposed framework consists of Component Service Model with Semantics (CoSMoS), Component Runtime Environment (CoRE), and Semantic Graph based Service Composition (SeGSeC). CoSMoS models the semantics of components and contexts of users. CoRE is a middleware to support CoSMoS on various distributed computing technologies. SeGSeC is a mechanism to compose an application by synthesizing its workflow based on the semantics of components and contexts of users. The proposed framework is capable of composing applications requested in a natural language by leveraging the semantic information of components. The proposed framework composes applications differently to individual users based on their contexts and preferences. The proposed framework acquires user preferences from user-specified rules and also via learning. The proposed framework also adapts to dynamic environments by autonomously composing a new application upon detecting context change. This article describes the design and mechanism of the proposed framework, and also presents simulation experiments to evaluate the proposed framework.
Substrate step-edge YBa2Cu3O7 rf SQUIDs (1991)

We have developed a technique which permits high-yield fabrication of microbridges and low noise YBa2Cu3O7 superconducting quantum interference devices (SQUIDs) in epitaxial thin films. These SQUIDs operate over a wide temperature range extending from 4 K to close to the superconducting transition temperature. Measurements of an rf SQUID operating at 77 K give a peak-to-peak flux sensitivity of 36 μV/Φ0 and a flux noise at 10 Hz of 1.5× 10−4 Φ0/√Hz. Device yields over 80% have been obtained.
Peptides corresponding to helices 5 and 6 of Bax can independently form large lipid pores (2006)

Proteins of the B-cell lymphoma protein 2 (Bcl2) family are key regulators of the apoptotic cascade, controlling the release of apoptotic factors from the mitochondrial intermembrane space. A helical hairpin found in the core of water-soluble folds of these proteins has been reported to be the pore-forming domain. Here we show that peptides including any of the two alpha-helix fragments of the hairpin of Bcl2 associated protein X (Bax) can independently induce release of large labelled dextrans from synthetic lipid vesicles. The permeability promoted by these peptides is influenced by intrinsic monolayer curvature and accompanied by fast transbilayer redistribution of lipids, supporting a toroidal pore mechanism as in the case of the full-length protein. However, compared with the pores made by complete Bax, the pores made by the Bax peptides are smaller and do not need the concerted action of tBid. These data indicate that the sequences of both fragments of the hairpin contain the principal physicochemical requirements for pore formation, showing a parallel between the permeabilization mechanism of a complex regulated protein system, such as Bax, and the much simpler pore-forming antibiotic peptides.