gebhart/patrepeval huggingface dataset:
Chimeric RNA and 2′- O , 4′- C -Ethylene-Bridged Nucleic Acids Have Stronger Activity Than Phosphorothioate Oligodeoxynucleotides in Induction of Exon 19 Skipping in Dystrophin mRNA (2004)

Antisense phosphorothioate oligodeoxynucleotides against exon 19 of the dystrophin gene have been shown to induce exon 19 skipping and promote the expression of internally deleted dystrophin by correcting the translational reading frame. Because phosphorothioate oligonucleotides are associated with a variety of toxic nonantisense effects, several modifications of nucleic acid have been introduced to alleviate this toxicity. Recently, a 2'-O, 4'-C-ethylene-bridged nucleic acid (ENA trade mark, Sankyo Lifetech Co., Ltd., Tokyo, Japan) was reported to have high affinity to complementary RNA strands and be resistant to nuclease digestion. Here, we examined the ability of this modified nucleic acid to induce exon skipping. Oligonucleotides having the same sequence as the phosphorothioate oligonucleotides but with some stretches of modified backbone (2'-O-methyl RNA with an ENA5-mer at the 5'-end and 3'-end) (RNA/ENA chimera) were transfected into myocytes, and the expressed dystrophin mRNA was analyzed. The RNA/ENA chimera induced exon 19 skipping in a dose-dependent and time-dependent manner. Remarkably, the exon 19-skipping activity of the RNA/ENA chimera was more than 40 times stronger than that of the corresponding conventional phosphorothioate oligodeoxynucleotide. This is the first report of such strong activity of an RNA/ENA chimera in the induction of exon skipping in the dystrophin gene. This new technology will allow the development of less toxic antisense drugs, making long-term therapy possible.
O-acetylation and de-O-acetylation of sialic acids (1989)

We have previously described the preparation and use of 9-O-[acetyl-3H]acetyl-N-acetylneuraminic acid to identify sialic acid O-acetylesterases in tissues and cells (Higa, H. H., Diaz, S., and Varki, A. (1987) Biochem. Biophys. Res. Commun. 144, 1099-1108). All tissues of the adult rat showed these activities, with the exception of plasma. Rat liver contained two major sialic acid esterases: a cytosolic nonglycosylated enzyme and a membrane-associated glycosylated enzyme. The two enzymes were found in similar proportions and specific activities in a buffer extract of rat liver acetone powder. By using the latter as a source, the two enzymes were separated, and the glycosylated enzyme was purified to apparent homogeneity by multiple steps, including ConA-Sepharose affinity chromatography and Procion Red-agarose chromatography (yield, 13%; fold purification, approximately 3000). The homogeneous enzyme is a 61.5-kDa disulfide-linked heterodimeric protein, whose serine active site can be labeled with [3H]diisopropyl fluorophosphate. Upon reduction, two subunits of 36 kDa and 30 kDa are generated, and the 30-kDa subunit carries the [3H]diisopropyl fluorophosphate label. The protein has N-linked oligosaccharides that are cleaved by Peptide N-glycosidase F. These chains are cleaved to a much lesser extent by endo-beta-N-acetylglycosaminidase H, indicating that they are mainly complex-type glycans. The enzyme activity has a broad pH optimum range between 6 and 7.5, has no divalent cation requirements, is unaffected by reduction, and is inhibited by the serine active site inhibitors, diisopropyl fluorophosphate (DFP) and diethyl-p-nitrophenyl phosphate (Paraoxon). Kinetic studies with various substrates show that the enzyme is specific for sialic acids and selectively cleaves acetyl groups in the 9-position. It shows little activity against a variety of other natural compounds bearing O-acetyl esters. It appears to deacetylate di-O-acetyl- and tri-O-acetyl-N-acetylneuraminic acids by first cleaving the O-acetyl ester at the 9-position. The 7- and 8-O-acetyl esters then undergo spontaneous migration to the 9-position, where they can be cleaved, resulting in the production of N-acetylneuraminic acid. In view of its interesting substrate specificity, complex N-linked glycan structure, and neutral pH optimum, it is suggested that this enzyme is involved in the regulation of O-acetylation in membrane-bound sialic acids.
Selective expression of the chicken platelet‐derived growth factor α (PDGFα) receptor during limb bud development (1993)

Platelet-derived growth factor (PDGF) affects proliferation and differentiation of chicken limb bud mesoderm in vitro. However, no PDGF receptor has been characterized in the chicken wing bud in vivo. In this study, we used reverse transcription PCR (rtPCR), Northern blot analysis, and Western blot analysis to identify a molecule, in the developing wing bud, which represents the chicken homolog of the PDGF alpha receptor. The chicken PDGF alpha receptor mRNA was present in both mesoderm and ectoderm and all stages of the developing limb bud examined. Cultured limb bud mesoderm also expressed the PDGF alpha receptor transcript. In addition, the PDGF alpha receptor protein was present in whole limb buds and cultured limb bud mesoderm. Expression of the PDGF alpha receptor in cultured mesoderm was independent of the presence of ectoderm cells. The relative sizes of both the mRNA and protein for the PDGF alpha receptor in the chicken limb bud were similar to mammalian counterparts. Using similar approaches, neither the mRNA nor protein representing the chicken homolog of the PDGF beta receptor was detected. These data demonstrate for the first time that a PDGF alpha receptor is present in the embryonic chicken limb bud and may help regulate growth and differentiation of the embryonic limb.
Intravenous secretin for autism spectrum disorders (ASD) (2012)

There is no evidence that single or multiple dose intravenous secretin is effective and as such currently it should not be recommended or administered as a treatment for ASD. Further experimental assessment of secretin's effectiveness for ASD can only be justified if there is new high-quality and replicated scientific evidence that either finds that secretin has a role in neurotransmission in a way that could benefit all children with ASD or identifies important subgroups of children with ASD who could benefit from secretin because of a proven link between the action of secretin and the known cause of their ASD, or the type of problems they are experiencing.
Specific DNA cleavage and binding by vaccinia virus DNA topoisomerase I. (1990)

Cleavage of a defined linear duplex DNA by vaccinia virus DNA topoisomerase I was found to occur nonrandomly and infrequently. Approximately 12 sites of strand scission were detected within the 5372 nucleotides of pUC19 DNA. These sites could be classified as having higher or lower affinity for topoisomerase based on the following criteria. Higher affinity sites were cleaved at low enzyme concentration, were less sensitive to competition, and were most refractory to religation promoted by salt, divalent cations, and elevated temperature. Cleavage at lower affinity sites required higher enzyme concentration and was more sensitive to competition and induced religation. Cleavage site selection correlated with a pentameric sequence motif (C/T)CCTT immediately preceding the site of strand scission. Noncovalent DNA binding by topoisomerase predominated over covalent adduct formation, as revealed by nitrocellulose filter-binding studies. The noncovalent binding affinity of vaccinia topoisomerase for particular subsegments of pUC19 DNA correlated with the strength and/or the number of DNA cleavage sites contained therein. Thus, cleavage site selection is likely to be dictated by specific noncovalent DNA-protein interactions. This was supported by the demonstration that a mutant vaccinia topoisomerase (containing a Tyr----Phe substitution at the active site) that was catalytically inert and did not form the covalent intermediate, nevertheless bound DNA with similar affinity and site selectivity as the wild-type enzyme. Noncovalent binding is therefore independent of competence in transesterification. It is construed that the vaccinia topoisomerase is considerably more stringent in its cleavage and binding specificity for duplex DNA than are the cellular type I enzymes.
Evidence for the requirement for CD40–CD154 interactions in resistance to infections with attenuated <I>Salmonella</I> (2005)

Salmonella species include facultative intracellular pathogens which reside preferentially within cells of the host's reticulo-endothelial system. Resistance to Salmonella involves a collaboration between cells of the innate and adaptive immune systems, and protective immunity requires cell-mediated and humoral-immune responses. CD40-CD154 interactions are of central importance in the induction of cellular immune responses. In the present study, CD154-deficient (CD154(-/-)) mice were used to assess the role of CD40-CD154 interactions in immunity to Salmonella infection. Compared to C57BL/6 (CD154(+/+)) controls, CD154(-/-) mice were hypersusceptible to infection by an attenuated strain of Salmonella enterica serovar Typhimurium (S. typhimurium), as evidenced by a significantly decreased survival rate. CD154(-/-) mice exhibited a defect in the production of IFN-gamma and NO in the acute phase of the disease, which resulted in a failure to control bacterial replication. We conclude that intercellular communications via the CD40-CD154 pathway play a critical role in the induction type-1 cytokine responses and protection against primary infections with attenuated Salmonella.
Stroke-Order Independent On-Line Recognition Of Handwritten Chinese Characters (1989)

This paper proposes an on-line handwritten Chinese character recognition system based on stroke-sequence feature extraction. The character to be recognized can be stroke-order and stroke-number free, tolerance for combined strokes, size flexible, but within the constraint of normal hand-writing. Firstly, the recognizer, using the finite state matching mechanism, is used to extract primitive strokes, represented as stroke string, from the input character. Secondly, the recognizer, using a modified dynamic programming matching method, is employed to perform recognition processes with the stroke-string features. Reference patterns have been generated 2500 Chinese characters with stroke-numbers ranging from 1 to 29. The recognition results are based upon the 1800 handwritten characters by 10 people. The obtained recognition rate is 94.5%, and the cumulative classification rate of choosing fourth most similar characters is up to 98.7%. In the last part, a secondary recognition mechanism is used to further tell apart the candidates involved. The final recognition rate may be promoted up to 99%.
Issues and characteristics of the unmarried population. (1990)

The author examines characteristics of the never-married population in China. Consideration is given to sex ratio, geographical distribution, educational levels, and rates for rural and urban populations. Data are from the 1982 census and 1987 sample survey of one percent of the population.
Genomic analysis of primordial dwarfism reveals novel disease genes (2014)

Primordial dwarfism (PD) is a disease in which severely impaired fetal growth persists throughout postnatal development and results in stunted adult size. The condition is highly heterogeneous clinically, but the use of certain phenotypic aspects such as head circumference and facial appearance has proven helpful in defining clinical subgroups. In this study, we present the results of clinical and genomic characterization of 16 new patients in whom a broad definition of PD was used (e.g., 3M syndrome was included). We report a novel PD syndrome with distinct facies in two unrelated patients, each with a different homozygous truncating mutation in CRIPT. Our analysis also reveals, in addition to mutations in known PD disease genes, the first instance of biallelic truncating BRCA2 mutation causing PD with normal bone marrow analysis. In addition, we have identified a novel locus for Seckel syndrome based on a consanguineous multiplex family and identified a homozygous truncating mutation in DNA2 as the likely cause. An additional novel PD disease candidate gene XRCC4 was identified by autozygome/exome analysis, and the knockout mouse phenotype is highly compatible with PD. Thus, we add a number of novel genes to the growing list of PD-linked genes, including one which we show to be linked to a novel PD syndrome with a distinct facial appearance. PD is extremely heterogeneous genetically and clinically, and genomic tools are often required to reach a molecular diagnosis.
Bioengineered Cardiac Grafts : A New Approach to Repair the Infarcted Myocardium? (2000)

Alginate scaffolds provide a conducive environment to facilitate the 3D culturing of cardiac cells. After implantation into the infarcted myocardium, the biografts stimulated intense neovascularization and attenuated LV dilatation and failure in experimental rats compared with controls. This strategy can be used for regeneration and healing of the infarcted myocardium.
How Cations Can Assist DNase I in DNA Binding and Hydrolysis (2010)

DNase I requires Ca²+ and Mg²+ for hydrolyzing double-stranded DNA. However, the number and the location of DNase I ion-binding sites remain unclear, as well as the role of these counter-ions. Using molecular dynamics simulations, we show that bovine pancreatic (bp) DNase I contains four ion-binding pockets. Two of them strongly bind Ca²+ while the other two sites coordinate Mg²+. These theoretical results are strongly supported by revisiting crystallographic structures that contain bpDNase I. One Ca²+ stabilizes the functional DNase I structure. The presence of Mg²+ in close vicinity to the catalytic pocket of bpDNase I reinforces the idea of a cation-assisted hydrolytic mechanism. Importantly, Poisson-Boltzmann-type electrostatic potential calculations demonstrate that the divalent cations collectively control the electrostatic fit between bpDNase I and DNA. These results improve our understanding of the essential role of cations in the biological function of bpDNase I. The high degree of conservation of the amino acids involved in the identified cation-binding sites across DNase I and DNase I-like proteins from various species suggests that our findings generally apply to all DNase I-DNA interactions.
Mild Hypothermia Improves Recovery of Cortical Extracellular Potassium Ion Activity and Excitability After Middle Cerebral Artery Occlusion in the Rat (1999)

The data suggest that transient focal ischemia is accompanied by early disturbances of potassium ion homeostasis during reperfusion, which are accompanied by loss of excitability and which may contribute ultimately to cortical infarction.
Understanding Polymer Properties Important for Crystal Growth Inhibition—Impact of Chemically Diverse Polymers on Solution Crystal Growth of Ritonavir (2012)

The use of supersaturating dosage forms, such amorphous dispersions, is an increasingly common approach for improving delivery of poorly water-soluble drugs. Crystallization must be prevented to maintain supersaturation, and so, the presence of an effective crystal growth inhibitor in solution is desirable to prolong supersaturation. In this study, the effectiveness of a group of chemically diverse polymers, including a number of novel cellulose derivatives, at inhibiting the crystal growth of ritonavir from solution was quantified, enabling key polymer properties important for crystal growth inhibition of ritonavir to be elucidated. In general, the greater effectiveness of the cellulose derivatives relative to the synthetic polymers was ascribed to a moderate level of hydrophobicity, the semirigid structure of the cellulose polymers, and their amphiphilicity. Interestingly, some of the novel cellulose polymers were found to be more effective crystal growth inhibitors than commercially available cellulose derivatives. Orthogonal partial least-squares analysis further pointed to the importance of polymer hydrophobicity. These properties of the cellulose-based polymers are likely to promote adsorption onto the crystallizing drug surface. Given the diversity of impact of polymers on crystal growth inhibition, it is clearly important to consider this factor when choosing a polymer for a supersaturating dosage form.
Cell growth and lambda phage development controlled by the same essential Escherichia coli gene, ftsH/hflB. (1993)

The lambda phage choice between lysis and lysogeny is influenced by certain host functions in Escherichia coli. We found that the frequency of lambda lysogenization is markedly increased in the ftsH1 temperature-sensitive mutant. The ftsH gene, previously shown to code for an essential inner membrane protein with putative ATPase activity, is identical to hflB, a gene involved in the stability of the phage cII activator protein. The lysogenic decision controlled by FtsH/HflB is independent of that controlled by the protease HflA. Overproduction of FtsH/HflB suppresses the high frequency of lysogenization in an hflA null mutant. The FtsH/HflB protein, which stimulates cII degradation, may be a component of an HflA-independent proteolytic pathway, or it may act as a chaperone, maintaining cII in a conformation subject to proteolysis via such a pathway. Suppressor mutations of ftsH1 temperature-sensitive lethality, located in the fur gene (coding for the ferric uptake regulator), did not restore FtsH/HflB activity with respect to lambda lysogenization.
Prolactin Regulation of Cytological Differentiation of Mammary Epithelial Cells in Periparturient Cows* (1981)

The influence of periparturient secretion of PRL on cytological differentiation of mammary epithelial cells was studied in 17 multiparous, monotocous Holstein cows. Mammary tissue was obtained 10 days prepartum and 10 days postpartum from untreated cows and from cows treated with CB154 (2-Br-alpha-ergokryptin) or CB154 plus PRL. CB154 was administered from 12 days before expected parturition through 10 days postpartum to reduce serum PRL concentrations, whereas exogenous PRL was administered for 6 days during the periparturient period to mimic the normal periparturient surge of the hormone. On day 10 postpartum, mammary epithelial cells of cows given CB154 alone were classified 18% undifferentiated, 65% intermediately differentiated, and 18% fully differentiated. In contrast, there were no undifferentiated epithelial cells in either postpartum controls or cows treated with CB154 plus PRL, and 73% and 79% of epithelial cells, respectively, were fully differentiated. Ultrastructural analysis demonstrated a relative lack of cellular differentiation in cows given CB154 alone. Specifically, the rough endoplasmic reticulum occupied 24% and 27% of the epithelial cell area in postpartum controls and cows treated with CB154 plus PRL, respectively; but the rough endoplasmic reticulum occupied only 16% of the cellular area in cows treated with CB154 alone (P less than 0.01). The relative area occupied by Golgi membranes and vacuoles was approximately 11% lower (P less than 0.01) in cows treated with CB154 than in lactating controls or cows that received PRL replacement therapy. The data demonstrate that periparturient secretion of PRL is necessary for complete structural differentiation of bovine mammary alveolar epithelium.
Identification and Cloning of a Novel Family of Coiled-coil Domain Proteins That Interact with O-GlcNAc Transferase (2003)

The abundant and dynamic post-translational modification of nuclear and cytosolic proteins by beta-O-linked N-acetylglucosamine (O-GlcNAc) is catalyzed by O-GlcNAc transferase (OGT). Here we used the yeast two-hybrid approach to identify and isolate GABA(A) receptor-associated protein, GRIF-1 (Beck, M., Brickley, K., Wilkinson, H. L., Sharma, S., Smith, M., Chazot, P. L., Pollard, S., and Stephenson, F. A. (2002) J. Biol. Chem. 277, 30079-30090), and its novel homolog, OIP106 (KIAA1042), as novel OGT-interacting proteins. The proteins are highly similar to each other but are encoded by two separate genes. Both GRIF-1 and OIP106 contain coiled-coil domains and interact with the tetratricopeptide repeats of OGT. GRIF-1 and OIP106 are modified by O-GlcNAc and therefore are substrates for OGT. However, unlike another high affinity protein substrate, such as nucleoporin p62, OIP106 and GRIF-1 co-immunoprecipitate with OGT, exhibiting stable in vitro and in vivo associations. Whereas GRIF-1 has been reported to be expressed only in excitable tissue, OIP106 is expressed in all human cell lines that were examined. Confocal and electron microscopy show that OIP106 localizes to nuclear punctae in HeLa cells and co-localizes with RNA polymerase II. Co-immunoprecipitation experiments confirm the presence of an in vivo RNA polymerase II-OIP106-OGT complex, suggesting that OIP106 may target OGT to transcriptional complexes for glycosylation of transcriptional proteins, such as RNA polymerase II, and transcription factors. Similarly, GRIF-1 may serve to target OGT to GABA(A) receptor complexes for mediating GABA signaling cascades.
Safety and efficacy of high-dose intravenous iron carboxymaltose vs. iron sucrose for treatment of postpartum anemia (2012)

IV ICM is as safe as IS in the management of postpartum (IDA) iron deficiency anemia despite five times of higher dosage. Both drugs are effective and offer a rapid normalization of Hb after delivery. The single application of ICM shows advantages of lower incidence of side effects at the injection site, a shorter treatment period, and better patient compliance.
Mechano- or Acid Stimulation, Two Interactive Modes of Activation of the TREK-1 Potassium Channel (1999)

TREK-1 is a member of the novel structural class of K(+) channels with four transmembrane segments and two pore domains in tandem (1,2). TREK-1 is opened by membrane stretch and arachidonic acid. It is also an important target for volatile anesthetics (2,3). Here we show that internal acidification opens TREK-1. Indeed, lowering pH(i) shifts the pressure-activation relationship toward positive values and leads to channel opening at atmospheric pressure. The pH(i)-sensitive region in the carboxyl terminus of TREK-1 is the same that is critically involved in mechano-gating as well as arachidonic acid activation. A convergence, which is dependent on the carboxyl terminus, occurs between mechanical, fatty acids and acidic stimuli. Intracellular acidosis, which occurs during brain and heart ischemia, will induce TREK-1 opening with subsequent K(+) efflux and hyperpolarization.
The Pattern of Evolution in Public Sector Purchasing Consortia (1999)

ABSTRACT This research is concerned with how and why public sector organisations implement purchasing consortia. Case-based research was conducted at four public sector purchasing consortia in Canada, consisting of 18 separate public sector organisations. While cost factors were found to be an important reason why the consortia were created, other factors, such as the ability to attract new suppliers, support specialisation of staff, and provide supply with greater resources and stronger management capabilities were also seen as attractive features. A five phase life cycle model is presented to explain the evolution of the public sector purchasing consortia in the study. This research also observed high levels of organisational change in the public sector purchasing organisations studied, consistent with previous research on purchasing organisations in the private sector.