gebhart/patrepeval huggingface dataset:
Cloning and characterization of rabbit liver UDP-glucuronosyltransferase cDNAs. Developmental and inducible expression of 4-hydroxybiphenyl UGT2B13 (1993)

A polyclonal antibody generated against rabbit liver p-nitrophenol UDP-glucuronosyltransferase (UGT) was used to screen a rabbit liver cDNA expression library constructed in lambda gt11. A 500-base pair cDNA clone, termed pPNP, generated a fusion protein that was antigenic with the antibody. Clone pPNP encoded the 3' region of a UGT. To identify larger recombinants, clone pPNP was used as a probe to screen a second cDNA library constructed in lambda ZAP. Two different cDNA clones were identified by DNA sequence analysis. Based upon their predicted amino acid sequence analysis, the clones encode transferases belonging to the UGT2 subfamily, and have been identified as UGT2B13 and UGT2B14. The predicted N-terminal sequence of UGT2B13 is identical to that determined for the purified rabbit liver estrone UGT. However, expression of the UGT2B13 cDNA in COS-1 cells displayed no activity in the presence of estrone but efficiently conjugated 4-hydroxybiphenyl. Results of Southern blot analysis using the 5' divergent region of the UGT2B13 cDNA that encodes exon 1 demonstrates that multiple genes share sequence homology to UGT2B13, an observation which indicates that the estrone UGT and UGT2B13 genes are encoded by separate alleles. When the 5' variable regions of the cDNAs where used in Northern blot analysis, the expression of UGT2B13 and UGT2B14 were shown to be expressed primarily in adult rabbits. However, when neonatal rabbits were treated with either dexamethasone or rifampicin, UGT2B13 mRNA levels were induced. The neonatal induction of UGT2B13 mRNA corresponded with similar increases in 4-hydroxybiphenyl UGT activity. The expression and induction of UGT2B13 paralleled that of the developmentally regulated rabbit liver progesterone 6 beta-hydroxylase P4503A6.
Gene Therapy of a Rat Follicular Thyroid Carcinoma Model with Adenoviral Vectors Transducing Murine Interleukin-12 (2003)

Interleukin-12 (IL12) is a heterodimeric cytokine that plays an important role in the development of cellular immunity. We previously reported the antitumor activity of mouse IL12 (mIL12) transduced by adenovirus in a medullary thyroid carcinoma model. In this study, a rat thyroid follicular cancer cell line (RTC-R2) was employed to develop tumors after sc injection in Wistar rats. In five of five animals, RTC-R2 cells infected with mIL12 transducing adenovirus (AdCMVmIL12) in vitro failed to be tumorigenic in vivo in syngenic rats, whereas four of five animals developed tumors after injection of luciferase transducing adenovirus (AdCMVLuc)-infected cells. After intratumoral treatment with AdCMVmIL12 at 1 x 10(9) plaque-forming units per rat, 90% (26/29) of animals bearing small (<100 mm(3)) tumors were apparently cured. Larger tumors treated by injection of AdCMVmIL12 became significantly smaller than AdCMVLuc-treated animals, and growth stabilized. Challenge studies showed that only 3 of 28 animals previously treated and cured with AdCMVmIL12 developed a tumor after sc reinjection of RTC-R2 cells, whereas all animals developed tumors in naïve animals. Thus, AdCMVmIL12-treated animals developed long-term antitumor immunity. We also studied animals with two tumors, injecting virus in one. Tumors regressed at both sites in five of six animals after treatment of one tumor with AdCMVmIL12, and in the sixth animal one site tumor regressed and another tumor continued to grow. In AdCMVLuc-treated animals, both tumors regressed in only one animal, and the reminder continued to grow. To detect toxicity to liver and other tissues after administration of AdCMVmIL2, the vector was administrated intratumorally or iv at the dose of 2 x 10(9) plaque-forming units per rat. No change in behavior was observed in any of the treated animals. Rats were killed at different time after virus administration. An overt increase of spleen size was observed 7 d after infection in all animals treated with AdCMVmIL12. All animals given virus IV had some lymphocyte infiltration in the sinusoids and triads of the liver, whereas AdCMVmIL12 injected intratumorally did not cause this effect. Spleens of some virus-treated animals showed decreased white pulp, with apparently increased hematopoiesis. No specific changes were found in lungs and kidneys. Iv administration of AdCMVmIL12 induced a moderate increase of glutamic-oxalacetic transaminase and glutamic-pyruvic transaminase, whereas AdCMVmIL12 injected intratumorally did not. This study confirms the efficient antitumor activity of an adenovirus expressing mIL12 after in vivo delivery in an animal model and indicates the possibility of application to patients because of the low toxicity.
A single-nucleotide polymorphism in the human beta-defensin 1 gene is associated with HIV-1 infection in Italian children (2004)

In this study we show a significant correlation between a single-nucleotide polymorphism in the 5'-untranslated region of the DEFB1 gene, which probably regulates the gene expression of human beta defensin 1 (hBD-1) and the risk of HIV-1 infection in an Italian paediatric population (97 HIV-1 perinatally infected children), pointing to the importance of innate immunity in HIV-1 infection.
A 90nm CMOS PA module for 4G applications with embedded PVT gain compensation circuit (2012)

A 90nm CMOS dual band power amplifier flip-chip module for 4G (WiMAX/LTE) applications with embedded process and temperature gain compensation circuit, is presented. The gain compensation circuit reduces the gain variation over temperature from 3dB/stage to 0.25dB/stage. Mask compliance is achieved at power (efficiency) of 26.7/26.3dBm (24/23%) and 27.9/27.3dBm (29/26%) for 10MHz WiMAX and LTE packets, at 2.5/3.5GHz bands, respectively.
The influence of the central region containing residues 19−25 on the aggregation properties and secondary structure of Alzheimer's β‐amyloid peptide (1998)

Alzheimer's beta-amyloid peptide (Abeta) is a 39- to 43-amino-acid peptide that is the major component of neuritic plaques found in Alzheimer's disease (AD). The central region of Abeta plays a crucial role in many of its properties, including aggregation, neurotoxicity, proteolytic processing and interactions with other proteins, such as apolipoprotein E. Two mutations in this region, Ala21-->Gly and Glu22-->Gln, give rise to early onset forms of disease. We have studied several peptides based on the central region of Abeta in order to clarify the influence of specific amino acid residues on physicochemical behaviour. To avoid difficulties due to oxidation of Met35, the latter was replaced by the amino acid isostere, norleucine (Ahx), giving [Ahx35]Abeta-(25-35)-amide as a prototype structure. To this prototype, addition of pairs of amino acid residues from the sequence of Abeta, forming the corresponding 23-, 21- and 19-35 derivatives, resulted in peptides that aggregated to form fibrils of diameter 6-10 nm. The rate of aggregation was more rapid as peptide length increased. Circular dichroism spectra of aged solutions of peptides revealed that aggregation was accompanied by a transition from random structure to beta sheet for some, but not all, peptides. The mutation from Ala to Gly at position 21 increased the rate of aggregation and altered the tendency to adopt secondary structure in the direction away from alpha helix and towards beta sheet. In individuals with the Ala21-->Gly mutation, these results would suggest that truncated species with N-termini in the region containing residues 17-20 would be more amyloidogenic than the wild type homologues.
Control of selectivity of chemical reaction via control of wave packet evolution (1985)

A time-dependent formulation of two-photon spectroscopy is employed to show that selectivity of reactivity can be achieved via coherent two-photon processes. The problem of finding the optimum waveform (i.e., coherent pulse sequence) that will maximize the formation of a desired chemical species is formulated as a problem in the calculus of variations, and solved for two different cases.
Fucosyl neoglycoprotein binds to mouse epididymal spermatozoa and inhibits sperm binding to the egg zona pellucida (2012)

Glycan epitopes of cellular glycoconjugates act as versatile biochemical signals, and this sugar coding plays an important role in cell-to-cell recognition processes. In this study, our aims were to determine the distribution of sperm receptors with activity for fucosyl- and galactosyl glycans and to address whether monosugar neoglycoproteins functionally mimic the binding between zona pellucida (ZP) glycoproteins and spermatozoa. In mouse epididymal spermatozoa with intact acrosomes, fucopyranosyl bovine serum albumin (BSA-Fuc) bound to the segment of the acrosome, the equatorial segment, and the postacrosome region of the sperm head. Galactosyl BSA (BSA-Gal) binding activity was similar to that of BSA-Fuc, but was weaker. In acrosome-reacted spermatozoa treated with the Ca(2+) ionophore A23187, BSA-zuc binding was lost in the apical segment of the acrosome but remained in the equatorial segment and postacrosome regions. BSA-Gal binding to the equatorial region was increased. In the presence of 2.5 μg ml(-1) BSA-Fuc, in vitro sperm-ZP binding was significantly decreased, indicating that fucosyl BSA functionally mimics ZP glycoproteins during sperm-egg ZP interactions. At the same concentration, BSA-Gal was not effective. Fucosyl BSA that efficiently inhibited the sperm-ZP binding can mimic the ZP glycoconjugate and has potential for use as a sperm fertility control agent in mouse.
Nitric Oxide-Releasing Polymers Containing the [N(O)NO]-Group (1996)

Ions of structure X[N(O)NO]- display broad-spectrum pharmacological activity that correlates with the rate and extent of their spontaneous, first-order decomposition to nitric oxide when dissolved. We report incorporation of this functional group into polymeric matrices that can be used for altering the time course of nitric oxide release and/or targeting it to tissues with which the polymers are in physical contact. Structural types prepared include those in which the [N(O)NO]- group is attached to heteroatoms in low molecular weight species that are noncovalently distributed throughout the polymeric matrix, in groupings pendant to the polymer backbone, and in the polymer backbone itself. They range in physical form from films that can be coated onto other surfaces to microspheres, gels, powders, and moldable resins. Chemiluminescence measurements confirm that polymers to which the [N(O)NO]- group is attached can serve as localized sources of nitric oxide, with one prototype providing sustained NO release for 5 weeks in pH 7.4 buffer at 37 degrees C. The latter composition, a cross-linked poly-(ethylenimine) that had been exposed to NO, inhibited the in vitro proliferation of rat aorta smooth muscle cells when added as a powder to the culture medium and showed potent antiplatelet activity when coated on a normally thrombogenic vascular graft situated in an arteriovenous shunt in a baboon's circulatory system. The results suggest that polymers containing the [N(O)NO]- functional group may hold considerable promise for a variety of biomedical applications in which local delivery of NO is desired.
Targeting anticomplement agents (2002)

Biological targeting is normally thought of as a process of specific direction of one molecule (the agent) to another (the target) in vivo. However, an addressive approach in which the agent is concentrated, first within the vasculature and then at a disease site containing one or more targets, may be more suitable for delivering therapeutic quantities of certain drugs. This approach has been applied to complement regulatory molecules expressed in recombinant soluble forms and attached post-translationally to highly soluble synthetic peptide derivatives comprising two addressin units, one with affinity for the membrane bilayer interior and the other for phospholipid headgroups. This combination conferred affinity for outer cell membranes in general, and areas of translocated acidic phospholipid in particular. Large increases in potency in cell-based antihaemolytic assays accompanied modification and were shown to be associated with membrane binding. Modified agents co-localized with glycosylphosphatidyl- inositol-anchored proteins in lipid rafts on cell membranes. One agent, a modified fragment of human complement receptor-1 (APT070), has been prepared on a large scale and has been shown to be an active anti-inflammatory agent when administered locally and systemically in animal models of vascular shock, rheumatoid arthritis and transplantation reperfusion injury. APT070 has been shown to be well tolerated in human subjects when given intravenously and is currently under study in rheumatoid arthritis patients to explore the therapeutic potential of localized complement inhibition in the synovial space.
Promising AIDS Vaccine's Failure Leaves Field Reeling (2007)

The failure of a promising AIDS vaccine in a large human trial, dubbed STEP, has stunned researchers and raised concerns about the broader T-cell vaccine concept and the future of AIDS vaccine research and development.
Comprehensive gene expression analysis of prostate cancer reveals distinct transcriptional programs associated with metastatic disease. (2002)

The identification of genes that contribute to the biological basis for clinical heterogeneity and progression of prostate cancer is critical to accurate classification and appropriate therapy. We performed a comprehensive gene expression analysis of prostate cancer using oligonucleotide arrays with 63,175 probe sets to identify genes and expressed sequences with strong and uniform differential expression between nonrecurrent primary prostate cancers and metastatic prostate cancers. The mean expression value for >3,000 tumor-intrinsic genes differed by at least 3-fold between the two groups. This includes many novel ESTs not previously implicated in prostate cancer progression. Many differentially expressed genes participate in biological processes that may contribute to the clinical phenotype. One example was a strong correlation between high proliferation rates in metastatic cancers and overexpression of genes that participate in cell cycle regulation, DNA replication, and DNA repair. Other functional categories of differentially expressed genes included transcriptional regulation, signaling, signal transduction, cell structure, and motility. These differentially expressed genes reflect critical cellular activities that contribute to clinical heterogeneity and provide diagnostic and therapeutic targets.
The N-terminal ERK-binding Site of MEK1 Is Required for Efficient Feedback Phosphorylation by ERK2 in Vitro and ERK Activation in Vivo (1999)

An ERK2-binding site at the N terminus of MEK1 was reported to mediate their stable association. We examined the importance of this binding site in the feedback phosphorylation of MEK1 on Thr(292) and Thr(386) by ERK2, the phosphorylation and activation of ERK2 by MEK1, and the interaction of MEK1 with ERK2 and Raf-1. Deletion of the binding site from MEK1 reduced its phosphorylation by ERK2, but had no effect on its phosphorylation by p21-activated protein kinase-1 (PAK1). A MEK1 N-terminal peptide containing the binding site inhibited MEK1 phosphorylation by ERK2. However, it did not affect MEK1 phosphorylation by p21-activated protein kinase or myelin basic protein phosphorylation by ERK2. Deletion of the N-terminal ERK-binding domain of MEK1 also reduced its ability to phosphorylate ERK2 in vitro, to co-immunoprecipitate with ERK2, and to stimulate ERK2 activation in transfected cells, but it did not alter the association with endogenous Raf-1. Using ERK2-p38 chimeras and an ERK2 deletion mutant, a MEK1-binding site of ERK2 was localized to its N terminus.
Size-Exclusion Chromatography Purification of High-Titer Vesicular Stomatitis Virus G Glycoprotein-Pseudotyped Retrovectors for Cell and Gene Therapy Applications (2003)

Vesicular stomatitis virus G glycoprotein (VSV-G)-pseudotyped replication-defective retroviral particles are pantropic and amenable to concentration to high titer by ultracentrifugation. These features have allowed development of effective retroviral transduction protocols for stem cells in vitro as well as for tissue engineering in vivo. However, retroparticle ultracentrifugation protocols will also copellet cellular and subcellular debris released from retroviral producer cell lines during vector manufacture. We have analyzed concentrated vector preparations by chromatography and have found that a significant amount of genomic DNA released from producer cells coconcentrates with retroviral particles. In an effort to generate high-purity retroparticle preparations, devoid of subcellular contaminants and contaminating genomic DNA, we have developed a process using size-exclusion chromatography combined with host cell nucleic acid digestion and concentration by ultrafiltration. The procedure allowed for a final recovery of 19 +/- 0.4% infectious viral particles from unfractionated starting material, with an average retroparticle concentration of 7.7 x 10(7) +/- 1.5 x 10(6)/ml. The intact virus is of high purity, >90% as determined by anion-exchange high-performance liquid chromatography. Retroparticle structure appeared intact as determined by negative stain electron microscopy and purified virus was functional and allowed for efficient transduction of primary human bone marrow stromal cells in vitro. In conclusion, we have developed a VSV-G retrovector purification process that can be applied to large-scale retroviral production ideal for cell and gene therapy applications.
Cationic polymerization of glycidol: coexistence of the activated monomer and active chain end mechanism (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCationic polymerization of glycidol: coexistence of the activated monomer and active chain end mechanismR. Tokar, P. Kubisa, S. Penczek, and A. DworakCite this: Macromolecules 1994, 27, 2, 320–322Publication Date (Print):January 1, 1994Publication History Published online1 May 2002Published inissue 1 January 1994https://pubs.acs.org/doi/10.1021/ma00080a002https://doi.org/10.1021/ma00080a002research-articleACS PublicationsRequest reuse permissionsArticle Views1925Altmetric-Citations196LEARN 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 InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Syntheses of 5-substituted oxazole-4-carboxylic acid derivatives with inhibitory activity on blood platelet aggregation. (1983)

Methyl 5-substituted oxazole-4-carboxylates were synthesized by the reaction of methyl α-isocyanoacetate with acylating reagents in the presence of bases. The oxazole methyl esters were converted into the carboxylic acids and the carboxamides. Then, N-alkyl-oxazole-4-carboxamides were prepared through the oxazole-4-carboxylic acid chloride. Furthermore, 2-substituted oxazoles were synthesized by cyclization of N-acyl-α-benzoylglycine methyl esters. which were obtained by acylation of α-benzoylglycine methyl ester followed by ammonolysis of the resulting oxazole methyl esters. These oxazole compounds were evaluated for inhibitory activity on blood platelet aggregation in vitro and ex vivo. Some of these compounds showed the inhibitory activity comparable to that of aspirin. Of these, 5-(3, 4, 5-trimethoxyphenyl) oxazole-4-carboxamide was the most active compound in the ex vivo test.
Initiation of Apoptotic Signal by the Peroxidation of Cardiolipin of Mitochondria (2004)

A bstract : Overexpression of phospholipid hydroperoxide glutathione peroxidase (PHGPx) in mitochondria of RBL2H3 cells (M15 cells) prevented the release of cytochrome c (cyt.c), the activation of caspase‐3, and apoptosis caused by 2‐deoxyglucose (2DG), whereas cells overexpressing nonmitochondrial PHGPx(L9) and control (S1) cells were induced to apoptosis. Hydro‐peroxide levels in mitochondria of L9 and S1 cells were significantly enhanced by 2DG‐induced apoptosis. In contrast, generation of hydroperoxide in mitochondria was protected in M15 cells, which also showed resistance to apoptosis by etoposide, staurosporine, UV irradiation, cycloheximide, and actinomycin D, stimuli that induce apoptosis by the liberation of cyt.c from mitochondria. Cyt.c preferentially binds to the monolayer of cardiolipin (CL), the specific phospholipid of the inner membrane of mitochondria. The amount of cyt.c bound to the monolayer of cardiolipin hydroperoxide (CL‐OOH) was much lower than that bound to CL. Cyt.c bound to liposome containing CL was released by peroxidation with a radical initiator. Adenine nucleotide translocator (ANT), which regulates the opening and closing the permeability transition (PT) pore, potentially was inactivated in apoptosis‐induced S1 cells 4 h after the addition of 2DG, coincidentally with cyt.c release from mitochondria. ANT activity was suppressed by the fusion of isolated mitochondria with liposomes containing CL‐OOH. ANT activity was expressed in proteoliposomes containing 10% CL, but it was competitively inhibited by the addition of CL‐OOH. This study suggests that CL peroxidation might have an initiating role in the liberation of cyt.c from the inner membrane, and in the opening of the PT pore via inactivation of ANT. Mitochondrial PHGPx might play a role as an anti‐apoptotic factor by protecting CL and reducing CL‐OOH.
Isolation and characterization of cDNA clones encoding a functional p34cdc2 homologue from Zea mays. (1991)

We describe the isolation of cDNA clones encoding a p34cdc2 homologue from a higher plant, Zea mays (maize). A full-length cDNA clone, cdc2ZmA, was isolated, sequenced, and shown to complement a cdc28 mutation in Saccharomyces cerevisiae. Comparison of the deduced amino acid sequence of the maize p34cdc2 protein with other homologues showed that it was 64% identical to human p34cdc2 and 63% identical to Schizosaccharomyces pombe and S. cerevisiae p34cdc2 proteins. Studies of expression of the maize cdc2 gene(s) by Northern blot analysis indicated a correlation between the abundance of cdc2 mRNA and the proliferative state of the tissue. Southern blot analysis, as well as isolation of another cDNA clone, cdc2ZmB, which is 96% identical to cdc2ZmA, indicates that maize has multiple cdc2 genes.
Evaluation of methods for the isolation and detection of Escherichia coli O157 in minced beef (1995)

This study has evaluated enrichment and detection procedures for the isolation and detection of Escherichia coli O157 inoculated into minced beef. The use of a 24 h enrichment in modified EC broth containing novobiocin allowed low numbers of contaminating cells to multiply to levels detectable on culture media and by ELISA test kits. Total analysis time was reduced by the use of the Dynabead immunomagnetic separation system. The use of the Petrifilm Test Kit-HEC for E. coli O157:H7 and Organon Teknika EHEC-TEK system detected low numbers of contaminating cells following enrichment and reduced analysis time by 1 d. The incorporation of cefixime and tellurite into Sorbitol MacConkey Agar increased the rate and ease of isolation of E. coli O157 and its use is therefore recommended.