gebhart/patrepeval huggingface dataset:
Construction of a recombinant adenovirus containing the den V gene from bacteriophage T4 which can partially restore the DNA repair deficiency in xeroderma pigmentosum fibroblasts (1991)

The denV gene from bacteriophage T4 encodes a pyrimidine dimer-specific endonuclease that has the capacity to initiate excision repair of DNA. Cells from excision repair-deficient xeroderma pigmentosum (XP) patients are able to carry out excision repair initiated by the denV gene product and introduction of the denV gene into XP cells results in the partial restoration of colony-forming ability after irradiation with UV light. In this work we have constructed a helper-independent recombinant human adenovirus, Ad5denV, which contains the denV gene. A 1.9 kb cartridge consisting of the denV gene flanked by the long terminal repeat (LTR) promoter from Rous sarcoma virus (RSV) and the simian virus 40 (SV40) polyadenylation (poly A) splice signals, was inserted into the E3 region of an E3 deletion mutant (Ad5d1E3) of adenovirus type 5. Infection of human fibroblasts and other permissive human cells with Ad5denV resulted in lytic infection and expression of the denV gene was confirmed by primer extension of infected cell RNA. The ability of the denV gene to restore the DNA repair deficiency in XP fibroblasts was examined using host cell reactivation of viral structural antigen formation for UV-irradiated adenovirus. The control virus, Ad5VSV, was also a recombinant which contained the gene for vesicular stomatitis virus glycoprotein G inserted into the E3 region of Ad5d1E3. UV survival of Ad5denV was similar to that of Ad5VSV following infection of two normal fibroblast strains and a Cockayne syndrome fibroblast strain, CS7SE, from complementation group B. In contrast, UV survival of Ad5denV was significantly greater than that for Ad5VSV after infection of three unrelated XP fibroblast strains from complementation groups A, C and E. However, UV survival of Ad5denV in the XP fibroblasts did not reach levels obtained in normal fibroblasts, indicating that restoration of the XP defect was partial.
Breaking of B cell tolerance toward a highly conserved self protein (1996)

Self proteins are processed and presented by APCs in the same way as foreign proteins. Presentation of fragments derived from self proteins does not, however, lead to Th cell stimulation because of T cell tolerance. In this study, a novel approach was used to investigate whether B cell tolerance toward a self Ag could be due to the absence of this Th cell recognition. The highly conserved nonimmunogenic protein ubiquitin was used as a model protein. Two modified ubiquitin molecules were constructed with ubiquitin segments exchanged either with the T cell epitope, OVA(325-336), which binds to the mouse A(d) MHC class II molecule, or with the T cell epitope, hen egg lysozyme(50-61), which binds to the A(k) molecule. Mice were immunized with the resulting proteins. Both modified proteins elicited strong autoantibody responses toward soluble native ubiquitin, demonstrating that insertion of a single foreign T cell epitope can overcome the B cell nonresponsiveness. The T cell regulatory role of one of the inserted foreign T cell epitopes in ubiquitin was studied, and at least two different Th cell specificities were found to operate in the response. The T cells were directed against: 1) the inserted epitope, and 2) a combination of the inserted epitope and parts of the neighboring ubiquitin regions. Therefore, the absence of T cell help seems to be an important reason for B cell tolerance toward self proteins.
Probiotics under the regulatory microscope (2005)

This review examines current knowledge regarding the safety of probiotic bacteria in man. Tighter and more comprehensive standards and regulations will be developed as probiotic therapy moves from a limited number of products used in the food industry, into more defined therapeutic categories and more complex organisms. A new framework considering probiotics as nonspecific promoters of mucosal immunity, defines probiotic characteristics and the clinical circumstances in which it is used. For example, those with immune deficiency taking a high dose of viable bacteria may have an increased risk. A wider range of bacteria is now being used, sometimes in territories other than the gut mucosa. The question of competition with multiple isolates must be addressed, as does the use of nonselected faecal isolates. Transfer of antibiotic resistance with probiotics acting as a 'shuttle' needs clarification. These issues are addressed and reviewed as probiotics evolve into a new therapeutic arena.
Drugs Five Years Later: Methotrexate (1977)

The folic acid antagonists, aminopterin and then methotrexate, have been the primary systemically administered drugs for the treatment of severe psoriasis for 25 years. Methotrexate was finally approved by the FDA 5 years ago and was recently estimated to be used for approximately 25,000 psoriatic patients annually. With the small but chronic doses used for psoriasis, methotrexate has been relatively safe, except for a limited occurrence of significant hepatotoxicity. The good to excellent results obtained in most patients must, therefore, be weighted against the small risk of liver damage. Methotrexate has also been used with some effectiveness in several other dermatologic conditions, including mycosis fungoides, dermatomyositis, pityriasis rubra pilaris, and others, although they are not yet FDA-approved indications. The recent successful introduction of photochemotherapy (psoralen and ultraviolet light) for moderate and severely affected psoriatics will probably lead to a substantial decrease in the number of patients requiring methotrexate.
Targeted delivery of antisense oligonucleotides to hepatocytes using triantennaryN-acetyl galactosamine improves potency 10-fold in mice (2014)

Triantennary N-acetyl galactosamine (GalNAc, GN3: ), a high-affinity ligand for the hepatocyte-specific asialoglycoprotein receptor (ASGPR), enhances the potency of second-generation gapmer antisense oligonucleotides (ASOs) 6-10-fold in mouse liver. When combined with next-generation ASO designs comprised of short S-cEt (S-2'-O-Et-2',4'-bridged nucleic acid) gapmer ASOs, ∼ 60-fold enhancement in potency relative to the parent MOE (2'-O-methoxyethyl RNA) ASO was observed. GN3: -conjugated ASOs showed high affinity for mouse ASGPR, which results in enhanced ASO delivery to hepatocytes versus non-parenchymal cells. After internalization into cells, the GN3: -ASO conjugate is metabolized to liberate the parent ASO in the liver. No metabolism of the GN3: -ASO conjugate was detected in plasma suggesting that GN3: acts as a hepatocyte targeting prodrug that is detached from the ASO by metabolism after internalization into the liver. GalNAc conjugation also enhanced potency and duration of the effect of two ASOs targeting human apolipoprotein C-III and human transthyretin (TTR) in transgenic mice. The unconjugated ASOs are currently in late stage clinical trials for the treatment of familial chylomicronemia and TTR-mediated polyneuropathy. The ability to translate these observations in humans offers the potential to improve therapeutic index, reduce cost of therapy and support a monthly dosing schedule for therapeutic suppression of gene expression in the liver using ASOs.
Effects of Pemirolast and Tranilast on Intimal Thickening After Arterial Injury in the Rat (1997)

We previously reported that tranilast, an antiallergic agent, reduced intimal thickening after endothelial injury in rats. In this study, to verify whether or not antiallergic agents inhibit intimal thickening, we investigated the effect of pemirolast on intimal thickening after endothelial injury and compared its effect with that of tranilast. Administration of two antiallergic agents, pemirolast (0.1, 1, and 10 mg/kg, p.o.) and tranilast (300 mg/kg, p.o., daily), was begun 2 days before endothelial injury and continued until the animals were killed. Endothelial injury in the rat femoral artery was induced by a photochemical reaction between localized irradiation by green light and intravenously administered rose bengal. To evaluate intimal hyperplasia, we measured the cross-sectional area of the intima 21 days after endothelial damage. Pemirolast at doses of 0.1, 1, and 10 mg/kg reduced the intimal area to 2.10 +/- 0.33, 1.36 +/- 0.19, and 1.35 +/- 0.18 (x0.01 mm2), respectively, and tranilast showed a tendency to reduce the intimal area, which was 1.86 +/- 0.35 x 0.01 mm2, compared with findings for controls (2.83 +/- 0.49 x 0.01 mm2). In rat A10 vascular smooth-muscle cells, we investigated the effects of antiallergic agents on migration by using a modified Boyden chamber assay and on proliferation by using the bromodeoxyuridine-incorporation assay. Two antiallergic agents inhibited in a concentration-dependent manner both migration and proliferation of smooth muscle cells stimulated by platelet-derived growth factor. These results suggest that antiallergic agents directly inhibit migration of smooth-muscle cells to the intima from the media and proliferation in the intima, and that pemirolast has more potent antihyperplastic action than does tranilast. Antiallergic agents may be effective in preventing restenosis after coronary angioplasty.
A G Protein-Linked Receptor for Parathyroid Hormone and Parathyroid Hormone-Related Peptide (1991)

The complementary DNA encoding a 585-amino acid parathyroid hormone-parathyroid hormone-related peptide (PTH-PTHrP) receptor with seven potential membrane-spanning domains was cloned by COS-7 expression using an opossum kidney cell complementary DNA (cDNA) library. The expressed receptor binds PTH and PTHrP with equal affinity, and both ligands equivalently stimulate adenylate cyclase. Striking homology with the calcitonin receptor and lack of homology with other G protein-linked receptors indicate that receptors for these calcium-regulating hormones are related and represent a new family.
The Lentiviral Integrase Binding Protein LEDGF/p75 and HIV-1 Replication (2008)

Retroviral replication proceeds through a stable proviral DNA intermediate, and numerous host cell factors have been implicated in its formation. In particular, recent results have highlighted an important role for the integrase-interactor lens epithelium-derived growth factor (LEDGF)/p75 in lentiviral integration. Cells engineered to over-express fragments of LEDGF/p75 containing its integrase-binding domain but lacking determinants essential for chromatin association are refractory to HIV-1 infection. Furthermore, both the levels of HIV-1 integration and the genomic distribution of the resultant proviruses are significantly perturbed in cells devoid of endogenous LEDGF/p75 protein. A strong bias towards integration along transcription units is a characteristic feature of lentiviruses. In the absence of LEDGF/p75, HIV-1 in large part loses that preference, displaying concomitant integration surges in the vicinities of CpG islands and gene promoter regions, elements naturally targeted by other types of retroviruses. Together, these findings highlight that LEDGF/p75 is an important albeit not strictly essential cofactor of lentiviral DNA integration, and solidify a role for chromatin-associated LEDGF/p75 as a receptor for lentiviral preintegration complexes. By now one of the best characterized virus-host interactions, the integrase-LEDGF/p75 interface opens a range of opportunities for lentiviral vector targeting for gene therapy applications as well as for the development of novel classes of antiretroviral drugs.
Inductive Isolation in Stacked SQUID Amplifiers (2007)

Amplification of SFQ pulses to higher signal levels has been achieved using the general technique of inductive isolation. A multiple-flux-quantum generator, which produces quantum-accurate waveforms suitable for ADC applications, and an output data link were demonstrated. Both circuits were implemented using critically damped, dc-powered SQUIDs stacked in series. In the past, the voltage output achievable with this approach has been severely limited by parasitic capacitance to ground and to the control lines. Parasitic capacitance inhibits SQUID operation both at turn-on and turn-off. Using inductive isolation between SQUIDs, parasitic capacitance was completely tuned out. A 100-flux-quantum waveform generator, based on a series stack of 100 SQUIDs, operated at 6 Gb/s, fabricated in a 4.5 kA-per-square-cm Josephson junction process. The output amplifier produced a 1 mV swing at 12 Gb/s non-return-to-zero. This circuit is based on a stack of only two SQUIDs, and uses both inductive isolation and asymmetric resistive shunting to enhance the out-of-phase oscillation mode.
Quantitative analysis of DNA methylation at all human imprinted regions reveals preservation of epigenetic stability in adult somatic tissue (2011)

Our validated pyrosequencing methylation assays can be widely used as a tool to investigate DNA methylation levels of imprinted genes in clinical samples. This first comprehensive analysis of normal methylation levels in adult somatic tissues at human imprinted regions confirm that, despite intra-individual variability and tissue specific expression, imprinted genes faithfully maintain their DNA methylation in healthy adult tissue. DNA methylation levels of a selection of imprinted genes are, therefore, a valuable indicator for epigenetic stability.
Candidate gene approach evaluates association between innate immunity genes and breast cancer risk in Korean women (2009)

This study suggests that common genetic variants in the OR10J3 and FCER1A be strongly associated with breast cancer risk among Korean women.
Stem Cells in Clinical Practice (2003)

Evers, Mark B MD, FACSa; Weissman, Irving L MDb; Flake, Alan W MD, FACSc; Tabar, Viviane MDd; Weisel, Richard D MD, FACSe Author Information
Structural characterization of pressure-induced amorphous silicon (2009)

We investigate the structure and mechanical properties of pressure-induced (PI) amorphous silicon $(a\text{-Si})$ and compare this to the more extensively characterized case of $a\text{-Si}$ created by ion implantation. To study the effect of thermal history we also examine the structure of both PI and ion-implanted $a\text{-Si}$ after a low-temperature ``relaxation'' anneal $(450\text{ }\ifmmode^\circ\else\textdegree\fi{}\text{C})$. Indentation testing suggests that structural changes are induced by thermal annealing. As-prepared forms of $a\text{-Si}$ deform via plastic flow, while relaxed forms of $a\text{-Si}$ transform to high-pressure crystalline phases. These structural changes are confirmed by more explicit measurements. Raman microspectroscopy shows that the short-range order as expressed by the average bond-angle distortion of the as-prepared amorphous phases is the same and reduced by the same amount following the low-temperature anneal. Fluctuation electron microscopy demonstrates that the as-prepared PI $a\text{-Si}$ displays a much lower variance of the diffracted intensity, a feature directly correlated with the medium-range order, than the as-prepared ion-implanted $a\text{-Si}$. However, relaxation brings this variance of the two networks to the same intermediate level. The mechanical tests and structural probes indicate that annealing the amorphous silicon network can bring it to a common state with the same structure and properties regardless of the initial state. This final state might be the closest attainable to the continuous random network model.
Aflibercept in wet AMD: specific role and optimal use (2013)

Two Phase III clinical trials, VEGF Trap-eye Investigation of Efficacy and Safety in Wet AMD (VIEW) 1 and 2, comparing VEGF Trap-eye to ranibizumab demonstrated the noninferiority of this novel compound. The clinical equivalence of this compound against ranibizumab is maintained even when the injections are administered at 8-week intervals, which indicates the potential to reduce the risk of monthly intravitreal injections and the burden of monthly monitoring.
Polymethylhydrosiloxane: a versatile reducing agent for organic synthesis (1999)

N. J. Lawrence, M. D. Drew and S. M. Bushell, J. Chem. Soc., Perkin Trans. 1, 1999, 3381 DOI: 10.1039/A903662H
Detection of Undegraded Oligonucleotides in Vivo by Fluorescence Resonance Energy Transfer (1996)

A method was investigated for monitoring the integrity of oligonucleotides in solution and in cells using fluorescence resonance energy transfer between two different fluorochromes attached to a single oligonucleotide. Ten-mer oligodeoxyribonucleotides labeled with fluorescein at one end and with rhodamine X at the other end were used. The oligomer had a specific absorption spectrum with peaks at 497 and 586 nm, which corresponded to fluorescein and rhodamine X, respectively. When excited at 494 nm, the oligomer had a specific fluorescence spectrum with peaks at 523 and 610 nm. The fluorescence intensity at 610 nm was 6-8 times higher than that at 523 nm. After digestion of the oligomer with an endonuclease, the fluorescence at 523 nm increased more than 12-15-fold but its fluorescence peak at 610 nm almost completely disappeared. To examine effects in vivo, sea urchin eggs were injected with a solution of the oligomer and excited with blue light at 470-490 nm. Two fluorescent images, a green image at 520-560 nm and a red image at above 580 nm, were obtained when a single egg was viewed under a fluorescence microscope. The ratio of the intensities of red to green fluorescence decreased in dependence on time after injection of the oligomer. These changes were not observed in eggs that had been injected with a solution of similarly double-labeled, phosphorothioate oligomer. These results indicated that unfertilized sea urchin eggs had nucleolytic activity. Analysis in vitro on supernatant of the egg homogenate indeed demonstrated the existence of nucleases. All together, our results indicate that the integrity of oligonucleotides can be estimated in living cells by monitoring the fluorescence resonance energy transfer of the double-labeled oligonucleotide.
Effect of Twenty-Four-Week Treatment with the Antiestrogen EM-800 on Estrogen-Sensitive Parameters in Intact and Ovariectomized Mice (1998)

Treatment with the antiestrogen EM-800, at the daily oral dose of 3 g, 10 g, 30 g, or 100 g for 24 weeks, caused a marked inhibition of uterine and vaginal weight in both intact and ovariectomized mice.Maximal 64% and 41% inhibitions of uterine weight were achieved in intact and ovariectomized animals, respectively.Similar inhibitory effects of EM-800 were observed on vaginal weight with maximal inhibitions of 71% and 35%, in intact and ovariectomized animals, respectively.The pure antiestrogenic activity of EM-800 on the hypothalamo-pituitary-ovarian axis is illustrated by the 76 -91% increases in ovarian weight observed in intact animals treated with the 10 -100 g doses of the antiestrogen.Serum 17-estradiol was 93% increased at the 100 g daily dose of EM-800, whereas serum androstenedione, testosterone, and dihydrotestosterone were 141-713% increased over control at the same dose of the antiestrogen.Serum LH was increased by treatment with EM-800 in intact animals, whereas no effect was observed on the elevated gonadotropin levels in ovariectomized animals.At all doses used in intact animals, the antiestrogen caused a complete disappearance of the glandular elements of Materials and Methods AnimalsFemale BALB/c mice (BALB/cAnNCrlBR) approximately 50 days old and weighing 19 -20 g were obtained from Charles-River, Inc. (St-Constant, Que bec, Canada) and housed 4 -5 per cage in a temperature (23 1 C)-and light (12 h light/day, lights on at 0715 h)-controlled environment.The mice were fed rat chow and tap water ad libitum.Animals were randomly divided into groups, each group containing 20 mice.Animals of the appropriate groups were bilaterally ovariectomized under general anesthesia (Avertin), whereas intact mice were
Amyloid Protein Precursor Messenger RNAs: Differential Expression in Alzheimer's Disease (1988)

In situ hybridization was used to assess total amyloid protein precursor (APP) messenger RNA and the subset of APP mRNA containing the Kunitz protease inhibitor (KPI) insert in 11 Alzheimer's disease (AD) and 7 control brains. In AD, a significant twofold increase was observed in total APP mRNA in nucleus basalis and locus ceruleus neurons but not in hippocampal subicular neurons, neurons of the basis pontis, or occipital cortical neurons. The increase in total APP mRNA in locus ceruleus and nucleus basalis neurons was due exclusively to an increase in APP mRNA lacking the KPI domain. These findings suggest that increased production of APP lacking the KPI domain in nucleus basalis and locus ceruleus neurons may play an important role in the deposition of cerebral amyloid that occurs in AD.
Post‐Translational Modification of Proteins (1993)

This chapter contains sections titled: Introduction Post-translational Reactions The Specificity of Post-translational Reactions Biological Functions of Modified Amino Acids in Proteins Concluding Remarks
Relationship between hydrogen consumption, dehalogenation, and the reduction of sulfur oxyanions by Desulfomonile tiedjei (1991)

Resting-cell suspensions of Desulfomonile tiedjei consumed H2 with 3-chloro-, 3-bromo-, and 3-iodobenzoate as electron acceptors with rates of 0.50, 0.44, and 0.04 mumol h-1 mg-1, respectively. However, benzoate and 3-fluorobenzoate were not metabolized by this bacterium. In addition, H2 uptake was at least fourfold faster when sulfate, sulfite, or thiosulfate was available as the electron acceptor instead of a haloaromatic substrate. When sulfite and 3-chlorobenzoate were both available for this purpose, the rate of H2 uptake by D. tiedjei was intermediate between that obtained with either electron acceptor alone. Hydrogen concentrations were reduced to comparably low levels when either 3-chlorobenzoate, sulfate, or sulfite was available as an electron acceptor, but significantly less H2 depletion was evident with benzoate or nitrate. Rates of 3-chlorobenzoate dechlorination increased from an endogenous rate of 14.5 to 17.1, 74.0, 81.1, and 82.3 nmol h-1 mg-1 with acetate, pyruvate, H2, and formate, respectively, as the electron donors. Sulfite and thiosulfate inhibited dehalogenation, but sulfate and NaCl had no effect. Dehalogenation and H2 metabolism were also inhibited by acetylene, molybdate, selenate, and metronidazole. Sulfite reduction and dehalogenation were inhibited by the same respiratory inhibitors. These results suggest that the reduction of sulfite and dehalogenation may share part of the same electron transport chain. The kinetics of H2 consumption and the direct inhibition of dehalogenation by sulfite and thiosulfate in D. tiedjei cells clearly indicate that the reduction of sulfur oxyanions is favored over aryl dehalogenation for the removal of reducing equivalents under anaerobic conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
GmFT2a, a Soybean Homolog of FLOWERING LOCUS T, Is Involved in Flowering Transition and Maintenance (2011)

GmFT2a expression is associated with flowering induction and maintenance. Therefore, GmFT2a is a potential target gene for soybean breeding, with the aim of increasing geographic adaptation of this crop.