gebhart/patrepeval huggingface dataset:
Peripheral Androgen Receptor Gene Suppression Rescues Disease in Mouse Models of Spinal and Bulbar Muscular Atrophy (2014)

Spinal and bulbar muscular atrophy (SBMA) is caused by the polyglutamine androgen receptor (polyQ-AR), a protein expressed by both lower motor neurons and skeletal muscle. Although viewed as a motor neuronopathy, data from patients and mouse models suggest that muscle contributes to disease pathogenesis. Here, we tested this hypothesis using AR113Q knockin and human bacterial artificial chromosome/clone (BAC) transgenic mice that express the full-length polyQ-AR and display androgen-dependent weakness, muscle atrophy, and early death. We developed antisense oligonucleotides that suppressed AR gene expression in the periphery but not the CNS after subcutaneous administration. Suppression of polyQ-AR in the periphery rescued deficits in muscle weight, fiber size, and grip strength, reversed changes in muscle gene expression, and extended the lifespan of mutant males. We conclude that polyQ-AR expression in the periphery is an important contributor to pathology in SBMA mice and that peripheral administration of therapeutics should be explored for SBMA patients.
A Precision Baseline Offset and Drift Corrector for Low-Frequency Applications (1985)

An analog technique for correcting baseline offset and drift in low-frequency systems is analyzed. The described method applies to periodic and nearly periodic signals, characterized by a time interval in which they may be considered at rest (electrocardiogram (ECG) signals, for instance), and is limited to linear drifts. Two different circuits have been developed and are discussed here. Signal conditioning performed on suitable input waveforms is presented. Noise effects have been theoretically considered and experimentally evaluated.
Altered DNA-binding specificity mutants of EKLF and Sp1 show that EKLF is an activator of the β-globin locus control region in vivo (1998)

The locus control region of the beta-globin cluster contains five DNase I hypersensitive sites (5'HS1-5) required for locus activation. 5'HS3 contains six G-rich motifs that are essential for its activity. Members of a protein family, characterized by three zinc fingers highly homologous to those found in transcription factor Sp1, interact with these motifs. Because point mutagenesis cannot distinguish between family members, it is not known which protein activates 5'HS3. We show that the function of such closely related proteins can be distinguished in vivo by matching point mutations in 5'HS3 with amino acid changes in the zinc fingers of Sp1 and EKLF. Testing their activity in transgenic mice shows that EKLF is a direct activator of 5'HS3.
Reactions of the Cumyloxyl and Benzyloxyl Radicals with Tertiary Amides. Hydrogen Abstraction Selectivity and the Role of Specific Substrate-Radical Hydrogen Bonding (2013)

A time-resolved kinetic study in acetonitrile and a theoretical investigation of hydrogen abstraction reactions from N,N-dimethylformamide (DMF) and N,N-dimethylacetamide (DMA) by the cumyloxyl (CumO(•)) and benzyloxyl (BnO(•)) radicals was carried out. CumO(•) reacts with both substrates by direct hydrogen abstraction. With DMF, abstraction occurs from the formyl and N-methyl C-H bonds, with the formyl being the preferred abstraction site, as indicated by the measured kH/kD ratios and by theory. With DMA, abstraction preferentially occurs from the N-methyl groups, whereas abstraction from the acetyl group represents a minor pathway, in line with the computed C-H BDEs and the kH/kD ratios. The reactions of BnO(•) with both substrates were best described by the rate-limiting formation of hydrogen-bonded prereaction complexes between the BnO(•) α-C-H and the amide oxygen, followed by intramolecular hydrogen abstraction. This mechanism is consistent with the very large increases in reactivity measured on going from CumO(•) to BnO(•) and with the observation of kH/kD ratios close to unity in the reactions of BnO(•). Our modeling supports the different mechanisms proposed for the reactions of CumO(•) and BnO(•) and the importance of specific substrate/radical hydrogen bond interactions, moreover providing information on the hydrogen abstraction selectivity.
Far-field superfocusing with an optical fiber based surface plasmonic lens made of nanoscale concentric annular slits (2011)

We present experimental demonstration of light superfocusing by using an optical fiber based surface plasmonic (SP) lens with nanoscale concentric annular slits. A far-field, sub-diffraction-limit sized focus was achieved with an optical fiber based device. The performance of SP lenses with three and four annular slits was experimentally characterized. Guidelines and suggestions on designing the SP lens are provided. As a microscale device with nanoscale features, the fiber-based SP lens can provide a solution to bridging nanophotonics and conventional optics.
Single-Walled Carbon Nanotubes in the Intact Organism:  Near-IR Imaging and Biocompatibility Studies in Drosophila (2007)

The ability of near-infrared fluorescence imaging to detect single-walled carbon nanotubes (SWNTs) in organisms and biological tissues has been explored using Drosophila melanogaster (fruit flies). Drosophila larvae were raised on food containing approximately 10 ppm of disaggregated SWNTs. Their viability and growth were not reduced by nanotube ingestion. Near-IR nanotube fluorescence was imaged from intact living larvae, and individual nanotubes in dissected tissue specimens were imaged, structurally identified, and counted to estimate a biodistribution.
Improving resolution in photolithography with a phase-shifting mask (1982)

The phase-shifting mask consists of a normal transmission mask that has been coated with a transparent layer patterned to ensure that the optical phases of nearest apertures are opposite. Destructive interference between waves from adjacent apertures cancels some diffraction effects and increases the spatial resolution with which such patterns can be projected. A simple theory predicts a near doubling of resolution for illumination with partial incoherence σ < 0.3, and substantial improvements in resolution for σ < 0.7. Initial results obtained with a phase-shifting mask patterned with typical device structures by electron-beam lithography and exposed using a Mann 4800 10X tool reveals a 40-percent increase in usuable resolution with some structures printed at a resolution of 1000 lines/mm. Phase-shifting mask structures can be used to facilitate proximity printing with larger gaps between mask and wafer. Theory indicates that the increase in resolution is accompanied by a minimal decrease in depth of focus. Thus the phase-shifting mask may be the most desirable device for enhancing optical lithography resolution in the VLSI/VHSIC era.
A mobile 12 GHz DBS television receiving system (1989)

A practical, mobile, 12-GHz direct broadcast satellite (DBS) television receiving system for receivers on vehicles is described. The system is housed in a cylindrical radome of 350 mm height and 862 mm diameter, and it weighs 50 kg. Two pairs of high performance flat-panel antenna units (640*180 mm each) are used to reduce the system. For rapid recatch of DBS, antenna control is based on a gyroscope that is corrected using a phase-comparison monopulse. To simplify the system, the antenna units and receivers are used for antenna tracking as well as signal reception. The antenna units are in-phase combined to allow electronic tracking, which reduces the influence of pointing error caused by vibration of vehicles. The system maintains a reception rate of more than 90% on expressways.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Fiberized laser ultrasonic source for process monitoring and biomedical applications (2000)

A new design for a fiberized laser ultrasonic source for process monitoring and bio-medical applications is proposed. The laser ultrasonic source consists of a pulsed laser, a fiber-optic cable, and a generation head. The generation head is a miniature hermetically sealed chamber, which can be embedded into solid structures or immersed in liquid media. The face of the chamber acts as a target for the laser irradiation. Bulk ultrasonic waves generated inside of the target are transmitted into the surrounding liquid media or solid structure. It is shown that ultrasonic pulses of 1 microsecond(s) to 30 ns duration can be generated. Sources with different radiation patterns with respect to the optical axis of the fiber, such as normal, angular, and focused, have been devised. An example use of these sources combined with a fiber optic ultrasonic sensor for inspection of small tubes is presented.
Fetal Homotransplants (Ventral Mesencephalon and Adrenal Tissue) to the Striatum of Parkinsonian Subjects (1990)

Fetal ventral mesencephalon and fetal adrenal tissue grafted to the caudate nucleus of four and three parkinsonian patients, respectively, have been shown to be an alternative treatment for the amelioration of the signs of the disease. The ventral mesencephalon patients had a significant amelioration of rigidity, bradykinesia, postural imbalance, gait disturbance, and facial expression. Three of these four patients have returned to work. The fatal adrenal group only showed amelioration of rigidity and bradykinesia. Though these patients are now able to perform their basic daily living activities, and one of them has renewed her household tasks, the other two have not yet been able to return to work. The differences observed between the ventral mesencephalon- and the fetal adrenal-transplanted patients may be related to the heterogeneity of their disease and/or the type of graft implanted. However encouraging our results may be, this experimental procedure obviously requires further studies, and should not be practiced outside of highly qualified clinical research centers.
The Effect of Co-Culturing Lactobacillusn salivarius with Clostridium difficile on the Production of Clostridium difficile Toxi A and Toxin B (2012)

Antibiotics alter the composition, and numbers of the normal gastrointestinal (GI) microflora, providing Clostridium difficile , a spore forming, Gram-positive bacillus, the opportunity to colonize the GI tract. 1,2,3 C. difficile is the leading cause of hospital-acquired diarrhea, resulting in death of 1% to 2% of infected patients. 2,3 It is responsible for GI diseases ranging from antibiotic-associated diarrhea to the more severe pseudomembranous colitis. 4 In addition to having resistance to various antimicrobial drugs, the treatment of C. difficile infections with specific antibiotics such as metronidazole often results in relapse, resistance development, and further disruption of the GI microflora. 4 Thus, the establishment of an alternative method to combat C. difficile is crucial. Previous studies show  that Lactobacillus salivarius , a promising probiotic organism, produces a potent two-peptide bacteriocin that hinders C. difficile growth. 5 Previous research indicates that L. salivarius is effective in reducing C. difficile cell count, although none investigated the effect of L. salivarius on the two major virulence factors – toxin A (TcdA) and toxin B (TcdB). 6 To this end, this investigation aimed to investigate the influence of L. salivarius on TcdA and Tcd B production. L. salivarius and C. difficile were co-cultured, growth curves of C. difficile , L. salivarius , and the co-culture were generated, and cell-free supernatants at various stages were examined to quantify TcdA and TcdB concentrations. Although there was no noticeable decrease in TcdA and TcdB concentration in the co-culture, C. difficile toxin production was observed to be more multi-phasic in co-culture. Moreover, co-culturing L. salivarius with C. difficile significantly hindered C. difficile growth, confirming previous results. Taken together, the data suggests that the presence of L. salivarius enhances C. difficile toxin production per cell, implying the potential dangers of initiating clinical trials without a comprehensive investigation of the effects of probiotics and the production of C. difficile virulence factors.
Abnormal Alzheimer‐like phosphorylation of tau‐protein by cyclin‐dependent kinases cdk2 and cdk5 (1993)

We have shown earlier that certain proline-directed kinases such as MAP kinase or GSK-3 can phosphorylate tau protein in an abnormal manner reminiscent of tau from Alzheimer paired helical filaments [Drewes et al. (1992); Mandelkow et al. (1992)]. Both kinases are abundant in brain tissue and associate physically with microtubules through several cycles of assembly and disassembly. In this report we show that cdk2/cyclin A incorporates = 5 Pi into recombinant tau, and that it also induces the MR shift and antibody reactivity typical of Alzheimer tau. However, since there is no cdk2 in brain [Meyerson et al. (1992)] we looked for other members of this family of kinases. Using an antibody against the conserved N-terminus we isolated a cdk-like kinase from brain which was capable of inducing the Alzheimer-like characteristics in tau by phosphorylation. Its size (31 kDa), target specificity (proline-directed), chromatographic behavior, and abundance in brain suggest that this kinase is similar or identical to the neuronal cdc2-like kinase nclk alias PSSARLE or cdk5 [Hellmich et al. (1992); Meyerson et al. (1992); Xiong et al. (1992); Tsai et al. (1993)]. This was confirmed by an antibody specific for cdk5. Like MAP kinase and GSK-3, this kinase is physically associated with microtubules and can be enriched by cycles of microtubule assembly and disassembly. Thus, cdk5 should be regarded as another kinase that could be held responsible for the changes in tau protein during Alzheimer disease progression.
Evolution of the FAD2‐1 fatty acid desaturase 5′ UTR intron and the molecular systematics of Gossypium (Malvaceae) (2001)

The FAD2-1 microsomal omega-6 desaturase gene contains a large intron ( approximately 1133 bp [base pairs]) in the 5' untranslated region that may participate in gene regulation and, in GOSSYPIUM:, is evolving at an evolutionary rate useful for elucidating recently diverged lineages. FAD2-1 is single copy in diploid GOSSYPIUM: species, and two orthologs are present in the allotetraploid species. Among the diploid species, the D-genome FAD2-1 introns have accumulated substitutions 1.4-1.8 times faster than the A-genome introns. In the tetraploids, the difference between the D-subgenome introns and their A-subgenome orthologs is even greater. The substitution rate of the intron in the D-genome diploid G. gossypioides more closely approximates that of the A genome than other D genome species, highlighting its unique evolutionary history. However, phylogenetic analyses support G. raimondii as the closest living relative of the D-subgenome donor. The Australian K-genome species diverged 8-16 million years ago into two clades. One clade comprises the sporadically distributed, erect to suberect coastal species; a second clade comprises the more widely spread, prostrate, inland species. A comparison of published gene trees to the FAD2-1 intron topology suggests that G. bickii arose from an early divergence, but that it carries a G. australe-like rDNA captured via a previously undetected hybridization event.
Anti-gene Effect in Live Cells of AG Motif Triplex-Forming Oligonucleotides Containing an Increasing Number of Phosphorothioate Linkages (2001)

The murine Ki-ras promoter contains a unique polypurine--polypyrimidine [poly(R.Y)] sequence between -290 and -320 from the 3' boundary of exon phi. Previously we demonstrated triplex formation and transcription inhibition promoted by GT and AG oligonucleotides directed against this site [Alunni-Fabbroni et al. (1996) Biochemistry 35, 16361--16369]. In this work, we have investigated triplex formation and anti-gene activity of five 20-mer AG motif triplex-forming oligonucleotides specific for the Ki-ras poly(R.Y) target, derived from 5'-AGGGAGGGAGGAAGGGAGGG (20AG) by replacing an increasing number of phosphodiester linkages with phosphorothioate linkages (S(i)-20AG; i = 2, 3, 4, 5, 19). Electrophoretic mobility-shift experiments (EMSA) showed that four thioate oligonucleotides, S(i)-20AG (i = 2, 3, 4, 5), recognized the Ki-ras target and exhibited dissociation constants similar to that of 20AG: K(d) = 12 +/- 2 nM, while the all-thioate S(19)-20AG exhibited a K(d) of 128 +/- 15 nM. Moreover, the binding between the Ki-ras promoter and oligonucleotides S(i)-20AG (i = 2, 3, 4, 5, 19) was characterized by DMS/piperidine and DNase I footprinting experiments. We observed that the introduction in the phosphodiester oligonucleotide 20AG of sulfur atoms reduced its aggregation significantly and increased its nuclease resistance. Transient transfection experiments using preformed triplexes with a recombinant plasmid containing the reporter chloramphenicol acetyltransferase (CAT) gene under the control of Ki-ras promoter showed that oligonucleotides S(i)-20AG (i = 2, 3, 4, 5, 19) promote a strong inhibition of up to 75% of the CAT expression when compared with control Ki-ras unspecific oligonucleotides. Taken together, these data provide a guideline for designing triplex-forming effector molecules capable of controlling Ki-ras expression in vivo.
Characterization of fully 2'-modified oligoribonucleotide hetero- and homoduplex hybridization and nuclease sensitivity (1995)

The nuclease stability and melting temperatures (Tm) were compared for fully modified oligoribonucleotide sequences containing 2'-fluoro, 2'-O-methyl, 2'-O-propyl and 2'-O-pentyl nucleotides. Duplexes formed between 2' modified oligoribonucleotides and RNA have typical A-form geometry as observed by circular dichroism spectroscopy. Modifications, with the exception of 2'-O-pentyl, were observed to increase the Tm of duplexes formed with complementary RNA. Modified homoduplexes showed significantly higher Tms, with the following Tm order: 2'-fluoro:2'fluoro > 2'-O-propyl:2'-O-propyl > 2'-O-methyl:2'-O- methyl > RNA:RNA > DNA:DNA. The nuclease stability of 2'-modified oligoribonucleotides was examined using snake venom phosphodiesterase (SVPD) and nuclease S1. The stability imparted by 2' modifications was observed to correlate with the size of the modification. An additional level of nuclease stability was present in oligoribonucleotides having the potential for forming secondary structure, but only for 2' modified oligoribonucleotides and not for 2'-deoxy oligoribonucleotides.
The ALG10 locus of Saccharomyces cerevisiae encodes the alpha-1,2 glucosyltransferase of the endoplasmic reticulum: the terminal glucose of the lipid-linked oligosaccharide is required for efficient N-linked glycosylation (1998)

The biosynthesis of the lipid-linked oligosaccharide substrate for N-linked protein glycosylation follows a highly conserved pathway at the membrane of the endoplasmic reticulum. Based on the synthetic growth defect in combination with a reduced oligosaccharyltransferase activity (wbp1), we have identified alg10 mutant strains which accumulate lipid-linked Glc2Man9GlcNAc2. We cloned the corresponding wild-type gene and show in a novel in vitro assay that Alg10p is a dolichyl-phosphoglucose-dependent glucosyltransferase which adds the terminal alpha-1,2 glucose to the lipid-linked Glc2Man9GlcNAc2 oligosaccharide. Hypoglycosylation of secreted proteins in alg10 deletion strains demonstrates that the terminal alpha-1,2-linked glucose residue is a key element in substrate recognition by the oligosaccharyltransferase. This ensures that primarily completely assembled oligosaccharide is transferred to protein.
Pharmacokinetics of Terfenadine in Healthy Elderly Subjects (1992)

The pharmacokinetics of the terfenadine active metabolite, metabolite I, was examined in ten healthy elderly adults and ten younger adults after single-dose oral administration of 120-mg terfenadine. All subjects successfully completed the study without reporting sedation or other adverse events. Absorption was rapid in both the young and elderly. The mean Cmax was the same for both groups, 501 ng/mL, and occurred at 2.3 hours in the young subjects and 2.5 hours in elderly subjects. However, the apparent clearance was reduced by about 25% in the elderly. After correcting clearance for bodyweight, this difference was not statistically significant.
Operational amplifier with 1-V rail-to-rail multipath-driven output stage (1991)

A bipolar operational amplifier (op amp) with a rail-to-rail multipath-driven output stage that operates at supply voltages down to 1 V is presented. The bandwidth of this output stage is as high as possible, viz, equal to that of one of the output transistors, loaded by the output capacitance. The output voltage can reach both supply rails within 100 mV and the output current is +or-15 mA. The op amp is designed to be loaded by a 100-pF capacitor and the unity-gain bandwidth is 3.4 MHz at a 60 degrees phase margin. The voltage gain is 117 dB and the CMRR is 100 dB. The frequency behavior of the multipath-driven (MPD) topology has an improved performance when compared to that of previously presented low-voltage output stages. A figure of merit F/sub M/ for low-voltage op amps has been defined as the bandwidth-power ratio.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
S-2,4,6-trimethoxybenzyl (Tmob): a novel cysteine protecting group for the N.alpha.-(9-fluorenylmethoxycarbonyl) (Fmoc) strategy of peptide synthesis (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTS-2,4,6-trimethoxybenzyl (Tmob): a novel cysteine protecting group for the N.alpha.-(9-fluorenylmethoxycarbonyl) (Fmoc) strategy of peptide synthesisMark C. Munson, Carlos Garcia-Echeverria, Fernando Albericio, and George BaranyCite this: J. Org. Chem. 1992, 57, 11, 3013–3018Publication Date (Print):May 1, 1992Publication History Published online1 May 2002Published inissue 1 May 1992https://pubs.acs.org/doi/10.1021/jo00037a013https://doi.org/10.1021/jo00037a013research-articleACS PublicationsRequest reuse permissionsArticle Views1913Altmetric-Citations48LEARN 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
Regulation of Ornithine Decarboxylase (2006)

Ornithine decarboxylase (ODC) initiates the polyamine biosynthetic pathway. The amount of ODC is altered in response to many growth factors, oncogenes, and tumor promoters and to changes in polyamine levels. Susceptibility to tumor development is increased in transgenic mice expressing high levels of ODC and is decreased in mice with reduced ODC due to loss of one ODC allele or elevated expression of antizyme, a protein that stimulates ODC degradation. This review describes key factors that contribute to the regulation of ODC levels, which can occur at the levels of transcription, translation, and protein turnover.