gebhart/patrepeval huggingface dataset:
Identification and cloning of endogenous retroviral sequences present in human DNA. (1981)

Using nonstringent annealing conditions and a 2.75-kilobase segment of cloned African green monkey DNA that specifically hybridizes to the proviruses of AKR ecotropic murine leukemia virus (MuLV) and baboon endogenous virus (BaEV) as a probe, we detected related sequences in three different preparations of human brain DNA fragments. The blot-hybridization pattern obtained with cleaved human DNA was similar to that previously reported for the interaction of MuLV cDNA and cleaved mouse DNA and suggested the presence of numerous copies of retrovirus-related sequences in the human genome. The labeled 2.75-kilobase fragment derived from cloned monkey DNA was used to screen a human DNA library in Charon 4A. One clone obtained hybridized to three contiguous MuLV-and BaEV-reactive fragments of the cloned monkey DNA and to multiple fragments of human DNA including a prominent 1.0-kilobase EcoRI fragment also present in the clone.
Abnormal Regional Cerebral Blood Flow in Cognitively Normal Elderly Subjects With Hypertension (2008)

rCBF is affected in normal subjects with HTN, not only in the subcortical regions, but also in limbic and paralimbic structures. We hypothesize that the HTN creates a vulnerability state for the development of neurodegenerative disorders, especially Alzheimer disease.
S-Adenosyl-L-methionine: macrocin O-methyltransferase activities in a series of Streptomyces fradiae mutants that produce different levels of the macrolide antibiotic tylosin (1982)

A series of mutants of Streptomyces fradiae selected for increased production of the macrolide antibiotic tylosin was analyzed for levels of expression of macrocin O-methyltransferase, the enzyme which catalyzes the final step in the biosynthesis of tylosin. Increased tylosin production was accompanied by increased macrocin O-methyltransferase in some of the mutants. Increased expression of macrocin O-methyltransferase was due to more rapid early biosynthesis of the enzyme, to reduced decay of enzyme specific activity late in the fermentation, or to combinations of both. Mutant strains which showed rapid loss of enzyme specific activity late in the fermentation converted large amounts of tylosin to relomycin. The most productive mutants, which synthesized elevated levels of macrocin O-methyltransferase, also produced large amounts of macrocin, the substrate for the enzyme. Incomplete conversion of macrocin to tylosin by these mutants may be due to substrate and product inhibition (E. T. Seno and R. H. Baltz, Antimicrob. Agents Chemother. 20:370-377, 1981). The results suggest that both the levels of precursors and the levels of expression of tylosin biosynthetic enzymes are important for efficient production of tylosin.
Evidence for the Presence of Three Distinct Binding Sites for the Thioflavin T Class of Alzheimer's Disease PET Imaging Agents on β-Amyloid Peptide Fibrils (2004)

Imaging the progression of Alzheimer's disease would greatly facilitate the discovery of therapeutics, and a wide range of ligands are currently under development for the detection of beta-amyloid peptide (Abeta)-containing plaques by using positron emission tomography. Here we report an in-depth characterization of the binding of seven previously described ligands to in vitro generated Abeta-(1-40) polymers. All of the compounds were derived from the benzothiazole compound thioflavin T and include 2-[4'-(methylamino)phenyl]benzothiazole and 2-(4'-dimethylamino-)phenyl-imidazo[1,2-a]-pyridine derivatives, 2-[4'-(dimethylamino)phenyl]-6-iodobenzothiazole and 2-[4'-(4''-methylpiperazin-1-yl)phenyl]-6-iodobenzothiazole, and a benzofuran compound (5-bromo-2-(4-dimethylaminophenyl)benzofuran). By using a range of fluorescent and radioligand binding assays, we find that these compounds display a more complex binding pattern than described previously and are consistent with three classes of binding sites on the Abeta fibrils. All of the compounds bound with very high affinity (low nm K(d)) to a low capacity site (BS3) (1 ligand-binding site per approximately 300 Abeta-(1-40) monomers) consistent with the previously recognized binding site for these compounds on the fibrils. However, the compounds also bound with high affinity (K(d) approximately 100 nm) to either one of two additional binding sites on the Abeta-(1-40) polymer. The properties of these sites, BS1 and BS2, suggest they are adjacent or partially overlapping and have a higher capacity than BS3, occurring every approximately 35 or every approximately 4 monomers of Abeta-(1-40)-peptide, respectively. Compounds appear to display selectivity for BS2 based on the presence of a halogen substitution (2-[4'-(dimethylamino)phenyl]-6-iodobenzothiazole, 2-[4'-(4''-methylpiperazin-1-yl)phenyl]-6-iodobenzothiazole, and 5-bromo-2-(4-dimethylaminophenyl)benzofuran) on their aromatic ring system. The presence of additional ligand-binding sites presents potential new targets for ligand development and may allow a more complete modeling of the current positron emission tomography data.
Serotypes VI and VIII Predominate among Group B Streptococci Isolated from Pregnant Japanese Women (1999)

Infection by group B streptococcus (GBS) is an important cause of bacterial disease in neonates, pregnant women, and nonpregnant adults. Whereas serotypes Ia, Ib, II, III, and V are most commonly associated with colonization and disease in the United States, strains of other serotypes have been isolated from patients in Japan. By use of an inhibition ELISA, the serotypes of 73 vaginal colonizing GBS strains isolated from healthy pregnant Japanese women were investigated. Twenty-six (35.6%) were type VIII, 18 (24.7%) were type VI, and the remaining 29 were distributed among more traditional serotypes. Strains were also tested by immunoblot for the presence of GBS surface proteins. Fifty-three (72.6%) of the 73 strains expressed one or more laddering GBS proteins. These data show that type VI and VIII GBS strains are common vaginal isolates in pregnant Japanese women and that one or more laddering proteins are present in most GBS strains.
New mediators of immunity and inflammation in inflammatory bowel disease (2006)

The clarification of the complex network of immune-inflammatory mediators operating in the gut of patients with inflammatory bowel disease has led to the identification of new targets that could, in turn, drive the development of effective biological therapies.
A smart range image sensor (1998)

In the present paper we discuss a smart image sensor, specifically designed for sheet of light range imaging. The image sensor is capable of measuring the projection of a light stripe on an object. The sensor consists of an array of Position Sensitive Detectors (PSD's), as well as some on-chip electronics. The sensors are made in a standard 3GHz bipolar process. Each PSD measures a light center of gravity, and this way the line of light is sampled in the plane of the image sensor. 3D information is computed by means of triangulation. On chip circuitry takes care of preamplification of the sensorsignals, and multiplexing of the different sensor signals to a single output channel.
The human hepatitis B virus enhancer requires trans-acting cellular factor(s) for activity. (1986)

The activity of the hepatitis B viral enhancer element was studied in various cell lines. This enhancer shows strict host and tissue specificity in that it is functional only in liver cells of human origin. Further, it requires trans-acting factor(s) present in liver cells for activity, and this activity is independent of hepatitis B virus gene products in the cell lines tested.
Heat shock protein 90 (Hsp90) chaperone complex inhibitor, Radicicol, potentiated radiation-induced cell killing in a hormone-sensitive prostate cancer cell line through degradation of the androgen receptor (2005)

Until now, there has not been enough information on how androgens or androgen deprivation may influence the response of cancer cells to radiation. In this study, the effect of dihydrotestosterone (DHT) on cellular proliferative activity and radiosensitivity was examined in a hormone-sensitive human prostate cancer cell line, LNCaP. In addition, the study also examined how a heat shock protein 90 (Hsp90) chaperone complex inhibitor modified the effect of DHT on the radiosensitivity of the cells, because binding of the androgen receptor (AR) to Hsp90 is required to maintain the stability and functioning of AR. The hormone-sensitive human prostate cancer cell line, LNCaP, was used. Radicicol was used as one of the known Hsp90 chaperone complex inhibitors, and the cells were incubated in the presence of this compound at a concentration of 500 nM. Cellular radiosensitivity was determined by the clonogenic assay; the changes in the protein expression were examined by Western blotting or immunofluorescence. DHT at a concentration of 1 nM caused enhancement of the proliferative activity and reduction of the radiosensitivity of the cells. Radicicol at a concentration of 500 nM abolished the DHT-induced decrease in cellular radiosensitivity and potentiated the radiation-induced cell killing synergistically. Consistent with the changes in the cellular radiosensitivity, radicicol degraded AR, Raf-1 and HER2/neu via reduced binding of AR to Hsp90, although selective degradation of HER2/neu caused by Herceptin, a monoclonal antibody against HER2, did not affect the cellular radiosensitivity. The results suggest that the Hsp9O chaperone complex may be a potential molecular target for potentiation of radiation-induced cell killing in a hormone-sensitive prostate cancer cell line.
Movement Disorder Society‐sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS‐UPDRS): Scale presentation and clinimetric testing results (2008)

We present a clinimetric assessment of the Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). The MDS-UDPRS Task Force revised and expanded the UPDRS using recommendations from a published critique. The MDS-UPDRS has four parts, namely, I: Non-motor Experiences of Daily Living; II: Motor Experiences of Daily Living; III: Motor Examination; IV: Motor Complications. Twenty questions are completed by the patient/caregiver. Item-specific instructions and an appendix of complementary additional scales are provided. Movement disorder specialists and study coordinators administered the UPDRS (55 items) and MDS-UPDRS (65 items) to 877 English speaking (78% non-Latino Caucasian) patients with Parkinson's disease from 39 sites. We compared the two scales using correlative techniques and factor analysis. The MDS-UPDRS showed high internal consistency (Cronbach's alpha = 0.79-0.93 across parts) and correlated with the original UPDRS (rho = 0.96). MDS-UPDRS across-part correlations ranged from 0.22 to 0.66. Reliable factor structures for each part were obtained (comparative fit index > 0.90 for each part), which support the use of sum scores for each part in preference to a total score of all parts. The combined clinimetric results of this study support the validity of the MDS-UPDRS for rating PD.
Inhibitors of Nitric Oxide Synthesis and TNF-α Expression from Magnolia obovata in Activated Macrophages (2000)

Nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) are the major mediators produced in activated macrophages which contribute to the circulatory failure associated with septic shock. An activity-guided fractionation of an MeOH extract of stem bark of Magnolia obovata afforded two inhibitors of NO production in lipopolysaccharides (LPS)-activated macrophages by the suppression of i-NOS expression. Their structures were elucidated by spectroscopic methods to be magnolol and honokiol with IC50 values of 16.8 and 6.4 microM, respectively. They also inhibited the production of TNF-alpha in LPS-activated macrophages. Thus, these compounds may be possible candidates for the development of new drugs to treat endotoxemia accompanied by the overproduction of NO and TNF-alpha.
In Vivo Noninvasive Monitoring of Glucose Concentration in Human Epidermis by Mid-Infrared Pulsed Photoacoustic Spectroscopy (2012)

The noninvasive determination of glucose in the interstitial layer of the human skin by mid-infrared spectroscopy is reported. The sensitivity for this measurement was obtained by combining the high pulse energy from an external cavity quantum cascade laser (EC-QCL) tunable in the infrared glucose fingerprint region (1000-1220 cm(-1)) focused on the skin, with a detection of the absorbance process by photoacoustic spectroscopy in the ultrasound region performed by a gas cell coupled to the skin. This combination facilitates a quantitative measurement for concentrations of skin glucose in the range from <50 mg/dL to >300 mg/dL, which is the relevant range for the glucose monitoring in diabetes patients. Since the interstitial fluid glucose level is representative of the blood glucose level and follows it without significant delay (<10 min), this method could be applied to establish a noninvasive, painless glucose measurement procedure that is urgently awaited by diabetes patients. We report here the design of the photoacoustic experiments, the spectroscopy of glucose in vivo, and the calibration method for the quantitative determination of glucose in skin. Finally, a preliminary test with healthy volunteers and volunteers suffering from diabetes mellitus demonstrates the viability of a noninvasive glucose monitoring for patients based on the combination of infrared QCL and photoacoustic detection.
Microfluidic Self-Sorting of Mammalian Cells to Achieve Cell Cycle Synchrony by Hydrophoresis (2009)

Cell cycle studies for examining regulatory mechanisms and progression invariably require synchronization of cell cultures at a specific phase of the cell cycle. Current implementations to produce synchronous cell populations, however, tend to perturb normal cellular progression and metabolism and typically require complex, time-consuming preparations. Thus, it is challenging for the development of a simple, noninvasive, and effective means for cell cycle synchronization. We demonstrate the use of hydrophoretic size separation to sort cells in target phases of the cell cycle entirely based on a hydrodynamic principle. With this method, we found that there is a linear relationship between a cell's size and its position distribution in the hydrophoretic device. We also demonstrate the robustness of the hydrophoretic method for practical applications by sorting cells in the G(0)/G(1) and G(2)/M phases out of the original, asynchronous cells with a high level of synchrony of 95.5% and 85.2%, respectively. These results show that the hydrophoretic size separation can be used in order to collect cells at the same phase of the cell cycle in a gentle, noninvasive way.
Design for an Interactive Television Advertising System (2006)

The importance of information systems in the advertising industry is increasing as entertainment media incorporate functionality from new electronic technologies. Interactive television is a new entertainment medium that has the potential for enabling new paradigms of advertising. Most information systems research in the interactive television domain focuses on improving methods for choosing program content. The studies that address advertising concentrate on techniques for implementing personalization. Few studies consider how to improve interactivity of advertising in the new medium. This investigation developed an information systems artifact that incorporates models of interactivity into a design for an advertising system architecture. A proof-of-concept prototype based on this design was implemented and validated in a pilot test. Implications for the advertising industry and for future research are discussed.
Semiconductors for room temperature nuclear detector applications (1995)

Since its inception in 1966, the series of numbered volumes known as Semiconductors and Semimetals has distinguished itself through the careful selection of well-known authors, editors, and contributors. The"Willardson and Beer"Series, as it is widely known, has succeeded in publishing numerous landmark volumes and chapters. Not only did many of these volumes make an impact at the time of their publication, but they continue to be well-cited years after their original release. Recently, Professor Eicke R. Weber of the University of California at Berkeley joined as a co-editor of the series.
The Streptococcus thermophilus CRISPR/Cas system provides immunity in Escherichia coli (2011)

The CRISPR/Cas adaptive immune system provides resistance against phages and plasmids in Archaea and Bacteria. CRISPR loci integrate short DNA sequences from invading genetic elements that provide small RNA-mediated interference in subsequent exposure to matching nucleic acids. In Streptococcus thermophilus, it was previously shown that the CRISPR1/Cas system can provide adaptive immunity against phages and plasmids by integrating novel spacers following exposure to these foreign genetic elements that subsequently direct the specific cleavage of invasive homologous DNA sequences. Here, we show that the S. thermophilus CRISPR3/Cas system can be transferred into Escherichia coli and provide heterologous protection against plasmid transformation and phage infection. We show that interference is sequence-specific, and that mutations in the vicinity or within the proto-spacer adjacent motif (PAM) allow plasmids to escape CRISPR-encoded immunity. We also establish that cas9 is the sole cas gene necessary for CRISPR-encoded interference. Furthermore, mutation analysis revealed that interference relies on the Cas9 McrA/HNH- and RuvC/RNaseH-motifs. Altogether, our results show that active CRISPR/Cas systems can be transferred across distant genera and provide heterologous interference against invasive nucleic acids. This can be leveraged to develop strains more robust against phage attack, and safer organisms less likely to uptake and disseminate plasmid-encoded undesirable genetic elements.
Autologous Fat Grafting for Treatment of Breast Implant Capsular Contracture: A Study in Pigs (2014)

Results in this animal model indicate that pericapsular lipoinjection may be a promising treatment for CC in humans.
[Comparison of plasma concentration and tolerance of a single dose of human calcitonin by intradermal and subcutaneous administration]. (1991)

Tmax were at 23.6 +/- 10 min and 16.2 +/- 7.5 min for SC and ID routes respectively. With ID route, Tmax was reached simultaneously or earlier (3 times). Cmax is significantly higher with ID route. Neither mean plasmatic levels at each plasmatic dosage nor mean areas under the curve between 0 to 1,440 min or between 0 to 480 min (this latest AUC calculate to minimize the importance of calcitonin basal level) were significantly different with ID and SC routes. 16 mild side effects (8 with each administration) were observed in 4 subjects. They appeared before 5 min. and were transient (1 hour) for cutaneous manifestations, and later between hours 3 and 7 for nausea and vomiting or asthenia. The mean lowering of calcemia was 0.29 +/- 0.21 and 0.18 +/- 0.11 mmol/l respectively for SC and ID route. In this study ID and SC routes for calcitonin administration are not different with regard to plasma levels and side effects.
Mutation in the CYP21B gene (Ile-172----Asn) causes steroid 21-hydroxylase deficiency. (1988)

Steroid 21-hydroxylase deficiency is the most common cause of congenital adrenal hyperplasia. It results from a deficiency in a specific cytochrome P450, P450c21 (P450XXIA). The gene encoding this protein (CYP21B) and a closely linked pseudogene (CYP21A) are located in the HLA complex on chromosome 6p. Many mutant alleles are associated with deletions of CYP21B; we report the cloning and characterization of a nondeleted mutant CYP21B gene. This mutant gene is expressed on transfection into mouse Y1 adrenal cells, producing mRNA levels similar to those seen after transfection of the normal CYP21B gene. In codon 172 of the mutant gene, the normal codon ATC, encoding isoleucine, has been changed to AAC, encoding asparagine. This mutation is normally present in the CYP21A pseudogene, so that it may have been transferred to the mutant CYP21B gene by gene conversion. Hybridization of oligonucleotide probes corresponding to this and two other mutations normally present in CYP21A demonstrated that 4 out of 20 patients carried the codon 172 mutation; in one of these patients, the mutation was present as part of a larger gene conversion involving at least exons 3-6. Gene conversion may be a frequent cause of 21-hydroxylase deficiency alleles due to the presence of six chi-like sequences (GCTGGGG) in the CYP21 genes and the close proximity of the CYP21A pseudogene, which has several potentially deleterious mutations.
Discovery and Development of VX-950, a Novel, Covalent, and Reversible Inhibitor of Hepatitis C Virus NS3.4A Serine Protease (2006)

The hepatitis C virus (HCV) NS3.4A protease, which is essential for viral replication, is considered one of the most attractive targets for developing novel anti-HCV therapies. However, discovery of potent and selective small-molecule inhibitors of HCV NS3.4A protease as oral drug candidates has been hampered by the shallow substrate-binding groove of the protease. Serine trap warheads have been used to covalently anchor inhibitor scaffolds and to increase their affinity to the protease. This review will examine the evolution of covalent inhibitors of the HCV NS3.4A protease from early aldehyde molecules to alpha-ketoamide inhibitors. Kinetic and structural studies of alpha-ketoacid and alpha-ketoamide inhibitors revealed an unusual mechanism of binding in the catalytic site. Optimization of alpha-ketoamide scaffolds by scientists at Vertex and Eli Lilly led to the discovery of VX-950, a novel, potent, selective inhibitor of HCV NS3.4A protease. VX-950 possesses excellent antiviral activity in both HCV replicon cells and human fetal hepatocytes infected with HCV-positive patient sera. In addition, VX-950 exhibits a favorable pharmacokinetic profile in several animal species and demonstrates potent inhibition of the HCV NS3.4A protease activity in a mouse model. In a recent phase 1b clinical trial, VX-950 was able to rapidly reduce the plasma viral load of patients chronically infected with genotype 1 HCV by a mean approximately 3 log(10) in 2 days. The median viral load reduction was 4.4 log(10) for the best dose group after 14 days of dosing. The pre-clinical profile and early clinical data of VX-950 will be discussed in this review.
Structural studies on the carbohydrate portion of fetuin. (1979)

The O-glycosidically linked carbohydrate chains of fetuin have been cleaved off by alkaline borohydride treatment and separated from the iV-glycosidically linked carbohydrate chains still bound to the protein. Both types of carbohydrate chains have been studied by sugar and methylation analysis before and after removal of Wacetylneuraminic acid (NeuNAc) residues. The iV-glycosidically linked carbohydrate chains have been further analyzed by Smith degradation, trifluoroacetolytic degradation, and degradation after chromium trioxide oxidation. As a result of these studies, the following structures for the carbohydrate chains of fetuin are proposed: ~-N~uNAc-(Z-~)-~-~-G~~~-(~-~)-CY-~-G~C~-(~-CI)-Eerine or threonine] L!J (1) a-N;uNAc and o-NeuNAc-(2-3)-~-~-Galp-(l-3)-~-~-GalNAcp-(l-~-perine or threonine] (2) Galp, galactopyranose; GalNAcp, 2-acetamido-2-deoxygalactopyranose; Manp, mannopyranose; GlcNacp, 2-acetamido-2-deoxyglucopyranose are the abbreviations used in the structures. Fetuin is the major glycoprotein in fetal calf serum. It has been shown by Spiro and co-workers (1, 2) that fetuin has three oligosaccharide chains per molecule 0-glycosidically linked to serine or threonine. These carbohydrate chains have either the structure a-NeuNAc'-(2