gebhart/patrepeval huggingface dataset:
16 Models, Mutants, and Man: Searching for Unique Phenotypes and Genes in the Dog Model of Inherited Retinal Degeneration (2006)

The past 15 years has seen a virtual explosion of gene and phenotype discovery in medical ophthalmology. Since the mapping of an autosomal dominant retinitis pigmentosa (ADRP) locus to the long arm of human chromosome 3 in the region of the rhodopsin ( RHO ) gene (McWilliam et al. 1989; Farrar et al. 1990), and the subsequent identification of the first disease-associated mutation (Dryja et al. 1990), there has been very rapid progress in identification of multiple loci and genes that are responsible for inherited visual dysfunction or blindness occurring alone or as part of more complex syndromes. Approximately 150 retinal disease loci have been mapped to date; of these, disease-causing mutations have been found in approximately 100 genes (Fig. 1; http://www.sph.uth.tmc.edu/RetNet/). Even for the RHO gene, over 100 disease-causing mutations have been identified, and, although most are inherited as autosomal dominant (AD) and cause RP, autosomal recessive RP (ARRP) and AD congenital stationary nightblindness (CSNB) forms also are recognized (Rivolta et al. 2002). Thus, allelic and genetic heterogeneity are the rule when considering the inherited diseases of the retina. Despite this complexity, rapid progress has been possible because of the very thorough earlier studies that critically defined the phenotypic characteristics of many of these disorders in man (for review, see Berson 1993; see also Berson et al. 1968, 1969; Kemp et al. 1988; Cideciyan and Jacobson 1993; Jacobson et al. 1994). Dogs also suffer from various forms of inherited retinal blindness, the principal one termed progressive retinal atrophy (PRA). This is...
Chemotaxis of skeletal muscle satellite cells (1997)

Migration of myogenic cells occurs extensively during both embryogenesis and regeneration of skeletal muscle and is important in myoblast gene therapy, but little is known about factors that promote chemotaxis of these cells. We have used satellite cells from adult rats purified by Percoll density gradient centrifugation to test growth factors and wound fluids for chemotactic activity in blind-well Boyden chambers. Of a variety of growth factors tested only hepatocyte growth factor (HGF) and transforming growth factor-beta (TGF-beta) exhibited significant chemotactic activity. The dose-response curves for both of these factors was bell-shaped with maximum activity in the 1-10 ng/ml range. Checkerboard analysis of TGF-beta showed that chemotaxis occurred only in response to a positive concentration gradient. An extract of rat platelets also exhibited chemotactic activity for satellite cells. Half-maximal activity of this material was about 3 micrograms/ml, and there was no evidence of inhibition of migration at high concentrations. Checkerboard analysis of platelet extract exhibited evidence of both chemotaxis and chemokinesis, or increase in random motility of cells. Inhibition experiments showed that most, but not all, of the chemotactic activity in platelet extract could be blocked with a neutralizing antibody to TGF-beta. A saline extract of crushed muscle was found to contain both mitogenic and motogenic factors for satellite cells. The two activities were present in different fractions after heparin affinity chromatography. We propose that the proliferation and migration of satellite cells during regeneration is regulated by overlapping gradients of several effector molecules released at the site of muscle injury. These molecules may also be useful for enhancing the dispersion of injected myoblasts during gene therapy.
Capsule Filling Performance of Powdered Formulations in Relation to Flow Characteristics (2011)

A successful pharmaceutical capsule filling operation requires a balance of, often conflicting, powder properties – the flowability of the powder, its compressibility, and adequate lubrication to facilitate plug ejection.
A powder's flowability is complex and its effect on capsule filling is difficult to predict, but there are dynamic, bulk and shear properties that in combination can provide increased understanding of how powders perform in such processes.
This study examines the dosing weight variation and the required ejection force during a capsule filling process for twelve different lactose based formulations and shows how the results correlate with the powder characteristics obtained using a Powder Rheometer. These characteristics include dynamic flowability, bulk density, permeability, compressibility and shear properties.
The results clearly show that those formulations containing higher percentage of Acetaminophen (APAP) consistently have higher Specific Energy, Compressibility and Cohesion, along with lower Aeration Ratio – all suggesting higher cohesivity – are associated with higher ejection forces. The powder cohesivity is the dominant factor in relation to the ejection force.
Those formulations containing APAP have increased capsule weight variation. However, the formulations containing 10wt.% APAP, showing moderate cohesivity, have consistently higher weight variability than 40wt.% APAP. This is because there is a balance between two separate stages encountered in the filling process – gravity filling and forced filling. Gravity fill is favoured by powders with lower cohesivity and higher permeability. Forced filling is favoured by powders with higher cohesivity and lower permeability.
Characterization of Vesicular Stomatitis Virus Pseudotypes Bearing Essential Entry Glycoproteins gB, gD, gH, and gL of Herpes Simplex Virus 1 (2016)

Herpes simplex viruses (HSVs) are human pathogens that can cause cold sores, genital herpes, and blindness. No vaccines or preventatives are available. HSV entry into cells-a prerequisite for a successful infection-is a complex process that involves multiple viral and host proteins and occurs by different routes. Detailed mechanistic knowledge of the HSV entry is important for understanding its pathogenesis and would benefit antiviral and vaccine development, yet the presence of more than a dozen proteins on the viral envelope complicates the dissection of the HSV entry mechanisms. In this study, we generated heterologous virions displaying the four essential entry proteins of HSV-1 and showed that they are capable of cell entry and, like HSV-1, require all four entry glycoproteins along with a gD receptor. This HSV pseudotyping system pioneered in this work opens doors for future systematic exploration of the herpesvirus entry mechanisms.
Propane Oxidation over Pt/SrTiO<sub>3</sub> Nanocuboids (2011)

Pt/SrTiO3 shows promise as a low temperature hydrocarbon combustion catalyst for automotive applications. In this study, SrTiO3 nanocuboid supports were synthesized using sol-precipitation coupled with hydrothermal synthesis, and platinum was deposited on the nanocuboids with 1, 3, and 5 cycles of atomic layer deposition (ALD). The platinum particles have a highly uniform distribution both before and after reaction testing, and range from 1 to 5 nm in size, depending upon the number of ALD cycles. These materials have a >50 °C lower light-off temperature for propane oxidation than a conventional Pt/Al2O3 catalyst, turn over frequencies up to 3 orders of magnitude higher, and show improved resistance to deactivation. The increased activity is attributed to the stabilization of a Pt/PtO core/shell structure during operating conditions by the strong epitaxy between the Pt and the SrTiO3 support.
Abstract 1304: Clinical pharmacokinetics of GDC-0973, an oral MEK inhibitor, in cancer patients: data from a Phase 1 study (2011)

Abstract Background: GDC 0973 is a potent, selective, orally administered MEK1/2 inhibitor. It has shown antitumor activity in preclinical models. A first-in-human, phase 1 dose escalation study in cancer patients was conducted using a 3+3 design with two dosing schedules, followed by an expansion at the MTD for each dosing schedule. The pharmacokinetic objective was to evaluate GDC-0973 PK in patients on both dosing schedules. Methods: GDC-0973 was administered orally, once daily on a 21 day on/7 day off (21/7) or on a 14 day on/14 day off (14/14) dosing schedule. Plasma samples for PK analysis were collected on Day 1 and Day 21 (for 21/7) or Day 14 (14/14) of Cycle 1, and during the dosing holiday to determine half-life of GDC-0973. Urine samples were collected on Day 1 and on Day 21 (21/7) or Day 14 (14/14) over a 24-hour period for exploratory analysis. Plasma samples were analyzed using a validated LC/MS/MS method. GDC-0973 pharmacokinetic data was analyzed using a non-compartmental approach with the program WinNonlin. Results: GDC-0973 pharmacokinetics was evaluated at doses administered in the 21/7 schedule (0.05, 0.1 and 0.2 mg/kg in a liquid solution and 10, 20, 40, 60, and 80 mg as capsules) and the 14/14 schedule (60, 80, 100 and 125 mg as capsules). Pharmacokinetic data was available in 41 patients on the 21/7 and 11 patients on the 14/14 schedule. GDC-0973 Cmax was observed at 1-4 hours post-dose, and was similar across the entire dose range. Cmax and AUC increased dose proportionally in the dose range up to 100 mg. The mean apparent oral clearance ranged from 4.30 to 11.7 L/h in the 0.05 mg/kg-100 mg dose range. The mean elimination half-life ranged from 31.6 to 53.5 hours in all dose levels in both schedules. Following daily oral dosing, the mean accumulation ratio was 2.0 to 4.0, which is consistent with its half-life and dosing interval, indicating that the PK was constant over time. Given the mean half-life of ∼40 hours, steady-state exposures are expected to be achieved in 8-10 days. Preliminary data suggest that approximately 1-8% of intact drug is excreted in urine; hence, renal excretion is a minor pathway for elimination. Exploratory analysis showed no clear association between exposure and demographic factors (age, weight, sex) or concomitant medications. PK was consistent between patients in the 21/7 and 14/14 dose escalation stages, as well as the expansion stages when compared at the same doses. Doses of 40 mg or higher in patients achieved steady-state concentrations consistent with antitumor activity observed in xenograft models. Conclusion: GDC-0973 preliminary PK analysis shows a moderate rate of absorption; with generally dose-proportional increases in Cmax and AUC. Updated data will be presented. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1304. doi:10.1158/1538-7445.AM2011-1304
Performance analysis of a servo system with high-bandwidth torque disturbance observer (2003)

The paper analyzes the performance of a servo system with torque disturbance observer when the observer bandwidth is high enough to affect the servo dynamics. The main outcome of the analysis is the under-damped or even unstable behavior of the system. Another outcome is the limited range allowable for the parameter mismatch to keep the system stable. The analysis, carried out in the discrete time, is substantiated by experimental results.
An Alternative to the Mixed Probe Method in DNA Hybridization: Synthetic "lure" Nucleotide for the Ambiguous Position of Codons (1986)

Abstract Two deoxynucleoside analogues, 1-(2-deoxy-β-D-ribofuranosyl)-2-oxo-4-imidazoline-4-carbox-amide (1) and 5-carbamoyl-2′-deoxyuridine (2), were synthesized and incorporated into decamer deoxynucleotides, which were hybridized to their complementary strands. The duplices in which 1 paired with A or G showed higher melting temperatures (Tm's) than those containing G -T or A -C mismatch, although lower than the Tm of intact totally complementary duplex. The incor­poration of 2 into a strand resulted in extreme destabilization of the duplex.
Independent Control of Drop Size and Velocity in Microfluidic Flow-Focusing Generators Using Variable Temperature and Flow Rate (2009)

This paper describes a method to control the volume and the velocity of drops generated in a flow-focusing device dynamically and independently. This method involves simultaneous tuning of the temperature of the nozzle of the device and of the flow rate of the continuous phase; the method requires a continuous phase liquid that has a viscosity that varies steeply with temperature. Increasing the temperature of the flow-focusing nozzle from 0 to 80 degrees C increased the volume of the drops by almost 2 orders of magnitude. Tuning both the temperature and the flow rate controlled the drop volume and the drop velocity independently; this feature is not possible in a basic flow-focusing device. This paper also demonstrates a procedure for identifying the range of possible drop volumes and drop velocities for a given flow-focusing device and shows how to generate drops with a specified volume and velocity within this range. This method is easy to implement in on-chip applications where thermal management is already incorporated in the system, such as DNA amplification using the polymerase chain reaction and nanoparticle synthesis.
Changes in Nanoscaled Mechanical and Rheological Properties of Asphalt Binders Caused by Aging (2015)

Aging of an asphalt binder causes the changes in the microstructure and, consequently, in the nanomechanical and rheological properties of the aged asphalt binder. Short‐term aging on asphalt binders was simulated using rotating thin film oven (RTFO). These changes in the microstructure and nanomechanical and rheological properties were measured using atomic force microscope (AFM) and dynamic shear rheometer (DSR). The results indicated that (1) the adhesive force of the asphalt binder from AFM tests was increased after RTFO aging; (2) G * of the asphalt binder from DSR tests increased after RTFO aging; (3) the results from AFM were consistent with those from DSR, explaining the mechanism of the changes of rheological properties.
Atherosclerosis in LDL-receptor knockout mice is accelerated by immunization with anticardiolipin antibodies (1997)

Atherosclerosis is a process initiated by accumulation of macrophages in distinct areas of endothelial cell damage and uptake of large amounts of lipids. Recently, it has been shown that the immune system plays an active part in the progression of the atherosclerotic plaque although its precise role has not yet been elucidated. Anticardiolipin antibodies (aCL) are generally found in the sera of patients with the antiphospholipid syndrome (APS) and are associated with a prothrombotic state. Several authors have demonstrated that aCL can activate platelets and endothelial cells as well as increase oxidized low density lipoprotein (LDL) uptake by macrophages. In the present study we sought to assess the effect of immunization with aCL (Ab1, leading to the production of mouse aCL-Ab3) on the progression of atherosclerosis. Two groups of 8-weeks old female LDL-receptor knockout mice (n = 13 per group) were immunized with IgG purified from the serum of an APS patient or with normal human IgG, respectively. The aCL immunized mice developed high titres of 'self' aCL (detected using the standard aCL ELISA) as compared with the normal human IgG immunized mice, whereas no differences were noted between both study groups with respect to the serum lipid levels. The extent of fatty streak formation was significantly higher in the aCL immunized mice in comparison with the human IgG injected mice (mean aortic lesion size of 5308 +/- 471 microns2 vs 1027 +/- 184 microns2, respectively, P < 0.01). The immunohistochemical analysis of the atherosclerotic plaques from both mouse groups did not display differences in cellular composition. The results of the study show that mouse aCL induced by immunization with human aCL from an APS patient enhance atherogenesis in LDL-RKO mice and imply that these antibodies may play a role in atherosclerosis development in patients with the APS.
[Evaluation of the effectiveness of the use of various anti-adhesion agents in an experiment]. (1993)

The study of the efficacy of the use of different materials recommended for the adhesion prevention was carried out in 15 white rats. On the parietal front-lateral peritoneum of the abdomen, adhesion formation was induced using an adhesion induction model of 10--nodes suture (catgut 3/0) both sides. In the experimental group, fibrin glue FG1 produced at the Surgery Centre of the Russian Academy of Medical Sciences, and oxidized cellulose barrier-Interceed, manufactured by the Johnson & Johnson company (USA); were applied while the control group was made up of the untreated rodents. 5 days after the operation, these animals were opened and the degree of the spread, type, intensity and rigidity of the formed adhesion were studied using the grade system. It was observed, that fibrin glue and Interceed barrier never caused any tissue reaction; a reduction in the frequency of adhesion formation was also noted in the treated group.
Fractional Photothermolysis: A Novel Aesthetic Laser Surgery Modality (2007)

The ubiquity of increased sun exposure, oral contraceptives, and phototoxic drugs has led to an increased prevalence of conditions such as dyschromia, melasma, rhytides, and other signs of photoaging over the past few decades. Through the application of selective photothermolysis, laser surgery has attempted to create therapeutic options for these medically recalcitrant conditions. To date, however, this technology has been met with limited success, due to a high incidence of posttreatment side effects, inability to treat off the face, and a safety profile tailored to Fitzpatrick skin types I to III. More recently, a novel approach coined "fractional photothermolysis" was developed in an attempt to overcome these limitations. This new laser treatment modality has allowed for effective treatment of a diverse array of dermatologic conditions on and off the face with a wider therapeutic index and improved safety profile independent of Fitzpatrick skin type. This review sheds light on the technical aspects, biologic mechanisms, and clinical effects of fractional photothermolysis that help set it apart from previous modes of laser surgery.
Studies on a New Antibiotic, Laurusin (1965)

Studies on a New Antibiotic, Laurusin Get access Shojiro Aizawa, Shojiro Aizawa Institute of Applied Microbiology The University of Tokyo Bunkyo-ku, Tokyo Search for other works by this author on: Oxford Academic Google Scholar Tetsuro Hidaka, Tetsuro Hidaka Institute of Applied Microbiology The University of Tokyo Bunkyo-ku, Tokyo Search for other works by this author on: Oxford Academic Google Scholar Noboru Ōtake, Noboru Ōtake Institute of Applied Microbiology The University of Tokyo Bunkyo-ku, Tokyo Search for other works by this author on: Oxford Academic Google Scholar Hiroshi Yonehara, Hiroshi Yonehara Institute of Applied Microbiology The University of Tokyo Bunkyo-ku, Tokyo Search for other works by this author on: Oxford Academic Google Scholar Kiyoshi Isono, Kiyoshi Isono Antibiotic Laboratory The Institute for Physical and Chemical Research Bunkyo-ku, Tokyo Search for other works by this author on: Oxford Academic Google Scholar Noriko Igarashi, Noriko Igarashi Institute of Applied Microbiology The University of Tokyo Bunkyo-ku, Tokyo Search for other works by this author on: Oxford Academic Google Scholar Saburo Suzuki Saburo Suzuki Antibiotic Laboratory The Institute for Physical and Chemical Research Bunkyo-ku, Tokyo Search for other works by this author on: Oxford Academic Google Scholar Agricultural and Biological Chemistry, Volume 29, Issue 4, 1 April 1965, Pages 375–376, https://doi.org/10.1080/00021369.1965.10858402 Published: 01 April 1965 Article history Received: 13 February 1965 Published: 01 April 1965
Parallel Metallocenes of Germanium, Tin, and Lead (2000)

The reaction of 2 equiv of LiCps (Cps = C5Me4(SiMe2But)) with GeCl2·diox, SnCl2, or PbCl2 in ethereal solvents affords the metallocenes [M(η5-Cps)2] (M = Ge, 1; M = Sn, 2; M = Pb, 3) in 96, 89, and 84% yields, respectively. A single-crystal X-ray structural analysis of each reveals that, for the first time, the cyclopentadienyl rings are parallel for all three metallocenes. Both solid- and solution-state multinuclear NMR spectroscopic data for 2 and 3 are reported. An examination of 1−3 using DFT has also been performed, and in the case of 1 a comparison with its C5H5 analogue has been carried out.
Treatment of atrial fibrillation with radiofrequency ablation and simultaneous multipolar mapping of the pulmonary veins (2001)

Selective and simultaneous catheterization of the 4 pulmonary veins with microcatheters for simultaneous recording of their electrical activity is a feasible and safe procedure that may help ablation of atrial fibrillation.
Clinically Relevant Concentrations of Anticancer Drugs: A Guide for Nonclinical Studies (2017)

Approved and marketed drugs are frequently studied in nonclinical models to evaluate the potential application to additional disease indications or to gain insight about molecular mechanisms of action. A survey of the literature reveals that nonclinical experimental designs (<i>in vitro</i> or <i>in vivo</i>) often include evaluation of drug concentrations or doses that are much higher than what can be achieved in patients (i.e., above the maximally tolerated dose or much higher than the clinically relevant exposures). The results obtained with these high concentrations may be particularly helpful in elucidating off-target effects and toxicities, but it is critical to have a dose-response curve that includes the minimally effective or clinically effective concentration for comparison. We have reviewed the clinical literature and drug product labels for all small molecules and biological agents approved by the FDA for use in oncology to identify and compile the available pharmacokinetic parameters. The data summarized here can serve as a guide for selection of <i>in vitro</i> concentrations and <i>in vivo</i> plasma exposures for evaluation of drug effects in nonclinical studies. Inclusion of drug concentrations or exposures that are relevant to those observed in clinical practice can improve translation of nonclinical mechanism of action findings into potentially relevant clinical effects. <i>Clin Cancer Res; 23(14); 3489-98. ©2017 AACR</i>.
Pentafluorobenzenesulfonyl chloride: a new electrophoric derivatizing reagent with application to tyrosyl peptide determination by gas chromatography with electron capture detection (1984)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPentafluorobenzenesulfonyl chloride: a new electrophoric derivatizing reagent with application to tyrosyl peptide determination by gas chromatography with electron capture detectionAbdellah. Sentissi, Markus. Joppich, Kathleen. O'Connell, Albert. Nazareth, and Roger W. GieseCite this: Anal. Chem. 1984, 56, 13, 2512–2517Publication Date (Print):November 1, 1984Publication History Published online1 May 2002Published inissue 1 November 1984https://pubs.acs.org/doi/10.1021/ac00277a056https://doi.org/10.1021/ac00277a056research-articleACS PublicationsRequest reuse permissionsArticle Views171Altmetric-Citations14LEARN 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