gebhart/patrepeval huggingface dataset:
AAV-mediated photoreceptor transduction of the pig cone-enriched retina (2011)

Recent success in clinical trials supports the use of adeno-associated viral (AAV) vectors for gene therapy of retinal diseases caused by defects in the retinal pigment epithelium (RPE). In contrast, evidence of the efficacy of AAV-mediated gene transfer to retinal photoreceptors, the major site of inherited retinal diseases, is less robust. In addition, although AAV-mediated RPE transduction appears efficient, independently of the serotype used and species treated, AAV-mediated photoreceptor gene transfer has not been systematically investigated thus so far in large animal models, which also may allow identifying relevant species-specific differences in AAV-mediated retinal transduction. In the present study, we used the porcine retina, which has a high cone/rod ratio. This feature allows to properly evaluate both cone and rod photoreceptors transduction and compare the transduction characteristics of AAV2/5 and 2/8, the two most efficient AAV vector serotypes for photoreceptor targeting. Here we show that AAV2/5 and 2/8 transduces both RPE and photoreceptors. AAV2/8 infects and transduces photoreceptor more efficiently than AAV2/5, similarly to what we have observed in the murine retina. The use of the photoreceptor-specific rhodopsin promoter restricts transgene expression to porcine rods and cones, and results in photoreceptor transduction levels similar to those obtained with the ubiquitous promoters tested. Finally, immunological, toxicological and biodistribution studies support the safety of AAV subretinal administration to the large porcine retina. The data presented here on AAV-mediated transduction of the cone-enriched porcine retina may affect the development of gene-based therapies for rare and common severe photoreceptor diseases.
Randomised double blind trial of oral versus intravenous flecainide for the cardioversion of acute atrial fibrillation (2000)

Intravenous flecainide restored sinus rhythm more rapidly than oral flecainide, but at two hours and eight hours after treatment there was no difference in the proportion of patients cardioverted by the two approaches. These results suggest a role for oral loading doses of flecainide in the treatment of acute or symptomatic paroxysmal atrial fibrillation.
Identification of three physically and functionally distinct binding sites for C3b in human complement factor H by deletion mutagenesis. (1996)

Human complement factor H controls spontaneous activation of complement in plasma and appears to play a role in distinguishing host cells from activators of the alternative pathway of complement. In both mice and humans, the protein is composed of 20 homologous short consensus repeat (SCR) domains. The size of the protein suggests that portions of the structure outside the known C3b binding site (SCR 1-4) possess a significant biological role. We have expressed the full-length cDNA of factor H in the baculovirus system and have shown the recombinant protein to be fully active. Mutants of this full-length protein have now been prepared, purified, and examined for cofactor activity and binding to C3b and heparin. The results demonstrate (i) that factor H has at least three sites that bind C3b, (ii) that one of these sites is located in SCR domains 1-4, as has been shown by others, (iii) that a second site exists in the domain 6-10 region, (iv) that a third site resides in the SCR 16-20 region, and (v) that two heparin binding sites exist in factor H, one near SCR 13 and another in the SCR 6-10 region. Functional assays demonstrated that only the first C3b site located in SCR 1-4 expresses factor I cofactor activity. Mutant proteins lacking any one of the three C3b binding sites exhibited 6- to 8-fold reductions in affinity for C3b on sheep erythrocytes, indicating that all three sites contribute to the control of complement activation on erythrocytes. The identification of multiple functionally distinct sites on factor H clarifies many of the heretofore unexplainable behaviors of this protein, including the heterogeneous binding of factor H to surface-bound C3b, the effects of trypsin cleavage, and the differential control of complement activation on activators and nonactivators of the alternative pathway of complement.
Autonomic Tone Variations Before the Onset of Paroxysmal Atrial Fibrillation (2002)

The occurrence of PAF greatly depends on variations of the autonomic tone, with a primary increase in adrenergic tone followed by an abrupt shift toward vagal predominance.
Allelic Variation Within the Emv-15 Locus Defines Genomic Sequences Closely Linked to the agouti Locus on Mouse Chromosome 2 (1987)

Gene(s) at the agouti locus act within the microenvironment of the hair follicle to switch pigment synthesis in the melanocyte between eumelanin (black or brown pigment) and phaeomelanin (yellow pigment). Many phenotypic variants of this locus have been described. The mechanism(s) of gene action causing such variation in coat-color phenotype is not known. The close linkage of an endogenous ecotropic murine leukemia provirus, Emv-15, to the lethal yellow mutation of the agouti locus provides a means to molecularly access genes at or near the agouti locus. We have identified and used a unique mouse sequence flanking the Emv-15 provirus to define three alleles of the Emv-15 locus. We found a correlation between the presence of specific Emv-15 alleles and the origins of specific agouti locus mutations, confirming close linkage. However, we found some exceptions which suggest that the Emv-15 locus is closely linked to, but genetically separable from, the agouti locus.
Clinical efficacy of cyclosporin a neoral in the treatment of paediatric lupus nephritis with heavy proteinuria (1998)

Cyclosporin A (CsA) was introduced in recent years for the treatment of lupus nephritis in patients with steroid resistance or in those with severe corticosteroid toxicity. Our previous study on paediatric patients showed that Neoral (a new microemulsion formulation) had better bioavailability than CsA capsules. To evaluate the clinical efficacy of Neoral in children with lupus nephritis compared with conventional therapy, we performed an open randomized study on 40 children, ranging from 9 to 14 yr old, with class III-V lupus nephritis and heavy proteinuria. They were randomly assigned to either Neoral (5 mg/kg/day), administered q.12.h, or prednisolone (2 mg/kg/day) plus cyclophosphamide (2 mg/kg/day) for 1 yr. Both groups showed a significant decrease in proteinuria (Neoral: 4.62 +/- 1.93 to 0.35 +/- 0.29 g/day, P < 0.05; prednisolone plus cyclophosphamide: 4.52 +/- 1.86 to 0.62 +/- 0.21 g/day, P < 0.01). The CH50 haemolytic assay titre decreased after 1 yr of Neoral treatment (26.5 +/- 0.9 to 21.4 +/- 2.2 U/ml, P < 0.05). Serum C3 and anti-double-stranded (ds) DNA antibody levels also fell with Neoral (C3: 86.2 +/- 6.8 to 76.3 +/- 4.5 mg/dl; anti-ds DNA antibodies: 14.1 +/- 3.2 to 8.2 +/- 1.4 IU/ml, P < 0.05). The Neoral group had a significant increase in growth rate over the prednisolone plus cyclophosphamide group (8.2 +/- 1.1 cm/yr vs 2.7 +/- 0.6 cm/yr, P < 0.01) with improvement of growth status. During the study period, patients tolerated Neoral well with no significant changes in renal function, liver function or lipid profile. Our study implies that Neoral appears to be effective in suppressing proteinuria. Neoral should be regarded as being adjunctive therapy, perhaps with a steroid-sparing effect, in paediatric lupus nephritis. However, its long-term use awaits further studies.
Directional differences of impulse spread in trabecular muscle from mammalian heart. (1976)

Trabecular bundles from the right ventricle of calf hearts were used. Electrical properties measured by the application of longitudinal current were compared to those measured by the application of transverse current. 2. The following data were obtained on the basis of classical cable analysis: (i) a ratio of 3-0 for longitudinal to transverse conduction velocity, (ii) a ratio of 3-6 for intra- to extracellular longitudinal resistance, (iii) a ratio of 12-6 for intra- to extracellular transverse resistance, (iv) a ratio of 9-4 for intracellular transverse to intracellular longitudinal resistance, (v) a ratio of 2-7 for the extracellular transverse to the extracellular longitudinal resistance. 3. The disparity in conduction velocity could be explained on the sole grounds of differences in the resistivity of the intracellular and extracellular paths for current flow in the two directions, confirming theoretical predictions. 4. The value of the transverse internal resistance can be accounted for on the ground of frequent branching in a three-dimensional network. There is no need to make the additional assumption of current flow through lateral low resistance pathways between parallel fibres.
Multiple hepatocyte-enriched nuclear factors function in the regulation of transthyretin and alpha 1-antitrypsin genes. (1989)

Transthyretin (TTR) and alpha 1-antitrypsin (alpha 1-AT) are expressed at high levels in the liver and also in at least one other cell type. We report here a detailed analysis of the proximal regulatory region of the TTR gene, which has uncovered two new DNA-binding factors that are present mainly (or only) in hepatocytes. One of these new factors, hepatocyte nuclear factor 3 (HNF-3), binds to two sites that are crucial in TTR expression as well as to two additional sites in the alpha 1-AT proximal enhancer region. The second new factor, HNF-4, binds to two sites in TTR that are required for gene activity. We had previously identified binding sites for another hepatocyte-enriched DNA-binding protein (C/EBP or a relative thereof), and additional promoter-proximal sites for that protein in both TTR and alpha 1-AT are also reported here. From these results it seems clear that cell-specific expression is not simply the result of a single cell-specific factor for each gene but the result of a combination of such factors. The variation and distribution of such factors among different cell types could be an important basis for the coordinate expression of the TTR and alpha 1-AT genes in the liver or the discordant transcriptional activation of these genes in a few other cell types. The identification of such cell-enriched factors is a necessary prelude to understanding the basis for cell specificity.
Reduction in viscoelasticity in cystic fibrosis sputum in vitro using combined treatment with Nacystelyn and rhDNase (1996)

The objective of this study was to evaluate the individual and combined effects of Nacystelyn (NAL) and rhDNase in vitro on the rheological properties of cystic fibrosis (CF) sputum. Sputum samples were collected from 11 CF patients and subjected to the following protocols: 1) negative control sample without any treatment; 2) positive control sample incubated with 0.02 ml of normal saline; 3) incubation of CF sputum with 0.02 mL DNase (25 micrograms/mL in normal saline) at 37 degrees C to achieve 2.5 micrograms/g final sputum concentration (approximately 100 nM); 4) incubation of CF sputum with 0.02 mL NAL (30.9 micrograms/mL in normal saline) at 37 degrees C to achieve 3.09 micrograms/g final sputum concentration (10 microM); and 5) combination of protocols 3 and 4 with half the concentration of each drug. The samples in protocols 2 through 5 were incubated for 30 minutes at 37 degrees C. For each protocol, spinnability by filancemeter and viscoelasticity (log G*) by magnetic microrheometer were measured at baseline and 30 minutes. Treatment of the sputum with rhDNase alone or NAL alone decreased spinnability more than control treatment with saline. Combining NAL with rhDNase at half the concentration of each drug significantly decreased spinnability more than either treatment by itself. There were no significant changes in log G* or the derivative parameters, mucociliary clearability index (MCI) and cough clearability index (CCI). The enhanced reduction in sputum spinnability by the combination of NAL and rhDNase indicates additative effects between these two mucolytic treatments. These results suggest that combined treatment with rhDNase and NAL should be considered as a potential therapy for CF patients.
Safety and efficacy of cryolipolysis for non‐invasive reduction of submental fat (2015)

The results of this clinical evaluation of 60 patients treated in a pivotal IDE study demonstrate that submental fat can be reduced safely and effectively with a small volume cryolipolysis applicator. Patient surveys revealed that submental cryolipolysis was well-tolerated, produced visible improvement in the neck contour, and generated high patient satisfaction. These study results led to FDA clearance of cryolipolysis for submental fat treatment.
Fluidic Systems Design (1972)

A book on how to design control systems using fluidics. The first 1.1 GB document is an uncompressed high resolution PDF. I have also uploaded a compressed 97.2MB version of the document for an easier downloading and usage.
Emerging Strategies to Combat ESKAPE Pathogens in the Era of Antimicrobial Resistance: A Review (2019)

The acronym ESKAPE includes six nosocomial pathogens that exhibit multidrug resistance and virulence: <i>Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa</i>, and <i>Enterobacter</i> spp. Persistent use of antibiotics has provoked the emergence of multidrug resistant (MDR) and extensively drug resistant (XDR) bacteria, which render even the most effective drugs ineffective. Extended spectrum β-lactamase (ESBL) and carbapenemase producing Gram negative bacteria have emerged as an important therapeutic challenge. Development of novel therapeutics to treat drug resistant infections, especially those caused by ESKAPE pathogens is the need of the hour. Alternative therapies such as use of antibiotics in combination or with adjuvants, bacteriophages, antimicrobial peptides, nanoparticles, and photodynamic light therapy are widely reported. Many reviews published till date describe these therapies with respect to the various agents used, their dosage details and mechanism of action against MDR pathogens but very few have focused specifically on ESKAPE. The objective of this review is to describe the alternative therapies reported to treat ESKAPE infections, their advantages and limitations, potential application <i>in vivo</i>, and status in clinical trials. The review further highlights the importance of a combinatorial approach, wherein two or more therapies are used in combination in order to overcome their individual limitations, additional studies on which are warranted, before translating them into clinical practice. These advances could possibly give an alternate solution or extend the lifetime of current antimicrobials.
Regulation of cellulase biosynthesis and secretion in fungi (1985)

Conference Article| April 01 1985 Regulation of cellulase biosynthesis and secretion in fungi HANNELE MERIVUORI; HANNELE MERIVUORI 1Department of Biology and the Biotechnology Research Center, Lehigh University, Bethlehem, PA 18015, U.S.A. Search for other works by this author on: This Site PubMed Google Scholar KATHERINE M. SIEGLER; KATHERINE M. SIEGLER 1Department of Biology and the Biotechnology Research Center, Lehigh University, Bethlehem, PA 18015, U.S.A. Search for other works by this author on: This Site PubMed Google Scholar JEFFREY A. SANDS; JEFFREY A. SANDS 1Department of Biology and the Biotechnology Research Center, Lehigh University, Bethlehem, PA 18015, U.S.A. Search for other works by this author on: This Site PubMed Google Scholar BLAND S. MONTENECOURT BLAND S. MONTENECOURT * *To whom correspondence should be addressed Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1985) 13 (2): 411–414. https://doi.org/10.1042/bst0130411 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation HANNELE MERIVUORI, KATHERINE M. SIEGLER, JEFFREY A. SANDS, BLAND S. MONTENECOURT; Regulation of cellulase biosynthesis and secretion in fungi. Biochem Soc Trans 1 April 1985; 13 (2): 411–414. doi: https://doi.org/10.1042/bst0130411 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search This content is only available as a PDF. © 1985 Biochemical Society1985 Article PDF first page preview Close Modal You do not currently have access to this content.
Enhanced heat deposition using ultrasound contrast agent - modeling and experimental observations (2006)

Ultrasound contrast agents (UCA), created originally for visualization and diagnostic purposes, recently have been suggested as efficient enhancers of ultrasonic power deposition in tissue. The ultrasonic energy absorption by the contrast agents, considered as problematic in diagnostic imaging, might have beneficial impact in therapeutic applications such as targeted hyperthermia-based or ablation treatments. Introduction of gas microbubbles into the tissue to be treated can improve the effectiveness of current treatments by limiting the temperature rise to the treated site and minimizing the damage to the surrounding healthy tissues. To this end, proper assessment of the governing parameters of energy absorption by ultrasonically induced stabilized bubbles is important for both diagnostic and therapeutic ultrasound applications. The current study was designed to predict theoretically and measure experimentally the dissipation and heating effects of encapsulated UCA in a well-controlled and calibrated environment. The ultrasonic effects of the microbubble concentration, transmitted intensity, and frequency on power dissipation and stability of the UCA have been studied. The maximal temperature elevation obtained during 300 s experiments was 21 degrees C, in a 10 ml volume target containing UCA, insonifled by unfocused 3.2 MHz continuous wave (CW) at spatial average intensity of 1.1 W/cm2 (182 kPa). The results also suggest that higher frequencies are more efficiently absorbed by commonly used UCA. In particular, for spatial average intensity of 1.1 W/cm2 and concentration of 5 x 10(6) microspheres/cm3, no significant reduction of UCA absorption was noticed during the first 150 s for insonation at 3.2 MHz and the first 100 s for insonation at 1 MHz. In addition, when lower average intensity of 0.5 W/cm2 (160 kPa) at 3.2 MHz was used, the UCA absorptivity sustained for almost 200 s. Thus, when properly activated, UCA may be suitable for localized hyperthermic therapies.
Identification and Characterization of ICH-2, a Novel Member of the Interleukin-1β-converting Enzyme Family of Cysteine Proteases (1995)

Interleukin-1 beta converting enzyme (ICE) is a cytoplasmic cysteine protease required for generating the bioactive form of the interleukin-1 beta cytokine from its inactive precursor. We report the identification of ICH-2, a novel human gene encoding a member of the ICE cysteine protease family, and characterization of its protein product. ICH-2 mRNA is widely expressed in human tissues in a pattern similar to, but distinct from, that of ICE. Overexpression of ICH-2 in insect cells induces apoptosis. Purified ICH-2 is functional as a protease in vitro. A comparison of the inhibitor profiles and substrate cleavage by ICH-2 and ICE shows that the enzymes share catalytic properties but may differ in substrate specificities, suggesting that the two enzymes have different functions in vivo.
Electrochemical Reduction of Carbon Dioxide to Ethane Using Nanostructured Cu2O-Derived Copper Catalyst and Palladium(II) Chloride (2015)

A method to facilitate the electrochemical reduction of carbon dioxide (CO2) to ethane (C2H6) was developed. The electrolyte used was aqueous 0.1 M KHCO3. Chronoamperometry, scanning electron microscopy, X-ray photoelectron spectroscopy, X-ray diffraction, online gas chromatography, and nuclear magnetic resonance spectroscopy were used to characterize the electrochemical system and products formed. Carbon dioxide reduction using a Cu2O-derived copper working electrode gave ethylene (C2H4) and ethanol as main C2 products, with optimized faradic efficiencies (FE) of 32.1 and 16.4% at −1.0 V vs RHE. The active catalysts were ∼500 nm-sized crystalline Cu0 particles, which were formed via the reduction of the Cu2O precursor during the initial phase of the CO2 reduction reaction. When palladium(II) chloride was added to the electrolyte, C2H6 formation could be achieved with a significant FE of 30.1% at the said potential. The production of C2H4 was, on the other hand, suppressed to a FE of 3.4%. The alternate use of Pd0, PdO, or Pd–Al2O3 dopants did not afford the same conversion efficiency. Extensive mechanistic studies demonstrate that C2H4 was first produced from CO2 reduction at the Cu0 sites, followed by hydrogenation to C2H6 with the assistance of adsorbed PdClx. Interestingly, we discover that both Cu and PdClx sites are necessary for the efficient reduction of C2H4 to C2H6. The PdCl2 was “consumed” during the reaction, and a hypothesis for how it contributes to the reduction of CO2 to ethane is proposed.
Degradation, Fatigue, and Failure of Resin Dental Composite Materials (2008)

The intent of this article is to review the numerous factors that affect the mechanical properties of particle- or fiber-filler-containing indirect dental resin composite materials. The focus will be on the effects of degradation due to aging in different media, mainly water and water and ethanol, cyclic loading, and mixed-mode loading on flexure strength and fracture toughness. Several selected papers will be examined in detail with respect to mixed and cyclic loading, and 3D tomography with multi-axial compression specimens. The main cause of failure, for most dental resin composites, is the breakdown of the resin matrix and/or the interface between the filler and the resin matrix. In clinical studies, it appears that failure in the first 5 years is a restoration issue (technique or material selection); after that time period, failure most often results from secondary decay.
Spectrally encoded confocal microscopy (1998)

An endoscope-compatible, submicrometer-resolution scanning confocal microscopy imaging system is presented. This approach, spectrally encoded confocal microscopy (SECM), uses a quasi-monochromatic light source and a transmission diffraction grating to detect the reflectivity simultaneously at multiple points along a transverse line within the sample. Since this method does not require fast spatial scanning within the probe, the equipment can be miniaturized and incorporated into a catheter or endoscope. Confocal images of an electron microscope grid were acquired with SECM to demonstrate the feasibility of this technique.
Local Application of Optic Flow to Analyse Rigid versus Non-Rigid Motion (1999)

Optic flow has been a research topic of interest for many years. It has, until recently, been largely inapplicable to real-time video applications due to its computationally expensive nature. This paper presents a new, reliable flow technique called dynamic region matching, based on the work of Anandan[1], Lucas and Kanade[10] and Okutomi and Kanade[11], which can be combined with a motion detection algorithm (from stationary or stabilised camera image streams) to allow flow-based analyses of moving entities in real-time. If flow vectors need only be calculated for &amp;quot;moving&amp;quot; pixels, then the computation time is greatly reduced, making it applicable to real-time implementation on modest computational platforms (such as standard Pentium II based PCs). Applying this flow technique to moving entities provides some straightforward primitives for analysing the motion of those objects. Specifically, in this paper, methods are presented for: analysing rigidity and cyclic motion using residual ...