gebhart/patrepeval huggingface dataset:
Viral-Mediated Gene Transfer to Mouse Primary Neural Progenitor Cells (2002)

Neural progenitor cells may provide for cell replacement or gene delivery vehicles in neurodegen-erative disease therapies. The expression of therapeutic proteins by neural progenitors would be enhanced by viral-mediated gene transfer, but the effects of several common recombinant viruses on primary progenitor cell populations have not been tested. To address this issue, we cultured cells from embryonic day 16-18 mouse brain in serum-free medium containing epidermal growth factor or basic fibroblast growth factor, and investigated how transduction with recombinant viral vectors affected maintenance and differentiation properties of progenitor cells. Neurosphere cultures were incubated with feline immunodeficiency virus (FIV), adeno-associated virus (AAV) or ade-noviral (Ad) constructs expressing either beta-galactosidase or enhanced green fluorescent protein at low multiplicity of infection. Nestin-positive neurospheres were regenerated after incubation of single progenitor cells with FIV, indicating that FIV-mediated gene transfer did not inhibit progenitor cell self-renewal. In contrast, adenovirus induced differentiation into glial fibrillary acidic protein (GFAP)-positive astrocytes. The AAV serotypes tested did not effectively transduce progenitor cells. FIV-transduced progenitors retained the potential for differentiation into neurons and glia in vitro, and when transplanted into the striatum of normal adult C57BL/6 mice differentiated into glia, or remained undifferentiated. In the presence of tumor cells, FIV-transduced progenitors migrated significantly from the injection site. Our results suggest that FIV-based vectors can transduce progenitor cell populations in vitro, with maintenance of their ability to differentiate into multiple cell types or to respond to injury within the central nervous system. These results hold promise for the use of genetically manipulated stem cells for CNS therapies.
The Impact of Virtualization on Network Performance of Amazon EC2 Data Center (2010)

Cloud computing services allow users to lease computing resources from large scale data centers operated by service providers. Using cloud services, users can deploy a wide variety of applications dynamically and on-demand. Most cloud service providers use machine virtualization to provide flexible and cost-effective resource sharing. However, few studies have investigated the impact of machine virtualization in the cloud on networking performance. In this paper, we present a measurement study to characterize the impact of virtualization on the networking performance of the Amazon Elastic Cloud Computing (EC2) data center. We measure the processor sharing, packet delay, TCP/UDP throughput and packet loss among Amazon EC2 virtual machines. Our results show that even though the data center network is lightly utilized, virtualization can still cause significant throughput instability and abnormal delay variations. We discuss the implications of our findings on several classes of applications.
Simple, Efficient, and Modular Syntheses of Polyene Natural Products via Iterative Cross-Coupling (2007)

This communication describes the discovery of air-stable and highly versatile B-protected haloalkenylboronic acid building blocks for iterative cross-coupling. These reagents enable the total synthesis of polyene natural products with extraordinary levels of simplicity, efficiency, and modularity. Specifically, all-trans-retinal, β-parinaric acid, and one-half the amphotericin B macrolide skeleton were prepared using only the Suzuki-Miyaura reaction in an iterative manner to bring together collections of simple and readily-accessible building blocks. In contrast to their boronic acid counterparts, the intermediate polyenylboronate esters are remarkably stable (to both column purification and storage), which is critical to their successful utilization. Moreover, the reactive boronic acids can be cleanly liberated using very mild aqueous base. These advances have enabled preparation of the longest polyene ever synthesized using the SM reaction. We additionally report, to the best of our knowledge, the first triply metal selective (Zn vs. Sn and B) cross-coupling reaction, the first selective cross-coupling with a differentially-ligated diboron reagent, and the first cross-couplings between polyenylchlorides and vinylboronic acids. Collectively, these new building blocks and methods can dramatically improve the way polyene natural products and their derivatives are synthesized in the laboratory. [Image: see text]
Isolation and Characterization of Noncytopathic Pestivirus Mutants Reveals a Role for Nonstructural Protein NS4B in Viral Cytopathogenicity (2001)

Isolates of bovine viral diarrhea virus (BVDV), the prototype pestivirus, are divided into cytopathic (cp) and noncytopathic (ncp) biotypes according to their effect on cultured cells. The cp viruses also differ from ncp viruses by the production of viral nonstructural protein NS3. However, the mechanism by which cp viruses induce cytopathic effect in cell culture remains unknown. Here we used a genetic approach to isolate ncp variants that arose from a cp virus at low frequency. A bicistronic BVDV (cp strain NADL) was created that expressed puromycin acetyltransferase as a dominant selectable marker. This bicistronic virus exhibited slightly slower growth kinetics and smaller plaques than NADL but remained cp. A number of independent ncp variants were isolated by puromycin selection. Remarkably, these ncp variants produced NS3 and viral RNA at levels comparable to those of the cp parent. Sequence analyses uncovered no change in NS3, but for all ncp variants a Y2441C substitution at residue 15 of NS4B was found. Introduction of the Y2441C substitution into the NADL or bicistronic cp viruses reconstituted the ncp phenotype. Y2441 is highly conserved among pestiviruses and is located in a region of NS4B predicted to be on the cytosolic side of the endoplasmic reticulum membrane. Other engineered substitutions for Y2441 also affected viral cytopathogenicity and viability, with Y2441V being cp, Y2441A being ncp, and Y2441D rendering the virus unable to replicate. The ncp substitutions for Y2441 resulted in slightly increased levels of NS2-3 relative to NS3. We also showed that NS3, NS4B, and NS5A could be chemically cross-linked in NADL-infected cells, indicating that they are associated as components of a multiprotein complex. Although the mechanism remains to be elucidated, these results demonstrate that mutations in NS4B can attenuate BVDV cytopathogenicity despite NS3 production.
Electroporation of human microvascular endothelial cells: evidence for an anti-vascular mechanism of electrochemotherapy (2001)

Recent studies have indicated that the antitumour effectiveness of electrochemotherapy, a combination of chemotherapeutic drugs with application of high voltage electric pulses applied to the tumour nodule (electroporation), result in a significant reduction in tumour blood flow and may therefore be mediated by an anti-vascular mechanism. The aim of this study was to evaluate the cytotoxicity of electroporation with bleomycin or cisplatin on cultured human microvascular endothelial cells (HMEC-1). The sensitivity of HMEC-1 cells to a 5 min treatment by electroporation with bleomycin or cisplatin (8 electric pulses, pulse duration 100 micros, frequency 1 Hz, electric field intensity 1400 V x cm(-1)) was compared to the sensitivity of cells treated continuously for 3 days with drugs alone. HMEC-1 cells were moderately sensitive to continuous exposure to cisplatin, but showed greater sensitivity to bleomycin. Combination of a 5 min drug exposure with electric pulses increased cytotoxicity approximately 10-fold for cisplatin and approximately 5000-fold for bleomycin. The electroporation of HMEC-1 cells with bleomycin for a 5 min exposure was approximately 250-fold better than a continuous exposure to the drug alone. The results of this study indicate that the anti-tumour action of electrochemotherapy is likely to be due, in part, to the highly sensitive response of vascular endothelial cells. Further studies are necessary to identify the determinants of endothelial response and its relationship to the anti-vascular action of electrochemotherapy in vivo.
Stereotactic Craniotomy with the Exoscope (1997)

A three-dimensional computer graphic program has been developed to guide the surgeon through the resection of a brain tumor. It consists of a video camera mounted on a stereotactic frame which visualizes the operative field in real time. Superimposed on the video monitor is a computer generated model of the tumor or other resection target mass. The mass can be displayed in several modes. The computer image of the mass is adjusted to correspond to the surgeon's eye view, with appropriate settings for the stereotactic apparatus indicated. Prior to incision, the image of the mass is superimposed on the scalp to guide placement and size of the scalp and bone flaps. As the resection proceeds, a cross-section of the mass is illustrated on the video picture of the operative field. The distance from the camera to the surface is measured, and the cross-section at that depth is displayed. A small window indicates the surgeon's eye view and the tangential view of the mass with an indication of the cross-section currently being displayed. As resection proceeds, the distance to the bottom of the resection cavity is measured repeatedly. The image is updated to indicate only that level of the tumor under resection. As the far side of the tumor is encountered, the mass disappears from the monitor, signaling completion of the resection.
Identification of Immunogenic Regions of the Major Coat Protein of Human Papillomavirus Type 16 that Contain Type-restricted Epitopes (1989)

We have identified regions of the major capsid protein, L1, of the human papillomavirus (HPV) type 16 (HPV-16 L1), that are recognized by five monoclonal antibodies (MAbs) raised to a bacterial fusion protein containing residues 172 to 375 of HPV-16 L1. All five MAbs recognized HPV-16-infected tissue sections by immunohistochemistry, but not sections infected with HPV-1a (cutaneous warts), HPV-6b or -11 (genital warts). MAbs 3D1, 5A4 and 1D6 also recognized HPV-2-infected sections (cutaneous warts); MAb 8C4 recognized only sections containing HPV-16. Four MAbs (8C4, 3D1, 1D6 and 5A4) recognized a synthetic peptide corresponding to residues 269 to 284 of HPV-16 L1; within this region a minimum antibody binding site was identified, a tripeptide 276 to 278. However the complete epitope appears to extend beyond these residues and beyond HPV-16 L1 (269 to 284). The fifth MAb, 1C6, recognized bacterial fusion proteins containing HPV-6b L1, -16 L1 or -18 L1 using immunoblots, yet appeared HPV-16-specific when tested on infected tissue sections. This MAb recognized five amino acids within a different region of HPV-16 L1 (residues 299 to 313).
Depression of Ventilation by Dopamine in Man (1978)

Dopamine is present in the carotid body and has been postulated to be an inhibitory neurotransmitter. The purpose of this study was to determine the effects of dopamine on ventilation in man and to examine its mechanism of action. Dopamine (0.5-10 mug/kg per min) was infused in eight normal men at different levels of arterial chemoreceptor activity, produced by varying the inspired Po(2). During normoxia dopamine produced a small decrease in minute ventilation (Ve) and an increase in arterial Pco(2). When arterial chemoreceptors were stimulated by hypoxia, infusion of dopamine produced a marked initial depression of Ve followed by a sustained although less pronounced decrease in Ve. An increase in Pa(co) (2) and a decrease in Pao(2) were also observed. When arterial chemoreceptor activity was suppressed by hyperoxia, infusion of dopamine did not affect ventilation. Subjects also breathed a hypercarbic, hyperoxic gas mixture. The hypercarbia produces hyperventilation by stimulating central chemoreceptors, whereas the hyperoxia suppresses peripheral chemoreceptors. Dopamine did not alter ventilation while the subjects were breathing this gas mixture. These studies suggest that dopamine suppresses ventilation in man through an action on the arterial chemoreceptor reflex. These findings support the hypothesis that dopamine is an inhibitory neurotransmitter in the carotid body, and that release of dopamine may modulate the sensitivity of peripheral arterial chemoreceptors.
Microwave-cut silicon layer transfer (2005)

Microwave heating is used to initiate exfoliation of silicon layers in conjunction with the ion-cut process for transfer of silicon layers onto insulator or heterogeneous layered substrates. Samples were processed inside a 2.45 GHz, 1300 W cavity applicator microwave system for time durations as low as 12 s. This is a significant decrease in exfoliation incubation times. Sample temperatures measured by pyrometry were within previous published ranges. Rutherford backscattering spectrometry and cross-sectional transmission electron microscopy were used to determine layer thickness and crystallinity. Surface quality was measured by using atomic force microscopy. Hall measurements were used to characterize electrical properties as a function of postcut anneal time and temperature.
A peptidoglycan hydrolase similar to bacteriophage endolysins acts as an autolysin in Neisseria gonorrhoeae (1997)

We have identified a gene encoding an autolysin (atlA) from Neisseria gonorrhoeae. The deduced amino acid sequence of AtlA shows significant similarity to the peptidoglycan degrading transglycosylases (endolysins) of bacteriophages lambda and P2, suggesting that the encoded protein also functions in peptidoglycan hydrolysis. An atlA mutant was identical to the wild-type strain in exponential growth rate, but demonstrated reduced lysis and peptidoglycan turnover in the stationary phase of growth. When transferred into a buffer solution, at a pH non-permissive for other gonococcal autolysins, an autolytic activity was detectable in the wild-type strain that was not present in the mutant. The most dramatic phenotype of the mutant occurred after extended time in stationary phase. After approximately 16h in stationary phase, both strains underwent an apparent replication event, after which the wild-type strain died rapidly whereas the atlA mutant survived considerably longer. Even after both the wild-type and mutant cells were dead, many of the mutant cells maintained intact morphology, whereas the wild-type cells were lysed. These results suggest that AtlA is a peptidoglycan transglycosylase related to bacteriophage endolysins and acts as an autolysin in the stationary phase.
Patterned negative electron affinity photocathodes for maskless electron beam lithography (1998)

This work focuses on two issues crucial to achieving high throughput with a negative electron affinity semiconductor photocathode source. Monte Carlo simulations indicate that for a 50 kV system, as much as 8 μA of current may be delivered to the wafer to achieve a raw throughput of 20 8 in. wafers per hour with 0.1 μm minimum feature size (assuming a resist sensitivity of 10 μC/cm2). In order to achieve the throughput potential of this approach, suboptical emission areas are required; this suggests the use of cathode patterning. Two patterning alternatives have been investigated experimentally, and both approaches have been used to generate arrays of more than 100 electron beams with source sizes as small as 150 nm. However, each type of patterned cathode presents unique challenges to fabrication and performance in a practical multibeam system. Different source configurations (number of beams, beam current, beam spacing, etc.) create a system-level tradeoff between resolution and throughput. Results from patterned cathode experiments and system modeling are presented.
Fighting Against the “Hypertriglyceridaemic Waist”: A New International Institute for the Metabolic Syndrome (2003)

About 17 million people throughout the world die every year from cardiovascular disease (CVD) according to the World Health Organization. This accounts for about 40 % of all deaths in industrialized countries like USA and UK, which is far more than cancer deaths which amount to about 25 %. There has been a downward trend of CV mortality over the last 2 decades resulting from consideration of major risk factors such as smoking, and treatment of hypertension, hypercholesterolaemia and diabetes, including the use of well-defined therapeutic strategies based on safe and effective drugs. However, CV mortality appears to finally have reached a plateau in the northern European countries and also the USA. Cardiovascular mortality, being higher in women than in men, contrary to the popular believe, is even increasing today in US-women. In eastern European countries CVD is progressing more substantially, and also in many developing countries, in parallel with industrialization, urbanization and changes in lifestyle. The percentage of people with a body-mass-index BMI ≥ 30 is growing not only in the USA but also in countries like e.g. Brazil.
Targeting Mitochondrial STAT3 with the Novel Phospho-Valproic Acid (MDC-1112) Inhibits Pancreatic Cancer Growth in Mice (2013)

New agents are needed to treat pancreatic cancer, one of the most lethal human malignancies. We synthesized phospho-valproic acid, a novel valproic acid derivative, (P-V; MDC-1112) and evaluated its efficacy in the control of pancreatic cancer. P-V inhibited the growth of human pancreatic cancer xenografts in mice by 60%-97%, and 100% when combined with cimetidine. The dominant molecular target of P-V was STAT3. P-V inhibited the phosphorylation of JAK2 and Src, and the Hsp90-STAT3 association, suppressing the activating phosphorylation of STAT3, which in turn reduced the expression of STAT3-dependent proteins Bcl-xL, Mcl-1 and survivin. P-V also reduced STAT3 levels in the mitochondria by preventing its translocation from the cytosol, and enhanced the mitochondrial levels of reactive oxygen species, which triggered apoptosis. Inhibition of mitochondrial STAT3 by P-V was required for its anticancer effect; mitochondrial STAT3 overexpression rescued animals from the tumor growth inhibition by P-V. Our results indicate that P-V is a promising candidate drug against pancreatic cancer and establish mitochondrial STAT3 as its key molecular target.
A Microfluidic Approach for Screening Submicroliter Volumes against Multiple Reagents by Using Preformed Arrays of Nanoliter Plugs in a Three‐Phase Liquid/Liquid/Gas Flow (2005)

Plugging a gap in screening: Arrays of nanoliter-sized plugs of different compositions can be preformed in a three-phase liquid/liquid/gas flow. The arrays can be transported into a microfluidic channel to test against a target (see schematic representation), as demonstrated in protein crystallization and an enzymatic assay. Supporting Information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2005/z462857_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
The Gene for C10, a Member of the β-Chemokine Family, Is Located on Mouse Chromosome 11 and Contains a Novel Second Exon Not Found in Other Chemokines (1993)

C10 is a recently described member of the beta-chemokine subfamily of the chemokine superfamily of cytokine proteins. Genomic clones encoding murine C10 were isolated and sequenced. The other members of the beta-chemokine family have a three-exon genomic structure containing, among other sequence similarities, four cysteines spaced in a highly conserved manner. In each of these genes, the second exon contains the first three of the four conserved cysteines, and the third exon contains the last. In contrast to this genomic structure, the C10 gene has four exons, with a novel second exon of 48 nucleotides. Exons 3 and 4 of C10 contain four cysteines distributed in the same manner as in exons 2 and 3 of other beta-chemokine family members. The novel second exon codes for a large number of charged amino acids, and this exon shows no homology to any previously described sequences in computer databases. Linkage studies showed that the C10 gene (Scya6) is closely linked to the Scya2 locus on mouse chromosome 11, indicating that the C10 gene is located in the same region of mouse chromosome 11 as other members of the beta-chemokine family. Thus, although the C10 gene contains a novel exon not found in any other members of the chemokine superfamily, its chromosomal location and conservation of cysteine residues and other structural features suggest that it evolved from the same ancestral gene as other members of the beta-chemokine family.
The prevalence of neutralizing antibodies against AAV serotype 1 in healthy subjects in China: Implications for gene therapy and vaccines using AAV1 vector (2013)

Recombinant adeno-associated virus serotype 1 (AAV1) has attracted tremendous interest as a promising vector for gene therapy and vaccine applications. However, the presence of AAV1 neutralizing antibodies as a consequence of exposure to wild type AAV1 can limit significantly effective gene transfer for biologics based AAV1 vector. Prior studies have reported that a prevalence of AAV1 neutralizing antibodies ranged from 10% to 50% in different countries around the world, and up to 79% in Dutch subjects. However, few studies have reported on the AAV1 neutralizing antibody prevalence in Chinese subjects. In this study, a high-throughput luciferase-based virus neutralization assay was established and standardized for critical parameters, including the appropriate cell line, and the optimal viral infection dose, and the infection time with homologous AAV1 vaccinated mice and guinea pig sera. Then, a total of 500 healthy individual serum samples from two separate regions of China were screened for the AAV1 neutralizing antibodies by conducting a non-randomized, cross-sectional analysis. Interestingly, a high prevalence of AAV1 neutralizing antibody (69.8%) was found in all individuals. There was significant difference observed for prevalence by gender (P = 0.042), age range (P = 0.011) and geographic origin (P < 0.001). The percentage of positive AAV1 neutralizing antibodies (NT50 > 10) in teenagers (year <18, as of 2012) was significant lower than that of adults (19-56, as of 2012) (P = 0.011), indicating the optimal vaccination period of childhood. The current study provides a useful insight for the future development of AAV1-based vaccination and gene therapy strategies in Beijing and Anhui provinces of China.
Highly Selective and Near-Quantitative Conversion of Fructose to 5-Hydroxymethylfurfural Using Mildly Acidic Ionic Liquids (2014)

The room-temperature ionic liquid, [C4C1im][HSO4], provides a multi-faceted medium in which to convert fructose to the versatile chemical building block, 5-hydroxymethylfurfural (HMF). A range of metal salts have been investigated in order to establish some of the properties required for the optimization of this process. This has led to almost quantitative conversion of fructose to 5-HMF in a system that is both selective for the desired product, less energy intensive, and more environmentally benign than the commercial process.