gebhart/patrepeval huggingface dataset:
Plasmid DNA Malaria Vaccine: The Potential for Genomic Integration after Intramuscular Injection (1999)

Plasmid-based (naked DNA) genetic vaccines are now entering clinical trials to test their safety and efficacy in healthy human volunteers. A safety concern unique to this new class of vaccines is the potential risk of deleterious integration into host cell genomic DNA following direct intramuscular injection. To address this issue experimentally, a preclinical safety study was conducted in mice to determine the structural nature of plasmid DNA sequences persisting in total muscle DNA at both 30 and 60 days following a single intramuscular injection of a plasmid expressing the Plasmodium falciparum circumsporozoite protein. In a protocol described for the first time, total DNA was extracted from muscle tissue and was subsequently linearized with a restriction endonuclease to enable agarose gel size fractionation of all extrachromosomal plasmid DNAs from high molecular weight mouse genomic DNA. Using PCR assays to quantitate plasmid-specific sequences, it was found that the amount of plasmid DNA persisting in muscle tissue varied but averaged about 10 fg per microgram of genomic DNA (in the range of 1500 copies per 150,000 genomes). In two of four separate experimental injections of mouse muscle, PCR assays of genomic DNA fractions indicated that agarose gel purification removed plasmid DNA down to a level of 3 copies per 150,000 mouse genomes. In the two other experimental samples, 3-30 copies of plasmid DNA remained associated with purified genomic DNA. The time following injection (i.e., 30 or 60 days) was not a factor in the number of copies of plasmid associating with genomic DNA and it was not possible to conclude if such sequences were covalently linked to genomic DNA or simply adventitiously associated with the genomic DNA. However, if an assumption is made that the highest level plasmid DNA found associated with genomic DNA (i.e., 30 copies) represented covalently integrated plasmid inserts and that each insert resulted in a mutational event, the calculated rate of mutation would be 3000 times less than the spontaneous mutation rate for mammalian genomes. This level of integration, if it should occur, was not considered to pose a significant safety concern.
Robotic Tools for Minimally Invasive Urologic Surgery (2005)

Surgical robots have begun to appear on the market in the last few years and have started to populate the operating rooms in large medical centers. These systems have already established their ability to augment a surgeon’s dexterity in minimally invasive procedures and have the potential to maximize patient outcome on a larger basis even though, for the moment, their cost is prohibitively high for widespread application. As surgeons become increasingly aware of the clinical benefits of these systems and costs are driven down by technological advance and availability, we foresee that robots will become standard operating room tools. Initial applications of a handful of robots have already demonstrated their surgical potential. As technology evolves, robots could not only improve performance in minimally invasive procedures, but also enhance other existing procedures or even enable entirely new kinds of surgeries.
Pandemrix® vaccination is not associated with increased risk of islet autoimmunity or type 1 diabetes in the TEDDY study children (2017)

Children with an increased genetic risk for type 1 diabetes who received the Pandemrix® vaccine during the A/H1N1 2009 pandemic had no increased risk of islet autoimmunity, multiple islet autoantibodies or type 1 diabetes. In Finland, the vaccine was associated with a reduced risk of islet autoimmunity and type 1 diabetes.
Development of an Optimal Vehicle-to-Grid Aggregator for Frequency Regulation (2010)

For vehicle-to-grid (V2G) frequency regulation services, we propose an aggregator that makes efficient use of the distributed power of electric vehicles to produce the desired grid-scale power. The cost arising from the battery charging and the revenue obtained by providing the regulation are investigated and represented mathematically. Some design considerations of the aggregator are also discussed together with practical constraints such as the energy restriction of the batteries. The cost function with constraints enables us to construct an optimization problem. Based on the developed optimization problem, we apply the dynamic programming algorithm to compute the optimal charging control for each vehicle. Finally, simulations are provided to illustrate the optimality of the proposed charging control strategy with variations of parameters.
Effect of Ultrasonic Vibration and Applied Pressure on the Microstructure and Mechanical Property of Al-5.0Cu-0.6Mn-0.6Fe Alloys (2016)

Al-5.0Cu-0.6Mn-0.6Fe alloy was obtained for the first time using ultrasonic vibration and squeeze casting simultaneously. The effect of ultrasonic vibration and applied pressure on the microstructures and hardness of Al-5.0Cu-0.6Mn-0.6Fe alloy were studied. The results indicated that the ultrasonic vibration and applied pressure promoted the formation of smaller α-Al globular grains. In particularly, with the treatment of ultrasonic vibration or applied pressure during solidification, the brittle Fe-rich imtermetallic compounds in Al-5.0Cu-0.6Mn-0.6Fe alloy became more refined and changed from Chinese script shape to polyhedral shape, which improved the mechanical property. Furthermore, these effects on the grain refinement and Fe-rich intermetallic compounds became more significant by using ultrasonic vibration and applied pressure concurrently during solidification. This process technology is helpful for the development of high performance aluminum alloys with low cost as well as for green casting.
Ionic strength-dependent persistence lengths of single-stranded RNA and DNA (2011)

Dynamic RNA molecules carry out essential processes in the cell including translation and splicing. Base-pair interactions stabilize RNA into relatively rigid structures, while flexible non-base-paired regions allow RNA to undergo conformational changes required for function. To advance our understanding of RNA folding and dynamics it is critical to know the flexibility of these un-base-paired regions and how it depends on counterions. Yet, information about nucleic acid polymer properties is mainly derived from studies of ssDNA. Here we measure the persistence lengths (l(p)) of ssRNA. We observe valence and ionic strength-dependent differences in l(p) in a direct comparison between 40-mers of deoxythymidylate (dT(40)) and uridylate (rU(40)) measured using the powerful combination of SAXS and smFRET. We also show that nucleic acid flexibility is influenced by local environment (an adjoining double helix). Our results illustrate the complex interplay between conformation and ion environment that modulates nucleic acid function in vivo.
Modulation of HeLa cell growth by transfected 7SL RNA and Alu gene sequences. (1991)

Alu and 7SL RNA gene sequences were tested for the potential to regulate mammalian cell growth by introducing these sequences into HeLa cells in a coupled DEAE-dextran transfection/affinity cell sorting system. Both Alu and 7SL RNA genes mediated inhibition of [3H]thymidine and [35S]methionine incorporation in recipient cells. In addition, short term growth curves were performed on calcium phosphate/DNA cotransfected, affinity-purified cells. This second assay revealed that transfected Alu and 7SL RNA can also cause suppression of HeLa cell proliferation. To investigate whether transcription or polymerase III (pol III) transcription factor binding was required for inhibitory activity, mutations were introduced into RNA pol III B block promoter elements in each of these genes. Suppression of [3H]thymidine incorporation was dependent on the presence of this pol III element in both genes; likewise, 7SL RNA-mediated growth suppression required the presence of the pol III B block promoter element. The results of this study indicate that Alu and 7SL RNA gene sequences interact with cellular factors that are important for HeLa cell proliferation and suggest that these pol III-transcribed elements may be involved in the regulation of cellular growth.
Preventing the Infiltration of Leukocytes by Monoclonal Antibody Blocks the Development of Progressive Ischemia in Rat Burns (1995)

Tissue loss as a consequence of thermal trauma occurs in two stages. There is immediate necrosis in tissues directly killed by the thermal energy, followed by a delayed secondary necrosis in neighboring tissues. The infiltration of neutrophils into traumatized tissues is a hallmark of the inflammatory response. Neutrophils have the machinery to kill invading microorganisms, but these same weapons have the capacity to destroy the host's viable tissues as well. Leukocyte infiltration requires their adherence to the vascular endothelial cell surface. Masking these adhesion sites on neutrophils will block the adhesion of neutrophils to the endothelium. A monoclonal antibody (mAb) was developed to guinea pig leukocyte adhesion sites CD11b/ CD18, and this mAb cross-reacts with rat leukocytes, blocking their adherence. Rats received a “comb burn” composed of four rectangular full-thickness burns placed in a row and separated by three areas left unburned. The four individual burns convert into a single large wound because the blood flow to the interspaces was terminated, blood vessels were occluded, and leukocytes were present in the extravascular space. The systemic administration of the mAb (50 to 150 μl) immediately following a comb burn promoted the survival of the interspace, demonstrated by the prevention of loss of blood flow by laser Doppler monitoring, maintained patent vessels by latex vascular casts, blocked extravascular migration of neutrophils histologically at 2 hours, and limited the tissue loss to the original four burns.
A New Marketing Paradigm for Electronic Commerce (1997)

The World Wide Web possesses unique characteristics that distinguish it in important ways from traditional commercial communications environments. Because the Web presents a fundamentally different environment for marketing activities than traditional media, conventional marketing activities are becoming transformed, as they are often difficult to implement in their present form. In this article, we discuss the idea that these changes portend an evolution in the ''marketing concept'' and argue that in order for marketing efforts to be successful in this new medium, a new business paradigm is required. In this new approach, the marketing function must be reconstructed to facilitate electronic commerce in the emerging electronic society underlying the Web.
Von Willebrand factor-binding protein is a hysteretic conformational activator of prothrombin (2009)

Von Willebrand factor-binding protein (VWbp), secreted by Staphylococcus aureus, displays secondary structural homology to the 3-helix bundle, D1 and D2 domains of staphylocoagulase (SC), a potent conformational activator of the blood coagulation zymogen, prothrombin (ProT). In contrast to the classical proteolytic activation mechanism of trypsinogen-like serine proteinase zymogens, insertion of the first 2 residues of SC into the NH(2)-terminal binding cleft on ProT (molecular sexuality) induces rapid conformational activation of the catalytic site. Based on plasma-clotting assays, the target zymogen for VWbp may be ProT, but this has not been verified, and the mechanism of ProT activation is unknown. We demonstrate that VWbp activates ProT conformationally in a mechanism requiring its Val(1)-Val(2) residues. By contrast to SC, full time-course kinetic studies of ProT activation by VWbp demonstrate that it activates ProT by a substrate-dependent, hysteretic kinetic mechanism. VWbp binds weakly to ProT (K(D) 2.5 microM) to form an inactive complex, which is activated through a slow conformational change by tripeptide chromogenic substrates and its specific physiological substrate, identified here as fibrinogen (Fbg). This mechanism increases the specificity of ProT activation by delaying it in a slow reversible process, with full activation requiring binding of Fbg through an exosite expressed on the activated ProT*.VWbp complex. The results suggest that this unique mechanism regulates pathological fibrin (Fbn) deposition to VWF-rich areas during S. aureus endocarditis.
Plant Tissue Culture: Techniques and Experiments (2000)

Tissue Culture, Second Edition provides laboratory exercises in plant tissue culture that demonstrate major educational concepts. The experiments can be conducted with a variety of plant materials that are available year round from easily accessible sources. This course book will give students diverse learning experiences in a semester course. New and experienced plant scientists in agriculture, university, and industry settings will also find this concise manual to be of great value. It presents unique laboratory exercises using a variety of plant materials and step-by-step protocols and provides detailed line drawings that complement both introductions and experiments. It includes supplementary sections and scheduling and interrelationships of exercises for teachers. It covers tissue culture laboratory setup, supplies, media, and explant preparation, and measurements. It includes a glossary of terms and exercises rigorously tested for practicality through years of course use . It contains two new chapters. History of Plant Cell Culture is written by Trevor Thorpe. Woody Plants and Shrubs is written by Brent McCown. It is adaptable by teachers, students, researchers, and technicians.
beta IFN- Interferes with the Differentiation of Dendritic Cells from Peripheral Blood Mononuclear Cells: Selective Inhibition of CD40-Dependent Interleukin-12 Secretion (1999)

We studied the effects of interferon-beta (IFN-beta) on the differentiation of dendritic cells (DC) obtained by culturing plastic-adherent peripheral blood mononuclear cells (PBMC) from a total of 30 healthy volunteers in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). First, we found that the addition of IFN-beta at the initiation of the culture did not modify DC morphology but caused a reproducible and statistically significant upregulation of HLA-DR, CD86, and CD80 surface expression. CD1a expression was significantly reduced, and CD40 expression was unchanged. We then determined the influence of IFN-beta on the production of cytokines by DC. DC differentiated in the presence of IFN-beta secreted significantly less IL-12 (p40 and p70) both spontaneously and on activation by fibroblasts transfected with the CD40L gene. This effect of IFN-beta was dose dependent and selective, as it was not observed for IL-6, IL-8, and tumor necrosis factor-alpha (TNF-alpha). As a consequence, DC differentiated in the presence of IFN-beta induced significantly less IFN-gamma secretion by alloreactive T cells, whereas they were more efficient than control DC in eliciting IL-5 secretion. We conclude that the direct action of IFN-beta on DC causes inhibition of their ability to secrete IL-12 in response to CD40 ligation and to elicit Th1 type responses.
Critical role of tumor necrosis factor receptor 1, but not 2, in hepatic stellate cell proliferation, extracellular matrix remodeling, and liver fibrogenesis (2011)

TNF regulates HSC biology through its binding to TNFR1, which is required for HSC proliferation and MMP-9 expression. These data indicate a regulatory role for TNF in extracellular matrix remodeling and liver fibrosis, suggesting that targeting TNFR1 may be of benefit to attenuate liver fibrogenesis.
Demonstration that Glycoprotein G Is the Attachment Protein of Respiratory Syncytial Virus (1987)

Two monospecific rabbit antisera to the G glycoprotein, one induced with purified G and the second with a recombinant vaccinia virus containing the gene for G, inhibit the attachment of purified [35S]methionine-labelled Long strain of respiratory syncytial virus to monolayers of HeLa cells. Attachment was not inhibited by monospecific rabbit antisera to glycoprotein F induced with either purified F or with a recombinant vaccinia virus containing the gene for F.
Irinotecan Combined with Gemcitabine, 5-Fluorouracil, Leucovorin, and Cisplatin (G-FLIP) is an Effective and Noncrossresistant Treatment for Chemotherapy Refractory Metastatic Pancreatic Cancer (2001)

Adding a single new drug such as irinotecan to the same first-line chemotherapy combination upon disease progression may be an important alternative to switching to different drug classes for treatment of relapsed/resistant cancer. The promising clinical outcomes and moderate toxicity associated with G-FLIP in this heavily pretreated group warrant development of this novel regimen including tests as first-line therapy in patients with diseases likely to be responsive to the drugs contained in this combination.
New therapeutic approach for brain tumors: Intranasal delivery of telomerase inhibitor GRN163 (2008)

The blood-brain barrier is a substantial obstacle for delivering anticancer agents to brain tumors, and new strategies for bypassing it are greatly needed for brain-tumor therapy. Intranasal delivery provides a practical, noninvasive method for delivering therapeutic agents to the brain and could provide an alternative to intravenous injection and convection-enhanced delivery. We treated rats bearing intracerebral human tumor xenografts intranasally with GRN163, an oligonucleotide N3'-->P5'thio-phosphoramidate telomerase inhibitor. 3'-Fuorescein isothiocyanate (FITC)-labeled GRN163 was administered intranasally every 2 min as 6 microl drops into alternating sides of the nasal cavity over 22 min. FITC-labeled GRN163 was present in tumor cells at all time points studied, and accumulation of GRN163 peaked at 4 h after delivery. Moreover, GRN163 delivered intranasally, daily for 12 days, significantly prolonged the median survival from 35 days in the control group to 75.5 days in the GRN163-treated group. Thus, intranasal delivery of GRN163 readily bypassed the blood-brain barrier, exhibited favorable tumor uptake, and inhibited tumor growth, leading to a prolonged lifespan for treated rats compared to controls. This delivery approach appears to kill tumor cells selectively, and no toxic effects were noted in normal brain tissue. These data support further development of intranasal delivery of tumor-specific therapeutic agents for brain tumor patients.
Abl-interactor-1, a novel SH3 protein binding to the carboxy-terminal portion of the Abl protein, suppresses v-abl transforming activity. (1995)

A novel cellular protein, Abl-interactor-1 (Abi-1), which specifically interacts with the carboxy-terminal region of Abl oncoproteins, has been identified in a mouse leukemia cell line. The protein exhibits sequence similarity to homeotic genes, contains several polyproline stretches, and includes a src homology 3 (SH3) domain at its very carboxyl terminus that is required for binding to Abl proteins. The abi-1 gene has been mapped to mouse chromosome 2 and is genetically closely linked to the c-abl locus. The gene is widely expressed in the mouse, with highest levels of mRNA found in the bone marrow, spleen, brain, and testes. The Abi-1 protein coimmunoprecipitates with v-Abl and serves as a substrate for kinase activity. When overexpressed in NIH-3T3 cells, abi-1 potently suppresses the transforming activity of Abelson leukemia virus expressing the full-length p160v-abl kinase but does not affect the transforming activity of viruses expressing a truncated p90v-abl or v-src kinases. We suggest that the Abi-1 protein may serve as a regulator of Abl function in transformation or in signal transduction.
Synthesis and Selective Cytotoxicity of a Hyaluronic Acid−Antitumor Bioconjugate (1999)

A cell-targeted prodrug was developed for the anti-cancer drug Taxol, using hyaluronic acid (HA) as the drug carrier. HA-Taxol bioconjugates were synthesized by linking the Taxol 2'-OH via a succinate ester to adipic dihydrazide-modified HA (HA-ADH). The coupling of Taxol-NHS ester and HA-ADH provided several HA bioconjugates with different levels of ADH modification and different Taxol loadings. A fluorescent BODIPY-HA was also synthesized to illustrate cell targeting and uptake of chemically modified HA using confocal microscopy. HA-Taxol conjugates showed selective toxicity toward the human cancer cell lines (breast, colon, and ovarian) that are known to overexpress HA receptors, while no toxicity was observed toward a mouse fibroblast cell line at the same concentrations used with the cancer cells. The drug carrier HA-ADH was completely nontoxic. The selective cytotoxicity is consistent with the results from confocal microscopy, which demonstrated that BODIPY-HA only entered the cancer cell lines.
Polarization-Enhanced NMR Spectroscopy of Biomolecules in Frozen Solution (1997)

Large dynamic nuclear polarization signal enhancements (up to a factor of 100) were obtained in the solid-state magic-angle spinning nuclear magnetic resonance (NMR) spectra of arginine and the protein T4 lysozyme in frozen glycerol-water solutions with the use of dynamic nuclear polarization. Polarization was transferred from the unpaired electrons of nitroxide free radicals to nuclear spins through microwave irradiation near the electron paramagnetic resonance frequency. This approach may be a generally applicable signal enhancement scheme for the high-resolution solid-state NMR spectroscopy of biomolecules.
Using occupancy grids for mobile robot perception and navigation (1989)

An approach to robot perception and world modeling that uses a probabilistic tesselated representation of spatial information called the occupancy grid is reviewed. The occupancy grid is a multidimensional random field that maintains stochastic estimates of the occupancy state of the cells in a spatial lattice. To construct a sensor-derived map of the robot's world, the cell state estimates are obtained by interpreting the incoming range readings using probabilistic sensor models. Bayesian estimation procedures allow the incremental updating of the occupancy grid, using readings taken from several sensors over multiple points of view. The use of occupancy grids from mapping and for navigation is examined. Operations on occupancy grids and extensions of the occupancy grid framework are briefly considered.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>