gebhart/patrepeval huggingface dataset:
Retroviral Vectors for High-Level Transgene Expression in T Lymphocytes (2003)

Efficient expression of genes transferred by retroviral vectors is a prerequisite for gene therapy, especially when the biological effect depends on the amount of transgene product. High-level gene expression is desirable for several gene therapy approaches involving T lymphocytes. We evaluated standard retroviral vectors with cis-regulatory control elements of the Moloney murine leukemia virus (Mo-MLV) with or without the human T cell-specific CD2 enhancer. For comparison, vectors containing the long terminal repeat (LTR) of myeloproliferative sarcoma virus (MPSV) and an improved 5' untranslated region were used (MP71 vectors), with or without the woodchuck hepatitis virus posttranscriptional regulatory element (PRE). All vectors expressed the enhanced green fluorescent protein (GFP) to measure transgene expression. In mouse T cells MP71 vectors with and without the PRE yielded an up to 10-fold higher expression level compared with the Mo-MLV-based vectors currently used for gene transfer into T lymphocytes. A high multiplicity of infection (MOI) of standard Mo-MLV vectors could not reach expression levels obtained with a low MOI of MP71 vector. Ex vivo-transduced mouse T lymphocytes maintained the vector-dependent differences in level of transgene expression in Rag-1-deficient mice when adoptively transferred. In four human T cell lines and human primary T lymphocytes MP71 vectors yielded an up to 75-fold higher GFP expression level in comparison with the standard Mo-MLV vector. In contrast to mouse T cells, the integration of the PRE into MP71 vectors induced in human T cells a further significant increase in transgene expression level. Southern blot analysis of CEM T cells revealed that the superior performance of MP71 vectors was not due to a higher rate of viral integration. In summary, MP71 vectors are useful tools for stable, high-level gene expression in T lymphocytes, for example, in the expression of T cell receptor genes.
Acurhagin‐C, an ECD disintegrin, inhibits integrin αvβ3‐mediated human endothelial cell functions by inducing apoptosis via caspase‐3 activation (2010)

Acurhagin-C elicited endothelial anoikis via disruption of alphavbeta3/focal adhesion kinase/phosphatidylinositol 3-kinase/Akt survival cascade and subsequent initiation of the procaspase-3 apoptotic signalling pathway.
Precise Detection of Uninitialized Variables Using Dynamic Analysis - Extending to Aggregate and Vector Types (2012)

Uninitialized variable is a variable in a program that is declared but is not assigned a definite known value before it is used. Compilers of modern programming languages (like Java) check for their presence, but in languages like C and COBOL, they are a critical reason for incorrect results, wrong data entries, and run-time failures. Tools based on static and dynamic analysis techniques are available that detect use of uninitialized variables. However, the static analysis tools face the issue of false positives (precision) while the dynamic analysis tools are not able to cover all the classes of variables (completeness). In this paper, we present a technique based on dynamic program analysis and results of the prototype tool to detect the first use of uninitialized variables. Using a combination of source and binary instrumentation, the technique is able to track variables of basic types, individual array elements, and fields of structures. We verified the completeness and precision of the technique using two open source case-studies with very large input datasets. We present the comparison of the results with other open source tools. The prototype tool is a clear winner in terms of precision and the coverage of variables, but more work is required to further optimize the size of instrumentation information, and the performance of its analyzer.
Small-area parallel syndrome calculation for strong BCH decoding (2012)

This paper presents a new optimization method to reduce the hardware complexity of syndrome calculation in strong BCH decoding. All the operations required in the parallel syndrome calculation are reformulated as a single matrix computation to enlarge the search area for common sub-expressions. The computational complexity of syndrome calculation is significantly reduced by finding and sharing common terms in the single matrix computation. Implementation results show that the proposed architecture saves 55% of area overheads compared to the conventional structure.
Two cystic fibrosis transmembrane conductance regulator mutations have different effects on both pulmonary phenotype and regulation of outwardly rectified chloride currents. (1995)

Cystic fibrosis (CF), a disorder of electrolyte transport manifest in the lungs, pancreas, sweat duct, and vas deferens, is caused by mutations in the CF transmembrane conductance regulator (CFTR). The CFTR protein has been shown to function as a cAMP-activated chloride channel and also regulates a separate protein, the outwardly rectifying chloride channel (ORCC). To determine the consequence of disease-producing mutations upon these functions, mutant CFTR was transiently expressed in Xenopus oocytes and in human airway epithelial cells lacking functional CFTR. Both G551D, a mutation that causes severe lung disease, and A455E, a mutation associated with mild lung disease, altered but did not abolish CFTR's function as a chloride channel in Xenopus oocytes. Airway epithelial cells transfected with CFTR bearing either A455E or G551D had levels of chloride conductance significantly greater than those of mock-transfected and lower than those of wild-type CFTR-transfected cells, as measured by chloride efflux. A combination of channel blockers and analysis of current-voltage relationships were used to dissect the contribution of CFTR and the ORCC to whole cell currents of transfected cells. While CFTR bearing either mutation could function as a chloride channel, only CFTR bearing A455E retained the function of regulating the ORCC. These results indicate that CF mutations can affect CFTR functions differently and suggest that severity of pulmonary disease may be more closely associated with the regulatory rather than chloride channel function of CFTR.
Expression of vascular endothelial growth factor by macrophages is up-regulated in poorly vascularized areas of breast carcinomas (2000)

Angiogenesis is essential to the growth and metastasis of solid tumours. Vascular endothelial growth factor (VEGF) is a potent pro-angiogenic cytokine that is overexpressed in malignant tumours such as invasive carcinoma of the breast. The low oxygen tensions (hypoxia) present in these tumours are known to up-regulate the expression of VEGF by tumour cells. Human macrophages also respond to hypoxia by increasing their release of VEGF in vitro, although the effect of hypoxia on VEGF expression by macrophages in vivo has yet to be demonstrated. The present study compared the expression of VEGF by macrophages in areas of low and high vascularity in 24 invasive breast carcinomas (12 lobular, 12 ductal). The cellular distributions of VEGF protein, CD31 (vessels), and CD68 (macrophages) were compared in sequential sections for each tumour. In ten tumours, both tumour cells and macrophages were immunoreactive for VEGF protein. Use of non-isotopic in situ hybridization to localize VEGF mRNA showed that these cell types also expressed VEGF mRNA. No significant differences in the cellular distribution of VEGF protein were found between lobular and ductal carcinomas. In all tumours, macrophages accumulated in higher numbers in poorly vascularized than in highly vascularized areas. In VEGF-positive tumours, macrophages were immunoreactive for VEGF only in avascular areas where tumour cells also expressed VEGF. This suggests that VEGF expression by these two cell types may be regulated by the same microenvironmental stimuli in breast carcinomas. In addition, significantly more macrophages were present in poorly vascularized areas of VEGF-positive than VEGF-negative tumours. This suggests that VEGF may exert a chemotactic action on macrophages in vivo and guide their migration into avascular tumour sites.
Mobile internetworking protocols for wireless networks with ATM backbones (2002)

Protocols for the interoperable implementation of internetworking protocols (IF) and asynchronous transfer mode (ATM) address the issues of address resolution and routing of IP datagrams in an ATM environment to support stationary hosts. To provide mobile computing a protocol, called Mobile IP allows users to move around in the network and yet maintain continuous network connectivity. Mobile IP and IP over ATM protocols have been designed for commercial networks, with less stringent quality and survivability requirements than military networks. We discuss the limitations of the Mobile IP and IP over ATM protocols for tactical military network applications. We define solutions for providing mobility support to mobile IP hosts in an integrated network environment comprised of IP and ATM networks. We present a solution interworking Mobile IP and a specific IP over ATM protocol-Next Hop Resolution Protocol (NHRP) for an initial architecture with wireless access to ATM backbones.
The Notch/Jagged Pathway Inhibits Proliferation of Human Hematopoietic Progenitors In Vitro (1999)

The cell surface receptor Notch1 is expressed on CD34+ hematopoietic precursors, whereas one of its ligands, Jagged1, is expressed on bone marrow stromal cells. To examine the role of Notch signaling in early hematopoiesis, human CD34+ cells were cultured in the presence or absence of exogenous cytokines on feeder layers that either did or did not express Jagged1. In the absence of recombinant growth factors, Jagged1 decreased myeloid colony formation by CD34+ cells, as well as 3H-thymidine incorporation and entry into S phase. In the presence of a strong cytokine signal to proliferate and mature, (interleukin 3 [IL-3] and IL-6, stem cell factor [SCF], and G-CSF), Jagged1 did not significantly alter either the fold expansion or the types of colonies formed by CD34+ cells. However, in the presence of SCF alone, Jagged1 increased erythroid colony formation twofold. These results demonstrate that Notch can modulate a growth factor signal, and that in the absence of growth factor stimulation, the Jagged1-Notch pathway preserves CD34+ cells in an immature state.
Adenoviral Transfer of the Viral IL-10 Gene Periarticularly to Mouse Paws Suppresses Development of Collagen-Induced Arthritis in Both Injected and Uninjected Paws (1999)

Gene therapy is a promising new approach in the treatment of rheumatoid arthritis. Gene delivery to diseased joints offers the prospect of achieving high, local concentrations of a therapeutic gene product in a sustained manner, while minimizing exposure of nontarget organs. We report that a single administration of a modified adenovirus encoding the Epstein-Barr-derived homologue of IL-10 can suppress the development of disease for extended periods of time when injected locally within the periarticular tissue surrounding the ankle joints of mice with collagen type II-induced arthritis. Furthermore, we show that injection of an adenoviral vector carrying the IL-10 gene into a single paw can suppress development of arthritis in other, noninjected paws of the same individual. The systemic protection resulting from local gene therapy occurred in the absence of detectable levels of viral IL-10 in the serum. Circulating Ab levels to heterologous collagen were unaffected; however, treatment with viral IL-10 significantly suppressed the development of Abs to autologous mouse type II collagen. Thus, the treatment of a single joint by local delivery of the vIL-10 gene may protect multiple joints of the same individual while avoiding deleterious side effects often associated with systemic therapy.
Diabetes, Other Risk Factors, and 12-Yr Cardiovascular Mortality for Men Screened in the Multiple Risk Factor Intervention Trial (1993)

These findings emphasize the importance of rigorous sustained intervention in people with diabetes to control blood pressure, lower serum cholesterol, and abolish cigarette smoking, and the importance of considering nutritional-hygienic approaches on a mass scale to prevent diabetes.
Alpha Slider: Searching Textual Lists with Sliders (1993)

Abstract: AlphaSlider is a query interface that uses a direct manipulation slider to select words, phrases, or names from an existing list. This paper introduces a prototype of AlphaSlider, describes the design issues, reports on an experimental evaluation, and offers directions for further research. The experiment tested 24 subjects selecting items from lists of 40, 80, 160, and 320 entries. Mean selection times only doubled with the 8-fold increase in list length. Users quickly accommodated to this selection method.
Targeting Cancer Gene Therapy with Magnetic Nanoparticles (2012)

Recent advances in cancer genomics have opened up unlimited potential for treating cancer by directly targeting culprit genes. However, novel delivery methods are needed in order for this potential to be translated into clinically viable treatments for patients. Magnetic nanoparticle technology offers the potential to achieve selective and efficient delivery of therapeutic genes by using external magnetic fields, and also allows simultaneous imaging to monitor the delivery in vivo. Compared to conventional gene delivery strategies, this technique has been shown to significantly increase gene delivery to human xenograft tumors models, as well as various internal organs (e.g. liver, kidney) and the central nervous system. Magnetic nanoparticle technology, therefore, has the potential to turn the challenge of gene therapy in vivo into a new frontier for cancer treatment.
Intracellular availability of unmodified, phosphorothioated and liposomally encapsulated oligodeoxynucleotides for antisense activity (1992)

We have studied factors which may effect the intracellular availability of oligonucleotides to achieve antisense activity. 15-20 mer unmodified, phosphorothioate modified and liposomally encapsulated oligodeoxynucleotides have been tested in leukemia MOLT-3 cells. Phosphorothioate analogs penetrated and accumulated intact in cells in contrast to unmodified oligomers, which showed a high instability in cell culture medium. A slow decrease of intracellular concentration of undegraded phosphorothioate oligodeoxynucleotides was observed after cell treatment and could be predominantly explained by a significant efflux transport. Using laser-assisted confocal microscopy we have observed that fluorescein 5-end-labeled phosphorothioate derivatives predominantly distributed in intracytoplasmic endocytic vesicles following cell treatment. The end-capped version of phosphorothioate oligodeoxynucleotides exhibited greater cellular uptake than fully modified analogues while exhibiting similar biological stability. Liposome encapsulation made possible oligomer protection in serum-containing medium and substantially improved cellular accumulation. Furthermore, the efflux rate of oligomer initially introduced within liposomes is 2-fold lower than that observed in cells which have been incubated with free oligonucleotides. Liposomal preparations of oligodeoxynucleotides facilitate release from endocytic vesicles, and thus, cytoplasmic and nuclear localization are observed following cell treatment. Furthermore, intracellular distribution studies demonstrate that intracellular transport of unmodified oligomers is effectively achieved using the liposomal carrier.
Characterization of the enzymatic activity of PSM: Comparison with brain NAALADase (1999)

The brain enzyme NAALADase and the prostate enzyme PSM are remarkably similar. The importance of the differences in substrate specificities and kinetic parameters remains to be elucidated.
RGD Inclusion in the Hexon Monomer Provides Adenovirus Type 5-Based Vectors with a Fiber Knob-Independent Pathway for Infection (1999)

Hypervariable region 5 (HVR5) is a hydrophilic, serotypically nonconserved loop of the hexon monomer which extrudes from the adenovirus (Ad) capsid. We have replaced the HVR5 sequence of Ad5 with that of heterologous peptides and studied their effects on virus viability and peptide accessibility. A poliovirus model epitope was first inserted in a series of nine "isogenic" viruses that differed in their flanking spacers. Whereas virus productivity was not profoundly altered by any of these modifications, immunoprecipitation experiments under nondenaturing conditions demonstrated that epitope recognition by its cognate monoclonal antibody (C3 MAb) was strongly linker dependent and correlated perfectly with the ability of C3 MAb to inhibit transgene delivery and expression. An alphav-specific ligand (DCRGDCF) was then inserted in a suitable linker context to investigate whether hexon-modified capsids would enhance the transduction of cells displaying limiting amounts of the virus attachment receptors. Interestingly, although hexon has never been implicated in Ad entry, the modified virus significantly increased the transduction of human vascular smooth muscle cells in vitro. Competition experiments with 293 cells saturated with recombinant knob further indicated that the hexon-modified virus could use an additional, knob-independent pathway for entry. We concluded that genetic engineering of the Ad5 hexon monomer constitutes a novel and feasible approach to equip the virus with additional targeting ligands.
Case 32-1995 (1995)

Presentation of CaseA 78-year-old woman was admitted to the hospital because of worsening dysphagia and odynophagia.For three years, she had had dysphagia, with a sensation of solid food catching in the upper esophagus, which had worsened during the six months before admission. The dysphagia was followed by the coughing up of mucus for as long as an hour and by painful “spasms” in the neck that were provoked by swallowing medication or food. She had lost 4 to 7 kg in weight during the two years before admission. A barium-swallow examination performed elsewhere 26 months before admission showed . . .
The 2-dimensional micro scanner integrated with PZT thin film actuator (2002)

The new silicon micromachined optical scanner integrated with a PZT thin film actuator has been developed for a super miniaturized scanning type optical sensor. The scanner driven by the PZT thin film microactuator is able to scan a light beam in two directions with a scanning angle of 4.7 degree. The size of the scanner is 2 mm/spl times/4 mm/spl times/0.4 mm. The design of the scanner used the design method including air damping consideration. The measurement value of the resonant frequency was in good agreement with the calculated value using this design method. This design method is useful to predict the dynamic characteristics of a microminiaturized scanner integrated with a PZT thin film actuator.
The vaccinia virus 14-kilodalton fusion protein forms a stable complex with the processed protein encoded by the vaccinia virus A17L gene (1993)

The mechanism by which the 14-kDa fusion protein of vaccinia virus (VV) is anchored in the envelope of intracellular naked virions (INV) is not understood. In this investigation, we demonstrate that the 14-kDa protein interacts with another virus protein with an apparent molecular mass of 21 kDa. Microsequence analysis of the N terminus of the 21-kDa protein revealed that this protein is encoded by the VV A17L gene. The 21-kDa protein is processed from a 23-kDa precursor, by cleavage at amino acid position 16, at the consensus motif Ala-Gly-Ala, previously identified as a cleavage site for several VV structural proteins. The 21-kDa protein contains two large internal hydrophobic domains characteristic of membrane proteins. Pulse-chase analysis showed that within 1 h after synthesis, the 14-kDa protein forms a stable complex with the 21-kDa protein. Formation of the complex was not inhibited by rifampin, indicating that the interaction between these two proteins occurs prior to virion morphogenesis. Immunoprecipitation analysis of disrupted virions showed the presence of the 21-kDa protein in the viral particle. Release of the 14-kDa-21-kDa protein complex from INV required treatment with the nonionic detergent Nonidet P-40 and a reducing agent. The protein complex consisted of 14-kDa trimers and of 21-kDa dimers. Since the 14-kDa fusion protein lacks a signal sequence and a large hydrophobic domain characteristic of membrane proteins, our findings suggest that the 21-kDa protein serves to anchor the 14-kDa protein to the envelope of INV.
Evaluation of the Mediseus® Epidural Simulator (2012)

The demand for increased patient safety has led to greater use of simulation training of health professionals performing medical procedures. The study aim was to evaluate the usefulness of the Mediseus® Epidural Simulator in teaching basic epidural needle-handling skills. Three groups of 15 anaesthetists (Novice=zero to two year anaesthesia trainees; Intermediate=three- to five-year anaesthesia trainees; Expert=consultants and regional-specialist anaesthetists) from three different medical centres participated. Each participant performed 20 simulated epidural needle insertions and was scored on several parameters (e.g. time, success of the insertion, bone collisions). Following familiarisation with the simulator and the needle insertions, participants answered seven questions on the applicability of the simulator to the teaching of basic epidural needle-handling skills. There was a clear learning effect with regard to the simulation procedure time, this decreasing throughout the experiment (P=0.037). There was no significant influence of either group or experience with the simulator in the study on the number or type of errors made. The quality of the simulation was scored 2.3 out of 5.0 (for bone simulation) and 4.7 (for loss-of-resistance simulation). All groups considered that the simulator was best suited for training prospective anaesthetists. Each group rated the usefulness of the simulator for training novices at greater than 3.0 out of 5.0. The Mediseus® Epidural Simulator seems to be an appropriate training device for an introduction to epidural needle insertion. For medical professionals with procedural knowledge, the simulation is not realistic enough and the simulator did not distinguish between the groups based on the errors made.