gebhart/patrepeval huggingface dataset:
Cellular Target of Cyclophosphamide Toxicity in the Murine Liver: Role of Glutathione and Site of Metabolic Activation (1996)

Hepatic venoocclusive disease (HVOD) is caused by the disruption of the microcirculation by an as-yet unknown mechanism. Previous in vitro studies with azathioprine, monocrotaline, and dacarbazine suggested that toxins that cause HVOD initially causing HVOD target sinusoidal endothelial cells (SEC) perhaps via profound glutathione (GSH) depletion. The current study examines cyclophosphamide toxicity in SEC and hepatocytes, as well as the interplay between the two cell types. Cyclophosphamide was not directly toxic to SEC, but in coculture of SEC and hepatocytes, cyclophosphamide was significantly more toxic to SEC. Two cyclophosphamide metabolites, 4-hydroperoxycyclophosphamide and acrolein, were equally toxic to SEC, and toxicity occurred at 20-fold-lower concentrations than in hepatocytes. 4-Hydroperoxycyclophosphamide depleted GSH by greater than 95% before inducing cell death in SEC. When hepatocyte-GSH levels were sustained with supplemental methionine and serine in coculture, toxicity in both cell types was diminished. In coculture, SEC are significantly more susceptible than hepatocytes to cyclophosphamide toxicity, and this is likely caused by acrolein generated by the hepatocyte. As seen with other toxins implicated in HVOD, the profound depletion of SEC GSH precedes the onset of toxicity. The degree of cyclophosphamide toxicity induced in SEC is determined by both metabolic activation and GSH detoxification in the hepatocytes.
Molecular cloning of the human gene for von Willebrand factor and identification of the transcription initiation site. (1987)

A series of overlapping cosmid genomic clones have been isolated that contain the entire coding unit of the human gene for von Willebrand factor (vWf), a major component of the hemostatic system. The cloned segments span approximately 175 kilobases of human DNA sequence, and hybridization analysis suggests that the vWf coding unit is approximately 150 kilobases in length. Within one of these clones, the vWf transcription initiation site has been mapped and a portion of the vWf promoter region has been sequenced, revealing a typical "TATA box," a downstream "CCAAT box," and a perfect downstream repeat of the 8 base pairs containing the transcription start site. Sequencing of a segment of another genomic clone has revealed the vWf translation termination codon. Where tested, comparative restriction analysis of cloned and chromosomal DNA segments strongly suggests that no major alterations occurred during cloning and that there is only one complete copy of the vWf gene in the human haploid genome. Similar analyses of DNA from vWf-producing endothelial cells and nonexpressing leukocytes suggest that vWf gene expression is not accompanied by gross genomic rearrangements. In addition, there is significant homology of C-terminal coding sequences among the vWf genes of several vertebrate species.
Matrix Metalloproteinases: Biologic Activity and Clinical Implications (2000)

Tumor progression is a complex, multistage process by which a normal cell undergoes genetic changes that result in phenotypic alterations and the acquisition of the ability to spread and colonize distant sites in the body. Although many factors regulate malignant tumor growth and spread, interactions between a tumor and its surrounding microenvironment result in the production of important protein products that are crucial to each step of tumor progression. The matrix metalloproteinases (MMPs) are a family of degradative enzymes with clear links to malignancy. These enzymes are associated with tumor cell invasion of the basement membrane and stroma, blood vessel penetration, and metastasis. They have more recently been implicated in primary and metastatic tumor growth and angiogenesis, and they may even have a role in tumor promotion. This review outlines our current understanding of the MMP family, including the association of particular MMPs with malignant phenotypes and the role of MMPs in specific steps of the metastatic cascade. As scientific understanding of the MMPs has advanced, therapeutic strategies that capitalize on blocking the enzymes have rapidly developed. The preclinical and clinical evolution of the synthetic MMP inhibitors (MMPIs) is also examined, with the discussion encompassing important methodologic issues associated with determining clinical efficacy of MMPIs and other novel therapeutic agents.
Human ethanol-inducible P450IIE1: complete gene sequence, promoter characterization, chromosome mapping, and cDNA-directed expression (1988)

The human P450IIE1 gene, coding for an ethanol-inducible nitrosamine-metabolizing P-450, was isolated from a lambda EMBL3 genomic library and completely sequenced. The human gene spanned 11,413 base pairs and contained nine exons and a typical TATA box. Upstream and downstream DNAs of 2788 and 559 base pairs were also sequenced and compared to the rat gene. Significant areas of sequence similarity were observed within 140 base pairs upstream of the transcription start site in the rat and human genes. Human DNA 539 base pairs upstream of the transcription start site was inserted into the expression vector pSVOAL delta 5', and luciferase activity was detected when the constructs were introduced into a rat hepatoma cell line. The activity was over 100-fold lower than that of pRSVL, a Rous sarcoma virus LTR-driven luciferase gene. By use of panels of rodent-human cell hybrids, the gene was mapped to chromosome 10 (CYP2E locus). A full-length cDNA, constructed with the first exon of the genomic clone and a partial cDNA clone, was expressed in COS cells and found to code for N-nitrosodimethylamine demethylase activity.
Technologies for Printing Sensors and Electronics Over Large Flexible Substrates: A Review (2014)

Printing sensors and electronics over flexible substrates are an area of significant interest due to low-cost fabrication and possibility of obtaining multifunctional electronics over large areas. Over the years, a number of printing technologies have been developed to pattern a wide range of electronic materials on diverse substrates. As further expansion of printed technologies is expected in future for sensors and electronics, it is opportune to review the common features, the complementarities, and the challenges associated with various printing technologies. This paper presents a comprehensive review of various printing technologies, commonly used substrates and electronic materials. Various solution/dry printing and contact/noncontact printing technologies have been assessed on the basis of technological, materials, and process-related developments in the field. Critical challenges in various printing techniques and potential research directions have been highlighted. Possibilities of merging various printing methodologies have been explored to extend the lab developed standalone systems to high-speed roll-to-roll production lines for system level integration.
Resolution limits in x-ray lithography (1992)

During an x-ray lithography proximity exposure x rays generate electrons in the resist which deposit energy along a finite range. This range combines with diffraction spreading to degrade the image resolution. The component of resolution arising from electron range is often taken as the Grun range of the most copiously generated photoelectrons, about 0.1 μm at an exposure wavelength of 10 Å. Although some experiments have shown much better resolutions, there is a widespread belief that photoelectron range limits resolution to about 0.1 μm. We have analytically modeled the distribution of energy deposited by Auger and photoelectrons. Near an edge the distribution is well-fit by an error function. The standard deviation of this error function, which we define as the ‘‘effective range,’’ is about 0.01 μm at 10 Å in poly(methylmethacrylate) (PMMA) resist. For all energies of interest to x-ray lithography the effective range of the electrons is much smaller than the Grun range, explaining the high-resolution results. It is diffraction which dominates the resolution of conventional x-ray lithography. Consequently, reducing the gap in proximity printing should produce resolutions far below 0.1 μm, while retaining all the latitude inherent in the x-ray lithography process.
Efficiency and Safety of Mechanical Ventilation with a Heat and Moisture Exchanger Changed Once a Week (2001)

The cost of mechanical ventilation (MV) is high. Efforts to reduce this cost, as long as they are not detrimental for the patients, are needed. MV with heat and moisture exchangers (HME) changed every 48 h is safe, efficient, and cost-effective. Preliminary reports suggest that the life span of these filters may be prolonged. We determined prospectively whether a hygroscopic and hydrophobic HME (Hygrobac-Dar; Mallinckrodt) provided safe and efficient heating and humidification of the inspired gases when changed only once a week. Patients who were considered to require mechanical ventilation for more than 48 h were included in the study. HMEs were initially set for 7 d. Efficient airway heating and humidification were assessed by clinical parameters (number of tracheal suctionings and instillations required, peak airway pressures) and hygrometric measurements performed by psychrometry. Resistance was measured from Day 0 to Day 7. Bacterial colonization of circuits and HMEs was studied. A total of 377 days ...
Transmission electron microscopy of defects in GaN films formed by epitaxial lateral overgrowth (1998)

We have investigated by transmission electron microscopy (TEM) defect morphology and structure in GaN films formed using an epitaxial lateral overgrowth (ELO) technique on SiO2-mask/window-stripe-patterned GaN layers in hydride vapor-phase epitaxy. In this experiment, the regions overgrown on the SiO2 masks were thoroughly examined. Cross-sectional TEM clearly revealed characteristic defects along the [0001] direction in the overgrown region, which consisted of arrays of dislocations running along the mask stripe direction. These defects caused crystallographic tilting in that region near the mask with respect to the other region grown from the window area. We also observed, at the coalesced site on the mask, vertical repropagation of dislocations that had propagated laterally during ELO. The origin of the observed defects and their influence on the residual dislocation distribution near the film surface are discussed.
Review of the sawfly genus Lagium (Hymenoptera: Tenthredinidae) (1986)

(Uploaded by Plazi from the Biodiversity Heritage Library) No abstract provided.
Spinal cord stimulation versus conventional medical management for neuropathic pain: A multicentre randomised controlled trial in patients with failed back surgery syndrome (2007)

Patients with neuropathic pain secondary to failed back surgery syndrome (FBSS) typically experience persistent pain, disability, and reduced quality of life. We hypothesised that spinal cord stimulation (SCS) is an effective therapy in addition to conventional medical management (CMM) in this patient population. We randomised 100 FBSS patients with predominant leg pain of neuropathic radicular origin to receive spinal cord stimulation plus conventional medical management (SCS group) or conventional medical management alone (CMM group) for at least 6 months. The primary outcome was the proportion of patients achieving 50% or more pain relief in the legs. Secondary outcomes were improvement in back and leg pain, health-related quality of life, functional capacity, use of pain medication and non-drug pain treatment, level of patient satisfaction, and incidence of complications and adverse effects. Crossover after the 6-months visit was permitted, and all patients were followed up to 1 year. In the intention-to-treat analysis at 6 months, 24 SCS patients (48%) and 4 CMM patients (9%) (p<0.001) achieved the primary outcome. Compared with the CMM group, the SCS group experienced improved leg and back pain relief, quality of life, and functional capacity, as well as greater treatment satisfaction (p<or=0.05 for all comparisons). Between 6 and 12 months, 5 SCS patients crossed to CMM, and 32 CMM patients crossed to SCS. At 12 months, 27 SCS patients (32%) had experienced device-related complications. In selected patients with FBSS, SCS provides better pain relief and improves health-related quality of life and functional capacity compared with CMM alone.
FilmArray, an Automated Nested Multiplex PCR System for Multi-Pathogen Detection: Development and Application to Respiratory Tract Infection (2011)

The ideal clinical diagnostic system should deliver rapid, sensitive, specific and reproducible results while minimizing the requirements for specialized laboratory facilities and skilled technicians. We describe an integrated diagnostic platform, the "FilmArray", which fully automates the detection and identification of multiple organisms from a single sample in about one hour. An unprocessed biologic/clinical sample is subjected to nucleic acid purification, reverse transcription, a high-order nested multiplex polymerase chain reaction and amplicon melt curve analysis. Biochemical reactions are enclosed in a disposable pouch, minimizing the PCR contamination risk. FilmArray has the potential to detect greater than 100 different nucleic acid targets at one time. These features make the system well-suited for molecular detection of infectious agents. Validation of the FilmArray technology was achieved through development of a panel of assays capable of identifying 21 common viral and bacterial respiratory pathogens. Initial testing of the system using both cultured organisms and clinical nasal aspirates obtained from children demonstrated an analytical and clinical sensitivity and specificity comparable to existing diagnostic platforms. We demonstrate that automated identification of pathogens from their corresponding target amplicon(s) can be accomplished by analysis of the DNA melting curve of the amplicon.
Amino acids acting as transmitters in amyotrophic lateral sclerosis (ALS) (1999)

The data from serum and CSF indicate that in ALS an imbalance between excitatory and inhibitory amino acids might be present in the brain, which may be induced in different ways in particular ALS patients. It may be an important factor for the mediation of neurons death.
Use of monoclonal antibodies in the purification and characterization of 1-aminocyclopropane-1-carboxylate synthase, an enzyme in ethylene biosynthesis (1986)

1-Aminocyclopropane-1-carboxylate (ACC) synthase (EC 4.4.1.14), extracted from tomato pericarp tissue, was purified 6500-fold by conventional and high-performance liquid chromatography. Two-dimensional gel electrophoresis of this preparation indicated that ACC synthase activity was associated with a protein band at 50 kDa, a value consistent with size determinations by gel filtration. Monoclonal antibodies against ACC synthase were obtained from murine hybridoma cell lines. These antibodies recognized the native enzyme, as shown with an immunoprecipitation assay. A monoclonal IgG immunoaffinity gel was used to isolate, from a relatively crude enzyme preparation, a single protein, which migrated at 50 kDa in a NaDodSO(4)/polyacrylamide gel. In vivo labeling of wounded tomato pericarp tissue with [(35)S]methionine followed by immunoaffinity purification of ACC synthase yielded a radioactive protein of 50 kDa. We conclude that the 50-kDa protein represents ACC synthase in extracts of wounded tomato pericarp tissue.
Gene Transfer and Expression (1990)

A practical manual of protocols for achieving expression of foreign genes in mammalian cells. It includes some very new techniques such as PCR-based expression. The author gives a theoretical introduc
Stabilization of Triple Helical DNA by a Benzopyridoquinoxaline Intercalator (1996)

Biophysical, footprinting, and chemical probing experiments are described which characterize the triple helix-stabilizing effects of a benzo[f]pyridoquinoxaline derivative BfPQ-4,3 structurally related to the previously reported benzo[f]pyridoindole compound BePI [Mergny et al. (1992) Science 256, 1681-1684]. Two parallel triple helix model systems have been investigated; one in which the third strand matched perfectly a 27 base pair purine-pyrimidine motif in target DNA and another in which the third strand was one nucleotide longer, i.e., a 28-mer. In the latter system, the pairing of the (Y)28 third strand to the (Y.R)27 target induces the formation of a bulge containing at least one unpaired base, which can be evidenced by chemical probing experiments with osmium tetroxide. BPQ, which uinwinds a duplex DNA by 17 degrees as judged by viscometric experiments and otherwise behaves as a typical nonspecific intercalculating drug, promotes the formation of Y.R.Y parallel triple helix containing both T.A.T and C.G.C+ triplets. Both DNase I and MPE.FeII footprinting experiments concur that triplex formation with the target (Y.R)27 sequence can be detected in the presence of BPQ at about 10-fold lower oligonucleotide concentrations than are required to produce an equivalent footprint in the absence of the drug. In addition, BPQ will promote binding to the polypurine-polypyrimidine target sequence by the longer mismatched oligonucleotide, providing significant stabilization of the parallel bulge-containing(Y.R)27,(Y)28 triplex with nearly the same efficiency as the bulge-free (Y.R)27.(Y)28 triplex. Thus in vivo BPQ might enhance the formation of both undesired and desired DNA triplexes. By performing an MPE*FeII probing reaction with a 5'-32 P-labeled oligonucleotide third strand, we have obtained evidence that BPQ is actually bound to the triplex region and may distort in a sequence-specific fashion.
IMPLEMENTATION OF LOW COST FPGA REMOTE LABORATORY (2014)

Traditional laboratories are being complemented by virtual and remote laboratories. Students attend traditional laboratories in class and after hours perform experiments remotely, often from their home. There have been several remote laboratories that have been developed for a range of disciplines. This paper proposes a remote laboratory for teaching FPGA and HDL at low cost. The remote laboratory is made of one server and multiple remote hardware sets. Each remote hardware set consists of one control board and at least one FPGA board. The Altera Development and Education (DE) Board is based on the Cyclone II 2C20 FPGA and is physically connected to the control broad. Both boards communicate with a computer server. The control board relays the FPGA inputs/outputs to the server, which in turns sends the status of the outputs to the client over the Internet to visually display the results. Students use a computer client to perform experiments remotely on the FPGA. This architecture is designed to have high scalability and low data bit rate communication link with the average client requiring only a data rate of 450B/s. A FPGA board is planned to be used as a traditional laboratory during day and reassemble with a control board and a server to become a remote laboratory at night.
Oral immunization against respiratory viruses in mice. (1995)

The results presented here extend our previous observations regarding oral immunization against respiratory viruses in three areas. First, from an experiment comparing Sendai virus with influenza virus it appears that the nature of the antigen as well as host-parasite interactions may play an important role in efficiency of oral immunization. Second, oral immunization with an inactivated virus can apparently induce a cell-mediated immune response. Preliminary evidence (not shown) indicated that the magnitude of effector cell killing versus virus-infected target cells was positively influenced by including cholera toxin in the oral immunization regimen. This is consistent with a recent report that cholera toxin could enhance T cell proliferative response to co-fed KLH. Finally, we have shown that oral immunization with inactivated virus plus cholera toxin combined with intranasal inactivated virus boosting, can protect mice from infection for nearly two years--their normal life span.
Benzodiazepine receptor binding activity of 8-substituted-9-(3-substituted-benzyl)-6-(dimethylamino)-9H-purines (1990)

A series of 8-substituted analogues of 9-(3-aminobenzyl)-6-(dimethylamino)-9H-purine (8) were synthesized and tested for their ability to bind to the benzodiazepine receptor (BZR) in rat brain tissue. The most active compound was the 8-bromo-9-(3-formamidobenzyl) analogue 16 (IC50 = 0.011 microM), which was 1000-fold more active than the parent 9-benzyl-6-(dimethylamino)-9H-purine (1) and nearly as active as diazepam. Although substitution of a m-formamido group and an 8-bromo substituent on 1 imparted potent BZR binding activity, neither 16 nor 11 analogues exhibited significant anxiolytic activity on a modified Geller-Seifter conflict schedule.
Dipeptidyl Peptidase IV Inhibitor Treatment Stimulates β-Cell Survival and Islet Neogenesis in Streptozotocin-Induced Diabetic Rats (2003)

Recent studies into the physiology of the incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) have added stimulation of beta-cell growth, differentiation, and cell survival to well-documented, potent insulinotropic effects. Unfortunately, the therapeutic potential of these hormones is limited by their rapid enzymatic inactivation in vivo by dipeptidyl peptidase IV (DP IV). Inhibition of DP IV, so as to enhance circulating incretin levels, has proved effective in the treatment of type 2 diabetes both in humans and in animal models, stimulating improvements in glucose tolerance, insulin sensitivity, and beta-cell function. We hypothesized that enhancement of the cytoprotective and beta-cell regenerative effects of GIP and GLP-1 might extend the therapeutic potential of DP IV inhibitors to include type 1 diabetes. For testing this hypothesis, male Wistar rats, exposed to a single dose of streptozotocin (STZ; 50 mg/kg), were treated twice daily with the DP IV inhibitor P32/98 for 7 weeks. Relative to STZ-injected controls, P32/98-treated animals displayed increased weight gain (230%) and nutrient intake, decreased fed blood glucose ( approximately 26 vs. approximately 20 mmol/l, respectively), and a return of plasma insulin values toward normal (0.07 vs. 0.12 nmol/l, respectively). Marked improvements in oral glucose tolerance, suggesting enhanced insulin secretory capacity, were corroborated by pancreas perfusion and insulin content measurements that revealed two- to eightfold increases in both secretory function and insulin content after 7 weeks of treatment. Immunohistochemical analyses of pancreatic sections showed marked increases in the number of small islets (+35%) and total beta-cells (+120%) and in the islet beta-cell fraction (12% control vs. 24% treated) in the treated animals, suggesting that DP IV inhibitor treatment enhanced islet neogenesis, beta-cell survival, and insulin biosynthesis. In vitro studies using a beta-(INS-1) cell line showed a dose-dependent prevention of STZ-induced apoptotic cell-death by both GIP and GLP-1, supporting a role for the incretins in eliciting the in vivo results. These novel findings provide evidence to support the potential utility of DP IV inhibitors in the treatment of type 1 and possibly late-stage type 2 diabetes.