gebhart/patrepeval huggingface dataset:
Gene Therapy of Cancer: Methods and Protocols (2000)

Despite various difficulties, the field of gene therapy, particularly with regard to cancer, has accumulated a tremendous amount of vital pre-clinical and clinical data. Gene Therapy of Cancer: Methods and Protocols, Second Edition fully updates the first edition with expert coverage of established and novel protocols involving both experimental and clinical approaches to cancer gene therapy. This state-of-the-art volume contains overviews of new concepts and strategies with chapters on regulatory and ethical issues, developments, problems and possible limitations of design and production of gene therapeutics as well as translational issues. Written in the highly successful Methods in Molecular Biology™ series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Cutting edge and authoritative, Gene Therapy of Cancer: Methods and Protocols, Second Edition is an ideal guide for all those who wish to explore the fast-paced and critical study of nonviral, viral, experimental and clinical cancer gene therapy
A comparative genomics and reductive dehalogenase gene transcription study of two chloroethene-respiring bacteria, Dehalococcoides mccartyi strains MB and 11a (2015)

Genomes of two trichloroethene (TCE)-respiring Dehalococcoides (Dhc) mccartyi, strains MB and 11a, were sequenced to identify reductive dehalogenases (RDase) responsible for oraganohalide respiration. Transcription analyses were conducted to verify the roles of RDase subunit A genes (rdhA) in chloroethene respiration. Some interesting features of the strain MB draft genome include a large genome size, two CRISPR-cas type I systems, and 38 rdhA genes. Strain 11a has a stream-lined genome with 11 rdhA genes, of which nine are distinct. Quantitative real-time PCR transcription analysis of RDase gene transcripts showed that a single RDase gene, designated mbrA, was up-regulated upon exposure to TCE and no other RDase genes were considerably expressed in strain MB. A single RDase gene, designated vcrA, was up-regulated upon exposure to TCE and expressed at a steady level until all chloroethenes were completely dechlorinated to ethene at 147 h in strain 11a. Overall, this study reports the genomes of two distinct Dhc strains; both contain numerous uncharacterized RDase genes, but in each strain only one such gene was expressed highly during organohalide respiration.
What's Really Needed to Effectuate Resource Protection in Communities (2002)

This article examines the challenges presented by the complexity of environmental laws at the local level, through the use of a case study. It documents the important role that comprehensive planning and local regulations play in protecting the natural resources in our communities. In considering "lessons learned," this article also considers what else is needed to continue protecting the environment at the local level. First, there is an overwhelming need for municipalities to develop a regional strategy to protect their natural resources. Second, local laws play an important role in protecting natural resources. While we often think of the state and federal statutes as being the guardians of our waterways and air, more and more local laws are catching what falls through the cracks of the state and federal system. Third, it is very challenging to be an effective local official. The system is complex; the job requires a tremendous amount of time and dedication, awareness and education. It's no wonder that many supervisors and mayors run unopposed or that it is difficult to find volunteers to serve on local boards. Fourth, if we don't focus on supporting the development of local leadership, then all the discussions about local environmental law and smart growth will be for nothing because the ideas will fall on fallow ground. Local officials need training, financial support and enhanced community process, within a regional framework.
Angiographic Features of Transgenic Mice With Increased Expression of Human Serine Protease HTRA1 in Retinal Pigment Epithelium (2014)

Transgenic hHTRA1(+) mice exhibit a rich spectrum of "clinical" features that closely mimic human PCV. This animal model will serve as an invaluable tool for future mechanistic and translational studies of PCV and other forms of choroidal vasculopathies.
Decentralised responsibility--a way forward for 'homeland' mental health care? (1990)

A case study of mental health services in Mhala, a district of the Gazankulu homeland area in South Africa, is reported; it is argued that more comprehensive mental health care could be promoted by transferring certain basic mental health functions (repeat prescriptions for stable psychosis and epilepsy) from the single itinerant community psychiatric nurse to general health nurses in the 22 clinics in the district. This would improve access to and continuity of care, and through the new 'freedom' of the community psychiatric nurse, allow for the introduction of mental health functions that are presently neglected. Training to safe levels of competence is attainable, and the additional load on clinics would be very small.
Inhibition of Bacillus subtilis deoxyribonucleic acid polymerase III by phenylhydrazinopyrimidines. Demonstration of a drug-induced deoxyribonucleic acid-enzyme complex (1975)

The interaction of 6-(phenylhydrazino)-pyrimidines and Bacillus subtilis DNA polymerase III was examined in experiments exploiting agarose gel filtration of mixtures of drug, DNA, and purified enzyme. 6-(p-Hdroxyphenylhydrazino)-uracil and 6-(p-hydroxyphenylhydrazino)-isocytosine were used as model inhibitors; both drugs induced the formation of a distinct polymerase-DNA complex. Comples formation required the inhibitory, hydrazino forms of the drugs and a form of DNA suitable as a primer-template for DNA polymerase III. dGTP and dATP, which respectively, competitively antagonize the inhibitory effects of the uracil and isocytosine derivatives, antagonized in an equally specific manner the respective capacities of these compounds to induce complex formation. Experiments exploiting both wild type and drug-resistant, mutant polymerases indicated that drug concentrations required for the half-maximal induction of complex formation were nearly identical with the apparent inhibitor constants (Ki) determined independently by kinetic analysis of enzyme inhibition. These results and those of experiments exploiting defined homopolymer-oligomer combinations as template-primers support a model of inhibitor action in which arylhydrazinopyrimidine forms a reversible, ternary complex with the enzyme and an appropriate timplate pyrimidine residue in an area adjacent to the 3-hydroxyl primer terminus.
Investigation of Preanalytical Variables Impacting Pathogen Cell-Free DNA in Blood and Urine (2019)

Pathogen cell-free DNA (pcfDNA) in blood and urine is an attractive biomarker; however, the impact of preanalytical factors is not well understood. Blood and urine samples from healthy donors spiked with cfDNA from <i>Mycobacterium tuberculosis</i>, <i>Salmonella enterica</i>, <i>Aspergillus fumigatus</i>, and Epstein-Barr virus (EBV) and samples from tuberculosis patients were used to evaluate the impact of blood collection tube, urine preservative, processing delay, processing method, freezing and thawing, and sample volume on pcfDNA. The PCR cycle threshold (<i>C<sub>T</sub></i> ) was used to measure amplifiable cfDNA. In spiked samples, the median <i>C<sub>T</sub></i> values for <i>M. tuberculosis</i>, <i>S. enterica</i>, and EBV cfDNA were significantly lower in blood collected in K<sub>2</sub>EDTA tubes than those in Streck and PAXgene blood collection tubes, and they were was significantly lower in urine preserved with EDTA (EDTA-urine) than in urine preserved with Streck reagent (Streck-urine). Blood and urine samples from TB patients preserved with K<sub>2</sub>EDTA and Tris-EDTA, respectively, showed significantly lower median <i>M. tuberculosis</i><i>C<sub>T</sub></i> values than with the Streck blood collection tube and Streck urine preservative. Processing delay increased the median pathogen <i>C<sub>T</sub></i> values for Streck and PAXgene but not K<sub>2</sub>EDTA blood samples and for urine preserved with Streck reagent but not EDTA. Double-spin compared with single-spin plasma separation increased the median pathogen <i>C<sub>T</sub></i> regardless of blood collection tube. No differences were observed between whole urine and supernatant and between fresh and thawed plasma and urine after 24 weeks at -80°C. Larger plasma and urine volumes in contrived and patient samples showed a significantly lower median <i>M. tuberculosis</i><i>C<sub>T</sub></i> These findings suggest that large-volume single-spin K<sub>2</sub>EDTA-plasma and EDTA-whole urine with up to a 24-h processing delay may optimize pcfDNA detection.
Homogeneous binary zirconocenium catalysts for propylene polymerization. II. Mixtures of isospecific and syndiospecific zirconocene systems (1999)

Isotactic polypropylene (i-PP) and syndiotactic polypropylene (s-PP) obtained with single-site C2- and Cs-symmetric zirconocenes, respectively, activated with triphenyl carbenium tetrakis(pentafluorophenyl)borate (3) are immiscible with one another. Physical mixture of the two PPs is macrophase separated and crystallizes very slowly as is characteristic of s-PP. A solution of C2- and Cs-symmetric zirconocenes with 3 also produces an incompatible mixture of i-PP and s-PP. However, in the presence of an excess of a crossover agent such as triisobutylaluminum (TIBA), a new polymeric material is obtained that exhibits lower Tm and ΔHf than either of the two homosteric polymers and a much faster rate of crystallization than that of s-PP or its physical mixture with i-PP. Thermal annealing of this product markedly reduces the relative amount of crystalline phase compared to the amorphous phase and atomic force microscopy finds only microphase separation but not macroscopic phase separation. Fractionation and 13C-NMR showed the material to contain not only the homosteric i-PP and s-PP but also a stereoblock PP (i-PP-b-s-PP). The stereoblock fraction acts as a compatibilizing agent; it probably is produced by the exchange of propagating polymer chains between the syndiospecific and the isospecific sites assisted by the crossover agent. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 2439–2445, 1999
Mulan: Multiple-sequence local alignment and visualization for studying function and evolution (2004)

Multiple-sequence alignment analysis is a powerful approach for understanding phylogenetic relationships, annotating genes, and detecting functional regulatory elements. With a growing number of partly or fully sequenced vertebrate genomes, effective tools for performing multiple comparisons are required to accurately and efficiently assist biological discoveries. Here we introduce Mulan (http://mulan.dcode.org/), a novel method and a network server for comparing multiple draft and finished-quality sequences to identify functional elements conserved over evolutionary time. Mulan brings together several novel algorithms: the TBA multi-aligner program for rapid identification of local sequence conservation, and the multiTF program for detecting evolutionarily conserved transcription factor binding sites in multiple alignments. In addition, Mulan supports two-way communication with the GALA database; alignments of multiple species dynamically generated in GALA can be viewed in Mulan, and conserved transcription factor binding sites identified with Mulan/multiTF can be integrated and overlaid with extensive genome annotation data using GALA. Local multiple alignments computed by Mulan ensure reliable representation of short- and large-scale genomic rearrangements in distant organisms. Mulan allows for interactive modification of critical conservation parameters to differentially predict conserved regions in comparisons of both closely and distantly related species. We illustrate the uses and applications of the Mulan tool through multispecies comparisons of the GATA3 gene locus and the identification of elements that are conserved in a different way in avians than in other genomes, allowing speculation on the evolution of birds. Source code for the aligners and the aligner-evaluation software can be freely downloaded from http://www.bx.psu.edu/miller_lab/.
Evaluation of the Pain Matrix Using EEG Source Localization: A Feasibility Study (2011)

The areas that were activated in the high pain state localized to the same regions reported by other neuroimaging methods and with frequency specificity. The frequency and regionally specific activation may indicate distinctive patterns of pathophysiology underlying the pain matrix. Although in a small number of patients, this work suggests that QEEG may be a useful tool in the exploration and quantification of the pain matrix in a clinical setting.
GLP-1-(7-36) amide, -(1-37), and -(1-36) amide: potent cAMP-dependent stimuli of rat parietal cell function (1991)

We investigated the effect of glucagon-like peptide 1 (GLP-1)-(7-36) amide and its molecular variants GLP-1-(1-37) and GLP-1-(1-36) amide on enzymatically dispersed enriched rat parietal cells using [14C]aminopyrine accumulation as a measure of H+ production. GLP-1-(7-36) amide was 100 times more potent than GLP-1-(1-37) and GLP-1-(1-36) amide in stimulating [14C]aminopyrine accumulation. At their maximally effective concentrations, GLP-1-(7-36) amide (10(-8) M), GLP-1-(1-37) (10(-6) M), and GLP-1-(1-36) amide (10(-6) M) reached 80-90% of the response to 10(-4) M histamine. However, the peptides were 100-10,000 times more potent than histamine, which induced maximal [14C]aminopyrine accumulation at 10(-4) M. Stimulation by GLP-1 was dependent on the presence of a phosphodiesterase inhibitor and was not altered by pertussis toxin. Ranitidine failed to affect the response to the GLP-1 variants. Stimulation of H+ production by GLP-1 was accompanied by an increase in the formation of adenosine 3',5'-cyclic monophosphate (cAMP) but not by changes in phosphoinositol breakdown. In stimulating [14C]aminopyrine accumulation, the GLP-1 variants acted additively to threshold but not to maximal concentrations of histamine, suggesting that histamine and GLP-1 activate the same cAMP pool. In contrast, in anesthetized rats GLP-1-(7-36) amide (10-500 ng.kg-1.h-1) had no effect on basal and pentagastrin-stimulated acid secretion in vivo. We conclude that GLP-1 exerts a direct stimulatory effect on rat parietal cells. This potent effect is mediated by cAMP and is independent of H2 receptors. In vivo direct stimulation by GLP-1 of the parietal cells might be counterbalanced by indirect inhibitory mechanisms that are excluded in the in vitro cell system.
The Protein Data Bank (2000)

The Protein Data Bank (PDB; http://www.rcsb.org/pdb/ ) is the single worldwide archive of structural data of biological macromolecules. This paper describes the goals of the PDB, the systems in place for data deposition and access, how to obtain further information, and near-term plans for the future development of the resource.
Kinematic analysis of jaw function in children following traumatic brain injury (2005)

Possible sub-clinical impairments of jaw movement for speech were exhibited by two children who had sustained a TBI, providing insight into the consequences of TBI on speech motor control development.
Membrane Mimetic Environments Alter the Conformation of the Outer Membrane Protein BtuB (2003)

Membrane mimetic environments formed from detergents or short-chain phospholipids are widely utilized in structural studies of membrane proteins. Using site-directed spin labeling (SDSL), we show that micelle and isotropic bicellar environments alter the N-terminal region of BtuB, the outer membrane vitamin B12 transporter found in Escherichia coli. These membrane mimetic systems promote an unfolding of the N-terminus of the protein that does not occur when the protein is in either native or reconstituted bilayers. The N-terminal Ton box of BtuB has been shown to exist in two conformations, depending upon the presence or absence of substrate. However, the detergent-destabilized conformation is different from either the substrate-free or the substrate-bound form of this transporter. This example demonstrates that membrane mimetic systems will not always substitute for the lamellar bilayer environment provided by a biological membrane.
P-glycoprotein and pharmacokinetics. (1995)

P-glycoprotein (P-gp) is a transmembrane protein associated with a phenotype of cross resistance to certain anticancer agents. P-gp is thought to act as an energy dependent pump that expels the anticancer drug out of the tumoral cell, reducing its accumulation and hence its activity. P-gp has been detected in vivo and in vitro in numerous tumor cell types but also in normal tissues and particularly in organs involved in the pharmacokinetic behaviour of xenobiotics. The physiologic functions of P-gp remain unclear but a growing amount of information suggests that it can play an important role at the different steps of pharmacokinetics (i.e., absorption, distribution, elimination). This review gives an update on what is known about the impact of P-gp on the disposition of drugs.
FPGA-based Implementation of an Ultrasonic Beacon for a Local Positioning System (2006)

Ultrasonic transducers have been often used to develop Local Positioning Systems (LPS) in the field of intelligent spaces. In these systems, it is necessary to design an ultrasonic beacon, which is distributed in the environment to cover a determined area where mobile robots or people can be located. This work describes the design and the implementation of an ultrasonic beacon in an FPGA-based platform. The design is flexible enough to allow the real-time configuration of the ultrasonic emission, according to parameters as efficient encoding or suitable modulation schemes. Furthermore, the beacons have available a I2C link, so they are in permanent communication for exchanging configuration parameters and synchronization, not only among them, but also with a central configuration module.
Systolic architecture for finite field exponentiation (1989)

A systolic pipline architecture which can perform exponentiation function in a concurrent environment is presented. This function is computed in Galois fields. Under a steady-state condition the throughput of the architecture is shown to be the maximum, with the results appearing at every clock cycle. Being systolic in nature, the architecture is amenable to easy implementation in VLSI.
Fibroblast Biomarkers of Sporadic Parkinson’s Disease and LRRK2 Kinase Inhibition (2015)

It has been uncertain whether specific disease-relevant biomarker phenotypes can be found using sporadic Parkinson's disease (PD) patient-derived samples, as it has been proposed that there may be a plethora of underlying causes and pathological mechanisms. Fibroblasts derived from familial PD patients harboring leucine-rich repeat kinase 2 (LRRK2), PTEN-induced putative kinase 1 (PINK1), and Parkin mutations show clear disease-relevant mitochondrial phenotypes, which are exacerbated under conditions of pharmacological stress. We utilized fibroblasts derived from non-familial sporadic PD patients (without LRRK2 mutations) or LRRK2 mutation carriers to directly compare the cellular phenotypes during and after mitochondrial stress. We then determined the effects of pharmacological LRRK2 kinase inhibition using LRRK2-in-1. We found that there were two distinct populations of sporadic PD patient-derived fibroblast lines. One group of sporadic PD lines was highly susceptible to valinomycin-induced mitochondrial depolarization, emulating the mutant LRRK2 phenotype. These lines showed elevated mitochondrial superoxide/ nitric oxide levels, displayed increased mitochondrial and lysosome co-localization, and an increased rate of mitochondrial collapse, which corresponded with changes in mitochondrial fission and fusion proteins. The application of LRRK2-in-1 reversed decreased levels of mitochondrial and lysosome co-localization and partially restored mitochondrial network associated proteins and the mitochondrial membrane potential in the fibroblasts. This study identifies novel mitochondrial biomarkers in sporadic PD patient-derived fibroblast lines, which could be used as preclinical tools in which to test novel and known neuroprotective compounds.
Tenascin and other adhesion-modulating proteins in cancer. (1993)

A loss in cell-cell adhesion and an increase in cell motility are clearly prerequisites for the development of invasive tumors and metastasis. Since disseminating tumor cells have to interact with and migrate through extracellular matrices it is of interest to compare the composition of extracellular matrix proteins in normal and tumor tissues, in order to determine whether the extracellular matrix could be critically involved in affecting tumor cell adhesion and migration. The question will be addressed whether tumor extracellular matrix contains increased amounts of potentially antiadhesive extracellular matrix components and whether cells behave differently depending on the extracellular matrix they encounter. The results reviewed support the hypothesis that changes in the extracellular matrix and the cellular receptors are indeed important in the process of tumorigenesis.
Mature autologous dendritic cell vaccines in advanced non-small cell lung cancer: a phase I pilot study (2011)

Current Controlled Trials: ISRCTN45563569.
Identification and expression of a human cytomegalovirus glycoprotein with homology to the Epstein-Barr virus BXLF2 product, varicella-zoster virus gpIII, and herpes simplex virus type 1 glycoprotein H (1988)

An open reading frame with the characteristics of a glycoprotein-coding sequence was identified by nucleotide sequencing of human cytomegalovirus (HCMV) genomic DNA. The predicted amino acid sequence was homologous with glycoprotein H of herpes simplex virus type 1 and the homologous protein of Epstein-Barr virus (BXLF2 gene product) and varicella-zoster virus (gpIII). Recombinant vaccinia viruses that expressed this gene were constructed. A glycoprotein of approximately 86 kilodaltons was immunoprecipitated from cells infected with the recombinant viruses and from HCMV-infected cells with a monoclonal antibody that efficiently neutralized HCMV infectivity. In HCMV-infected MRC5 cells, this glycoprotein was present on nuclear and cytoplasmic membranes, but in recombinant vaccinia virus-infected cells it accumulated predominantly on the nuclear membrane.
Inhibition of Phosphatidylinositol 3-Kinase Causes Apoptosis in Retinoic Acid-Differentiated HL-60 Leukemia Cells (2004)

Phosphatidylinositol 3-kinase (PI3-K) signaling may inhibit apoptosis in neoplastic cells. The PI-3K inhibitor wortmannin renders cells apoptosis-prone. Inducers of differentiation may also cause apoptosis. To detect the effect of wortmannin on the survival of differentiated human acute promyeloid leukemia cells, HL-60 cells were induced to differentiation with treatment of all trans-retinoic acid (ATRA) followed by treatment with wortmannin. Results showed that apoptosis occurred in cells that underwent differentiation, but not in undifferentiated HL-60 cells. The pro-apoptotic molecule, Bad, played a role in this apoptotic mechanism. Thus, the survival of differentiated HL-60 cells induced by ATRA depends on the ability of the PI3-K pathway to transduce survival signals; the PI3-K inhibitor, wortmannin, can induce apoptosis of differentiated HL-60 cells. These results may indicate a novel method for treating cancer with differentiation induction and signal pathway regulation.