gebhart/patrepeval huggingface dataset:
Simian virus 40 large tumor antigen-immortalized normal human liver epithelial cells express hepatocyte characteristics and metabolize chemical carcinogens. (1993)

Normal human liver tissue and cultured human hepatocytes are valuable models to study xenobiotic metabolism and toxicity, but they only have a limited in vitro life-span and are not readily available. This report describes the establishment of replicative cultures of human adult liver epithelial cells in serum-free medium. The longevity of three of these cultures, derived from different donors, was extended by introduction of the simian virus 40 large T antigen gene. Two cell lines, THLE-2 and -3, established with a recombinant simian virus 40 large T antigen virus have undergone > 100 population doublings, are nontumorigenic when injected into athymic nude mice, have near-diploid karyotypes, and do not express alpha-fetoprotein. The cells express cytokeratin 18 and albumin in early passage, whereas higher-passage cells in logarithmic-phase growth also express cytokeratin 19. THLE-2 and -3 cells metabolize benzo[a]pyrene, N-nitrosodimethylamine, and aflatoxin B1 to their ultimate carcinogenic metabolites that adduct DNA, which indicates functional cytochrome P450 pathways. Other enzymes involved in metabolism of chemical carcinogens, such as epoxide hydrolase, NADPH cytochrome P450 reductase, superoxide dismutase, catalase, glutathione S-transferases, and glutathione peroxidase are also retained by THLE cells. Thus, these immortalized human liver cells constitute an in vitro model for pharmacotoxicological studies and for the investigation of etiology and pathogenesis of human hepatocellular carcinoma.
Exoenzyme S of Pseudomonas aeruginosa is secreted by a type III pathway (1996)

Exoenzyme S is an extracellular ADP-ribosyltransferase of Pseudomonas aeruginosa. Transposon mutagenesis of P. aeruginosa 388 was used to identify genes required for exoenzyme S production. Five Tn5Tc insertion mutants were isolated which exhibited an exoenzyme S-deficient phenotype (388::Tn5Tc 469, 550, 3453, 4885, and 5590). Mapping experiments demonstrated that 388::Tn5Tc 3453, 4885, and 5590 possessed insertions within a 5.0 kb EcoRI fragment that is not contiguous with the exoenzyme S trans-regulatory operon. 388::Tn5Tc 469 and 550 mapped to a region downstream of the trans-regulatory operon which has been previously shown to contain a promoter region that is co-ordinately regulated with exoenzyme S synthesis. Nucleotide sequence analysis of a 7.2 kb region flanking the 388::Tn5Tc 469 and 550 insertions, identified 12 contiguous open reading frames (ORFs). Database searches indicated that the first ORF, ExsD, is unique. The other 11 ORFs demonstrated high homology to the YscB-L proteins of the yersiniae Yop type III export apparatus. RNase-protection analysis of wild-type and mutant strains indicated that exsD and pscB-L form an operon. To determine whether ExoS was exported by a type III mechanism, derivatives consisting of internal deletions or lacking amino- or carboxy-terminal residues were expressed in P. aeruginosa. Deletion analyses indicated that the amino-terminal nine residues are required for ExoS export. Combined data from mutagenesis, regulatory, expression, and sequence analyses provide strong evidence that P. aeruginosa possesses a type III secretion apparatus which is required for the export of exoenzyme S and potentially other co-ordinately regulated proteins.
Jupiter’s magnetosphere and aurorae observed by the Juno spacecraft during its first polar orbits (2017)

The Juno spacecraft acquired direct observations of the jovian magnetosphere and auroral emissions from a vantage point above the poles. Juno's capture orbit spanned the jovian magnetosphere from bow shock to the planet, providing magnetic field, charged particle, and wave phenomena context for Juno's passage over the poles and traverse of Jupiter's hazardous inner radiation belts. Juno's energetic particle and plasma detectors measured electrons precipitating in the polar regions, exciting intense aurorae, observed simultaneously by the ultraviolet and infrared imaging spectrographs. Juno transited beneath the most intense parts of the radiation belts, passed about 4000 kilometers above the cloud tops at closest approach, well inside the jovian rings, and recorded the electrical signatures of high-velocity impacts with small particles as it traversed the equator.
2-[N'-(3-Arylallylidene)hydrazino]adenosines Showing A2a Adenosine Agonist Properties and Vasodilation Activity (1995)

A series of 2-[N'-(3-arylallylidene)hydrazino]adenosines were prepared and studied in binding and functional assays to assess their potency for the A2a compared with the A1 adenosine receptor. These analogs possess A2a receptor affinity in the low nanomolar range associated with weak interaction with the A1 receptor. Among the compounds, in rat tissues, 2-[N'-[3-(4-nitrophenyl)allylidene] hydrazinoadenosine (5g) had the most potent affinity for the A2a receptor, the K(i) value being 23 nM. The type and position of substituents on the phenyl ring show a moderate influence on biological activity, allowing the conclusion that the latter is mostly due to the allylidenehydrazino side chain. From functional experiments 2-[N'-(2-furylmethylidene)hydrazino]adenosine (4b), 2-[N'-(3-phenylallylidene)hydrazino]adenosine (5a) and 2-[N'-[3-(2-furyl)allylidene]hydrazino]adenosine (5b) appeared to be potent in inducing vasorelaxation (an A2a-mediated response) without appreciable effects on the heart rate (an A1-mediated action). While the lack of effects on heart rate is clearly explained by the poor affinity for A1 receptors, more difficult appears the interpretation of vasorelaxant properties displayed by some compounds. Affinity for A2a has a major role, but other types of interactions, yet to be identified, may play a part.
Electroporation and RNA interference in the rodent retina in vivo and in vitro (2003)

The large number of candidate genes made available by comprehensive genome analysis requires that relatively rapid techniques for the study of function be developed. Here, we report a rapid and convenient electroporation method for both gain- and loss-of-function studies in vivo and in vitro in the rodent retina. Plasmid DNA directly injected into the subretinal space of neonatal rodent pups was taken up by a significant fraction of exposed cells after several pulses of high voltage. With this technique, GFP expression vectors were efficiently transfected into retinal cells with little damage to the operated pups. Transfected GFP allowed clear visualization of cell morphologies, and the expression persisted for at least 50 days. DNA-based RNA interference vectors directed against two transcription factors important in photoreceptor development led to photoreceptor phenotypes similar to those of the corresponding knockout mice. Reporter constructs carrying retinal cell type-specific promoters were readily introduced into the retina in vivo, where they exhibited the appropriate expression patterns. Plasmid DNA was also efficiently transfected into retinal explants in vitro by high-voltage pulses.
Biochemical interruption of membrane phospholipid renewal in retinal photoreceptor cells (1984)

The rabbit retina's synthesis of new phosphatidylcholine from extracellular choline was interrupted by an intravitreal injection of the choline analogue hemicholinium-3. This disrupted the process by which new membrane is added to the rod photoreceptor outer segments and eventually caused outer segment degeneration. During the first 2 days after hemicholinium-3 was injected, rows of vesicles replaced the newly formed membrane discs at the outer segment's base. The region of vesicles then expanded, and the distal outer segment detached and was quickly phagocytosed by the pigment epithelium. Two weeks after hemicholinium-3 injection, all of the retina's outer segments had been lost and the inner segments were reduced in length. The threshold concentration of hemicholinium-3 was approximately 20 microM intraocularly. At this dose, the cell bodies, intracellular organelles, and synapses of the rod cells survived. A small group of amacrine cells, possibly those that synthesize acetylcholine, became pyknotic; but the other retinal neurons remained normal to both light and electron microscopy even upon exposure to intraocular concentrations as high as 1 mM. Biochemical experiments indicated that at 20 microM hemicholinium-3, the perturbation of choline metabolism is partial and transient. That it has major selective consequences for the outer segments probably reflects the large amount of new phospholipid required for renewal of their membranes. The selectivity of the lesion was also evidenced by electrophysiological activity recorded from hemicholinium-3-treated retinas. Hemicholinium-3 was injected in vivo, and at various times retinas were isolated and incubated in vitro. The normal components of the electroretinogram were observed, but its amplitude rapidly declined; 12 days after injection, no response to light could be detected. Spontaneous firing of single ganglion cells was observed at all times following hemicholinium-3 injection. As the outer segments degenerated and the threshold of the electroretinogram rose, the thresholds of the ganglion cells also rose, but normal ganglion cell receptive fields could sometimes be plotted. Fourteen days after injection, when all of the outer segments were gone, ganglion cell responses to bright light could still be recorded; their thresholds were about 3.5 log units above normal. This finding is consistent with a previous report of light-evoked responses in mice after outer segment degeneration.(ABSTRACT TRUNCATED AT 400 WORDS)
Electron Transport in Molecular Wire Junctions (2003)

Molecular conductance junctions are structures in which single molecules or small groups of molecules conduct electrical current between two electrodes. In such junctions, the connection between the molecule and the electrodes greatly affects the current-voltage characteristics. Despite several experimental and theoretical advances, including the understanding of simple systems, there is still limited correspondence between experimental and theoretical studies of these systems.
Association of rheumatoid arthritis with an amino acid allelic variation of the T cell receptor. (1997)

OBJECTIVE: To investigate allelic variations of T cell receptor residues for a contribution to rheumatoid arthritis (RA) susceptibility. METHODS: We conducted an RA case-control study involving 1,579 northwest Europeans: 766 patients with erosive and rheumatoid factor-positive disease and 813 control subjects. Productive changes of segments TCRAV6S1, TCRAV7S1, TCRAV8S1, TCRAV10S2, and TCRBV6S1, TCRBV6S7 were investigated by single-strand conformation polymorphisms. The TCRAV8S1 association was confirmed by restriction fragment length polymorphism. RESULTS: In the systematic study (77 patients and 119 controls), an increase in 1 TCRAV8S1 genotype was found in the RA patients (P = 0.0004). This finding was replicated in 2 further populations, one from France (212 patients and 254 controls) and the other from Britain (477 patients and 440 controls), with a similar odds ratio (OR), which allowed pooling of the data and confirmation of the association (OR 1.3 [95% confidence interval 1.1-1.7], P = 0.008). CONCLUSION: These findings show evidence that TCRA is an RA susceptibility locus.
Electric field directed nucleic acid hybridization on microchips (1997)

Selection and adjustment of proper physical parameters enables rapid DNA transport, site selective concentration, and accelerated hybridization reactions to be carried out on active microelectronic arrays. These physical parameters include DC current, voltage, solution conductivity and buffer species. Generally, at any given current and voltage level, the transport or mobility of DNA is inversely proportional to electrolyte or buffer conductivity. However, only a subset of buffer species produce both rapid transport, site specific concentration and accelerated hybridization. These buffers include zwitterionic and low conductivity species such as: d- and l-histidine; 1- and 3-methylhistidines; carnosine; imidazole; pyridine; and collidine. In contrast, buffers such as glycine, beta-alanine and gamma-amino-butyric acid (GABA) produce rapid transport and site selective concentration but do not facilitate hybridization. Our results suggest that the ability of these buffers (histidine, etc.) to facilitate hybridization appears linked to their ability to provide electric field concentration of DNA; to buffer acidic conditions present at the anode; and in this process acquire a net positive charge which then shields or diminishes repulsion between the DNA strands, thus promoting hybridization.
Patterns of cytokine induction by gram-positive and gram-negative probiotic bacteria (2004)

Bacteria used in commercial probiotic preparations are most commonly gram-positive lactic acid-producing species, although there are also some probiotic products which utilise gram-negative coliform bacteria. Characterising how the innate immune system responds to these bacteria in vitro may give an indication as to the likely immunomodulatory events that can be triggered following probiotic administration in vivo. Here, an established gram-positive probiotic (Lactobacillus casei Shirota) was compared against a novel gram-negative probiotic strain (Escherichia coli Nissle 1917) for its ability to induce cytokine production in a cell type representative of the innate immune system; in addition, responses were contrasted against those induced by an enteropathogenic coliform, E. coli 2282. We investigated the ability of these three bacterial strains to modulate production of interleukins-10, -12 and -18; tumour necrosis factor-alpha; interferon-alpha; and transforming growth factor-beta, via a series of in vitro culture experiments involving the murine monocyte/macrophage cell line J774A.1. All bacteria induced marked secretion of IL-12 and TNFalpha by cells, while only coliforms induced production of IL-10; there was minimal or no induction of IL-18 or TGFbeta. Activation of cells with recombinant gamma-interferon promoted increased production of IL-12, but decreased production of IL-10, in response to the co-culture of coliform bacteria, indicating differential cytokine induction depending on the activation status of the target cell. In general, live bacteria stimulated higher levels of IL-10, IL-12 and TNFalpha secretion than heat-killed preparations, while only live coliforms induced IFNalpha. These findings are discussed in relation to the likely immunomodulatory effects of gram-positive and gram-negative bacteria on the innate immune system in vivo, with particular emphasis on the marked similarity in cytokine response patterns observed between probiotic versus pathogenic coliform bacteria.
Protein aggregation in amyotrophic lateral sclerosis (2013)

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the aggregation of ubiquitinated proteins in affected motor neurons. Recent studies have identified several new molecular constituents of ALS-linked cellular aggregates, including FUS, TDP-43, OPTN, UBQLN2 and the translational product of intronic repeats in the gene C9ORF72. Mutations in the genes encoding these proteins are found in a subgroup of ALS patients and segregate with disease in familial cases, indicating a causal relationship with disease pathogenesis. Furthermore, these proteins are often detected in aggregates of non-mutation carriers and those observed in other neurodegenerative disorders, supporting a widespread role in neuronal degeneration. The molecular characteristics and distribution of different types of protein aggregates in ALS can be linked to specific genetic alterations and shows a remarkable overlap hinting at a convergence of underlying cellular processes and pathological effects. Thus far, self-aggregating properties of prion-like domains, altered RNA granule formation and dysfunction of the protein quality control system have been suggested to contribute to protein aggregation in ALS. The precise pathological effects of protein aggregation remain largely unknown, but experimental evidence hints at both gain- and loss-of-function mechanisms. Here, we discuss recent advances in our understanding of the molecular make-up, formation, and mechanism-of-action of protein aggregates in ALS. Further insight into protein aggregation will not only deepen our understanding of ALS pathogenesis but also may provide novel avenues for therapeutic intervention.
ANTISENSE RNA-REGULATED PROGRAMMED CELL DEATH (1997)

Eubacterial plasmids and chromosomes encode multiple killer genes belonging to the hok gene family. The plasmid-encoded killer genes mediate plasmid stabilization by killing plasmid-free cells. This review describes the genetics, molecular biology, and evolution of the hok gene family. The complicated antisense RNA-regulated control-loop that regulates posttranscriptional and postsegregational activation of killer mRNA translation in plasmid-free cells is described in detail. Nucleotide covariations in the mRNAs reveal metastable stem-loop structures that are formed at the mRNA 5' ends in the nascent transcripts. The metastable structures prevent translation and antisense RNA binding during transcription. Coupled nucleotide covariations provide evidence for a phylogenetically conserved mRNA folding pathway that involves sequential dynamic RNA rearrangements. Our analyses have elucidated an intricate mechanism by which translation of an antisense RNA-regulated mRNA can be conditionally activated. The complex phylogenetic relationships of the plasmid- and chromosome-encoded systems are also presented and discussed.
Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer: AUA/SUO Guideline (2016)

The intensity and scope of care for NMIBC should focus on patient, disease, and treatment response characteristics. This guideline attempts to improve a clinician's ability to evaluate and treat each patient, but higher quality evidence in future trials will be essential to improve level of care for these patients.
Prediction of MYCN Amplification in Neuroblastoma Using Serum DNA and Real-Time Quantitative Polymerase Chain Reaction (2005)

Measurement of the serum M/N ratio seems to be a promising method for accurately assessing MYCN status in NB, although a larger set of patients needs to be examined to confirm this result.
Proposed FPGA Hardware Architecture for High Frame Rate (&#x226B;100 fps) Face Detection Using Feature Cascade Classifiers (2007)

Face detection is the first and most crucial step in any face recognition systems with applications to face tracking, recognition and automatic surveillance. AdaBoost based face detection training methods have been proposed for producing a rapidly fast detection implementation compared to other methods using the integral image for evaluating a series of weak classifiers very fast. Current software version implementations can achieve about 15-25 frames per second (fps) with a tunable compromise between detection accuracy and speed. In this paper, a novel hardware architecture design on FPGA based on AdaBoost face training and detection algorithm for detecting faces in high resolution images at high frame rates (>100 fps) is proposed. The proposed architecture can evaluate each sub-window in a single clock cycle, which is the fastest possible speed land is limited by the H/W clock running speed. Thus in this proposed approach, detection speed is independent from the number of weak classifiers implemented. The proposed architecture is verified on Xilinx Virtex-II Pro FPGA platform where experimental results show that the speed and memory outperform previous approaches in literature, achieving 143 fps for image size of 640 by 480 pixels using a single scan window. Parallelizing the scan window can lead to double/triple this speed and is dependent on the gate capacity of the FPGA.
Tamavidins – novel avidin‐like biotin‐binding proteins from the Tamogitake mushroom (2009)

Novel biotin-binding proteins, referred to herein as tamavidin 1 and tamavidin 2, were found in a basidiomycete fungus, Pleurotus cornucopiae, known as the Tamogitake mushroom. These are the first avidin-like proteins to be discovered in organisms other than birds and bacteria. Tamavidin 1 and tamavidin 2 have amino acid sequences with 31% and 36% identity, respectively, to avidin, and 47% and 48% identity, respectively, to streptavidin. Unlike any other biotin-binding proteins, tamavidin 1 and tamavidin 2 are expressed as soluble proteins at a high level in Escherichia coli. Recombinant tamavidin 2 was purified as a tetrameric protein in a single step by 2-iminobiotin affinity chromatography, with a yield of 5 mg per 100 mL culture of E. coli. The kinetic parameters measured by a BIAcore biosensor indicated that recombinant tamavidin 2 binds biotin with high affinity, in a similar manner to binding by avidin and streptavidin. The overall crystal structure of recombinant tamavidin 2 is similar to that of avidin and streptavidin. However, recombinant tamavidin 2 is immunologically distinct from avidin and streptavidin. Tamavidin 2 and streptavidin are very similar in terms of the arrangement of the residues interacting with biotin, but different with regard to the number of hydrogen bonds to biotin carboxylate. Recombinant tamavidin 2 is more stable than avidin and streptavidin at high temperature, and nonspecific binding to DNA and human serum by recombinant tamavidin 2 is lower than that for avidin. These findings highlight tamavidin 2 as a probable powerful tool, in addition to avidin and streptavidin, in numerous applications of biotin-binding proteins.
Replication efficiency of oncolytic vaccinia virus in cell cultures prognosticates the virulence and antitumor efficacy in mice (2011)

These data demonstrated that insertion of VACV promoter-driven transcriptional units into the viral genome for the purpose of insertional mutagenesis did modulate the efficiency of virus replication together with antitumor efficacy as well as virulence. Replication efficiency of oncolytic VACV in cell cultures can predict the virulence and therapeutic efficacy in nude mice. These findings may be essential for rational design of safe and potent VACV strains for vaccination and virotherapy of cancer in humans and animals.
Lab on a Chip for Live-Cell Manipulation (2007)

Precisely manipulating and sorting live cells on a lab on a chip is still a major challenge. This article shows how to use dielectrophoresis for cell sorting. The authors also describe a prototype CMOS chip with a sensor-actuator array, row-column addressing logic and readout circuitry. In this article, we examine the new microelectronic technology that gives scientists the ability to monitor, sort, and analyze vast populations of cells and interact with each cell individually. A microelectronic platform called a lab on a chip (LoC) allows precise manipulation of cells with no effect on their phenotypes. The motivation for developing this technology is that investigations in recent years have shown that a few cells changing their behavior unexpectedly can induce deadly diseases such as cancer. Current LoC design and manufacturing techniques are spawning new biotechnology methods with potential for research, diagnosis, and therapy.
Preventive Antibiotics in Stroke Study: Rationale and Protocol for a Randomised Trial (2010)

The primary end point will be functional outcome at a three-month follow-up on the modified Rankin Scale, dichotomised as a favourable outcome (0-2) or an unfavourable outcome (3-6). Secondary outcome measures will be death rate at discharge and three-months, infection rate during hospital admission, length of hospital admission, volume of poststroke care, use of antibiotics during the three-month follow-up, functional outcome using the full ordinal scoring range of the modified Rankin Scale, quality-adjusted life years and costs.