gebhart/patrepeval huggingface dataset:
Specific inhibition of human immunodeficiency virus type 1 replication by antisense oligonucleotides: an in vitro model for treatment. (1992)

We have developed a culture system, simulating in vivo conditions of human immunodeficiency virus type 1 (HIV-1) infection, to evaluate the long-term efficacy of antisense oligonucleotide treatment. Five oligonucleotide phosphorothioates (28-mers), complementary to different regions of HIV-1 RNA, blocked replication of the virus in a sequence-specific manner at 1 microM concentration. Variations in antiviral activity were seen among the different oligonucleotides, revealing an effect of target selection. Mismatched or random oligonucleotide phosphorothioates delayed, but did not completely inhibit, HIV-1 replication. In the case of inhibition by a splice-acceptor-site antisense oligodeoxynucleotide, a break-through phenomenon occurred after 25 days of treatment, suggesting the development of an "escape mutant." This result did not occur when the inhibitory oligodeoxynucleotides were complementary to the primary-sequence areas of the rev-responsive element and rev-1 genes. Sequential treatment of HIV-1-infected cells with a combination of different antisense oligonucleotides, each administered once, also prevented the development of escape mutants. Our results suggest that chemotherapy based on specifically targeted antisense-oligonucleotide phosphorothioates may be an effective method for reducing the viral burden in HIV-1-infected individuals at clinically achievable oligonucleotide concentrations.
[Progress in biostatistics correlated with the development of computer technics]. (1990)

The development of computers has positively influenced both Biostatistics and Medical Informatics. Close cooperation between Physicians, Biostatisticians and Experts of Medical Informatics is necessary. The leading role has to play the medical question, the medical problem to be solved, and not one of the cooperating disciplines. Both Biostatistics and Medical Informatics are parts of Medicine and must therefore taught as natural-scientific basic discipline of Medicine.
Structural Basis of Pilus Subunit Recognition by the PaPd Chaperone (1993)

The assembly of different types of virulence-associated surface fibers called pili in Gram-negative bacteria requires periplasmic chaperones. PapD is the prototype member of the periplasmic chaperone family, and the structural basis of its interactions with pilus subunits was investigated. Peptides corresponding to the carboxyl terminus of pilus subunits bound PapD and blocked the ability of PapD to bind to the pilus adhesin PapG in vitro. The crystal structure of PapD complexed to the PapG carboxyl-terminal peptide was determined to 3.0 A resolution. The peptide bound in an extended conformation with its carboxyl terminus anchored in the interdomain cleft of the chaperone via hydrogen bonds to invariant chaperone residues Arg8 and Lys112. Main chain hydrogen bonds and contacts between hydrophobic residues in the peptide and the chaperone stabilized the complex and may play a role in determining binding specificity. Site-directed mutations in Arg8 and Lys112 abolished the ability of PapD to bind pilus subunits and mediate pilus assembly in vivo, an indication that the PapD-peptide crystal structure is a reflection of at least part of the PapD-subunit interaction.
DE- AND RE-GENERATION OF CHLOROPLASTS IN THE CELLS OF <italic>CHLORELLA PROTOTHECOIDES</italic><subtitle>II. EFFECTS OF ACTINOMYCIN ON GREENING OF “GLUCOSE-BLEACHED” AND “ETIOLATED” ALGAL CELLS</subtitle> (1964)

The “glucose-bleached” and “etiolated” cells of Chlorella protothecoides having plastids of different degrees of degeneration were prepared by the methods previously reported, and the effects of actinomycin (C complex) upon the processes of greening of these cells were investigated under various experimental conditions. As has been shown previously, these cells formed normal chloroplasts on being incubated in the light with provision of nitrogen source (urea), but without glucose. The greening process of the glucose-bleached cells has been found to differ from that of the etiolated cells in the point that it involves a light-independent phase preceding a light-requiring phase. It was revealed that the greening of glucose-bleached cells is inhibited by actinomycin much more strongly than that of etiolated cells. On applying the antibiotic at different times during the chloroplast development in glucose-bleached cells, it was found that the inhibitory effect was remarkably reduced with the progress of the developmental process. This indicated that the antibiotic attacked more strongly the light-independent phase than the light-requiring phase in question. Based on these observations it was inferred that, in the process of chloroplast development in glucose-bleached cells, DNA and RNA are playing important roles, especially during the early light-independent phase of chloroplast development.
Tetramer of a 21-base pair synthetic element confers seed expression and transcriptional enhancement in response to water stress and abscisic acid. (1991)

A conserved 21-base pair element, designated as hex-1, located between -180 and -160 of the wheat histone H3 promoter, is known to interact with two tobacco nuclear factors, activating sequence factor 1 and hex-1-specific binding factor. We have shown previously that a mutant sequence (hex-3), which differs from hex-1 by three base pairs, can no longer bind these two factors significantly. In the present work, we examined the functional characteristics of these two sequences in transgenic tobacco. Surprisingly, we found that a tetramer of hex-3, but not of hex-1, confers high level expression in mature seeds. Expression of this synthetic promoter rapidly diminishes upon germination but can be reactivated in young seedlings and mature leaves by desiccation, NaCl, or the phytohormone abscisic acid (ABA). Treatment with auxin or cytokinin has no apparent effect on the expression. Since the endogenous ABA level of plant cells is known to increase upon water stress, our data suggest that hex-3, the mutated hex-1 sequence, is an abscisic acid-responsive element (abre). We propose that a tobacco nuclear factor, distinct from activating sequence factor 1 and hex-1-specific binding factor, interacts with this sequence and is involved in mediating the effects of ABA and water stress on gene expression.
A mutant α‐amylase with enhanced activity specific for short substrates (1992)

The 210th lysine (K210) at the active site in Saccharomycopsis fibuligera alpha-amylase was altered to arginine (R) or asparagine (N) by site-directed mutagenesis. Replacement of K210 by R strengthened the 7th and weakened the 8th subsite affinities. K210 was found to contribute to both the 8th and the 7th subsites. The catalytic activity of the K210R enzyme for the hydrolysis of maltose (G2) was three-times higher than that of the native enzyme due to an increase in the affinity of the 7th subsite adjacent to the catalytic site, whereas the activity of the K210N enzyme for G2 was decreased to 1% of that of the native enzyme by a reduction in the 7th subsite affinity.
Microstrip conductor loss models for electromagnetic analysis (2003)

This paper describes and rigorously validates single- and multiple-layer models of microstrip conductor loss appropriate for high-accuracy application in electromagnetic analysis software. The models are validated by comparison with measurement and by comparison with converged results. It is shown that in some cases an extremely small cell size is needed in order to achieve convergence. Several effects that make a significant contribution to loss and are not modeled by the classic square root of frequency loss model are investigated including dispersion and current on the side of transmission lines. Finally, the counterintuitive result that there is an optimum metal thickness for minimum planar conductor loss is explored.
Morphologic and biochemical studies of canine mucopolysaccharidosis I. (1984)

This report presents the necropsy and biochemical findings on the first dog to die with alpha-L-iduronidase deficiency (mucopolysaccharidosis I, MPS I). Gross pathologic features, light- and electron-microscopic findings, and tissue enzyme, glycosaminoglycan (GAG), and sphingolipid levels are compared with the human disease counterpart and the previously described feline model. Results lend further support for the similarities of the canine disease and human MPS I.
International Journal of Business and Management, Vol. 4, No. 12, December 2009, all in one PDF file (2009)

The European Community Regulation No. 1606No. /2002
High-Frequency Spectrophotometric Measurements of Total Dissolved Inorganic Carbon in Seawater (2013)

A new spectrophotometric method was developed to achieve continuous measurements of total dissolved inorganic carbon (DIC) in seawater. It uses a countercurrent flow design and a highly CO2-permeable membrane (Teflon AF 2400) to achieve flow-through CO2 equilibration between an acidified sample and an indicator solution with a fast response time of ~22 s. This method improves the spatiotemporal resolution by more than 1 order of magnitude compared to the existing spectrophotometric method. The flow-through equilibration allows for continuous (~1 Hz) detection and real-time data smoothing. The method had a short-term precision of ± 2.0 μmol kg(-1) for a given flow-through sample. It achieved a field precision of ± 3.6 μmol kg(-1) and successfully captured high DIC variability down to minute scales. Measurements by the new method over the typical range of oceanic DIC showed good agreement with measurements made by an established method (mean differences -1.6 to 0.3 μmol kg(-1) with 1σ ± 6.0-6.7 μmol kg(-1)). This level of precision and accuracy is comparable to that of the existing spectrophotometric method. The characteristics of the new method make it particularly suitable for high-frequency, submerged measurements required for mobile observing platforms in the ocean. It can also be adapted for high-frequency, spectrophotometric measurements of seawater CO2 fugacity.
Combination Therapy for the Treatment and Prevention of Hepatic Encephalopathy (2012)

The evidence evaluating the use of combination therapy for the treatment of HE does not support its widespread use. The combination of rifaximin and lactulose may be considered in the treatment of HE and in patients refractory to monotherapy. The combination of rifaximin and lactulose should be considered for the prevention of HE, especially after the second episode of HE recurrence.
Exploring Children's Ideas about the Holocaust (2013)

Pupils arrive with preconceptions about the Holocaust. This research note explains the nature of the research that I intend to carry out looking at the ideas that pupils arrive with when they first study the Holocaust in secondary school History lessons.
Brief Report (2015)

Vascular endothelial growth factor (VEGF) plays an important role in Kaposi's sarcoma (KS). We administered PTC299, a post-transcriptional inhibitor of pathogenic VEGF, to persons with HIV-related KS. Seventeen participants received 3 different doses of PTC299. Adverse events typically observed with VEGF inhibition were absent. Three participants had partial tumor responses and 11 had stable disease. There were no differences in exposure to PTC299 by antiretroviral regimen. Serum VEGF, but not KS-associated herpesvirus DNA, decreased on treatment. Given redundancies in the VEGF feedback loop, future trials should consider combining PTC299 with agents that inhibit different pathways implicated in KS and KS-associated herpesvirus proliferation.
Expression and Functional Importance of Collagen-Binding Integrins, α1β1 and α2β1, on Virus-Activated T Cells (2003)

Adhesive interactions are crucial to cell migration into inflammatory sites. Using murine lymphocytic choriomeningitis virus as an Ag model system, we have investigated expression and function of collagen-binding integrins, alpha(1)beta(1) and alpha(2)beta(1), on activated and memory T cells. Using this system and MHC tetramers to define Ag-specific T cells, we demonstrate that contrary to being VLAs, expression of alpha(1)beta(1) and alpha(2)beta(1) can be rapidly induced on acutely activated T cells, that expression of alpha(1)beta(1) remains elevated on memory T cells, and that expression of alpha(1)beta(1) parallels that of viral-specific effector CD8(+) T cells (defined by tetramer and IFN-gamma staining). In an adoptive transfer model, mAb-mediated blockade of these integrins on activated effector and memory T cells inhibited Ag-specific delayed-type hypersensitivity responses; similar decreased responses were seen upon transfer of alpha(1)-deficient activated/memory T cells. Thus, expression of alpha(1)beta(1) and alpha(2)beta(1) integrins on activated T cells is directly functionally important for generation of inflammatory responses within tissues. Finally, the inhibitory effect of alpha(1)beta(1) blockade on the delayed-type hypersensitivity response could be bypassed by direct injection of Ag-specific T cells to inflammatory sites, demonstrating for the first time in vivo that collagen-binding integrins are involved in leukocyte migration into tissues.
Attenuation of collagen-induced arthritis in 55-kDa TNF receptor type 1 (TNFR1)-IgG1-treated and TNFR1-deficient mice (1996)

The role of TNF and its type 1 receptor (TNFR1) in the pathogenesis of collagen-induced arthritis (CIA) was investigated in mice using two approaches. First, DBA/1 mice were treated after immunization with type II collagen by injecting TNFR1-IgG1 fusion protein to neutralize systemic TNF. CIA was prevented when treatment was administered shortly before the onset of clinical disease, suggesting that TNF is a crucial mediator in the late initiation phase of the arthritic process. In a second approach, TNFR1-deficient mice, generated by gene targeting and crossed to DBA/1, were used. These mice developed CIA with a low incidence and in a milder form. However, once a joint was afflicted, the disease progressed in this joint to the same end stage as that in wild-type mice. These data suggest that TNFR1 is the main transducer of TNF proinflammatory effects establishing CIA, but the progression of arthritis to tissue destruction and ankylosis is independent of TNFR1.
The La antigen is over-expressed in lung cancer and is a selective dead cancer cell target for radioimmunotherapy using the La-specific antibody APOMAB® (2014)

The La antigen represents a dead cancer cell-specific target in lung cancer, and DAB4 specifically targeted tumour tissue in vivo, particularly after chemotherapy. Tumour uptake of DAB4 increased further after the combination of PARPi and chemotherapy, which generated new dead tumour cell-binding targets. Consequently, combining 177Lu-DAB4 with PARPi and chemotherapy produced the greatest anti-tumour response. Therefore, the triple combination of PARPi, chemotherapy and RIT may have broad clinical utility.
Adenovirus–Mediated Cd40 Ligand Gene Therapy in A Rat Model of Orthotopic Hepatocellular Carcinoma (2001)

Unresectable hepatocellular carcinoma (HCC) lacks effective therapy and entails very poor prognosis. In this study, we have explored a gene-therapeutic approach to stimulate antitumor immunity by adenoviral-mediated transfer of CD40 ligand to treat HCC in rats. In vitro infection of a rat HCC cell line (McA-RH7777) with adenoviral vector expressing CD40 ligand (AdCMVmCD40L) induced CD40L expression in a dose-dependent manner. Expression of CD40L in McA-RH7777 cells did not alter their growth rate in vitro, but it abrogated their tumorigenicity when CD40L-expressing cells were implanted into the liver of syngenic Buffalo rats. In vivo gene therapy of established orthotopic HCC nodules (6.5 mm in diameter) in Buffalo rats by intratumor injection of AdCMVmCD40L vector led to complete tumor eradication and long-term survival in 69.5% of treated animals. Therapy with AdCMVmCD40L induced strong lymphocytic infiltration of the tumoral tissue and increased apoptosis of malignant cells. The observed antitumoral effect was mediated by CD8(+) T cells and was associated with increased interleukin (IL)-12 serum levels and enhanced natural killer (NK) activity. Animals that eliminated the tumor after in vivo gene therapy developed protective antitumor immunity being resistant to rechallenge with neoplastic cells. Toxicity of the therapy with AdCMVmCD40L was slight, with only a transient increase in the level of serum transaminases and minor lymphocyte infiltration of normal liver tissue. These data demonstrate that intratumoral administration of AdCMVmCD40L may provide an efficient and safe treatment for HCC.
Theoretical study of electrolyte gate AlGaN∕GaN field effect transistors (2005)

We predict the sensitivity of solution gate AlGaN∕GaN field effect transistors to pH values of the electrolyte and to charged adsorbates at the semiconductor–electrolyte interface. Invoking the site-binding model for the chemical reactions at the oxidic semiconductor–electrolyte interface and taking into account the large polarization fields within the nitride heterostructure, the spatial charge and potential distribution have been calculated self-consistently both in the semiconductor and the electrolyte. In addition, the source–drain current is calculated and its sensitivity to the electrolyte’s pH value is studied systematically. Comparison with experiment shows good agreement. A significantly enhanced resolution is predicted for AlGaN∕GaN structures of N-face polarity.
Human bone marrow‐derived mesenchymal stem cells induce Th2‐polarized immune response and promote endogenous repair in animal models of multiple sclerosis (2009)

Cell-based therapies are attractive approaches to promote myelin repair. Recent studies demonstrated a reduction in disease burden in mice with experimental allergic encephalomyelitis (EAE) treated with mouse mesenchymal stem cells (MSCs). Here, we demonstrated human bone marrow-derived MSCs (BM-hMSCs) promote functional recovery in both chronic and relapsing-remitting models of mouse EAE, traced their migration into the injured CNS and assayed their ability to modulate disease progression and the host immune response. Injected BM-hMSCs accumulated in the CNS, reduced the extent of damage and increased oligodendrocyte lineage cells in lesion areas. The increase in oligodendrocytes in lesions may reflect BM-hMSC-induced changes in neural fate determination, since neurospheres from treated animals gave rise to more oligodendrocytes and less astrocytes than nontreated neurospheres. Host immune responses were also influenced by BM-hMSCs. Inflammatory T-cells including interferon gamma producing Th1 cells and IL-17 producing Th17 inflammatory cells and their associated cytokines were reduced along with concomitant increases in IL-4 producing Th2 cells and anti-inflammatory cytokines. Together, these data suggest that the BM-hMSCs represent a viable option for therapeutic approaches.
Identification and Disruption of lisRK , a Genetic Locus Encoding a Two-Component Signal Transduction System Involved in Stress Tolerance and Virulence in Listeria monocytogenes (1999)

lisRK encodes a two-component regulatory system in the food pathogen Listeria monocytogenes LO28. Following identification of the operon in an acid-tolerant Tn917 mutant, a deletion in the histidine kinase component was shown to result in a growth phase variation in acid tolerance, an ability to grow in high ethanol concentrations, and a significant reduction in virulence.
Coupling of the Amide I Modes of the Glycine Dipeptide (2002)

Abstract Several approaches to calculate the coupling between the two amide I modes of the glycine dipeptide are compared. The full (φ, ψ) conformational space of the molecule is explored, and conditions for the validity of the different approaches are discussed.
Introduction to Macromolecular Binding Equilibria (2007)

Macromolecules in the body form noncovalent associations, such as DNA-protein or protein-protein complexes, that control and regulate numerous cellular functions. Understanding how changes in the concentration and conformation of these macromolecules can trigger physiological responses is essential for researchers developing drug therapies to treat
Investigation of mode coupling in normal-dispersion silicon nitride microresonators for Kerr frequency comb generation (2014)

Kerr frequency combs generated from microresonators are the subject of intense study. Most research employs microresonators with anomalous dispersion, for which modulation instability is believed to play a key role in initiation of the comb. Comb generation in normal dispersion microresonators has also been reported but is less well understood. Here we report a detailed investigation of few-moded, normal dispersion silicon nitride microresonators, showing that mode coupling can strongly modify the local dispersion, even changing its sign. We demonstrate a link between mode coupling and initiation of comb generation by showing experimentally, for the first time to our knowledge, pinning of one of the initial comb sidebands near a mode crossing frequency. Associated with this route to comb formation, we observe direct generation of coherent, bandwidth-limited pulses at repetition rates down to 75 GHz, without the need to first pass through a chaotic state.
Familial discrepancy between the one‐stage and two‐stage factor VIII methods in a subgroup of patients with haemophilia A (1994)

A higher result for plasma factor VIII:C measured by the one-stage as compared with the two-stage method has been described in some patients with haemophilia A or with von Willebrand's disorder. We used both methods to measure FVIII:C in 95 patients with haemophilia A. The results were equivalent in all 21 patients with severe haemophilia (16 families) and in 45 of the patients with mild or moderate haemophilia (18 families). However, the results were discrepant (FVIII:C by one-stage assay 2-7-fold higher than by two-stage assay) in the other 29 patients with mild or moderate haemophilia (12 other families). For each patient with discrepant FVIII:C results the classification was the same for all other affected members of his family. In some families with haemophilia A the gene defect leads to a discrepancy between the one-stage and two-stage FVIII:C results and may be more widespread than previously recognized.
MAKING ANALLY FROM ANENEMY: Plant Virology and the New Agriculture (2002)

Historically, the study of plant viruses has contributed greatly to the elucidation of eukaryotic biology. Recently, concurrent with the development of viruses into expression vectors, the biotechnology industry has developed an increasing number of disease therapies utilizing recombinant proteins. Plant virus vectors are viewed as a viable option for recombinant protein production. Employing pathogens in the process of creating added value to agriculture is, in effect, making an ally from an enemy. This review discusses the development and use of viruses as expression vectors, with special emphasis on (+) strand RNA virus systems. Further, the use of virus expression vectors in large-scale agricultural settings to produce recombinant proteins is described, and the technical challenges that need to be addressed by agriculturists and molecular virologists to fully realize the potential of this latest evolution of plant science are outlined.