gebhart/patrepeval huggingface dataset:
Sequence specific cleavage of the HIV‐1 coreceptor CCR5 gene by a hammer‐head ribozyme and a DNA‐enzyme: inhibition of the coreceptor function by DNA‐enzyme (1998)

The chemokine receptor CCR5 is used as a major coreceptor for fusion and entry by non-syncytia inducing macrophage tropic isolates of HIV-1, which is mainly involved in transmission. Individuals who are homozygous for the delta32 allele of CCR5 are usually resistant to HIV-1 infection and continue to lead a normal healthy life. Thus this gene is dispensable and is, therefore, an attractive target in the host cell for interfering specifically with the virus-host interaction. With the aim to develop a specific antiviral approach at the molecular level, we have synthesized a hammer-head ribozyme and a DNA-enzyme. Both ribozyme and DNA-enzyme cleaved the CCR5 RNA in a sequence specific manner. This cleavage was protein independent but Mg2+ dependent. The extent of cleavage increased with increasing concentration of magnesium chloride. DNA-enzyme was more effective in cleaving a full length (1376 bases) in vitro generated transcript of CCR5 gene. In this communication, we show that the DNA-enzyme when introduced into a mammalian cell, results in decreased CD4-CCR5-gp160 mediated fusion of cell membranes. Potential applications of these trans acting molecules are discussed.
Reduced cerebrospinal fluid production and intracranial pressure in mice lacking choroid plexus water channel Aquaporin‐1 (2004)

Aquaporin-1 (AQP1) is a water channel expressed strongly at the ventricular-facing surface of choroid plexus epithelium. We developed novel methods to compare water permeability in isolated choroid plexus of wild-type vs. AQP1 null mice, as well as intracranial pressure (ICP) and cerebrospinal fluid (CSF) production and absorption. Osmotically induced water transport was rapid in choroid plexus from wild-type mice and reduced by fivefold by AQP1 deletion. AQP1 deletion did not affect choroid plexus size or structure. By stereotaxic puncture of the lateral ventricle with a microneedle, ICP was 9.5 +/- 1.4 cm H2O in wild-type mice and 4.2 +/- 0.4 cm H2O in AQP1 null mice. CSF production, an isosmolar fluid secretion process, was measured by a dye dilution method involving fluid collections using a second microneedle introduced into the cisterna magna. CSF production in wild-type mice was (in microl min(-1)) 0.37 +/- 0.04 (control), 0.16 +/- 0.03 (acetazolamide-treated), and 1.14 +/- 0.15 (forskolin-treated), and reduced by approximately 25% in AQP1 null mice. Pressure-dependent CSF outflow, measured from steady-state ICP at different ventricular infusion rates, was not affected by AQP1 deletion. In a model of focal brain injury, AQP1 null mice had remarkably reduced ICP and improved survival compared with wild-type mice. The reduced ICP and CSF production in AQP1 null mice provides direct functional evidence for the involvement of AQP1 in CSF dynamics, suggesting AQP1 inhibition as a novel option for therapy of elevated ICP.
Multifiber angular compounding optical coherence tomography for speckle reduction (2016)

We report on an integrated fiber optic design to implement multifiber angular compounding optical coherence tomography, which enables angular compounding for speckle reduction. A multi-facet fiber array delivers three light beams to the sample with different incident angles. Back-reflective/back-scattered signals from these channels were simultaneously detected by a three-channel spectrometer. The axial and lateral resolution was measured to be ∼3 and ∼3.5 μm, respectively, in air with ∼100 dB sensitivity. We conducted ex vivo experiments on a rat esophagus to demonstrate a contrast to noise improvement of 1.58.
Contraceptive vaccines (1993)

Three major approaches to contraceptive vaccine development are being pursued at the present time. The most advanced approach, which has already reached the stage of phase 2 clinical trials, involves the induction of immunity against human chorionic gonadotrophin (hCG). Vaccines are being engineered based on conjugates incorporating tetanus or diphtheria toxoid linked to a variety of hCG-based peptides centred on the beta-subunit of this molecule. Clinical trials have revealed that such preparations are capable of stimulating the production of anti-hCG antibodies. However, the long term consequences of such immunity in terms of safety or efficacy are, as yet, unknown. The alternative approaches to contraceptive vaccine development involve the induction of immunity against gamete-specific antigens found on the surface of the human spermatozoon or the zona pellucida. There is an abundance of experimental and clinical data to suggest that this approach is feasible although the biochemical characterization and synthesis of candidate antigens is still incomplete.
Cellulose Acetate Templates for Porous Inorganic Network Fabrication (2000)

Fast and simple methods for the preparation of porous metal oxide networks are reported here that use readily available cellulose acetate membranes in two procedures that are expected to be of general utility. ZrO2 and TiO2 films were produced of ca. 80 μm thickness, with large pore structures (several hundred nm). The porous structure of the films was shown by TEM and SEM (see Figure, TiO2) to resemble the initial membranes.
Detection of staphylococcal enterotoxins by enzyme-linked immunosorbent assays and radioimmunoassays: comparison of monoclonal and polyclonal antibody systems (1986)

Murine monoclonal antibodies reactive with at least one of the serological types of staphylococcal enterotoxin were examined for use in assay systems for the detection of enterotoxin at the level of 1.0 ng of enterotoxin per ml. An antibody sandwich enzyme-linked immunosorbent assay was devised for each toxin type by identifying an effective antibody pair. One antibody (the coating antibody) was coated onto a polystyrene plate and removed the enterotoxin from the test solution; the second antibody (the probing antibody) was conjugated to horseradish peroxidase and detected the captured toxin. Enterotoxins A and E could be detected in the same system by the use of cross-reacting monoclonal antibodies. All subtypes of enterotoxin C could be detected in one assay system. Two effective systems were described for each of types B and D. Each of these systems, when compared with the homologous enterotoxin-specific polyclonal rabbit antibody systems, was found to compare favorably. The monoclonal enzyme-linked immunosorbent assay systems for the detection of enterotoxins A and C2 were examined for a variety of food extracts; no abnormal interference could be detected from these extracts. The monoclonal antibody systems were also compared with the homologous enterotoxin-specific polyclonal serum for the detection of enterotoxin by the competitive radioimmunoassay (RIA). Single monoclonal antibodies generally did not perform as well in the RIA as did the homologous toxin-specific polyclonal serum. However, pools of monoclonal antibodies were prepared that approached the sensitivity and precision of the polyclonal system for the detection of each toxin by the RIA.
Increased Regulatory T-Cell Fraction Amidst a Diminished CD4 Compartment Explains Cellular Immune Defects in Patients with Malignant Glioma (2006)

Immunosuppression is frequently associated with malignancy and is particularly severe in patients with malignant glioma. Anergy and counterproductive shifts toward T(H)2 cytokine production are long-recognized T-cell defects in these patients whose etiology has remained elusive for >30 years. We show here that absolute counts of both CD4(+) T cells and CD4(+)CD25(+)FOXP3(+)CD45RO(+) T cells (T(regs)) are greatly diminished in patients with malignant glioma, but T(regs) frequently represent an increased fraction of the remaining CD4 compartment. This increased T(reg) fraction, despite reduced counts, correlates with and is sufficient to elicit the characteristic manifestations of impaired patient T-cell responsiveness in vitro. Furthermore, T(reg) removal eradicates T-cell proliferative defects and reverses T(H)2 cytokine shifts, allowing T cells from patients with malignant glioma to function in vitro at levels equivalent to those of normal, healthy controls. Such restored immune function may give license to physiologic antiglioma activity, as in vivo, T(reg) depletion proves permissive for spontaneous tumor rejection in a murine model of established intracranial glioma. These findings dramatically alter our understanding of depressed cellular immune function in patients with malignant glioma and advance a role for T(regs) in facilitating tumor immune evasion in the central nervous system.
Identification of differentially expressed prostate genes: Increased expression of transcription factor ETS-2 in prostate cancer (1997)

Our method can be used to identify quickly genes that are differentially expressed between benign and cancerous prostate cells. Transcription factors, such as ETS-2, may play a significant role in cancer progression.
Pegylated IL‐10 induces cancer immunity (2013)

Recently, the development of several strategies based on immunotherapy has raised hopes for a more promising way to treat cancer patients. Here, we describe how interleukin (IL)-10, a seemingly unlikely candidate, stimulates the immune system in a particularly efficacious way. IL-10, an omnipotent anti-inflammatory cytokine, delivers an equally potent immune stimulation in the context of CD8(+) T cells and tumor immunity. By activation of tumor-resident, tumor-specific CD8(+) T cells, pegylated IL-10 can induce rejection of large and metastasizing tumors in mice. Here, we summarize the mechanisms of action of IL-10, the reasons why the mechanisms may be crucial for the treatment of cancer patients, and the rationale for applying pegylated IL-10 in the clinic.
Targeting Aurora-2 kinase in cancer. (2003)

Aurora-2 kinase has been shown to contribute to oncogenic transformation and is frequently overexpressed and amplified in many human tumor types. Aurora-2 belongs to a small family of mitotic serine/threonine kinases that regulate centrosome maturation, chromosome segregation, and cytokinesis. The mechanism behind the transforming activity of aurora-2 is not fully understood; however, the role of aurora-2 in regulating the centrosome cycle is likely responsible for its ability to transform cells. Aurora-2 overexpression has been correlated with centrosome amplification, which can be a driving cause of genomic instability in tumor cells. In addition, recent work has demonstrated that aurora-2 plays an active function in promoting entry into mitosis by regulating local translation of centrosomal stored mRNA, such as cyclin B1. These recent findings implicate aurora-2 as an important regulator of both genomic integrity and cell cycle progression in cancer cells and suggest that aurora-2 is an attractive target for anticancer drug development.
Recombination of influenza A virus strains: effect on pathogenicity. (1976)

Influenza viruses can recombine genetic information, and progeny virus can be selected for desired genetic traits. A newly isolated strain can develop the ability to grow to higher titer in embryonated eggs by acquiring this trait from the AOPR8(HON1) strain, and can be selected by the terminal dilution technique and by treatment with anti-HON1 antisera. In addition to acquiring the ability to grow to high titer, surface antigens may also be transferred, and the progeny can be selected by immunologic methods. It appeared likely that other genes, including those coding for virulence or attenuation might also be exchanged during the recombination procedure. We explored this question by infecting mice with recent strains of H3N2 influenza virus, and with some of their progeny which had been selected for high virus yields from eggs, after recombination with the AOPR8(HON1) virus, a strain known to be virulent for mice. Influenza (H3N2) virus strains A/Scotland, A/Port Chalmers and A/England which were isolated and passaged in embryonated eggs did not cause death when administered intranasally to three-week-old Swiss mice; however, after recombination with the A/PR8(HON1) virus, these viruses become lethal in mice. This acquisition of virulence appears to be secondary to exchange of genetic information from the parent AOPR8 virus. Virus isolated from mice infected with these recombinants is antigenically H3N2, the mice develop anti-H3N2 antibodies.
Effects of pleural pressure and abdominal pressure on diaphragmatic blood flow (1985)

The aim of this experiment was to determine if blood flow to the diaphragm is affected by generating the transdiaphragmatic pressure mainly with positive abdominal pressure or mainly with negative pleural pressure, during both sustained and intermittent diaphragmatic contractions. Diaphragmatic blood flow was measured in anesthetized mongrel dogs by the radionuclide-labeled microsphere method. Sustained and intermittent tetanic diaphragmatic contractions were produced with 1) free abdomen and closed chest (high negative pleural pressure) and 2) bound abdomen and open chest (high positive abdominal pressure). During sustained contractions, diaphragmatic blood flow at maximum levels of activation was significantly higher with negative pleural pressure (P less than 0.05). In contrast with this, intermittent diaphragmatic contractions did not yield a significant difference between diaphragmatic blood flow with negative pleural pressure and with positive abdominal pressure at maximal levels of transdiaphragmatic pressure. During both sustained and intermittent contractions, blood pressure, as measured from the carotid artery, did not vary significantly between negative pleural pressure and positive abdominal pressure. We conclude that during sustained tetanic diaphragmatic contractions, diaphragmatic blood flow is obstructed by high positive abdominal pressures, but during intermittent diaphragmatic contractions, high positive abdominal pressures do not affect total blood flow, since any inhibition of blood flow during the contractile period can be compensated for during the relaxation period between contractions.
Lasofoxitene: A new type of selective estrogen receptor modulatorfor the treatment of osteoporosis (2006)

Selective estrogen receptor modulators (SERMs) are structurally different compounds that interact with intracellular estrogen receptors in target organs as estrogen agonists and antagonists. Thus far SERMs have proven to be a highly versatile group and are being evaluated primarily for conditions associated with aging, including hormone-responsive cancer and osteoporosis. Tamoxifen and toremifene are currently used to treat advanced breast cancer and also have beneficial effects on bone mineral density and serum lipids in postmenopausal women. Raloxifene is the only SERM compound actually approved worldwide for the prevention and treatment of postmenopausal osteoporosis and fragility fractures. Unfortunately, although these SERMs possess many benefits, they are also responsible for some very serious side effects, such as thromboembolic disorders and, in the case of tamoxifen, uterine cancer. These contraindications represent a major concern for the type of long-term, chronic therapy that is required to prevent osteoporosis. Moreover, both preclinical and clinical reports suggest that these SERMs are considerably less potent than estrogen, probably due to their reduced bioavailability. Lasofoxifene (CP 336,156) is a naphthalene-derivative, third-generation SERM, structurally distinct from the first- and second-generation SERMs. This compound selectively binds to both estrogen receptor subtypes (estrogen receptor-alpha or -beta) with high affinity. It has a half-inhibition concentration similar to that seen with estradiol and thus at least 10-fold higher than those reported for raloxifene and tamoxifen. Moreover, due to increased resistance to intestinal wall glucuronidation, lasofoxifene has a remarkably improved oral bioavailability with respect to other SERMs. In both preclinical and short-term clinical studies lasofoxifene has shown a proven efficacy in preventing bone loss and lowering cholesterol levels. Dose modeling from phase II studies allowed the selection of lasofoxifene 0.25 mg/day as the lowest fully effective dose. The compound shows a favorable safety profile and is currently in phase III development for the prevention and treatment of osteoporosis in postmenopausal women.
Official Netscape JavaScript (1996)

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Oral administration of psk can improve the impaired anti‐tumor CD4 T‐cell response in gut‐associated lymphoid tissue (GALT) of specific‐pathogen‐free mice (1997)

We investigated both the effect and the mechanism of oral (p.o.) administration of PSK, a protein-bound polysaccharide derived from Bosidiomycetes, on the anti-tumor T-cell response in gut-associated lymphoid tissue (GALT). The p.o. administration of PSK significantly suppressed the growth of colon 26 carcinoma (C-26) inoculated into the subserosal space of the cecum (i.c.), and augmented the tumor-neutralizing activity of the draining mesenteric lymph node (LN) cells. PSK treatment also significantly decreased the levels of immunosuppressive factors such as plasma transforming growth factor (TGF)-β in the i.c. C-26-inoculated mice. We also evaluated the improving effect of PSK on the anti-tumor T-cell response in GALT by utilizing B7-transfected P815 mastocytoma (B7/P815). The PSK treatment promoted the rejection of i.c.-inoculated B7/P815 and restored the CD4+ T-cell-dependent proliferative response of the draining mesenteric LN cells against in vitro restimulation. Furthermore, the treatment also decreased the TGF-β production but increased the IFN-γ production of these cells. The p.o. administration of PSK, however, showed no effect in the CD8+ T-cell-dependent cytolytic activity of the draining mesenteric LN cells after in vitro restimulation. Overall, these results indicate that the p.o. administration of PSK can improve the impaired anti-tumor CD4+ T-cell response in GALT, mainly through a suppression of TGF-β production and a restoration of IFNγ-production. Int. J. Cancer, 70:362–372, 1997. © 1997 Wiley-Liss, Inc.
TRANSMEMBRANE SIGNALLING VIA THE T CELL ANTIGEN RECEPTOR HETERODIMER AND THE CD2 ANTIGEN (1989)

T cell surface proteins involved in transmembrane signalling resulting in the activation of T cells were investigated utilizing as probes monoclonal antibodies directed at T cell surface antigens. Here we report that mAbs that react with a framework determinant of alpha/beta heterodimer of T cell receptor for antigen, anti-TCR-1, and those with the SRBC-binding epitope of the CD2 antigen, OKT11, are synergistic in promoting T cell proliferation. The proliferative response is dependent upon crosslinking of anti-TCR-1 and OKT11, and is associated with a significant increase in the concentration of intracellular free calcium in T cells. Moreover, EGTA and a direct (staurosporine) or a competitive (1-[5-isoquinolinylsulfonyl]-2-methyl piperazine) inhibitor of protein kinase C prevents T cell proliferation accomplished with crosslinked anti-TCR-1 and OKT11. Our findings, in addition to demonstrating the synergism between the signals initiated via the T cell receptor for antigen and the CD2 antigen, suggest a role for calcium and protein kinase C in the transduction of signals generated with crosslinked anti-TCR-1 and OKT11.
Actual Financial Comparison of Four Strategies to Evaluate Patients with Potential Acute Coronary Syndromes (2008)

Compared to the other strategies, immediate CTA was as safe, identified as many patients with CAD, had the lowest cost, had the shortest LOS, and allowed discharge for the majority of patients. Larger prospective studies should confirm safety before immediate CTA replaces other strategies to rule out possible ACS.
InDrops and Drop-seq technologies for single-cell sequencing (2017)

Droplet-based single-cell sequencing pioneers Allon Klein and Evan Macosko summarise the growth of the technology and look ahead to future developments.
Association of Mutations in a Lysosomal Protein with Classical Late-Infantile Neuronal Ceroid Lipofuscinosis (1997)

Classical late-infantile neuronal ceroid lipofuscinosis (LINCL) is a fatal neurodegenerative disease whose defective gene has remained elusive. A molecular basis for LINCL was determined with an approach applicable to other lysosomal storage diseases. When the mannose 6-phosphate modification of newly synthesized lysosomal enzymes was used as an affinity marker, a single protein was identified that is absent in LINCL. Sequence comparisons suggest that this protein is a pepstatin-insensitive lysosomal peptidase, and a corresponding enzymatic activity was deficient in LINCL autopsy specimens. Mutations in the gene encoding this protein were identified in LINCL patients but not in normal controls.
A New High-Frequency Magnetic Stimulator with an Oil-Cooled Coil (1995)

A new high frequency magnetic stimulator, Labmag, is described which may be used in clinical neurophysiology and for the treatment of spasticity in multiple sclerosis. In order to avoid heating of the coil during repetitive stimulation, an oil/air cooling system was employed. The magnetic stimulus waveform is a half cosine with a rise time of 200 microseconds and a pulse width of 400 microseconds induced by alternating capacitor voltage. The Labmag product was compared with a commercially available high frequency stimulator, MagPro. The electric fields induced by Labmag were half the size of those induced by MagPro at identical stimulus intensities. Using a leaky integrator to simulate the effects on neurons, only minor differences in integrated electric fields were observed. There were no changes of the electric fields in relation to coil geometry. A minor difference in electric fields (1.0 +/- 0.8%) was observed when the polarity of the capacitor voltage alternated. Compound muscle action potentials (CMAPs) evoked by transcranial magnetic stimulation were recorded from the first dorsal interosseous muscle (FDI) in eight subjects. Threshold intensities of CMAPs evoked by Labmag (58 +/- 7%) were significantly smaller (p < 0.05) than threshold intensities obtained with MagPro (63 +/- 8%). Peak-to-peak amplitudes, P-Pamps, of CMAPs were significantly smaller after single stimulations with Labmag at stimulation intensities of 130 and 140% of threshold intensity.
Postinfection control in T4 bacteriophage infection: inhibition of the rep function (1981)

We suggest that the general mechanism by which T4 phage turns off host macromolecular synthesis involves specific phage proteins which react with key components in the synthetic pathway. Support for this mechanism exists for the inhibition of host RNA synthesis. Here we note that the host rep function was inhibited after T4 phage infection. Since rep functions are known to be involved in host DNA replication, inhibition of rep might alter the course of host DNA replication.