gebhart/patrepeval huggingface dataset:
Binding and Crosslinking of 125I-Labeled Recombinant Human Tumor Necrosis Factor to Cell Surface Receptors1 (1986)

Highly purified recombinant human tumor necrosis factor (TNF) (molecular mass determined as 17 kilodaltons (kDa) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and as 36 kDa by Sephadex G-100 gel chromatography) was labeled with 125I to a specific activity of 5 microCi/micrograms without appreciable loss of activity. The binding of 125I-TNF to eighteen human and twelve animal cell lines was examined. The binding varied considerably among different cell lines. In most cell lines, the binding was inhibited up to greater than 90% by the addition of a 100-fold excess of unlabeled TNF. Some human and mouse cell lines showed no significant binding above background levels, suggesting that these cell lines had no receptors for TNF. Among the TNF receptor-positive cell lines, there was no direct correlation between the level of specific TNF binding and the level of sensitivity to the cytotoxic or cytostatic effect of TNF. Some cell lines were sensitive to TNF, whereas others were not affected at all by TNF. The TNF receptor-negative cell lines were also resistant to TNF. Therefore, although the existence of TNF receptor seems to be necessary, it does not alone determine cellular sensitivity to TNF. Scatchard analysis of the binding data revealed that human HeLa S3 and THP-1 had about 50,000 and 10,000 receptors/cell with a dissociation constant (KD) of 0.3-0.5 nM, respectively. Similarly, mouse L-929 and L-M cells had about 5,000 receptors/cell with KD of 3-5 nM. 125I-TNF bound to HeLa S3 cells was rapidly internalized at 37 degrees C, presumably by receptor-mediated endocytosis, and degraded to acid-soluble products. The turnover of TNF receptors on HeLA S3 cells seemed to be rapid, since the level of specific binding quickly decreased after treatment with 100 micrograms/ml of cycloheximide at 37 degrees C with a half-life of about 1.5 h. The crosslinking of the cell-bound 125I-TNF with the use of disuccinimidyl suberate yielded a complex of 105 kDa for HeLa S3 and THP-1 cells, and a complex of 100 kDa for U937 cells. The crosslinking was completely inhibited by the addition of a 100-fold excess of unlabeled TNF. Assuming that the complex was due to a one-to-one association of the dimeric form of TNF (34 kDa) with the receptor, we estimated the molecular size of the human TNF receptor to be 71 kDa for HeLa S3 and THP-1, and 66 kDa for U937.
Costameres are sites of force transmission to the substratum in adult rat cardiomyocytes. (1992)

Costameres, the vinculin-rich, sub-membranous transverse ribs found in many skeletal and cardiac muscle cells (Pardo, J. V., J. D. Siciliano, and S. W. Craig. 1983. Proc. Natl. Acad. Sci. USA. 80:363-367.) are thought to anchor the Z-lines of the myofibrils to the sarcolemma. In addition, it has been postulated that costameres provide mechanical linkage between the cells' internal contractile machinery and the extracellular matrix, but direct evidence for this supposition has been lacking. By combining the flexible silicone rubber substratum technique (Harris, A. K., P. Wild, and D. Stopak. 1980. Science (Wash. DC). 208:177-179.) with the microinjection of fluorescently labeled vinculin and alpha-actinin, we have been able to correlate the distribution of costameres in adult rat cardiac myocytes with the pattern of forces these cells exert on the flexible substratum. In addition, we used interference reflection microscopy to identify areas of the cells which are in close contact to the underlying substratum. Our results indicate that, in older cell cultures, costameres can transmit forces to the extracellular environment. We base this conclusion on the following observations: (a) adult rat heart cells, cultured on the silicone rubber substratum for 8 or more days, produce pleat-like wrinkles during contraction, which diminish or disappear during relaxation; (b) the pleat-like wrinkles form between adjacent alpha-actinin-positive Z-lines; (c) the presence of pleat-like wrinkles is always associated with a periodic, "costameric" distribution of vinculin in the areas where the pleats form; and (d) a banded or periodic pattern of dark gray or close contacts (as determined by interference reflection microscopy) has been observed in many cells which have been in culture for eight or more days, and these close contacts contain vinculin. A surprising finding is that vinculin can be found in a costameric pattern in cells which are contracting, but not producing pleat-like wrinkles in the substratum. This suggests that additional proteins or posttranslational modifications of known costamere proteins are necessary to form a continuous linkage between the myofibrils and the extracellular matrix. These results confirm the hypothesis that costameres mechanically link the myofibrils to the extracellular matrix. We put forth the hypothesis that costameres are composite structures, made up of many protein components; some of these components function primarily to anchor myofibrils to the sarcolemma, while others form transmembrane linkages to the extracellular matrix.
DNA Priming-Protein Boosting Enhances Both Antigen-Specific Antibody and Th1-Type Cellular Immune Responses in a Murine Herpes Simplex Virus-2 gD Vaccine Model (1999)

It has previously been reported that herpes simplex virus (HSV)-2 gD DNA vaccine preferentially induces T-helper (Th) 1-type cellular immune responses, whereas the literature supports the view that subunit vaccines tend to induce potent antibody responses, supporting a Th2 bias. Here, using an HSV gD vaccine model, we investigated whether priming and boosting with a DNA or protein vaccine could induce both potent antibody and Th1-type cellular immune responses. When animals were primed with DNA and boosted with protein, both antibody and Th-cell proliferative responses were significantly enhanced. Furthermore, production of Th1-type cytokines (interleukin-2, interferon-gamma) was enhanced by DNA priming-protein boosting. In contrast, protein priming-DNA boosting produced antibody levels similar to those following protein-protein vaccination but failed to further enhance Th-cell proliferative responses or cytokine production. DNA priming-protein boosting resulted in an increased IgG2a isotype (a Th1 indicator) profile, similar to that induced by DNA-DNA vaccination, whereas protein priming-DNA boosting caused an increased IgG1 isotype (a Th2 indicator) profile similar to that seen after protein-protein vaccination. This result indicates that preferential induction of IgG1 or IgG2a isotype is determined by the type of priming vaccine used. Thus, this study suggests that HSV DNA priming-protein boosting could elicit both potent Th1-type cellular immune responses and antibody responses, both of which likely are important for protection against HSV infection.
An Inhibitor of p38 Mitogen-activated Protein Kinase Protects Neonatal Cardiac Myocytes from Ischemia (1999)

Cellular ischemia results in activation of a number of kinases, including p38 mitogen-activated protein kinase (MAPK); however, it is not yet clear whether p38 MAPK activation plays a role in cellular damage or is part of a protective response against ischemia. We have developed a model to study ischemia in cultured neonatal rat cardiac myocytes. In this model, two distinct phases of p38 MAPK activation were observed during ischemia. The first phase began within 10 min and lasted less than 1 h, and the second began after 2 h and lasted throughout the ischemic period. Similar to previous studies using in vivo models, the nonspecific activator of p38 MAPK and c-Jun NH2-terminal kinase, anisomycin, protected cardiac myocytes from ischemic injury, decreasing the release of cytosolic lactate dehydrogenase by approximately 25%. We demonstrated, however, that a selective inhibitor of p38 MAPK, SB 203580, also protected cardiac myocytes against extended ischemia in a dose-dependent manner. The protective effect was seen even when the inhibitor was present during only the second, sustained phase of p38 MAPK activation. We found that ischemia induced apoptosis in neonatal rat cardiac myocytes and that SB 203580 reduced activation of caspase-3, a key event in apoptosis. These results suggest that p38 MAPK induces apoptosis during ischemia in cardiac myocytes and that selective inhibition of p38 MAPK could be developed as a potential therapy for ischemic heart disease.
Uso del implante auditivo osteointegrado BAHA Attract system en el Instituto Nacional de Rehabilitación. Reporte del primer dispositivo colocado en México (2015)

For over 35 years, bone anchored hearing aids have proved useful for the treatment of conductive or mixed unilateral or bilateral hearing loss, as well as for sensorineural unilateral hearing loss. During the last years important improvements have been done in this type of implants and one which presents some of the best features is the BAHA Attract by Cochlear, which has the advantage of not requiring an external percutaneous abutment, instead it gets coupled by magnetism. In this article we report the case of a 40-year old female with bilateral otosclerosis, who had important problems with stapes surgery and didn’t gain hearing improvement after stapedectomy, but did improve hearing with the use of one of this bone anchored device.
Radiation Dosimetry by Transparent Plastics (1958)

The radiation-induced ultraviolet absorption in transparent plastics has been investigated in detail and found to be a convenient, rapid, inexpensive, and accurate method of measuring radiation doses between 10/sup 5/ and 2 x 10/sup 8/ rads. In methyl methacrylate (Perspex) the change in optical density at 2920 A is a linear function of the dose, up to about 3 megarads and of the irverse of the thickness of the sample. Various factors that may influence the reproductbility of results have been investigated. The calibration curve relating the change in optical density to the dose in rads measured calorimetrically is given. In polyethylene terephthalate (Melinex), which can be obtained in thin foils the induced absorption was measured at 3250 A and calibration curves obtained up to 200 megarads. The rate of fading of the induced absorption and its bearing on the results are discussed. Some examples are given of the application of this technique to dosimetry. (auth)
Lipid Nanoparticles Containing siRNA Synthesized by Microfluidic Mixing Exhibit an Electron-Dense Nanostructured Core (2012)

Lipid nanoparticles (LNP) containing ionizable cationic lipids are the leading systems for enabling therapeutic applications of siRNA; however, the structure of these systems has not been defined. Here we examine the structure of LNP siRNA systems containing DLinKC2-DMA(an ionizable cationic lipid), phospholipid, cholesterol and a polyethylene glycol (PEG) lipid formed using a rapid microfluidic mixing process. Techniques employed include cryo-transmission electron microscopy, (31)P NMR, membrane fusion assays, density measurements, and molecular modeling. The experimental results indicate that these LNP siRNA systems have an interior lipid core containing siRNA duplexes complexed to cationic lipid and that the interior core also contains phospholipid and cholesterol. Consistent with experimental observations, molecular modeling calculations indicate that the interior of LNP siRNA systems exhibits a periodic structure of aqueous compartments, where some compartments contain siRNA. It is concluded that LNP siRNA systems formulated by rapid mixing of an ethanol solution of lipid with an aqueous medium containing siRNA exhibit a nanostructured core. The results give insight into the mechanism whereby LNP siRNA systems are formed, providing an understanding of the high encapsulation efficiencies that can be achieved and information on methods of constructing more sophisticated LNP systems.
pH-Induced Conformational Changes in Clostridium difficile Toxin B (2000)

Toxin B from Clostridium difficile is a monoglucosylating toxin that targets substrates within the cytosol of mammalian cells. In this study, we investigated the impact of acidic pH on cytosolic entry and structural changes within toxin B. Bafilomycin A1 was used to block endosomal acidification and subsequent toxin B translocation. Cytopathic effects could be completely blocked by addition of bafilomycin A1 up to 20 min following toxin treatment. Furthermore, providing a low extracellular pH could circumvent the effect of bafilomycin A1 and other lysosomotropic agents. Acid pH-induced structural changes were monitored by using the fluorescent probe 2-(p-toluidinyl) naphthalene-6-sulfonic acid, sodium salt (TNS), inherent tryptophan fluorescence, and relative susceptibility to a specific protease. As the toxin was exposed to lower pH there was an increase in TNS fluorescence, suggesting the exposure of hydrophobic domains by toxin B. The change in hydrophobicity appeared to be reversible, since returning the pH to neutrality abrogated TNS fluorescence. Furthermore, tryptophan fluorescence was quenched at the acidic pH, indicating that domains may have been moving into more aqueous environments. Toxin B also demonstrated variable susceptibility to Staphylococcus aureus V8 protease at neutral and acidic pH, further suggesting pH-induced structural changes in this protein.
Thermal Comfort and the Heat Stress Indices (2006)

Thermal stress is an important factor in many industrial situations, athletic events and military scenarios. It can seriously affect the productivity and the health of the individual and diminish tolerance to other environmental hazards. However, the assessment of the thermal stress and the translation of the stress in terms of physiological and psychological strain is complex. For over a century attempts have been made to construct an index, which will describe heat stress satisfactorily. The many indices that have been suggested can be categorized into one of three groups: "rational indices", "empirical indices", or "direct indices". The first 2 groups are sophisticated indices, which integrate environmental and physiological variables; they are difficult to calculate and are not feasible for daily use. The latter group comprises of simple indices, which are based on the measurement of basic environmental variables. In this group 2 indices are in use for over four decades: the "wet-bulb globe temperature" (WBGT) index and the "discomfort index" (DI). The following review summarizes the current knowledge on thermal indices and their correlates to thermal sensation and comfort. With the present knowledge it is suggested to adopt the DI as a universal heat stress index.
Denatured states of human carbonic anhydrase II: an NMR study of hydrogen/deuterium exchange at tryptophan‐indole‐HN sites (1999)

Hydrogen/deuterium (H/D) exchange measurements in low and moderate concentrations of GuHCI were conducted on the side chain H(N) atoms of the seven tryptophans of pseudo wild-type human carbonic anhydrase II. Tryptophans 5, 16 and 245, situated in or close to the N-terminal domain were found to have little protection against exchange. The H/D exchange results for Trp-123, Trp-192 and Trp-209 showed that a previously identified molten globule and the native state gave a similar protection against exchange. Global unfolding of the protein is necessary for the efficient exchange at Trp-97, which is located in the central part of the beta-sheet.
MBNL1 binds GC motifs embedded in pyrimidines to regulate alternative splicing (2010)

Muscleblind-like 1 (MBNL1) regulates alternative splicing and is a key player in the disease mechanism of myotonic dystrophy (DM). In DM, MBNL1 becomes sequestered to expanded CUG/CCUG repeat RNAs resulting in splicing defects, which lead to disease symptoms. In order to understand MBNL1's role in both the disease mechanism of DM and alternative splicing regulation, we sought to identify its RNA-binding motif. A doped SELEX was performed on a known MBNL1-binding site. After five rounds of SELEX, MBNL1 selected pyrimidine-rich RNAs containing YGCY motifs. Insertion of multiple YGCY motifs into a normally MBNL1-independent splicing reporter was sufficient to promote regulation by MBNL1. MBNL1 was also shown to regulate the splicing of exon 22 in the ATP2A1 pre-mRNA, an exon mis-spliced in DM, via YGCY motifs. A search for YGCY motifs in 24 pre-mRNA transcripts that are mis-spliced in DM1 patients revealed an interesting pattern relative to the regulated exon. The intronic regions upstream of exons that are excluded in normal tissues relative to DM1, are enriched in YGCY motifs. Meanwhile, the intronic regions downstream of exons that are included in normal tissues relative to DM1, are enriched in YGCY motifs.
Telomerase and telomere stability: A new class of tumor suppressor? (2000)

Introduction of telomerase into normal cells provides telomere maintenance and an extended cellular life span, establishing the critical role of telomere attrition in cellular senescence. Additional data surrounding this observation suggest that expression of telomerase renders these “mortal” cells genomically stable with decreased frequencies of mutation, ultimately leading to continued proliferation without signs of changes typically associated with progression to a cancer-like phenotype. Interestingly, oncogenic insult after exogenous telomerase expression does not result in cellular transformation, yet addition of an oncogene first followed by telomerase does transform cells. Taken together, these results imply that order of addition is important for telomerase-mediated genomic protection and that telomerase expression is critical for the transformation process. The hypothesis proposed here is that telomerase, via its function in telomere stabilization, is capable of protecting cells from acquiring the required mutations and genomic instability necessary for malignant transformation, suggesting that telomerase is not an oncogene but may act as a novel class of tumor suppressor. Mol. Carcinog. 28:1–4, 2000. © 2000 Wiley-Liss, Inc.
A selenium-containing nucleoside at the first position of the anticodon in seleno-tRNAGlu from Clostridium sticklandii. (1985)

In previous studies, the single selenonucleoside component of a selenium-containing tRNAGlu isolated from Clostridium sticklandii has been shown to be 5-methyl-aminomethyl-2-selenouridine. Here, we show that this selenonucleoside is most likely located at the "wobble" position of the anticodon of the clostridial seleno-tRNAGlu. Nuclease T1 digestion of this seleno-tRNAGlu generated one major selenium-containing oligonucleotide (25 bases long). The selenium-containing residue within this oligonucleotide was located by sequence analysis of the oligonucleotide before and after removal of selenium by treatment with cyanogen bromide. The sequence of this oligonucleotide, A-A-C-C-G-C-C-C-U-U+-U-C-A+C-G-G-C-G-G-U-A-A-C-A-G, is homologous to that of the Escherichia coli tRNAGlu2 from residues 27 to 50, including the anticodon region and the variable loop, except that the E. coli tRNA has 5-methylaminomethyl-2-thiouridine instead of the selenonucleoside.
Sequential Probability Ratio Test for Nuclear Plant Component Surveillance (1991)

It is common practice in nuclear power plants to install redundant sensors to monitor critical physical variables such as pressures, temperatures, and radiation levels. The design and testing of an extremely sensitive component-operability surveillance algorithm based on the sequential probability ratio test (SPRT) are reported. The SPRT technique processes the stochastic components of digitized signals from identical sensors on two or more components in an operating reactor for the detection and annunciation of off-normal operation. Information from the SPRT can provide a reactor operator with early identification of conditions that could lead to plant operational degradation, thus enabling him or her to terminate or avoid events that might challenge safety or radiological performance guidelines. The SPRT enhances plant availability and economics by minimizing unnecessary reactor trips caused in conventional systems by occasional spurious data that might exceed a simple high/low limit check. An example application of the SPRT for the surveillance of primary coolant pump operability in the Experimental Breeder Reactor II is presented.
Effects of a monoclonal antibody directed against P-selectin after myocardial ischemia and reperfusion (1996)

Neutrophils (polymorphonuclear leukocytes, PMNs) play a role in tissue injury after ischemia and reperfusion. We investigated the effects of a monoclonal antibody (MAb), PB1.3, directed against P-selectin in an acute model of myocardial ischemia-reperfusion injury. Dogs were subjected to 120 min of coronary arterial occlusion and 240 min of reperfusion. MAb PB1.3 (1 mg/kg), the nonblocking P-selectin antibody, MAb PNB1.6 (1 mg/kg), or saline was administered 5 min before reperfusion. Dogs treated with saline (n = 7), MAb PB1.3 (n = 7), and MAb PNB1.6 (n = 5) all experienced similar myocardial blood flows during ischemia, and treatment with MAb PB1.3 failed to preserve postischemic myocardial blood flow. Measurement of myocardial contractility failed to demonstrate any beneficial effects of MAb PB1.3 on postischemic myocardial contractility. However, myocardial necrosis (% of area at risk) was significantly reduced (P < 0.01) in dogs receiving MAb PB1.3 (20.8 +/- 4.8%) compared with dogs receiving either normal saline (41.7 +/- 4.5%) or MAb PNB1.6 (46.7 +/- 7.6%). Myocardial myeloperoxidase activity in the ischemic zone was 4.8 +/- 0.6 in the vehicle group and 3.7 +/- 0.5 in the MAb PNB1.6 group compared with 2.0 +/- 0.5 in MAb PB1.3-treated dogs (P < 0.01 vs. saline; P < 0.05 vs. PNB1.6). In summary, treatment with MAb PB1.3 failed to preserve postischemic myocardial blood flow or myocardial contractility. In contrast, P-selectin immunoneutralization reduced PMN accumulation and myocardial tissue injury in a canine model of coronary occlusion and reperfusion.
Increased detection of specific tyrosine phosphoproteins correlates with tumor progression of Abelson virus-infected lymphocytes. (1995)

Leukemias induced with the v-abl or BCR/ABL oncogene undergo a process of tumor progression which suggests that the ABL oncogene is required but not sufficient for full transformation. In order to identify cellular changes that correlate with progression to full transformation in v-abl transformed lymphoblasts Abelson virus (A-MuLV)-infected murine bone marrow was plated over a pre-established stromal feeder layer. Shortly after A-MuLV infection, transformed lymphoblasts were poorly oncogenic, but over time, progressed in a stepwide manner to a more oncogenic state. The transformants first acquired the ability to grow efficiently in agar, but only over the feeder layer. They next progressed to efficient feeder-independent growth in liquid culture, and then to efficient feeder-independent growth in soft agar. Cell lines that reached the advanced stage of feeder-independent agar growth showed increased detection by antiphosphotyrosine Western blot of the GAP-associated p62 phosphoprotein as well as of a 55 kDa phosphoprotein while detection of the P160 v-abl phosphoprotein remained constant throughout all stages of progression. Although the identity of the p55 phosphoprotein and the mechanism by which detection of p55 and p62 phosphoproteins change on the Western blots during tumor progression are unknown, the data demonstrate that these changes strongly correlate with the stage of progression of v-abl-transformed cells and raise the possibility that these changes may play a role in tumor progression in this model.